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AMERICAN DIABETES ASSOCIATION-SELF-ASSESSMENT PROGRAM:

CARDIOMETABOLIC RISK

Target Audience

All health care professionals involved in treating individuals with, or at risk for, diabetes, including

physicians, physician assistants, nurses, nurse practitioners, dietitians, pharmacists, and other health care

professionals.

Learning Objectives

I. Identify cardiometabolic risk (CMR) factors associated with the pathophysiology of cardiovascular

(CV) disease in persons with, or at risk for, prediabetes or type 2 diabetes.

II. Implement screening strategies for individuals with CMR into clinical practice to promote early

detection and prevention of prediabetes or diabetes.

III. Discuss how preventing CMR factors can positively impact CV health in persons with, or at risk

for, prediabetes or type 2 diabetes.

IV. List treatment options and define goals of treatment directed toward CMR factors.

V. Incorporate into clinical practice evidence‐based data from clinical trials and recommendations

from clinical practice guidelines toward the optimal management of individuals with CMR.

Abbreviations used throughout this program:

A1c=glycosylated hemoglobin A1c

ACC=American College of Cardiology

ACCOMPLISH=Avoiding Cardiovascular Events in Combination Therapy in Patients Living with

Systolic Hypertension

ACCORD=Action to Control Cardiovascular Risk in Diabetes

ACE=angiotensin converting enzyme

AHA=American Heart Association

AHEAD=Action for Health in Diabetes

ARB=angiotensin receptor blocker

Association=American Diabetes Association

ATP-III=Adult Treatment Panel

BMI=body mass index

BP=blood pressure

CMR=cardiometabolic risk

CABG=coronary arterial bypass graft

CRP=c-reactive protein

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CV=cardiovascular

DASH=Dietary Approaches to Stop Hypertension

DBP=diastolic blood pressure

DPP=Diabetes Prevention Program

DSME= diabetes self-management education

DSMS=diabetes self-management support

DSE=diabetes support education

FDA=Food and Drug Administration

FPG=fasting plasma glucose

GDM=gestational diabetes mellitus

HDL-C=high-density lipoprotein cholesterol

IFG=impaired fasting glucose

IGT=impaired glucose tolerance

INSPIRE ME IAA=International Study of the Prediction of Intra-Abdominal Adiposity and its

Relationship with CMR/Intra-Abdominal Adiposity

ILI=intensive lifestyle intervention

IPG=impaired fasting glucose

LDL-C=low-density lipoprotein cholesterol

NHANES=National Health and Nutrition Examination Survey

OHS=obesity-hypoventilation syndrome

OGTT=oral glucose tolerance test

OmniHeart=Optimal Macronutrient Intake Trial for Heart Health

OSA=obstructive sleep apnea

PCI=percutaneous coronary intervention

PTDS=post-traumatic stress disorder

REMS= risk evaluation and mitigation strategy

SBP=systolic blood pressure

SSB=sugar-sweetened beverages

TZD=thiazolidinedione

TOS=The Obesity Society

U.S.=United States

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VLDL=very low-density lipoprotein cholesterol

WHR=waist-to-hip ratio

WHtR=waist-to-height ratio

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CASE STUDY #1

HT, a 39-year old Japanese-American male, comes in for a routine check-up. In reviewing his medical

record, you note that he has had difficulty controlling his blood glucose over the past 20 years, with FPG

levels fluctuating between 95 mg/dL and 115 mg/dL. Over that time period, you have consistently

counseled him to increase his level of exercise, but his work schedule was so erratic that he did not. In

addition, his occupation (actor) required him to intermittently add excessive weight (30-40 pounds) and

then is forced to lose that weight in a short amount of time.

Physical exam: height, 5’10” (177.8 cm); weight, 180 lbs (84 kg); BMI, 25.8 kg/m2; waist circumference,

38 inches (96.5 cm); SBP, 126 mmHg; DBP, 80 mmHg (average of 3 readings).

Social history: 1-2 glasses of wine a day; denies tobacco use; no structured exercise program, although his

work does involve physical activity at times.

Lab results (within the past week): A1c, 6.0%; fasting blood glucose, 108 mg/dL; total cholesterol, 190

mg/dL; LDL-C, 124mg/dL; HDL-C, 34 mg/dL; triglycerides, 160 mg/dL

Medications: None

Assessment: HT has prediabetes, but is otherwise is healthy and in no acute distress.

Questions 1-15

1. IFG is a condition in which the FPG level is between:

A. 75 and 100 mg/dL

B. 100 and 125 mg/dL

C. 125 and 150 mg/dL

D. 140 and 199 mg/dL

E. >200 mg/dL

Answer: B

Rationale:

Individuals with IFG and/or IGT have been referred to as having prediabetes, indicating the relatively

high risk for the future development of diabetes. By definition, IFG is a condition in which FPG levels

range between 100 mg/dL (5.6 mmol/L) and 125 mg/dL (6.9 mmol/L) after an 8 to 12 hour fast. IGT is

defined as having 2-hour plasma glucose values from an OGTT of 140 mg/dL (7.8 mmol/L) to 199

mg/dL (11.0 mmol/L). If the 2-hour blood glucose rises to 200 mg/dl or above, a person has diabetes.

For A1c, clinical research studies that used this measurement to predict the progression to diabetes

demonstrated a strong, continuous association between A1c and subsequent diabetes. An A1c range of

6.0–6.5% had a 5-year risk of developing diabetes between 25 to 50%, with a relative risk 20 times higher

compared with an A1c of 5.0%. Other analyses suggest that an A1c of 5.7% is associated with diabetes

risk similar to that in the high-risk participants in the Diabetes Prevention Program (DPP). The American

Diabetes Association’s Standards of Care state that it is reasonable to consider an A1c range of 5.7–6.4%

as identifying individuals with prediabetes. Thus, HT’s A1c of 6.3% meets the criteria for prediabetes.

Reference(s):

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Ackermann RT, Cheng YJ, Williamson DF, Gregg EW. Identifying adults at high risk for diabetes and

cardiovascular disease using hemoglobin A1c National Health and Nutrition Examination Survey 2005-

2006. Am J Prev Med. 2011;40:11–17.

Zhang X, Gregg EW, Williamson DF, et al. A1C level and future risk of diabetes: a systematic review.

Diabetes Care. 2010;33:1665–1673.

American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.

2014;37:S14-S80.

2. Prediabetes is a state in which:

A. One’s blood glucose level falls within the normal range.

B. A patient has IFG and/or IGT.

C. One’s blood glucose level is higher than normal, but not yet high enough to be diagnostic of diabetes.

D. Both b and c

E. All of the above

Answer: D

Rationale:

Recognizing clinical signs in individuals at risk for developing diabetes is a key to prevention. Two signs

that should alert clinicians are higher than normal blood glucose levels, based upon IFG, IGT, and/or an

elevated A1c level. Although these levels may not high enough to be classified as diabetes, many

clinicians disregard their significance. IFG and IGT should be viewed as risk factors for diabetes as well

as CV disease rather than clinical entities, as they are associated with obesity (especially abdominal or

visceral obesity), atherogenic dyslipidemia with high triglycerides and/or low HDL-C, and hypertension.

Thus, there is a relatively high risk for the future development of diabetes for individuals with IFG, IGT,

and/or elevated A1c despite not having diabetes by a clinical definition. This condition is called

prediabetes.

Reference(s):

Ferrannini E, Balkau B, Coppack SW, et al; RISC Investigators. Insulin resistance, insulin response, and

obesity as indicators of metabolic risk. J Clin Endocrinol Metab. 2007;92:2885-2892.

CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes

in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, CDC; 2011.

Available at http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed November 3, 2013.

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care.

2014;37 Suppl 1:S81-90.


2014;37:S14-S80.

3. Insulin resistance is a key feature in type 2 diabetes, as well as:

A. Dyslipidemia

B. Endothelial dysfunction

C. Obesity

http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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D. Acanthosis nigricans

E. All of the above

Answer: E

Rationale:

Insulin resistance is characterized by the impaired function of insulin to stimulate glucose disposal in

peripheral tissues and suppress hepatic glucose production. Insulin resistance is a key feature of type 2

diabetes, as well as dyslipidemia, obesity, hypertension, and endothelial dysfunction.

Reference(s):




2014;37:S14-S80.

4. Which of the following statement(s) are true?

A. CV disease risk escalates with increasing hyperglycemia and insulin resistance, which may occur

long before the clinical diagnosis of diabetes.

B. IFG confers a much greater risk of coronary heart disease, CV disease, and overall mortality than the

presence of the metabolic syndrome.

C. CMR only includes the major components of the metabolic syndrome and no other factors that affect

risk, such as lifestyle and genetic factors.

D. A and B above.

E. A and C above.

Answer: A

Rationale:

CMR is preferred term to denote both the cluster of risk factors traditionally known as metabolic

syndrome, which includes traditional parameters of CV disease risk (waist circumference, triglycerides,

HDL-C, blood pressure, IFG), as well as risk markers resulting from abdominal obesity (certain cytokines

and adipokines). The term captures all risk related to the metabolic changes associated with CV disease

and not just those fitting the metabolic syndrome definition. CV risk factors, such as hypertension,

diabetes, elevated cholesterol and atherogenic dyslipidemia, and cigarette smoking promote oxidative

stress to cause endothelial dysfunction, initiating a cascade of events. These events include alterations in

vasoactive mediators, inflammatory responses, and vascular remodeling, which culminate in target-organ

damage. Evidence indicates that these processes begin earlier in life than previously recognized,

indicating that CV disease occurs over decades, long before the clinical diagnosis of diabetes.

Reference(s)

Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical

evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors

through stable coronary artery disease). Circulation. 2006;114:2850-2870.

https://www.ncbi.nlm.nih.gov/pubmed/17179034



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Balkau B, Deanfield JE, Després JP, et al. International Day for the Evaluation of Abdominal Obesity

(IDEA): a study of waist circumference, cardiovascular disease, and diabetes mellitus in 168,000

primary care patients in 63 countries. Circulation. 2007;116:1942-1951.

5. The most common cause of acquired insulin resistance is:

A. BMI <23 kg/m2 without abdominal obesity

B. Abdominal (visceral) obesity

C. Increased subcutaneous fat deposition

D. CRP level <1.0 mg/L

E. FPG level <100 mg/dL

Answer: B

Rationale:

An important component of increased CMR is abdominal obesity (increased waist circumference), and is

caused by excess abdominal visceral fat. Approximately 85% of total adipose tissue mass is located

under the skin (subcutaneous fat), with the remainder, approximately 15%, being located within the

abdomen (intra-abdominal fat). The relative contribution of intra-abdominal fat mass to total body fat is

influenced by sex, age, race/ethnicity, physical activity, and total adiposity. The term “visceral fat” is

commonly used to describe intra-abdominal fat and includes both intraperitoneal fat (mesenteric and

omental fat), which drains directly into the portal circulation, and retroperitoneal fat, which drains into the

systemic circulation.

This excess visceral fat is more metabolically active than subcutaneous fat, has greater endocrine activity,

and causes greater adverse effect on metabolism and CV risk. Visceral fat also has a greater ability to

release cytokines and adipokines than subcutaneous fat. These cytokines and adipokines have an impact

on causing insulin resistance, elevating triglyceride and small-dense LDL-C levels, hyperinsulinemia, and

endothelial dysfunction, all of which can contribute to vascular damage. One study showed among

overweight/moderately obese men and women, after adjusting for BMI, increases in visceral adipose

tissue increased the risk for insulin resistance, whereas increases in subcutaneous adipose tissue decreased

the risk for insulin resistance.

A BMI of <25 kg/m2 is considered to be an optimal weight and not considered to be the most common

cause of insulin resistance, especially in the absence of abdominal obesity. CRP is a measurement of

inflammation and used to further evaluate underlying risk, but not a cause of insulin resistance. An

individual with a high-sensitivity-CRP level of <1.0 mg/L is considered at low risk.

Reference(s):

Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome.

Endocr Rev. 2000;21:697‐738.

Ballantyne CH, Nambi V. Markers of inflammation and their clinical significance. Atherosclerosis.

2005;6(suppl): 21-29.

Klein S, Allison DB, Heymsfield SB, et al; Association for Weight Management and Obesity Prevention;

NAASO; Obesity Society; American Society for Nutrition; American Diabetes Association. Waist

circumference and cardiometabolic risk: a consensus statement from Shaping America's Health:

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Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the

American Society for Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30:1647-

1652.

Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, et al. The metabolic

syndrome. Endocr Rev. 2008;29:777–822.

McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral

depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011;96:E1756-1760.


2014;37:S14-S80.

6. Excess fat within in the abdomen (visceral adiposity) is:

A. A traditional marker for CV disease risk

B. More strongly associated with CMR than overall weight or BMI

C. A less potent risk factor than BMI

D. Is less metabolically active than subcutaneous fat

E. A surrogate measure of increased insulin sensitivity

Answer: B

Rationale:

CMR comprises a cluster of risk factors that are good indicators of an individual’s overall risk for CV

disease and type 2 diabetes. CMR also includes visceral obesity and other markers not traditionally

considered in CV disease risk assessment. A more potent risk factor than BMI, excess fat within the

abdomen and other organs, as opposed to subcutaneous tissues, has been linked with glucose intolerance,

dyslipidemia, and hypertension, as well as insulin resistance. Visceral fat is more insulin resistant and

more metabolically active than subcutaneous fat and has been shown to release excess toxic cytokines,

proinflammatory molecules, and vasoactive hormones, as well as driving excess free fatty acids and

cortisol directly to the liver.

Reference(s):



Smith JD, Borel AL, Nazare JA, et al. Visceral adipose tissue indicates the severity of cardiometabolic

risk in patients with and without type 2 diabetes: results from the INSPIRE ME IAA study. J Clin

Endocrinol Metab. 2012;97:1517-1525.

7. Which of the following is currently the most widely used index of abdominal (visceral) obesity?

A. BMI

B. Absolute waist circumference

C. A1c

D. Total cholesterol/HDL-C ratio

E. A and B above

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Answer: B

Rationale:

BMI is an index of general adiposity. Because waist measurement is more prone to errors than measuring

height and weight, it is recommended to use all three. BMI best illustrates an estimate of the level of

obesity, while waist measurement gives an estimate of visceral fat and risk of obesity-related diseases,

such as diabetes. The relationship between waist circumference and clinical outcomes is consistently

strong for diabetes risk, and waist circumference is a stronger predictor of diabetes than is BMI. But,

waist circumference can identify persons who are at greater CMR than those identified by BMI alone.

Beyond waist circumference, the waist-to-hip ratio is used to determine the severity of central obesity.

Although total cholesterol/HDL-C ratio is used as a marker for increased insulin resistance, it is not a

marker of visceral obesity.

The most recent ACC/AHA/TOS guidelines on obesity note that is not necessary to measure waist

circumference in patients with BMI >35, as this measurement will likely be elevated and it adds no

additional risk information. As an indication of increased CMR, these guidelines continue to recommend

using the current cutpoints: >35 inches (88 cm) for women and >40 inches (102 cm) for men. Thus, a

large waist circumference is a key surrogate measure of insulin resistance when assessing risk of incident

diabetes and CV disease.

Reference(s):

Yusuf S, Hawken S, Ounpuu S, et al; INTERHEART Study Investigators. Effect of potentially

modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study):

case-control study. Lancet. 2004;364:937–952.



circumference and CMR: a consensus statement from shaping America's health: Association for Weight

Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for

Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30:1647-1652.


2014;37:S14-S80.

Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of

overweight and obesity in adults: a report of the American College of Cardiology/American Heart

Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:

http://circ.ahajournals.org.

8. Based upon results from the from the International Study of the INSPIRE ME IAA study, what

was the impact of diabetes treatment for achieving the American Diabetes Association's

(Association’s) goals for HDL-C or triglycerides despite the presence of excess visceral adipose

tissue and liver fat?

A. Fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for

the two lipid parameters compared to patients with low visceral adipose tissue or liver fat

regardless of diabetes treatment.

http://www.ncbi.nlm.nih.gov/pubmed/17360974




http://circ.ahajournals.org/

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B. More patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for

the two lipid parameters compared to patients with low visceral adipose tissue or liver fat.

C. Fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for

HDL-C but not triglycerides compared to patients with low visceral adipose tissue or liver fat.

D. Fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for

triglycerides but not HDL-C compared to patients with low visceral adipose tissue or liver fat.

E. None of the above

Answer: A

Rationale:

Both visceral adipose tissue and liver fat are strongly associated with insulin resistance and type 2

diabetes. In a cross-sectional analysis of baseline data (N = 3991) from the INSPIRE ME IAA study,

patients were divided into four groups: those without type 2 diabetes (n=1003 men, n=1027 women);

those with type 2 diabetes but not treated with diabetes medications (n=248 men, n=198 women); those

with type 2 diabetes and treated with diabetes medications but not yet using insulin (n=591 men, n=484

women), and those with type 2 diabetes and treated with insulin (n=233 men, n=207 women).

Results showed fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s

goals for HDL-C or triglycerides compared to patients with low visceral adipose tissue or liver fat. Both

visceral adiposity (p = .02 men, p = .003 women) and liver fat (p = .0002 men, p = .0004 women) were

increased among patients who met fewer of the Association treatment criteria, regardless of type 2

diabetes treatment. Residual CMR exists among patients with type 2 diabetes characterized by elevated

VAT and LF.

Reference(s):

Smith J, Nazare JA, Borel AL, et al. Assessment of CMR and prevalence of meeting treatment guidelines

among patients with type 2 diabetes stratified according to their use of insulin and/or other diabetic

medications: results from INSPIRE ME IAA. Diabetes Obes Metab. 2013;15:629-641.

9. Which of the following is INCORRECT regarding how to measure waist circumference?

A. There is a uniformly-accepted approach when measuring waist circumference.

B. Measurement should be made around an individuals’ bare midriff, after they exhale while standing

without shoes, both feet touching, and arms hanging freely.

C. The measuring tape should be made of a material that is not easily stretched.

D. The tape should be placed perpendicular to the long axis of the body and horizontal to the floor and

applied with sufficient tension to conform to the measurement surface.

E. All of the above.

Answer: A

Rationale:

Waist circumference measurements should be made around a patient's bare midriff, after the patient

exhales while standing without shoes, both feet touching, and arms hanging freely. The measuring tape

should be made of a material that is not easily stretched, such as fiberglass. The tape should be placed

perpendicular to the long axis of the body and horizontal to the floor and applied with sufficient tension to

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conform to the measurement surface. Although not normally performed in the office, waist

circumference measurements are typically taken three times and recorded to the nearest 0.1 cm in a

research setting. And although specific techniques have been recommended for measuring waist

circumference in the clinical setting, there is no uniformly accepted approach. However, it is essential

that both healthcare practitioners, technicians, and patients use appropriate techniques for measuring waist

circumference, so reliable data can be obtained.

Reference(s):



circumference and CMR: a consensus statement from Shaping America's Health: Association for

Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for

Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30:1647-1652.

10. HT has a waist circumference of 38 inches. For a male, this measurement is less than the

guidelines cite as having an increased CMR due to abdominal obesity. What would be a more

accurate measure to determine an increased risk from abdominal obesity?

A. BMI

B. Waist-to-hip ratio

C. Waist-to-height ratio (index of central obesity)

D. Total cholesterol/HDL-C ratio


Answer: C

Rationale:

Along with BMI, waist circumference and WHR are also associated with increased CMR and risk of

death. However, the WHtR (also referred to as the Index of Central Obesity) has emerged as a promising

index for identification of subjects at increased CMR in both adults and children, as the calculation takes

into account height, which is important particularly in shorter individuals and those of various ethnicities.

A proposed single value of <0.5 is recommend as a cutoff for increased risk, whether male or female,

adult or child, irrespective of ethnicity. Several studies support this conclusion.

Kodama et al showed that WHtR had a stronger association with incident diabetes than BMI and WHR.

Ashwell et al showed that WHtR had a better discriminatory power than BMI and WC in detecting

several CMR factors. And in a meta-analysis by Savva et al, the overall ratio of relative risks clearly

indicated WHtR is superior to BMI in detecting type 2 diabetes. Regarding ethnicity, the association of

WHtR with type 2 diabetes was stronger in both Asians and non-Asians, whether male or female.

Because of this, it is recommended WHtR be included in the routine screening and assessment of

overweight and obese children, and those with an elevated WHtR should undergo a further CMR

assessment.

With a WHtR of 0.54, HT is at increased CMR, despite having a waist circumference less than that

defined by the guidelines as a measure of increased CMR.

Reference(s):





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Savva SC, Tornaritis M, Savva ME, et al. Waist circumference and waist-to-height ratio are better

predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes Relat

Metab Disord. 2000;24:1453–1458.

Ashwell M, Hsieh SD. Six reasons why the waist-to-height ratio is a rapid and effective global indicator

for health risks of obesity and how its use could simplify the international public health message on

obesity. Int J Food Sci Nutr. 2005;56:303–307.

Parikh RM, Joshi SR, Pandia K. Index of central obesity is better than waist circumference in defining

metabolic syndrome. Metab. Syndr. Relat. Disord. 2009;7:525–527.

Schneider HJ, Friedrich N, Klotsche J, et al. The predictive value of different measures of obesity for

incident cardiovascular events and mortality. J Clin Endocrinol Metab. 2010;95:1777-1785.

Schneider HJ, Klotsche J, Silber S, Stalla GK, Wittchen HU. Measuring abdominal obesity: effects of

height on distribution of cardiometabolic risk factors risk using waist circumference and waist-to-height

ratio. Diabetes Care. 2011;34:e7.

Kodama S, Horikawa C, Fujihara K, et al. Comparisons of the strength of associations with future type 2

diabetes risk among anthropometric obesity indicators, including waist-to-height ratio: a meta-analysis.

Am J Epidemiol. 2012;176:959–969.

Browning LM, Hsieh SD, Ashwell M. A systematic review of waist-to-height ratio as a screening tool for

the prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global boundary value.

Nutr Res Rev. 2010;23:247–269.

Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference

and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Obes Rev.

2012;13:275-286.

Khoury M, Manlhiot C, McCrindle BW. Role of the waist/height ratio in the cardiometabolic risk

assessment of children classified by body mass index. J Am Coll Cardiol. 2013;62:742-751.

American Diabetes Association. Standards of Medical Care in Diabetes—2014. Diabetes Care.

2014;37:S81-S90.





11. Based upon clinical evidence, each of the following race/ethnicities may require a lower cutoff

level for waist circumference EXCEPT:

A. African American

B. Japanese

C. Caucasian

D. South Asians

E. Hispanic Americans

Answer: C






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Rationale:

In various guidelines and the Association’s Standards of Care, cutoff values for waist circumference (>40

inches for men; ≥35 inches for women) were derived from values that correlated with a BMI ≥30 kg/m2.

The International Diabetes Federation recommends ethnic-specific values for determining cutoffs for

waist circumference of different ethnicities, such as South Asians, Japanese, and Chinese. Accordingly,

certain races/ethnicities in the U.S. may require a lower cutoff, including African Americans, Hispanic

Americans, South Asians, Chinese, and Japanese because of a greater risk for developing CMR.

Reference(s):

National Institutes of Health, National Heart, Lung, and Blood Institute: Clinical guidelines on the

identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes

Res. 1998;6(Suppl. 2): 51S–209S.

Okosun IS, Liao Y, Rotimi CN, Prewitt TE, Cooper RS. Abdominal adiposity and clustering of multiple

metabolic syndrome in white, black and Hispanic Americans. Ann Epidemiol. 2000;10:263-270.

Carnethon MR, Loria CM, Hill JO, Sidney S, Savage PJ, Liu K. Risk factors for the metabolic syndrome:

the Coronary Artery Risk Development in Young Adults (CARDIA) Study, 1985-2001. Diabetes Care.

2004;27:2707-2715.

Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic

syndrome--a new worldwide definition. Lancet. 2005;366:1059-1062.

Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an

American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.

Circulation. 2005;112:2735-2752.





Case 1 Continuation

12. You discuss with HT some treatment options, including increasing his physical activity,

intensity of exercise, weight management, and diet. In a person with prediabetes, weight

management and routine exercise:

A. Are seldom advised for patients with clear CMR

B. Can delay or prevent the onset of diabetes

C. Improve risk factors for CV disease

D. Both b and c

E. All of the above

Answer: D

Rationale:

Persons with prediabetes, including those with regular access to health care, might benefit from

educational efforts aimed at increasing awareness that they are at risk for developing type 2 diabetes, as




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they can reduce that risk by making modest lifestyle changes. Evidence-based lifestyle programs that

encouraged dietary changes, moderate-intensity physical activity, and modest weight loss for persons diet

with prediabetes have shown a delay or prevention of type 2 diabetes. Exploratory analysis from the

Look AHEAD study results showed ILI was associated with a greater likelihood of partial remission of

type 2 diabetes compared with DSE. In the DPP, the incidence of type 2 diabetes in persons at high risk

was reduced by 58% in the lifestyle intervention group and 31% in the metformin group, as compared

with placebo; the lifestyle intervention was significantly more effective than metformin.

Reference(s):

Knowler WC, Barrett-Conner E, Fowler SE, et al; Diabetes Prevention Program Research Group.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med.

2002;346:393–403.

Gregg EW, Chen H, Wagenknecht LE; Look AHEAD Research Group. Association of an intensive

lifestyle intervention with remission of type 2 diabetes. JAMA. 2012;308:2489-2496.

13. The American Diabetes Association recommends a structured program that emphasizes lifestyle

changes for individuals at high risk for developing type 2 diabetes. This type of program includes

which of the following:

A. Regular physical activity of less than 90 minutes per week.

B. Moderate physical activity of at least 150 minutes per week.

C. Dietary strategies that include only a reduction in calories to achieve a targeted body weight loss of

3%.

D. Dietary strategies that include both a reduction in calories and reduced intake of dietary fat to achieve

a targeted body weight loss of 7%.

E. B and D above

Answer: E

Rationale:

Evidence-based lifestyle programs that encouraged dietary changes, moderate-intensity physical activity,

and modest weight loss for persons with prediabetes have shown a delay or prevention in the onset of type

2 diabetes. The Association recommends structured programs that emphasize lifestyle changes for

individuals at high risk for developing type 2 diabetes. These programs should include moderate physical

activity of 150 min per week or intense physical activity of 90 minutes per week, and dietary strategies

(reduced calories and reduced intake of dietary fat) in order to achieve a targeted body weight loss of 7%.

Reference(s):

Knowler WC, Barrett-Conner E, Fowler SE, et al; Diabetes Prevention Program Research Group.

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med.

2002;346:393–403.

Gregg EW, Chen H, Wagenknecht LE; Look AHEAD Research Group. Association of an intensive

lifestyle intervention with remission of type 2 diabetes. JAMA. 2012;308:2489-2496.

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2014;37:S14-S80.

Case 1 Continuation

It is important that HT is exercising, but he is only maintaining his weight, not losing nor gaining.

And his latest A1c is 6.3%. He asks what more can be done to reverse his prediabetes and prevent

type 2 diabetes.

14. As noted, exercise and weight reduction are important for preventing type 2 diabetes. What

percent of individuals with prediabetes who do not lose weight and/or do not engage in moderate

physical activity will progress to type 2 diabetes during the average 3 years of follow-up?

A. 1%

B. 4%

C. 11%

D. 17%

E. 21%

Answer: C

Rationale:

There is a relatively high risk for the future development of diabetes for individuals with IFG, IGT, and/or

elevated A1c despite not having diabetes by a clinical definition, a condition called prediabetes. In 2010,

approximately one in three U.S. adults aged ≥20 years (an estimated 79 million persons) had prediabetes.

Of these, only 11% of persons with prediabetes were aware that they had the condition. And each year

approximately 11% of persons with prediabetes who do not lose weight and/or do not engage in moderate

physical activity will progress to type 2 diabetes.

Reference(s):

CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes

in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, CDC; 2011.

Available at http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed October 9, 2013.

Geiss LS, James C, Gregg EW, et al. Diabetes risk reduction behaviors among U.S. adults with

prediabetes. Am J Prev Med. 2010;38:403–409.

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care.

2014;37 Suppl 1:S81 - 90.

Centers for Disease Control and Prevention (CDC). Awareness of prediabetes - United States, 2005-2010.

MMWR Morb Mortal Wkly Rep. 2013;62:209-212.

15. In addition to exercise as a cornerstone therapy for diabetes prevention, the Association’s

Standards of Care recommends healthcare practitioners consider which of the following for

individuals with IFG, IGT, and an A1c of 5.7–6.4%?

A. Sulfonylurea

B. DPP-4 antagonist

C. Metformin

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Centers%20for%20Disease%20Control%20and%20Prevention%20(CDC)%22%5BCorporate%20Author%5D


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D. GLP-1 receptor agonist

E. Alpha-glucosidase inhibitor

Answer: C

Rationale:

Metformin has been shown to activate the key regulatory enzymes that may prevent the transition from

prediabetes to type 2 diabetes. In one study, insulin sensitivity was considerably higher after 12 weeks of

exercise training and/or metformin for individuals with prediabetes. Other evidence showed a greater

weight loss (2-5 kg) occurred with the addition of metformin compared with lifestyle modification alone.

The DPP also demonstrated that either lifestyle modification (i.e., low-fat diet and increased physical

activity) or metformin can reduce the transition from prediabetes to type 2 diabetes.

In addition to exercise as a cornerstone therapy for diabetes prevention, the Association’s Standards of

Care also recommends healthcare practitioners consider metformin therapy for individuals with IGT, IFG,

or an A1c of 5.7–6.4%, especially for those with BMI ≥35 kg/m2, aged 60 years or older, and women with

prior GDM.

Reference(s):

Malin SK, Gerber R, Chipkin SR, Braun B. Independent and combined effects of exercise training and

metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2012;35:131-136.

Atabek ME, Pirgon O. Use of metformin in obese adolescents with hyperinsulinemia: a 6-month,

randomized, double-blind, placebo-controlled clinical trial. J Pediatr Endocrinol Metab. 2008;21:339–

348.

Love-Osborne K, Sheeder J, Zeitler P. Addition of metformin to a lifestyle modification program in

adolescents with insulin resistance. J Pediatr. 2008;152:817–822.

The Diabetes Prevention Program Research Group. Role of insulin secretion and sensitivity in the

evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and

metformin. Diabetes. 2005;54:2404–2414.


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Case Study #2

FD, a 68-year-old African American male, comes in for a routine clinic visit. He was diagnosed with

essential hypertension 8 years ago with a SBP, 146 mmHg; DBP, 98 mmHg; currently, his BP is

controlled on medication.

Social history: 40-year history as a 1 pack-per-day smoker; no family history of premature coronary

disease. Was a business executive in the pharmaceutical industry; he is currently employed as a

consultant in healthcare. Physical activity is limited to 20 minutes per day of walking to and from work.

Diet is erratic, frequently dining out with clients, including 2-3 glasses of wine a day.

Physical examination: SBP/DPB, 138/87 mmHg (average of 3 readings); body mass index (BMI), 31

kg/m2; waist circumference, 42 inches (102.9 cm).

Recent lab data: fasting lipid panel is notable for total cholesterol, 218 mg/dL; LDL-C, 144 mg/dL; HDL-

C, 29 mg/dL; triglycerides, 226 mg/dL; FPG, 115 mg/dL.

Medications: amlodipine 5 mg once daily.

Assessment: FD is an obese African American with essential hypertension, dyslipidemia, and several

factors contributing to CMR.

Questions 16-35

16. Which of the following are modifiable CMR factors?

A. Race/ethnicity

B. Family history

C. Hypertension

D. Age

E. Gender

Answer: C

Rationale:

CV disease is the leading cause of death in the U.S. and many parts of the world. Modifiable CV and

CMR factors include obesity, tobacco use, physical inactivity, unhealthy diet, hypertension, abnormal

lipid metabolism (e.g. elevated LDL-C), as well as a cluster of interrelated metabolic risk factors, such as

inflammation/hypercoagulation and insulin resistance.

FD has a total of 7 modifiable CMR factors. Of those listed above, he has hypertension; family history,

racial/ethnicity, gender, and age are non-modifiable. His other modifiable CMR factors include

physically inactive (walks only 20 minutes per day), being overweight, has dyslipidemia, smokes, eats an

unhealthy diet, and is insulin resistant. He probably has some level of vascular inflammation based upon

his an elevated triglyceride/HDL-C ratio (indicating insulin resistance), but a CRP level would help to

determine the presence of that risk factor.

Reference(s):

Grundy SM. Primary prevention of coronary heart disease: integrating risk assessment with intervention.

Circulation. 1999;100:988-998.

http://www.ncbi.nlm.nih.gov/pubmed/10468531?dopt=Abstract

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Cannon CP. Cardiovascular disease and modifiable cardiometabolic risk factors. Clin Cornerstone.

2008;9:24-38.


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17. Each of the following statements is correct regarding CMR in different ethnicities EXCEPT:

A. CV disease, diabetes and related risk factors occur at higher rates among certain racial and ethnic

groups, including African Americans and Hispanic Americans.

B. African American men and women have the highest age-adjusted prevalence of high blood pressure.

C. African American women have the highest age-adjusted prevalence of abdominal obesity.

D. Conventional risk criteria does not need to be adjusted to accommodate for differences across ethnic

groups and, in turn, gain a more accurate assessment of CMR and existing disease.

E. Death rates from heart disease are higher among adults that are African American than Caucasians.

Answer: D

Rationale:

The prevalence, impact, and control of diabetes and CV disease differ across racial and ethnic subgroups

of the U.S. population. For example, in African Americans, hypertension is more common, more severe,

and develops at an earlier age. This group also has a greater prevalence of other risk factors, especially

obesity. However, much of the disparity among ethnic groups may be attributable to differences in

socioeconomic condition, access to health care, or attitudes toward health-related information.

Demographic factors also influence the likelihood of other risk factors for type 2 diabetes and CV disease.

Overweight and obesity correlate with a higher incidence of type 2 diabetes, hypertension, and heart

disease. Hispanics, Native Americans, and African Americans are all more likely than Caucasians to be

overweight or obese, even as children, so their overall risk as demographic groups for developing diabetes

and/or CV disease is greater than that of the Caucasian population.

Reference(s):

Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National

Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High

Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National

Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7

report. JAMA. 2003;289:2560–2572.

Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults,

1999–2000. JAMA. 2002; 288:1723–1727.

Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from

the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–372.

Park Y-W, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome:

prevalence and associated risk factor findings in the US population from the Third National Health and

Nutrition Examination Survey, 1988–1994. Arch Intern Med. 2003;163:427–436.



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18. Which of the following statements is CORRECT regarding CMR?

A. Only pharmacologic interventions have been proven to benefit patients with CMR.

B. Treatment goals for patients with CMR include achieving targets for blood glucose, blood pressure,

and dyslipidemia.

C. All patients with elevated high-density lipoprotein cholesterol need to be treated aggressively with

lifestyle modifications and adjunctive drug therapies.

D. Research results are inconclusive in the need for primary prevention of obesity beginning in

childhood.

E. The risk of myocardial infarction, strokes, and CV death is not increased.

Answer: B

Rationale:

The primary treatment of elevated CMR is lifestyle modification, as it has been shown to provide benefit

in patients with CMR. In addition to glycemic control, both national and international guidelines on

management of diabetes emphasize control of blood pressure, dyslipidemia, and obesity. The

INTERHEART study revealed nine easily measurable and modifiable risk factors (abnormal lipids;

smoking; hypertension; diabetes; abdominal obesity; psychosocial factors; decreased consumption of

fruits, vegetables, and alcohol; decreased physical activity) account for most of the risk for myocardial

infarction in all regions of the world, irrespective of gender and age. For individuals with CMR, the risk

of myocardial infarction, strokes, and CV death is 13 times higher than for those without CMR.

Reference(s):

UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 16: Overview of 6 years’ therapy

of type II diabetes: a progressive disease. Diabetes. 1995;44:1249-1258.

Yusuf S, Hawken S, Ounpuu S, et al, for the INTERHEART Study Investigators. Effect of potentially

modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study):

case control study. Lancet. 2004;364:937-952.


2014;37:S14-S80.

19. Which factor(s) play(s) a clear role in increasing a person’s CMR, but are not included in the

traditional classification of metabolic syndrome?

A. HDL-C levels

B. Tobacco use

C. Hypertension

D. Waist circumference

E. All of the above

Answer: B

Rationale:

There are many individuals who have a constellation of major risk factors, life-habit risk factors, and

emerging risk factors that constitute a condition called the metabolic syndrome. Factors characteristic of

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this syndrome include abdominal obesity, atherogenic dyslipidemia (elevated triglyceride, small LDL

particles, low HDL cholesterol, raised SBP/DBP, insulin resistance (with or without glucose intolerance),

and prothrombotic and proinflammatory states.

The term metabolic syndrome serves a useful purpose in that it emphasizes risk factor clustering and the

importance of insulin resistance. However, it does not include other factors known to be strongly

correlated with CV risk. CMR encompasses those risk factors that predispose an individual for diabetes

and CV disease. It includes those factors in the definition of metabolic syndrome, as well as age, tobacco

use, and LDL-C.

Reference(s):

Eckel RH, Kahn R, Robertson RM, Rizza RA. Preventing cardiovascular disease and diabetes: a call to

action from the American Diabetes Association and the American Heart Association. Circulation

2006;113:2943-2946.

Leiter LA, Fitchett DH, Gilbert RE, Gupta M, Mancini GB, McFarlane PA, et al. Cardiometabolic risk in

Canada: a detailed analysis and position paper by the cardiometabolic risk working group. Can J

Cardiol. 2011;27(2):e1–33.


2014;37:S14-S80.

Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce

cardiovascular risk: a report of the American College of Cardiology American/Heart Association Task

Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.

20. The Association’s Standards of Care endorse the preferred use of which of the following as a

treatment target when triglycerides levels are >200 mg/dL because of ease of calculation and does

not rely on any statistical estimates?

A. LDL-C levels

B. HDL-C levels

C. Non-HDL-C levels

D. Triglyceride/VLDL cholesterol ratio

E. LDL-C/HDL-C ratio

Answer: C

Rationale:

Unlike LDL-C, non-HDL-C represents the cholesterol content that is present in all the atherogenic

lipoproteins. Non-HDL-C was added in ATP-III as a secondary treatment target in patients with elevated

triglycerides (>200 mg/dL), with a treatment target being 30 mg/dL above the LDL-C treatment target.

The addition of non-HDL-C as a treatment target reflects the recognition of this calculated value as a

predictive factor in CV disease. The Association’s Standards of Care still endorses this parameter.

The more recent ACC/AHA Guidelines on the management of cholesterol, however, makes no

recommendation either for or against specific non-HDL–C goals for the primary or secondary prevention

of arteriosclerotic CV disease.


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Reference(s):

Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol in Adults (Adult Treatment

Panel III) Executive Summary of The Third Report of The National Cholesterol Education Program

(NCEP). JAMA. 2001:2486–2497.

Lu W, Resnick HE, Jablonski KA, et al. Non-HDL cholesterol as a predictor of cardiovascular disease in

type 2 diabetes: the Strong Heart Study. Diabetes Care. 2003;26:16-23.


2014;37:S14-S80.

Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of

cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task


Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood

cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of

Cardiology/American Heart Association. Circulation 2013; available at: http://circ.ahajournals.org.

21. What formula is used to calculate non-HDL-C?

A. LDL-C level minus HDL-C level

B. Triglyceride level minus LDL-C level

C. Total cholesterol level minus HDL-C level

D. Total cholesterol level minus LDL-C level

E. Triglyceride level divided by 3 plus LDL-C level

Answer: C

Rationale:

Non-HDL-C is calculated as subtracting the HDL cholesterol level from the total cholesterol level (TC

minus HDL cholesterol). It can also be calculated by dividing the triglyceride level by 5 and add that

value to the LDL cholesterol level. The reference ranges for non-HDL-C are based on National

Cholesterol Education III guidelines:

* Desirable: <130 mg/dL

* Borderline high: 139-159 mg/dL

* High: 160-189 mg/dL

* Very high: ≥190 mg/dL

Reference(s):

Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol In Adults (Adult Treatment


(NCEP). JAMA. 2001:2486–2497.

Lu W, Resnick HE, Jablonski KA, et al. Non-HDL cholesterol as a predictor of cardiovascular disease in

type 2 diabetes: the Strong Heart Study. Diabetes Care. 2003;26:16-23.



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22. The more inclusive paradigm of CMR recognizes that:

A. Every risk factor should be weighted equally

B. The whole is not greater than the sum of its parts; that is, each risk factor has differential effects on

future CV disease risk

C. Most markers have similar predictive importance for CV disease across all patients

D. None of the above

E. All of the above

Answer: B

Rationale:

CMR is continuous. That is, individuals have varying levels of CMR depending on the number and

severity of their risk factors. When assessing a patient for comprehensive risk, a thorough documentation

of the patient’s history should be done, including documentation of age, ethnicity, smoking status,

physical activity level, diet, family history of premature CV disease risk or type 2 diabetes, and

comorbidities. In addition, physical examination should include measurement of waist circumference and

blood pressure (average of 3 readings), and calculation of body mass index. Lab results should include a

fasting lipid panel, FPG, and creatinine or estimated glomerular filtration rate. A majority of these

encompass CMR.

Evaluating patients for all contributory risk factors means there is more likelihood of identifying patients

at high risk for CV disease or diabetes, allowing clinicians to intervene sooner with education and

treatment. However, CMR recognizes that not all risk factors can be weighted equally, given their

differential effects on future risk of CV disease or diabetes.

Reference(s):

Vasudevan AR, Ballantyne CM. Cardiometabolic risk assessment: an approach to the prevention of

cardiovascular disease and diabetes mellitus. Clin Cornerstone. 2005;7:7-16.

Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical

evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors

through stable coronary artery disease). Circulation. 2006;114:2850-2870.

23. Which of the following are major risk factors for developing type 2 diabetes?

A. Overweight/obesity

B. Increase in insulin sensitivity

C. Increased physical activity

D. Elevated HDL-C level

E. All of the above

Answer: A

Rationale:

Recognizing clinical signs and identifying risk factors in individuals at risk for developing diabetes are

essential for preventing the onset of the disease. These signs/risk factors include insulin resistance, a lack

of physical activity, and reduced HDL-C level. Having a BMI >25 kg/m2 is defined as being overweight;




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a BMI >30 kg/m2 is defined as being obese. An elevated BMI is a risk factor for developing type 2

diabetes and should be assessed along with other risk factors to determine an individual’s level of CMR.

Reference(s):

Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease.

Nature. 2006;444:875–880.


2014;37:S14-S80.

24. According to the Association’s Standards of Care, which of the following lipid parameters is a

more accurate predictor of CV risk than serum total cholesterol levels, and thus is often the initial

target for treatment?

A. HDL-C

B. LDL-C

C. Triglycerides

D. VLDL-C

E. All of the above

Answer: B

Rationale:

Lipoprotein measurements are used to better assess CMR and prescribe tailored therapies to control blood

lipids to reduce the risk of disease and related complications. Of these, LDL-C has traditionally been

considered a more accurate predictor of CV risk than serum total-C level and is often the initial target for

therapy, according to the Association’s Standards of Care. High levels of LDL-C can lead to and advance

atherosclerosis.

However, the recent ACC/AHA Guidelines on Assessing CV risk employ a formula of various

parameters, including gender, age, racial background (either Caucasian or African American, but not

other ethnicities), SBP and blood pressure treatment, a ratio of total cholesterol to HDL-C, and the

presence or absence of diabetes and tobacco use. The guideline committee did not employ LDL-C as a

component of the risk calculator, nor does it make any recommendations either for or against specific

LDL–C goals for the primary or secondary prevention of atherosclerotic CV disease.

Reference(s):

Expert Panel on Detection, Evaluation, Treatment of High Blood Cholesterol in Adults (Adult Treatment

Panel III) Executive Summary of the Third Report of The National Cholesterol Education Program

(NCEP). JAMA. 2001:2486–2497.


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cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of


Case 2 Continuation

25. You discuss with FD the risk of being overweight. What does research data reveal about

survival in individuals with a BMI of 30-35 kg/m2?

A. Life expectancy is decreased by 1-2 years

B. Life expectancy is decreased by 2-4 years

C. Life expectancy is decreased by 8-10 years

D. Life expectancy is not changed compared to patients with BMI of 25 kg/m2

E. Hazard is equivalent to smoking

Answer: B

Rationale:

In a collaborative analyses of baseline BMI versus mortality from 57 prospective studies, results revealed

that median survival is decreased by 0–1 year for people who would, by about age 60 years, reach a BMI

of 25–27·5 kg/m2, decreased by 1–2 years for those who would reach 27·5–30 kg/m2, and decreased by

2–4 years for those who would become obese (30–35 kg/m2). There was less information available for

those with a BMI >35 kg/m2, although median survival appears to be decreased by approximately 8–10

years in those who would become morbidly obese, that is a BMI of 40–50 kg/m2.

Reference(s):

Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000

adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083-1096.

26. How does a body mass index (BMI) increase of 5 kg/m2 impact SBP and DBP?

A. SBP is increased but DBP is decreased

B. Neither SBP nor DBP are affected

C. SBP is decreased but DBP is increased

D. Both SBP and DBP are increased

E. SBP and DBP are increased in males but not in females

Answer: D

Rationale:

In collaborative analyses of baseline BMI versus mortality from 57 prospective studies, results revealed

that BMI (15–50 kg/m2) was associated positively (and nearly linearly) with both SBP and DBP. Results

showed that on average across all ages (15–89 years), every increase in BMI of 5 kg/m2 was associated

with at least 5 mm Hg increase in SBP and approximately a 4 mmHg increase in DBP in both males and

females.

Reference(s):

Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000

adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083-1096.


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27. At the start of FD’s appointment, you take his BP. He comments that you do it differently than

others who have taken his BP. Which of the following is CORRECT according to guidelines for the

measurement of BP?

A. Measured while the patient is standing

B. Feet dangling from the exam table without supporting the arm

C. Immediately upon entering the exam room

D. Cuff size should be appropriate for the upper arm circumference

E. Elevated values should be confirmed later in the day

Answer: D

Rationale:

Measurement of blood pressure in the office should be done by a trained individual and follow the

guidelines established for persons who do not have diabetes. These guidelines include taking

measurements while patient is in a seated position and taken after 5 min of rest, feet are on the floor, and

the cuffed arm is being supported at heart level. The cuff size should be appropriate for the upper arm

circumference. If any blood pressures are elevated, those values should be confirmed on a separate day.

Reference(s):


2014;37:S14-S80.

28. Which of the following statements is TRUE regarding the age-specific relevance of blood

pressure to vascular mortality in the general population?

A. A higher risk for CV events and mortality begins at a SBP/DBP of >115/75 mmHg and doubles for

every 20-mmHg SBP or 10-mmHg DBP increase.

B. A lower risk for CV events and mortality begins at a SPB/DBP of >115/75 mmHg and declines for

every 20-mmHg SBP or 10-mmHg DBP decrease.

C. A lower risk for CV events and mortality begins at a SBP/DBP of >120/80 mmHg and doubles for


D. A higher risk for CV events and mortality begins at a SBP/DBP of >135/85 mmHg and triples for


E. There is no increase in the risk of CV events and mortality related to increases in blood pressure.

Answer: A

Rationale:

Although much of the focus on CV disease risk has been on frank hypertension, it is clear that risks for

CV disease increase at higher BP levels, even within the so-called normal range. An epidemiologic

pooling study of nearly 1 million men and women revealed that risk of mortality from CV disease

increases in a continuous fashion at SBP levels starting as low as 115 mmHg and DBP as low as 75

mmHg.

Within each decade of age at death, the proportional difference in the risk of vascular death associated

with a given absolute difference in usual blood pressure is about the same down to at least 115 mmHg

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usual SBP and 75 mm Hg usual DBP, below which there is little evidence. At ages 40-69 years, each

difference of 20 mmHg usual SBP (or, approximately equivalently, 10 mmHg usual DBP is associated

with more than a twofold difference in the stroke death rate, and with twofold differences in the death

rates from ischemic heart disease and from other vascular causes.

Reference(s):

Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific

relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million

adults in 61 prospective studies. Lancet. 2002;360:1903–1913.

29. The ACCORD trial examined whether blood pressure lowering to SBP <120 mmHg provides

greater CV protection than a SBP level of 130–140 mmHg in patients with type 2 diabetes at high

risk for CV disease. Which of the following prespecified endpoint(s) was significantly reduced by

intensive blood pressure treatment?

A. All-cause mortality

B. Stroke and non-fatal stroke

C. CV mortality

D. Non-fatal myocardial infarction

E. All of the above

Answer: B

Rationale:

In ACCORD, blood pressure (BP) achieved in the intensive group was 119/64 mmHg and in the standard

group 133/70 mmHg; the goals were attained with an average of 3.4 hypertensive medications per

participant in the intensive group and 2.1 in the standard therapy group. The hazard ratio for the primary

end point (nonfatal MI, nonfatal stroke, and CV death) in the intensive group was 0.88 (p = .20). Of the

prespecified secondary end points, only stroke (p = .01) and nonfatal stroke (p = .03) were statistically

significantly reduced by intensive BP treatment.

Reference(s):

Cushman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-

pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575–1585.

30. With lifestyle modification, diet is a key component of managing a hypertensive patient with

several CMR factors. Which diet would you recommend for FD to adopt to reduce his blood

pressure?

A. A DASH eating plan

B. A Mediterranean diet eating plan

C. A variation of DASH with 10% protein replacement

D. Any of the above


Answer: D

Rationale:

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Non-pharmacological therapy is reasonable in individuals with diabetes who have mildly elevated blood

pressure (SBP >120 mmHg or DBP >80 mmHg). If the blood pressure is confirmed to be ≥140 mmHg

SBP and/or ≥80 mmHg DBP, pharmacological therapy should be initiated along with non-

pharmacological therapy.

The most common food in Mediterranean-style diets are a higher intake of in fruits (particularly fresh),

vegetables (emphasizing root and green varieties), whole grains (cereals, breads, rice, or pasta), and fatty

fish (rich in omega–3 fatty acids); lower in red meat (and emphasizing lean meats); substituted lower-fat

or fat-free dairy products for higher-fat dairy foods; and used oils (olive or canola), nuts (walnuts,

almonds, or hazelnuts) or margarines blended with rapeseed or flaxseed oils in lieu of butter and other

fats. When compared to individuals given minimal advice on dietary patterns, middle-aged or older

adults with type 2 diabetes or at least 3 CVD risk factors who were counseled on a Mediterranean low-fat

dietary pattern reduced BP by 6–7/2–3 mmHg. In an observational study of healthy younger adults,

adherence to a Mediterranean pattern was associated with lower SBP/DBP (2–3/1–2 mmHg).

The DASH dietary pattern is high in vegetables, fruits, low-fat dairy products, whole grains, poultry, fish,

and nuts, and rich in potassium, magnesium, and calcium, as well as protein and fiber. It is low in

saturated fat, total fat, and cholesterol, sweets, SSBs, and red meats. In one study of adults with a

SBP/DBP of 120–159/80–95 mmHg, whose body weight and sodium intake were kept stable, the DASH

dietary pattern, when compared to a typical American diet of the 1990s, lowered SBP/DBP by 5–6/3

mmHg. The effect was seen in women and men, African American and non-African American adults,

older and younger adults, and hypertensive and non-hypertensive adults.

In OmniHeart, variations of the DASH dietary pattern were compared to DASH. One dietary pattern

replaced 10% of total daily energy with protein rather than carbohydrate; the other pattern replaced the

same amount of carbohydrate with unsaturated fat. In adults with SBP/DBP of 120–159/80–95 mmHg,

modifying the DASH dietary pattern by replacing 10% of calories from carbohydrates with the same

amount of either protein or unsaturated fat (8% monounsaturated and 2% polyunsaturated) lowered SBP

by 1 mmHg compared to the DASH dietary pattern. Among adults with SBP/DBP 140–159/90–95

mmHg, these replacements lowered SBP by 3 mmHg relative to DASH.

The Association’s Standards of Care recommend lifestyle therapy for elevated blood pressure, which

consists of weight loss (if overweight); a DASH-style dietary pattern including reducing sodium and

increasing potassium intake; moderation of alcohol intake; and increased physical activity.

Reference(s):

Sacks FM, Svetkey LP, Vollmer WM, et al; DASH-Sodium Collaborative Research Group. Effects on

blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH)

diet. N Engl J Med. 2001;344:3–10.





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31. Which of the following statements is CORRECT regarding the daily requirement of sodium for

individuals with hypertension?

A. Consume up to 4,000 mg of sodium per day.

B. Reduce sodium intake to below 1,500 mg per day.

C. Consume no more than 2,400 mg of sodium per day.

D. There is no maximum daily amount of sodium.

E. None of the above.

Answer: B

Rationale:

Reduction of sodium intake can lower BP an additional 2-8 mmHg. The most recent ACC/AHA

guidelines recommend individuals with hypertension reduce their intake of sodium by at least 1,000 mg

per day since that will lower BP, even if the desired level of sodium intake is not achieved, which is no

more than 2,400 mg of sodium/day. If needed, further reduction of sodium intake to 1,500 mg per day is

desirable, since it is associated with even greater reduction in BP. The Association’s Standards of Care

recommend individuals with diabetes and hypertension reduce their sodium intake to below 1,500

mg/day.

Reference(s):





2014;37:S14-S80.

32. FD is taking amlodipine, a non-dihydropyridine calcium channel blocker (CCB) for BP control.

For patients with CMR and elevated blood pressure, which class of drugs is recommended as the

first choice treatment?

A. ACE inhibitor or ARB

B. Alpha blocker

C. Beta blocker

D. Non-dihydropyridine CCB

E. Diuretic

Answer: A

Rationale:

Lowering of BP with regimens based on a variety of antihypertensive drugs, including ACE inhibitors,

ARBs, β-blockers, diuretics, and calcium channel blockers, has been shown to be effective in reducing

CV events. The Association’s Standards of Care recommend pharmacological therapy for patients with

diabetes and hypertension should be with a regimen that includes either an ACE inhibitor or an ARB. If

one class is not tolerated, the other should be substituted. This conclusion is substantiated by results from

a recent meta-analysis that showed ACE inhibitors may produce better outcomes in patients with diabetes


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than other antihypertensive medications. A meta-analysis of 63 randomized clinical trials reporting all-

cause mortality, dialysis requirement and serum creatinine levels in persons with diabetes who received

antihypertensive therapies evaluated treatments included ACE inhibitors, ARBs, alpha- and beta-blockers,

calcium-channel blockers and diuretics, alone or in combination. Results indicated ACE inhibitors

significantly decreased doubling of creatinine compared with placebo by 42%, whereas beta-blockers

significantly increased mortality risk.

Reference(s):

Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National

Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High

Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National

Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7

report. JAMA. 2003;289:2560–2572.


2014;37:S14-S80.

Wu HY, Huang JW, Lin HJ, et al. Comparative effectiveness of renin-angiotensin system blockers and

other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-

analysis. BMJ. 2013;347:f6008.

Go AS, Bauman M, Coleman King et al. An effective approach to high blood pressure control: a science

advisory from the American Heart Association, the American College of Cardiology, and the Centers

for Disease Control and Prevention. Hypertension. 2013 Nov 15. [Epub ahead of print]

33. If BP is not controlled on monotherapy, combination antihypertensive therapy is recommended.

In the action plan of your progress notes, which combination would you recommend if FD’s BP is

not controlled in the future?

A. ACE inhibitor or ARB plus dihydropyridine CCB

B. Switch to an ACE inhibitor or ARB plus thiazide diuretic

C. ARB plus thiazide diuretic

D. Beta blocker plus thiazide diuretic

E. Alpha blocker plus dihydropyridine CCB

Answer: B

Rationale:

The American Society of Hypertension/International Society of Hypertension and National Institute for

Health and Clinical Excellence guidelines recommend a RAAS inhibitor (ACE inhibitor or ARB) plus a

CCB, whereas the ACC/AHA guidelines on the science advisory from the ACC/AHA/CDC underline the

pivotal role of thiazide diuretics. The combination of a RAAS inhibitor with a CCB demonstrated the

best efficacy in reducing CV endpoint. In ACCOMPLISH, the combination of an ACE inhibitor and CCB

was shown to be beneficial in reducing the primary composite endpoint of CV events plus death from CV

causes versus an ACE inhibitor plus thiazide diuretic. However, a subgroup analysis revealed the

combination of an ACE inhibitor with a diuretic was more beneficial for those of African American origin

or individuals with systolic heart failure.


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Reference(s):

National Clinical Guideline Centre. Hypertension. Clinical management of primary hypertension in

adults. London (UK): National Institute for Health and Clinical Excellence (NICE); 2011 Aug. 36 p.

(Clinical guideline; no. 127). Available at: http://www.guideline.gov/content.aspx?id=34824. Accessed

November 17, 2013.


2014;37:S14-S80.

Wu HY, Huang JW, Lin HJ, et al. Comparative effectiveness of renin-angiotensin system blockers and

other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-

analysis. BMJ. 2013;347:f6008.

Go AS, Bauman M, King SM, Fonarow GC, Lawrence W, Williams KA, Sanchez E. An Effective

Approach to High Blood Pressure Control: A Science Advisory from the American Heart Association,

the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension.

2013 Nov 15. [Epub ahead of print].

Case 2 Continuation

34. Part of your discussion with FD involves smoking cessation and its impact on his long-term

treatment goals. With smoking cessation, what percent reduction in mortality could be expected

for an individual with CHD?

A. 10%

B. 23%

C. 36%

D. 41%

E. 63%

Answer: C

Rationale:

The results of the INTERHEART study showed smoking even one cigarette per day can increase the risk

of myocardial infarction (MI) by 5%. And results from a meta-analysis of the medical literature by

Critchley et al revealed a 36% reduction in crude relative risk (RR) of mortality for patients with coronary

heart disease (CHD) who quit compared with those who continued smoking. Thus, smoking cessation is

associated with a substantial reduction in risk of all-cause mortality among patients with CHD.

Reference(s):

Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with

coronary heart disease: a systematic review. JAMA. 2003;290:86-97.

Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk

factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control

study. Lancet. 2004;364:937–952.

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35. You want to test FD for type 2 diabetes. His FPG is 115 mg/dL. Each of the following would

help to differentiate whether or not FD has diabetes EXCEPT:

A. A1c ≥6.5% performed in a laboratory using a method that is NGSP certified and standardized to the

DCCT assay.

B. FPG (defined as no caloric intake for at least 8 hours) ≥126 mg/dL (7.0 mmol/L).

C. A 2-hour plasma glucose level during a 75-gram OGTT of 140 mg/dL (7.8 mmol/L) to 199 mg/dL

(11.0 mmol/L).

D. A 2-hour plasma glucose ≥200mg/dL (11.1mmol/L) during a 75-gram OGTT.

E. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma

glucose≥200 mg/dL (11.1 mmol/L).

Answer: C

Rationale:

This patient has an elevated FPG value between 100 and 125 mg/dL, also known as IFG, and the presence

of IFG is highly predictive of type 2 diabetes and should be confirmed by an OGTT. If the OGTT 2-hour

plasma glucose value is between 140 and 199 mg/dL, then the patient has IGT and prediabetes

encompasses both IFG and IGT. A plasma glucose value of ≥200 mg/dL after an OGTT confirms a

diagnosis of type 2 diabetes. An A1c measurement of >6.5% confirms the diagnosis of type 2 diabetes.

According to the Association’s Standards of Care, criteria for diagnosing diabetes are:

Criteria Comment

A1c >6.5%. The test should be performed in a laboratory using a

method that is NGSP certified and standardized to

the DCCT assay.*

OR

FPG >126 mg/dL (7.0 mmol/L) Fasting is defined as no caloric intake for at least 8

hours.*

OR

2-h plasma glucose >200mg/dL

(11.1mmol/L) during an OGTT

The test should be performed as described by the

WHO, using a glucose load containing the equivalent

of 75 g anhydrous glucose dissolved in water.*

OR

A random plasma glucose >200

mg/dL (11.1 mmol/L)

For persons with classic symptoms of hyperglycemia

or hyperglycemic crisis

* In the absence of unequivocal hyperglycemia, result should be confirmed by repeat

testing

Reference(s):

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2014;37:S14-S80.

Case 2 Continuation

FD’s lab results come back and his FPG is 118 mg/dL and A1c is 6.2%. You assess that he does not have

type 2 diabetes and ask him to return in 6 months so you can reassess his adherence to your

recommendations of lifestyle modifications and management of his hypertension.

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Case Study #3

MR, a 37-year-old Hispanic male, comes in for an employment physical. He is currently employed as a

garage mechanic, but is applying for a position as manager of a parts department in an automobile

dealership. He states has been overweight since childhood, as were his parents, but cannot lose weight,

although he has tried many times. When trying to lose weight, he employed fad diets, some of which

were successful. Once he lost as much as 20 pounds, but eventually regained the weight and rebounded

past his baseline. MR does not exercise and leads a fairly sedentary life both at home and at work.

His family has recently begun to express concern about his risk of developing type 2 diabetes, and they

have convinced him to seek medical consultation. The patient states he has not seen a physician in 2

years because he has not adhered to either his hypertension or cholesterol-lowering therapy.

Past medical history: hypertension and hypercholesterolemia; no surgeries.

Family history: both mother and father are alive and both are diagnosed with hypertension and type 2

diabetes.

Physical Examination: height, 5’11” (180.3 cm); weight, 362 pounds (164.5 kg); body mass index (BMI),

46.2 kg/m2; waist circumference, 47 inches (119.3 cm); BP, 152/104 mmHg; heart rate, 82 bpm.

Laboratory results: total cholesterol 273 mg/dL; LDL-C 181 mg/dL; HDL-C, 37 mg/dL; triglycerides,

300 mg/dL; FPG, 113 mg/dL.

Social history: does not exercise; denies tobacco, illicit drug use; he drinks one or two beers a day after

work with his friends.

Medications: telmisartan 80 mg once daily; simvastatin 20 mg once daily (prescribed but non-adherent

with both).

Assessment: MR is a morbidly obese male, alert and oriented, in no acute distress. He is non-adherent to

antihypertensive and lipid-lowering therapies.

Questions 36-47

36. What is the most poorly controlled risk factor for individuals with type 2 diabetes?

A. A1c

B. Postprandial plasma glucose

C. Body weight

D. Waist circumference

E. FPG

Answer: C

Rationale:

With a population-based mean BMI remaining in the obese range (33 kg/m2) and waist circumference in

the range defining abdominal obesity, excess body weight remains the most poorly controlled risk factor

in those with type 2 diabetes. Study results show only 11% patients have a BMI <25 kg/m2 and 16%

meet the recommended waist circumference levels of ≤40 inches in males and ≤35 inches in females.

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This has implications for long-term control of A1c and therefore the development of diabetes-related

complications, including CVD, CKD, retinopathy and neuropathy

Reference(s):

Ross SA, Dzida G, Vora J, et al. Impact of weight gain on outcomes in type 2 diabetes. Curr Med Res

Opin. 2011;27:1431–1438.

Wong ND, Patao C, Wong K, Malik S, Franklin SS, Iloeje U. Trends in control of cardiovascular risk

factors among US adults with type 2 diabetes from 1999 to 2010: Comparison by prevalent

cardiovascular disease status. Diab Vasc Dis Res. 2013;10:505-513.


2014;37:S14-S80.





37. When taking this patient’s history of weight gain and loss over time, questions that should be

asked include:

A. Family history of obesity

B. Dietary habits

C. Level of physical activity

D. Details of previous weight loss attempts

E. All of the above

Answer: E

Rationale:

To determine a direction for management of a person’s obesity, clinicians need to assess weight and

lifestyle histories to determine potential contributory factors as to why they are obese. This assessment

includes asking questions about history of weight gain and loss over time, details of previous weight loss

attempts, dietary habits, physical activity, family history of obesity, and other medical conditions or

medications that may affect weight. The answer can provide useful information about the origins of or

maintaining factors for overweight and obesity, including success and difficulties with previous weight

loss or maintenance efforts, as well as assist the clinician in determining any adjustments to the patient’s

medical regimen and weight management efforts.

Reference(s):


2014;37:S14-S80.










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38. For obese individuals with type 2 diabetes, most common perceived barriers to exercise include:

A. Lack of time and physical discomfort

B. Easily measure results

C. Can vary the goals depending on their desired outcome

D. Self-evaluation of progress

E. Goals can be re-evaluated and adjusted periodically to maintain the desired therapeutic effect

Answer: A

Rationale:

The promotion of physical activity requires some understanding of the principles of behavior change and

of habit development. Additionally, barriers to physical activity and correlates of success with long-term

exercise should be considered. Five components of behavior change and self-regulation include: the

setting of realistic and simple goals, self-monitoring of personal behaviors linked to goal attainment,

feedback about progress toward goals, self-evaluation of progress, and corrective behavior leading to

effective movement toward goals.

For obese individuals with type 2 diabetes, the most common perceived barriers to exercise were lack of

time and physical discomfort, although these barriers varied with age, gender and marital status.

Exercises that are most likely to be successful in the long term are moderate in intensity, relatively

inexpensive, simple, and convenient and include a social component. Parameters for a successful

exercise program include being patient-appropriate, considers co-morbidities, is measurable, in a form

that allows the HCP to address barriers and patient adherence, will vary depending on the desired

outcomes, and is reevaluated and adjusted periodically to maintain the desired therapeutic effect.

Reference(s):

Egan AM, Mahmood WA, Fenton R, et al. Barriers to exercise in obese patients with type 2 diabetes.

QJM. 2013 Mar 23. [Epub ahead of print].

Williams MV, Davis T, Parker RM, Weiss BD. The role of health literacy in patient-physician

communication. Fam Med. 2002;34:383-289.

Brawley LR, Rejeski WJ, King AC. Promoting physical activity for older adults: the challenges for

changing behavior. Am J Prev Med. 2003;25(3 suppl 2):172–183.

Fletcher GF, Ades PA, Kligfield P, et al; American Heart Association Exercise, Cardiac Rehabilitation,

and Prevention Committee of the Council on Clinical Cardiology, Council on Nutrition, Physical

Activity and Metabolism, Council on Cardiovascular and Stroke Nursing, and Council on Epidemiology

and Prevention. Exercise standards for testing and training: a scientific statement from the American

Heart Association. Circulation. 2013;128:873-934.

39. MR was able to lose weight but was not able to maintain that weight loss. Factors that

contribute to a person’s inability to retain maximal weight loss include:

A. Socioeconomic status

B. An unsupportive environment

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C. Compensatory changes in circulating hormones that encourage weight regain after weight loss is

achieved

D. A and B above

E. All of the above

Answer: E

Rationale:

Long-term maintenance of weight, following weight reduction, is possible; however, research suggests an

intensive program with long-term support is required. As a result, many individuals will regain a portion

of their initial weight loss. Factors contributing to the individual’s inability to retain maximal weight loss

include socioeconomic status, an unsupportive environment, and physiological changes, such as

compensatory changes in circulating hormones that encourage weight regain after weight loss is achieved.

Reference(s):

Franz MJ, VanWormer JJ, Crain AL, et al. Weight-loss outcomes: a systematic review and meta-analysis

of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc. 2007;107:1755–1767.

Warshaw HS. Nutrition therapy for adults with type 2 diabetes. In: American Diabetes Association Guide

to Nutrition Therapy for Diabetes. Franz MJ, Evert AB, Eds. Alexandria, VA, American Diabetes

Association, 2012, p. 117–142.

Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2

diabetes. N Engl J Med. 2013;369:145–154.

40. In the Look AHEAD study, weight loss strategies associated with lower BMI in overweight or

obese individuals with type 2 diabetes included:

A. Weekly self-weighing

B. Skipping breakfast

C. Increased intake of fast foods

D. Increasing physical activity

E. A and D above

Answer: E

Rationale:

In the Look AHEAD study, weight loss strategies associated with lower BMI in overweight or obese

individuals with type 2 diabetes included weekly self-weighing, regular consumption of breakfast, and

reduced intake of fast foods. Other successful strategies included increasing physical activity, reducing

portion sizes, using meal replacements (as appropriate), and encouraging individuals with diabetes to eat

those foods with the greatest consensus for improving health.

Reference(s):

Raynor HA, Jeffery RW, Ruggiero AM, et al; Look AHEAD (Action for Health in Diabetes) Research

Group. Weight loss strategies associated with BMI in overweight adults with type 2 diabetes at entry

into the Look AHEAD (Action for Health in Diabetes) trial. Diabetes Care. 2008;31:1299–1304.

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41. According to guidelines for the management of obesity, what is the initial goal recommended for

weight reduction?

A. 1% to 3%

B. 3% to 5%

C. 5% to 10%

D. 12% to 15%

E. >15%

Answer: C

Rationale:

Although 3% to 5% of body weight may lead to clinically meaningful reductions, in some risk factors for

CV disease, larger weight losses produce greater benefits. The latest ACC/AHA/TOS guidelines

recommend a 5% to 10% reduction of baseline body weight within 6 months as an initial goal. The

Association’s Standards of Care note at least a 7% of reduction in body weight is recommended.

Reference(s):


2014;37:S14-S80.





42. MR has a history of hypertension. Each of the following has been shown to be implicated in the

pathophysiology of obesity-related hypertension EXCEPT:

A. Increase in adiponectin

B. Increases in leptin levels

C. Renin-angiotensin-aldosterone system

D. Obstructive sleep apnea

E. Impairment in salt excretion

Answer: A

Rationale:

Obesity predisposes the kidney to reabsorb sodium by neural (SNS), hormonal (aldosterone and insulin),

and renovascular (angiotensin II) mechanisms. Leptin is produced in adipocytes and secreted into

plasma, where the circulating concentration reflects the fat mass of the individual. A potent appetite

suppressant, leptin, like insulin, stimulates the SNS. With regard to the RAAS, several mechanisms have

been thought to underlie its activation in obesity, including SNS stimulation of renin release and

angiotensinogen production in adipose tissue, especially intra-abdominal adipocytes.

Other factors that may be implicated in the pathophysiology of obesity-related hypertension include a

decrease in adiponectin, and obstructive sleep apnea, which stimulates the SNS. One study showed a


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significant negative correlation between plasma adiponectin concentration and mean, SBP, and DBP,

which suggests a decrease adiponectin level contributes to the clinical course of essential hypertension.

Obstructive sleep apnea, a well-recognized complication of obesity, is associated with increased SNS

activity; this activity persists during daytime wakefulness. Obesity-related hypertension can also be

caused by a decrease in natriuretic peptides, resulting in a consequent impairment in salt excretion.

Reference(s):

Adamczak M, Wiecek A, Funahashi T, et al. Decreased plasma adiponectin concentration in patients with

essential hypertension. Am J Hypertens. 2003;16:72–75.

Ahmed SB, Fisher ND, Stevanovic R, Hollenberg NK. Body mass index and angiotensin-dependent

control of the renal circulation in healthy humans. Hypertension. 2005;46:1316–1320.

Goodfriend TL. Obesity, sleep apnea, aldosterone, and hypertension. Curr Hypertens Rep. 2008;10:222–

226.

Sarzani R, Salvi F, Dessi-Fulgheri P, Rappelli A. Renin-angiotensin system, natriuretic peptides, obesity,

metabolic syndrome, and hypertension: an integrated view in humans. J Hypertens. 2008;26:831–843.

43. Based upon his BMI category, MR is a candidate for which of the following interventions?

A. Diet and exercise

B. Diet, exercise, and behavioral counseling

C. Diet, exercise, and behavioral counseling; then pharmacotherapy

D. Diet, exercise, and behavioral counseling; then bariatric surgery

E. Diet, exercise, and behavioral counseling; pharmacotherapy; then bariatric surgery

Answer: E

Rationale:

Among overweight and obese adults, analyses of continuous BMI show that the greater the BMI, the

higher the risk of fatal CHD and combined fatal and nonfatal CHD in both men and women. With dietary

intervention in overweight and obese adults, average weight loss is maximal at 6 months with smaller

losses maintained for up to 2 years, while treatment and follow-up tapers. Weight loss achieved by

dietary techniques aimed at reducing daily energy intake ranges from 4 to 12 kg at 6-month follow-up.

Thereafter, slow weight regain is observed, with total weight loss at 1 year of 4 kg to 10 kg and at 2 years

of 3 kg to 4 kg.

The principal components of an effective high-intensity, on-site comprehensive-lifestyle intervention

includes prescription of a moderately-reduced calorie diet; a program of increased physical activity; and

the use of behavioral strategies to facilitate adherence to diet and activity recommendations. All 3

components should be included in the intervention.

If patients are unable to lose enough weight to meet weight or targeted health outcome goals with their

current treatment, consider offering or referring them for more intensive behavioral treatment than

currently being attempted, an alternate diet including options for meal replacement, referral to a nutrition

professional and the addition of obesity pharmacotherapy may be appropriate. The clinician should also

assess the patient’s medication regimen for drugs that may contribute to weight gain and consider

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adjustments if medically appropriate. If patients are unable to lose enough weight to meet weight or

targeted health outcome goals with their current treatment, consider offering or referring for more

intensive behavioral treatment than currently being attempted, and the patient may be referred for

evaluation for bariatric surgery.

According to the most recent clinical practice guidelines, those eligible for a bariatric surgical procedure

include individuals with a BMI >40 kg/m2 who have no coexisting medical problems and for which the

procedure would not be associated with excessive risks. In addition, individuals with a BMI >35 kg/m2

and 1 or more severe obesity-related co-morbidities, which include (but not inclusive of) type 2 diabetes,

hypertension, hyperlipidemia, OSA, OHS, or considerably impaired quality of life, may also be offered a

bariatric procedure.

Although those with BMI of 30–34.9 kg/m2 and with diabetes or at CMR may also be offered a bariatric

procedure, current evidence is limited by the number of subjects studied and lack of long-term data

demonstrating a net benefit. According to these guidelines, there is insufficient evidence for

recommending a bariatric surgical procedure independent of BMI criteria specifically for glycemic

control alone, lipid lowering alone, or CV disease risk reduction alone.

The following table outlines when weight-loss surgery is recommended after lifestyle modification and

pharmacotherapy.

Treatment Body Mass Index (Kg/m2)

25-26.9 27-29.9 30-34.9 35.0-39.9 >40

Diet, physical activity,

behavioral therapy Yes with comorbidities* Yes Yes Yes

Pharmacotherapy NO Yes with

comorbidities* Yes Yes Yes

Weight-loss surgery NO NO Yes Yes Yes

* Include but not limited to type 2 diabetes, hypertension, hyperlipidemia, OSA, OHS

According to the 2008 NIH guidelines, based upon his BMI, MR is a candidate for diet, exercise, and

pharmacotherapy for the management of his abdominal obesity, and a candidate for bariatric surgery if

these other interventions fail to accomplish his target weight goal.

Reference(s):





Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional,

metabolic, and nonsurgical support of the bariatric surgery patient-2013 update: co-sponsored by


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American Association of Clinical Endocrinologists, the Obesity Society, and American Society for

Metabolic & Bariatric Surgery. Endocr Pract. 2013;19:337-372.

National Institutes of Health, National Heart, Lung, and Blood Institute, North American Association for

the Study of Obesity. The Practical Guide: Identification, Evaluation and Treatment of Overweight and

Obesity in Adults. Rockville, MD: National Press Office; October 2000. NIH publication 00-4084.

Available at: http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf . Accessed November 13, 2013.

Case 3 Continuation

44. MR has implemented improved nutrition, physical activity, and behavior therapy. Which of the

following diets has been shown to improve CV risk factors, such as lipids, triglycerides, and blood

pressure in persons with diabetes?

A. Mediterranean

B. Vegetarian

C. Low fat

D. DASH

E. A and D above

Answer: E

Rationale:

Although mostly studied in the Mediterranean region, the Mediterranean-style eating pattern has been

observed to improve lipids, blood pressure, and triglycerides in persons with diabetes, as well as lowering

combined end points for CV disease events and stroke when supplemented with mixed nuts (including

walnuts, almonds, and hazelnuts) or olive oil. And for those following an energy-restricted

Mediterranean-style eating pattern, improvements in glycemic control were also achieved.

In a review of vegetarian and low-fat vegan studies in individuals with type 2 diabetes, diets ranging in

duration from 12 to 74 weeks did not consistently improve CV risk factors or glycemic control except

when energy intake was restricted and a loss of weight was measured.

There is limited evidence on the effects of the DASH eating plan on health outcomes specifically in

individuals with diabetes. One small study in individuals with type 2 diabetes revealed the DASH eating

plan, which included a sodium restriction of 2,300 mg/day, improved A1c, blood pressure, and other CV

risk factors. Despite this limited evidence, however, one would expect benefits of the DASH eating plan

in controlling blood pressure and lowering risk for CV disease that is seen for the general population

would also be beneficial for persons with diabetes.

Reference(s):

Franz MJ, Powers MA, Leontos C, et al. The evidence for medical nutrition therapy for type 1 and type 2

diabetes in adults. J Am Diet Assoc. 2010;110:1852–1889.

Esposito K, Maiorino MI, Ciotola M, et al. Effects of a Mediterranean-style diet on the need for

antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.

Ann Intern Med. 2009;151:306–314.

http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf

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Elhayany A, Lustman A, Abel R, Attal-Singer J, Vinker S. A low carbohydrate Mediterranean diet

improves cardiovascular risk factors and diabetes control among overweight patients with type 2

diabetes mellitus: a 1-year prospective randomized intervention study. Diabetes Obes Metab.

2010;12:204–209.

Estruch R, Ros E, Salas-Salvadó J, et al; PREDIMED Study Investigators. Primary prevention of

cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279–1290.

Wheeler ML, Dunbar SA, Jaacks LM, et al. Macronutrients, food groups, and eating patterns in the

management of diabetes: a systematic review of the literature, 2010. Diabetes Care. 2012;35:434–445.

Sacks FM, Svetkey LP, Vollmer WM, et al., DASH-Sodium Collaborative Research Group. Effects on

blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH)

diet. N Engl J Med. 2001;344:3–10.

Azadbakht L, Fard NR, Karimi M, et al. Effects of the Dietary Approaches to Stop Hypertension (DASH)

eating plan on CV risks among type 2 diabetic patients: a randomized crossover clinical trial. Diabetes

Care. 2011;34:55–57.

Festa A, D’Agostino R Jr, Howard G, et al. Chronic subclinical inflammation as part of the insulin

resistance syndrome: the insulin resistance atherosclerosis study (IRAS). Circulation 2000;102:42–7.

45. From a nutritional perspective, intake of which of the following has a direct effect on

postprandial glucose levels in people with diabetes and is the primary macronutrient of concern in

glycemic management?

A. Fats

B. Carbohydrates

C. Protein

D. A and B above

E. All of the above

Answer: B

Rationale:

The primary micronutrient of concern in the glycemic management is carbohydrate. A meta-analysis

showed that at 6 months, low-carbohydrate diets were associated with greater improvements in

triglyceride and HDL-C concentrations than low-fat diets; however, LDL cholesterol was significantly

higher on the low-carbohydrate diets.

Reference(s):

Franz MJ, Powers MA, Leontos C, et al. The evidence for medical nutrition therapy for type 1 and type 2

diabetes in adults. J Am Diet Assoc. 2010;110:1852–1889.

46. Which of the following statements is CORRECT regarding the effectiveness of nutritional

therapy?

A. As an effective component of an overall treatment plan, nutrition therapy is recommended only for

individuals with type 2 diabetes.

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B. Individuals who have diabetes should receive individualized medical nutritional therapy (MNT) as

needed to achieve treatment goals, preferably provided by an RD familiar with the components of

diabetes MNT.

C. For individuals using fixed daily insulin doses, consistent carbohydrate intake with respect to time

and amount has no impact for improving glycemic control and/or reduce the risk for hypoglycemia.

D. Despite cost savings from diabetes nutrition therapy, evidence shows no improved outcomes such as

reduction in A1c.

E. Individuals with diabetes should receive DSME according to national standards and DSMS only

when the diagnosis of diabetes is made.

Answer: B

Rationale:

DSME and DSMS are critical elements of care for all individuals with either type 1 or type 2 diabetes,

and are necessary to improve outcomes in a disease that is largely self-managed. According to the latest

nutrition therapy recommendations, individuals who have diabetes should receive individualized MNT as

needed to achieve treatment goals, preferably provided by a registered dietician familiar with the

components of diabetes MNT. For those administering fixed daily doses of insulin, consistent

carbohydrate intake with respect to time and amount can result in improved glycemic control and reduce

the risk for hypoglycemia. Persons with diabetes should receive DSME according to national standards

and DSMS when their diabetes is diagnosed and as needed thereafter. In addition, diabetes nutrition

therapy can result in cost savings and improved outcomes such as reduction in A1c.

Reference(s):

Haas L, Maryniuk M, Beck J, et al. 2012 Standards Revision Task Force. National Standards for Diabetes

Self-Management Education and Support. Diabetes Care. 2012;35:2393–2401.

Evert AB, Boucher JL, Cypress M, et al. Nutrition therapy recommendations for the management of

adults with diabetes. Diabetes Care. 2013;36:3821-3842.

47. After instituting lifestyle modifications, MR still has a BMI of 39 kg/m2. Your treatment plan is

to next initiate pharmacotherapy if he had not achieved his target weight. Which of the following

drugs are NOT APPROVED for the long-term management of abdominal obesity?

A. Orlistat

B. Sibutramine

C. Lorcaserin

D. Phenteramine-topiarmate

E. C and D above

Answer: B

Rationale:

There are currently 3 FDA-approved drugs for the long-term management of abdominal obesity: orlistat,

lorcaserin, and phenteramine-topiarmate. Each are indicated as an adjunct to a reduced-calorie diet and

increased physical activity for chronic weight management in adult patients with an initial body mass

index (BMI) of:

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30 kg/m² or greater (obese), or

27 kg/m² or greater (overweight) in the presence of at least one weight related comorbid

condition, such as hypertension, dyslipidemia, type 2 diabetes.

If after 12 weeks on a maximal dose of the medication the patient has not lost at least 5% of initial body

weight, the provider should reassess the risk-to-benefit ratio of that medication for the patient, and

consider discontinuation of that drug.

Orlistat, a pancreatic lipase inhibitor that targets intestinal lipases, prevents the hydrolysis of triglycerides

and absorption of fatty acids and monoacylglycerols from the gut. In a multicenter 57-week study versus

placebo, orlistat demonstrated an 8.9% decrease in body weight (p < .05), an 0.18% decrease in A1c (p <

.05), and a significant decrease in FPG levels (p < .05).

Lorcaserin affects central serotonin subtype 2A receptors, resulting in decreased food intake and

increased satiety. It has been studied in obese patients with type 2 diabetes, producing approximately an

average weight loss of 5.5 kg over the course of 12 months.

The effect of phentermine on chronic weight management is likely mediated by release of catecholamines

in the hypothalamus, resulting in reduced appetite and decreased food consumption, but other metabolic

effects may also be involved; the exact mechanism of action is not known. The effects of topiramate may

be due to its effects on both appetite suppression and satiety enhancement, induced by a combination of

pharmacologic effects. The phentermine-controlled-release topiramate formulation has been shown to

decrease weight by an average of 12.2 kg over 52–104 weeks of treatment in various clinical studies.

Because of its effects on intestinal lipases, orlistat also causes socially unacceptable side effects, which

include oily spotting, increased flatus with discharge, and fecal urgency. Thus, fat-soluble vitamin levels

must be carefully monitored. Lorcaserin has been reported to increase the risk of psychiatric, cognitive,

and serotonergic adverse effects and phentermine–topiramate may increase the risk of metabolic acidosis,

glaucoma, and psychiatric and cognitive adverse effects.

FDA approval of phentermine–topiramate required a REMS, which includes a medication guide, a patient

brochure, and a formal training program for prescribers. This program informs both patients and

prescribers of the teratogenic risk and stress the need for women of reproductive potential to use effective

forms of contraception. REMS also permits only specially certified pharmacies to dispense phentermine–

topiramate.

Sibutramine is a central inhibitor of norepinephrine and serotonin reuptake and, to a lesser extent,

dopamine reuptake. Although shown to significantly decrease abdominal adiposity, lower triglyceride

and raise serum HDL-C levels, it was removed from the market due to unacceptable side effects,

specifically myocardial infarction and stroke.

Reference(s):

James WP, Astrup A, Finer N, et al, for the STORM Study Group. Effect of Sibutramine on weight

maintenance after weight loss: a randomised trial. Sibutramine Trial of Obesity Reduction and

Maintenance. Lancet. 2000;356:2119-2125.

Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database

Syst Rev. 2003:CD004094.

http://www.rxlist.com/script/main/art.asp?articlekey=3866

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Henness S, Perry CM. Orlistat: A review of its use in the management of obesity. Drugs. 2006;66:1625-

1656.

Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for

weight management. N Engl J Med. 2010;363:245–256.

Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese

adults: a randomized controlled trial. Obesity. 2011;20:330–342.

Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus

topiramate combination on weight and associated comorbidities in overweight and obese adults

(CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341–1352.

Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs

for chronic weight management. N Engl J Med. 2012;367:1577–1579.

Taylor JR, Dietrich E, Powell J. Lorcaserin for weight management. Diabetes Metab Syndr Obes.

2013;6:209-216.






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Case Study #4:

ERL, a 12-year-old Caucasian male, comes in for a school physical accompanied by his mother.

Physical exam: height, 5’5” (165 cm); weight, 195 lbs (88.6 kg); BMI, 32.5 kg/m2; waist circumference:

32” (81.3 cm); SPB: 132 mmHg; DBP: 80 mmHg (average of 3 readings); pulse: 84 beats per minute

(average of 3 readings).

Family history: Both parents are alive, but overweight due to lack of physical activity; both employed full

time as computer programmers; father has hypertension and diabetes; mother was told she has

prediabetes. Neither parent exercises nor are involved in any structured activity program.

Social history: ERL denies tobacco use, alcohol intake, or illicit drug use; has no structured exercise

program as his school discontinued gym classes; spends 3-4 hours a day playing video games; another

couple of hours a day on the computer doing his homework. He enjoys snack foods, especially potato

chips and drinking sugar sweetened beverages.

Lab results (within the past week): A1c, 6.4%; FPG, 105 mg/dL; total cholesterol, 240 mg/dL; LDL-C,

165 mg/dL; HDL-C, 31 mg/dL; triglycerides, 220 mg/dL.

Medications: None; all of his vaccinations are up-to-date.

You document ERL has several factors related to CMR and prescribe treatment with the goal of

preventing him from progressing to type 2 diabetes.

Questions 48-58

48. According the Association’s Standards of Care, each of the following meet the parameters for

CMR factors in this patient EXCEPT:

A. FPG ≥90 mg/dL.

B. Waist circumference >40 inches (102 cm) in males; >35 inches (88 cm) in females

C. BP ≥130/85 mmHg.

D. HDL-C level ≤40 mg/dL in males.

E. Triglyceride level ≥150 mg/dL.

Answer: A

Rationale:

A comprehensive risk assessment should include a thorough documentation of the patient’s history (age,

ethnicity, smoking status, physical activity level, diet, family history of premature CV disease or type 2

diabetes, and comorbidities), physical examination (BMI, waist circumference, and BP), and laboratory

test results (FPG, creatinine or estimated glomerular filtration rate, and fasting lipid profile). This

assessment should help guide the clinician to determine the level of CMR in any given patient. However,

this assessment should not be reserved strictly for adults, but starts at a much younger age.

According to the Association’s Standards of Care, parameters of CMR are highly concordant; in

aggregate they enhance risk for coronary heart disease at any given LDL-C level. Parameters for factors

in adults risk include:

FPG ≥110 mg/dL.

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Waist circumference >40 inches (102 cm) in males; >35 inches (88 cm) in females

Blood pressure ≥130/85 mmHg.

HDL-C level ≤40 mg/dL in males; ≤50 mg/dL in females.

Triglyceride level ≥150 mg/dL.

However, the diagnosis of CMR in children and adolescents requires the assessment of the waist

circumference (or BMI), SBP/DBP, lipids, and plasma glucose levels. Parameters for

children/adolescents were fixed for blood pressure, lipids and glucose; abdominal circumference points

and assessed by percentile although, the cut-offs for metabolic and blood pressure variables were not well

defined in children aged 6-10 years; therefore, only adiposity levels were evaluated (considering waist

circumference above the 90th percentile). The same criteria would be used for children aged 10-16 as in

adults: FPG ≥100 mg/dL, triglycerides ≥150 mg/dL, HDL-C <40 mg/dL or the use lipid lowering drugs

were considered risk factors as well SBP ≥130 or DBP ≥85 mmHg.

In a study of individuals ranging in age from 2 to 39 years who died from various causes (principally

trauma), antemortem data revealed the presence of CV risk factors, including increased BMI, SBP and

DPB, and serum concentrations of total cholesterol, triglycerides, LDL-C, and HDL-C. As a group, these

risk factors were significantly associated with the extent of lesion formation in the aorta and coronary

arteries (p < .001). The mean percentage of the intimal surface covered by lesions in patients with

different numbers of risk factors (0, 1, 2, and 3 or 4) was reported, although a percentage increase for

each individual risk factor was not. For individuals with 0, 1, 2, and 3 or 4 risk factors, the percentage of

intimal surface covered with fatty streaks in the aorta was 19.1%, 30%, 38%, and 35%, respectively (p for

trend = .01). In the coronary arteries, 1.3%, 2.5%, 8%, and 11%, respectively (p for trend = .01) was

involved with fatty streaks and 0.6%, 0.7%, 2.4%, and 7.2%, respectively was involved with collagenous

fibrous plaques (p for trend = .003). In the coronary arteries, the extent of fatty-streak lesions was 8.5x as

great for individuals with three or four risk factors versus those with no risk factors (p = .03) and the

extent of fibrous-plaque lesions in the coronary arteries was 12x as great (p = .006).

Reference(s):

Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between

multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa

Heart Study. N Engl J Med. 1998;338:1650-1656.

Halpern A, Mancini MC, Magalhães ME, et al. Metabolic syndrome, dyslipidemia, hypertension and type

2 diabetes in youth: from diagnosis to treatment. Diabetol Metab Syndr. 2010 Aug 18;2:55.


2014;37:S14-S80.






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49. What of the following statements is CORRECT regarding ramifications of children/adolescents

being overweight or obese?

A. They are twice as likely to become overweight or obese adults as their non-obese peers.

B. They are 3 times as likely as to become overweight or obese adults as their non-obese peers.

C. They are 5 times as likely as to become overweight or obese adults as their non-obese peers.

D. They are 7 times as likely as to become overweight or obese adults as their non-obese peers.

E. There are no long-term risks for children who are overweight or obese.

Answer: C

Rationale:

Estimates from the NHANES indicate approximately one third of children in the U.S. are overweight or

obese, with approximately 17% meeting criteria for obesity, as measured by a BMI score ≥95th percentile.

Overweight or obese preschoolers are five times as likely as to become overweight or obese adults as

their non-obese peers. In an analysis of the literature, all included studies consistently report an increased

risk of overweight and obese youth becoming overweight adults, suggesting that the likelihood of

persistence of overweight into adulthood is moderate for overweight and obese youth. Because of the

effects of obesity on insulin resistance, weight loss is an important therapeutic objective for overweight or

obese individuals who are at risk for diabetes. Therefore, preventing obesity early in life is a public

health priority to improve health across the lifespan of an individual.

Reference(s):

Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ. Tracking of childhood overweight into

adulthood: a systematic review of the literature. Obes Rev. 2008;9:474-488.

Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among

US children and adolescents, 1999–2010. JAMA 2012;307:483–90.

Norris SL, Zhang X, Avenell A, et al. Long-term effectiveness of weight-loss interventions in adults with

pre-diabetes: a review. Am J Prev Med. 2005;28:126–139

Pulgaron ER. Childhood obesity: a review of increased risk for physical and psychological comorbidities.

Clin Ther. 2013;35:A18–32.

50. Potential negative psychological outcomes in overweight children include all of the following

EXCEPT:

A. High self-esteem

B. Depressive symptoms

C. Poor body image

D. Attention-deficit hyperactivity disorder

E. Sleep problems

Answer: A

Rationale:

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A systematic review of the literature concluded the health consequences of childhood obesity have

significant short-term and long-term adverse medical and psychosocial effects extending into adulthood.

These include health-related physical outcomes, such as high blood pressure; high cholesterol; metabolic

syndrome; type 2 diabetes; orthopedic problems; sleep apnea; asthma; and fatty liver disease, as well as

psychological, social, and behavioral consequences, such as risk for problems related to body image; self-

esteem; social isolation and discrimination; depression; and reduced quality of life.

Reference(s):

Reilly JJ , Methven E , McDowell ZC , et al. Health consequences of obesity. Arch Dis Child.

2003;88:748–752.

Pulgaron ER. Childhood obesity: a review of increased risk for physical and psychological comorbidities.

Clin Ther. 2013;35:A18–32.

Case 4 Continuation

51. You recommend to ERL’s mother that she focus on lifestyle modifications for her son. Lifestyle

modifications for managing CMR include:

A. Healthful diet

B. Weight loss

C. Calorie restriction

D. Increased physical activity

E. All of above

Answer: E

Rationale:

The primary treatment of elevated CMR is lifestyle modification. This includes regular exercise (3 to 5

days per week; 30 to 60 minutes per day), coupled with improved diet/nutrition, and weight reduction

through caloric restriction of at least reduction of 500 kcal per day, regardless of diet composition. The

goal is to achieve a sustainable weight loss of no more than 0.5 kg per week for those who are

overweight.

Reference(s):


2014;37:S14-S80.

52. Strategies to reduce energy intake in children and adolescents include increasing which of the

following?

A. Consumption of high energy-density foods

B. Consumption of fruits and vegetables

C. Consumption of sugar-sweetened beverages

D. Time spent watching television and exposure to food marketed to children.

E. All of the above

Answer: B

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Rationale:

Environmental determinants of childhood obesity in the United States include shifts in food consumption,

decreases in physical activity levels, and higher levels of television viewing, with the consequent

inactivity and marketing of food to children. Intervention programs should focus on strategies that alter

the food and physical activity environments in places where children live, learn, work, and play. These

strategies include decreasing consumption of high energy-density foods, decreasing consumption of

sugar-sweetened beverages (SSBs) and red meats, and decreasing time spent watching television and

exposure to food marketed to children.

Large increases in the consumption of SSBs have coincided with the epidemics of obesity and type 2

diabetes. Results of a meta-analysis of 8 prospective cohort studies revealed a diet high in consumption of

SSBs was associated with the development of type 2 diabetes. And those individuals in the highest

(versus lowest) quintile of SSB intake had a 26% greater risk of developing diabetes.

To positively impact reduction in LDL-C, ERL’s mother can plan meals that emphasize the intake of

vegetables, fruits, and whole grains, as well as low-fat dairy products, poultry, fish, legumes, non-tropical

vegetable oils and nuts. This type of dietary pattern can be adapted to appropriate calorie requirements,

personal and cultural food preferences, and nutrition therapy for other medical conditions, including

individuals with diabetes. In addition, ERL should reduce the percent of daily calories obtained from

saturated (<7% of total calories) and trans fats.

Reference(s):

Centers for Disease Control and Prevention (CDC). CDC grand rounds: childhood obesity in the United

States. MMWR Morb Mortal Wkly Rep. 2011;60:42-46.

Malik VS, Popkin BM, Bray GA, et al. Sugar-sweetened beverages and risk of metabolic syndrome and

type 2 diabetes: a meta-analysis. Diabetes Care. 2010;33:2477–2483.


2014;37:S14-S80.

Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce CV

risk: a report of the American College of Cardiology American/Heart Association Task Force on

Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.

53. ERL plays video games for 3-4 hours a day. According to the American Academy of Pediatrics,

what is the recommended timeframe for children to have entertainment-based screen time per day?

A. <1 hour

B. <2 hours

C. <3 hours

D. <4 hours

E. <5 hours

Answer: B

Rationale:


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An average 8-year-old spends eight hours a day using various forms of media, and teenagers often surpass

11 hours of media consumption daily. Research shows that children who spent >2 hours per day

watching television or using a computer were at increased risk of high levels of psychological difficulties,

and this risk increased if the children also failed to meet physical activity guidelines. Thus, the updated

guidelines from the American Academy of Pediatrics, children should be limited to less than two hours of

entertainment-based screen time per day and shouldn’t have TVs or Internet access in their bedrooms.

This updated guideline includes all forms of “screen media” like smart phones, tablets, TV, video games,

Twitter, Facebook. Clinicians are encouraged to take a media history and ask 2 media questions at every

well-child visit: How much recreational screen time does your child or teenager consume daily? Is there a

television set or Internet-connected device in the child's bedroom?

Reference(s):

Page AS, Cooper AR, Griew P, Jago R. Children's screen viewing is related to psychological difficulties

irrespective of physical activity. Pediatrics. 2010;126:e1011-1017.

Council on Communications and Media. Children, adolescents, and the media. Pediatrics. 2013;132:958-

961.

54. Routine physical activity has important, protective health benefits, including:

A. Improved blood glucose and lipid levels.

B. No significant change in SBP or DBP.

C. Possible increases in inflammation.

D. Increasing visceral fat accumulation.

E. No change in body weight.

Answer: A

Rationale:

Routine physical activity has important, protective health benefits. People who lead sedentary lives are at

heightened risk for developing diabetes and CV disease. In fact, roughly 35% of coronary heart disease

deaths in the U.S. can be attributed to an inactive lifestyle. Recent recommendations regarding physical

activity from various groups affirm the primary role of exercise in preventing chronic disease and in

maintaining health throughout the one’s lifetime. In addition, a considerable body of evidence shows that

consistent exercise can reduce CV disease risk by improving lipid levels, lowering blood pressure,

reducing inflammation and decreasing visceral fat accumulation. Furthermore, exercise helps control

body weight; contributes to healthy bones, muscles and joints; reduces falls and moderates fall-related

injuries among older adults; relieves symptoms of anxiety and depression and is associated with fewer

hospitalizations, physician visits and medications.

It has been suggested that in order to obtain beneficial health effects, mainly in order to reduce CV risk

factors, school-age children should participate in daily moderate to intense physical activities, for 60

minutes or more, and reduce sedentary behavior to less than two hours a day.

Reference(s):

Shephard RJ, Balady GJ. Exercise as cardiovascular therapy. Circulation. 1999;99:963-972.


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Thompson PD Buchner D, Pina IL, et al; American Heart Association Council on Clinical Cardiology

Subcommittee on Exercise, Rehabilitation, and Prevention; American Heart Association Council on

Nutrition, Physical Activity, and Metabolism Subcommittee on Physical Activity. Exercise and physical

activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the

Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the

Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity).

Circulation. 2003;107:3109–3116.

Andersen LB, Harro M, Sardinha LB. et al. Physical activity and clustered cardiovascular risk in children:

a cross sectional study - The European Youth Heart Study. Lancet. 2006;368:299–304.

Nelson ME, Rejeski WJ, Blair SN, et al. Physical activity and public health in older adults:

recommendation from the American College of Sports Medicine and the American Heart Association.

Circulation. 2007;116:1094–1105.

Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee

Report, 2008. Washington, DC: US Department of Health and Human Services; 2008.

http://www.health.gov/paguidelines/report/pdf/CommitteeReport.pdf. Accessed November 6, 2013.


2014;37:S14-S80.

Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce CV

risk: a report of the American College of Cardiology American/Heart Association Task Force on

Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.

Case 4 Continuation

ERL returns 6 months later without any success with lifestyle modification. His mother made nutritious

meals and snacks, but he refused to eat them, still eating strictly snack foods and drinking sugar

sweetened beverages. And he did not want to stop playing his video games. Thus, ERL’s weight

increased 4 pounds.

55. Based upon the number of ERL’s CMR factors, you decide to test for type 2 diabetes, despite

the patient’s lack of symptoms. Criteria for testing for type 2 diabetes in asymptomatic children

(persons aged 18 years and younger) include being overweight and which of the following,

EXCEPT:

A. Caucasian race

B. African American race

C. Maternal history of diabetes or GDM during the child’s gestation

D. Family history of type 2 diabetes in first- or second-degree relative

E. Signs of insulin resistance or conditions associated with insulin resistance, such as acanthosis

nigricans, hypertension, atherogenic dyslipidemia, polycystic ovary syndrome, or small-for-

gestational age birth weight

Answer: A

Rationale:

http://www.health.gov/paguidelines/report/pdf/CommitteeReport.pdf


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With the increase of type 2 diabetes in children, this group should be tested based upon certain criteria.

Criteria for testing for type 2 diabetes in asymptomatic children (persons aged 18 years and younger)

include being overweight (e.g., weight >120% of ideal for height) plus any two of the following risk

factors: family history of type 2 diabetes in first- or second-degree relative; race/ethnicity (Native

American, African American, Latino, Asian American, Pacific Islander); signs of insulin resistance or

conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic

ovary syndrome, or small-for-gestational-age birth weight); maternal history of diabetes or GDM during

the child’s gestation. Testing should be initiated at 10 years of age or at onset of puberty, if puberty

occurs at a younger age, and should be repeated every 3 years.

Reference(s):


2014;37:S14-S80.

56. Among children and adolescents, what percentage of new diabetes cases is type 2 diabetes?

A. 1%

B. 5%

C. 15%

D. 25%

E. 30%

Answer: C

Rationale:

In the 1980s, type 2 diabetes in teens was virtually unheard of. Unfortunately, over the last 30 years, the

prevalence of childhood obesity has increased dramatically in North America. This prevalence has

caused an increase in a variety of health problems, including type 2 diabetes, which previously was not

typically seen until later in life. Although the prevalence of type 2 diabetes in teens is very low, it is

estimated that 15% of new diabetes cases among children and adolescents are type 2 diabetes.

Reference(s):

SEARCH for Diabetes in Youth Study Group. The burden of diabetes mellitus among US youth:

prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006;118:1510-1518.

Springer SC, Silverstein J, Copeland K, et al; American Academy of Pediatrics. Management of type 2

diabetes mellitus in children and adolescents. Pediatrics. 2013;131:e648-e664.

Case 4 Continuation

Recent lab results reveal a FPG level of 134 mg/dL and an A1c of 7.3%. Assessment: ERL is diagnosed

with type 2 diabetes. You continue to stress ERL find an activity that he would enjoy and that would “get

him off the couch”. In addition, you recommend to his mother that she meet with a nutritionist to

determine which nutritious foods he might eat. Now that ERL is diagnosed with type 2 diabetes, other

interventions are needed.

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57. Which of the following statements is INCORRECT regarding pharmacologic intervention(s)

that are indicated to treat ERL’s type 2 diabetes and other parameters of his CMR?

A. TZDs are indicated for pediatric patients to treat hyperglycemia

B. Statins should NOT be started in an adolescent who has a LDL-C level >160 mg/dL

C. Aspirin (low dose) is NOT recommended in children or adolescents to reduce CV risk

D. Metformin and insulin are indicated for pediatric patients to treat hyperglycemia

E. All of the above

Answer: A

Rationale:

For children/adolescents with CMR factors, the initial treatment in this age-group is lifestyle

modification; however, pharmacological treatments are indicated in in the following cases: LDL-C is

persistently over 190 mg/dL although risk factors are absent; presence of risk factors, such as obesity,

hypertension or smoking and LDL-C over 160 mg/dL; and individuals with diabetes and an LDL-C over

130 mg/dL. Thus, to treat a lipid disorder, medications, such as statins, or other lipid-lowering therapies,

including bile acid–binding resins (cholestryramine), and cholesterol absorption inhibitors, each of which

are currently available for treatment of dyslipidemia in children and adolescents.

Despite the escalating rates of obesity-driven type 2 diabetes in youth, oral pharmacologic interventions

remain limited to metformin, the only FDA-approved oral hypoglycemic agent for children. If metformin

fails to achieve target goals, insulin is the other choice. Thiazolidinediones do not have an FDA-approved

indication for treating children/adolescents with type 2 diabetes.

For CV protection, low dose aspirin is recommended only for most men over the age of 50 and women

over the age of 60 with diabetes who have one or more additional heart disease risk factors. For those

with diabetes and a history of CV disease, aspirin (75-162 mg per day) is recommended in adults for

secondary prevention; however, the use of aspirin in persons under the age of 21 is contraindicated due to

the associated risk of Reye Syndrome.

Reference(s):

McCrindle BW, Urbina EM, Dennison BA, et al. Drug therapy of high-risk lipid abnormalities in children

and adolescents: a scientific statement from the American Heart Association. Circulation.

2007;115:1948–1967.

Daniels SR, Greer FR, the Committee on Nutrition. Lipid screening and cardiovascular health in

childhood. Pediatrics. 2008, 122:198-208.

Halpern A, Mancini MC, Magalhães ME, et al. Metabolic syndrome, dyslipidemia, hypertension and type

2 diabetes in youth: from diagnosis to treatment. Diabetol Metab Syndr. 2010;2:55.


2014;37:S14-S80.

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58. Which of the following statement is INCORRECT regarding the results of the TODAY Trial in

adolescents with type 2 diabetes:

A. Dyslipidemia and chronic inflammation were common in youth with type 2 diabetes and improved

over time.

B. Dyslipidemia and chronic inflammation were not commonly observed in youth with type 2 diabetes.

C. Those who failed to maintain glycemic control at the end of the trial had severe impairment of β-cell

function at baseline and experienced progressive and faster loss of β-cell function compared with

those with durable glycemic control.

D. Those who maintained glycemic control at the end of the trial had severe impairment of β-cell

function and experienced progressive and faster loss of β-cell function compared with those with

durable glycemic control.

E. A and D above

Answer: E

Rationale:

The TODAY Trial evaluated adolescents with type 2 diabetes, who were randomized to receive

metformin, metformin plus rosiglitazone (a TZD), or metformin plus ILI. Participants (N=699) were

tested periodically with an OGTT to determine insulin sensitivity, insulinogenic index or C-peptide index,

and β-cell function relative to insulin sensitivity. Study results showed the combination of metformin

plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and β-cell function

relative to insulin sensitivity during the first 6 months versus metformin monotherapy and versus

metformin plus lifestyle. Although these improvements were sustained over 48 months of the trial, the

participants who failed to maintain glycemic control had significantly lower β-cell function (~50%),

higher fasting glucose concentration, and higher A1c at randomization compared with those who did not

fail.

For those with a LDL-C >130 mg/dL or triglycerides ≥300 mg/dL, statin drugs were initiated. Various

parameters of dyslipidemia and inflammation were measured over the course of 36 months or until loss of

glycemic control, including lipids, apolipoprotein B (apoB), LDL particle size, hsCRP, homocysteine,

PAI-1, and A1c. Results showed that dyslipidemia and chronic inflammation were common in

adolescents with type 2 diabetes and worsened over time. Despite some treatment group differences in

lipid and inflammatory marker changed over time, diabetes treatment was generally inadequate to control

this worsening risk.

Reference(s):

TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle

on insulin sensitivity and β-cell function in TODAY. Diabetes Care. 2013;36:1749-1757.

TODAY Study Group. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with

type 2 diabetes: the TODAY clinical trial. Diabetes Care. 2013 Jun;36(6):1758-1764.



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Case Study #5

GRL, a 36-year old Caucasian male who is a staff sergeant in the Army, returns home from a 15-month

deployment in Afghanistan. He was stationed in the mountains in the northeast section of the country on

the Pakistani border. During his time there, his unit met resistance and were involved in intense “fire

fights” every night. Along with the intensity of battle and being at an elevation of 10,000 feet, GRL had

great difficulty in sleeping, which has continued upon his return to the U.S. He presents to you with

clinical depression, caring about nothing, including his family or those around him.

Physical exam: height, 173 cm (5’ 8”); weight, 98 kg (216 lbs); BMI, 32.7 kg/m2; waist circumference, 34

inches; SBP, 125 mmHg; DBP, 82 mmHg (average of 3 readings).

Social history: 8-12 cans of beer daily; 2 pack-a-day smoker; maintains a state of physical fitness through

daily calisthenics.

Family history: Both adopted mother and father are alive and well; he does not know the medical history

of his birth parents.

Lab results: A1c, 6.1%; fasting blood glucose, 100 mg/dL; total cholesterol, 275 mg/dL; LDL-C, 160

mg/dL; HDL-C, 33 mg/dL; triglycerides, 210 mg/dL.

Medications: None

Assessment: a 35-year old male suffering from post-traumatic stress disorder, prediabetes, and

dyslipidemia.

Questions 59-65

59. Which of the following statements is CORRECT regarding PTSD and CMR?

A. PTSD is simply a psychiatric disorder and not an important predictor for cardiac and metabolic

disorders.

B. PTSD is an isolated disorder that is only seen in combat military veterans.

C. Military veterans diagnosed with PTSD are at higher risk of developing insulin resistance and

metabolic syndrome than their counterparts without PTSD.

D. Individuals with PTSD have significantly less coronary artery disease and a lower mortality risk.

E. A and C above

Answer: C

Rationale:

PTSD is not simply a psychiatric disorder that affects combat military veterans, but is a severely disabling

neuropsychiatric anxiety disorder that develops in civilians, police officers, and others as a result of

experiencing horrifying trauma/stress. Someone may experience, witness, or be confronted with an event

or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of

self or others. The person's response involved intense fear, helplessness, or horror. PTSD is not limited

to adults; it can happen in children.

Normally one relates PTSD to combat exposure, but other traumatic experiences, such as motor vehicle,

motor vehicle accidents, and hurricanes, life-threatening illnesses, such as myocardial infarction (MI), can

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also cause PTSD. Results of a meta-analysis showed clinically significant prevalence (16%) of PTSD

symptoms after acute coronary syndromes (ACS); two-thirds of patients continue to suffer from PTSD

two years after an MI.

This traumatic stress increases the risk for inflammation-related somatic diseases and early mortality.

CMR is reflected by the increased health risks associated with stress and PTSD. As a result, obesity,

dyslipidemia, hypertension, diabetes mellitus, and CV disease are prevalent among individuals

experiencing PTSD.

Reference(s):

Vanitallie T. Stress: a risk factor for serious illness. Metabolism. 2002;51(6 suppl 1):40-45.

Tedstone JE, Tarrier N: Posttraumatic stress disorder following medical illness and treatment. Clin

Psychol Rev. 2003;23:409-448.

Spindler H, Pedersen SS: Posttraumatic stress disorder in the wake of heart disease: prevalence, risk

factors, and future research directions. Psychosom Med. 2005;67:715-723.

Abbas CC, Schmid JP, Guler E, Wiedemar L, Begré S, Saner H, Schnyder U, von Känel R. Trajectory of

posttraumatic stress disorder caused by myocardial infarction: a two-year follow-up study. Int J

Psychiatry Med. 2009;39:359–376.

Edmondson D, Richardson S, Falzon L, Davidson KW, Mills MA, Neria Y. Posttraumatic stress disorder

prevalence and risk of recurrence in acute coronary syndrome patients: a meta-analytic review. PLoS

One. 2012,7:e38915.

Edmondson D, Cohen BE. Posttraumatic stress disorder and cardiovascular disease. Prog Cardiovasc

Dis. 2013;55:548-556.

Levine AB, Levine LM, Levine TB. Posttraumatic stress disorder and cardiometabolic disease.

Cardiology. 2013;127:1-19.

60. The prevalence of CMR in military veterans who were involved in combat and suffered from

PTSD is:

A. 18%

B. 32%

C. 43%

D. 52%


Answer: C

Rationale:

Overweight and obesity among male veterans with PTSD strikingly exceeds national findings. In a study

of 1,710,032 Veteran men and 93,290 Veteran women, Das et al reported that 73.0% were at least

overweight, 32.9% were classified as obese, and 3.3% were found to be morbidly obese. This finding

illustrates the pervasiveness of overweight and obesity among military veterans. In addition, the

prevalence of the CMR in those with PTSD was 43%. The rates of CMR were higher in veterans than

those observed among adults in the general population as reported in the NHANES.


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Reference(s):

Das SR, Kinsinger LS, Yancy WS Jr, et al. Obesity prevalence among veterans at Veterans Affairs

medical facilities. Am J Prev Med. 2005;28:291-294.

Heppner PS, Crawford EF, Haji UA, et al. The association of posttraumatic stress disorder and metabolic

syndrome: a study of increased health risk in veterans. BMC Med. 2009;7:1.

61. PTSD influences CMR by causing:

A. Lower mean levels of triglycerides.

B. Lower SBP/DBP.

C. Elevated FPG levels.

D. Elevated levels of HDL-C.

E. All of the above

Answer: C

Rationale:

In persons with PTSD, there is chronic, high-level SNS arousal relative to controls, which is evidenced by

elevated plasma and 24-hour urinary catecholamine levels. Those with PTSD exhibit CV sympathetic

activation with significantly higher heart rates and SBP/DBP levels relative to controls, even during sleep,

with lower respiratory sinus arrhythmia. Sympathetic arousal plays a key role in activation of the renin-

angiotensin-aldosterone system and the pathogenesis of hypertension, and CV remodeling. When

compared with data from NHANES, military veterans had higher SBP and DBP levels:

SBP (130.8 mmHg versus 122.1 [women] and 123.1 mmHg [men])

DBP (81.7 mmHg versus 71.2 mmHg [women] and 74.4 mmHg [men])

The magnitude of the sympathetic response to mental stress is associated with increasing insulin

resistance. Thus, the incidence and prevalence of CMR in military personal is remarkably high, and even

higher than in the general population. In veterans, the most common identified risk factors for CMS were

decreased levels of HDL-C (34%), CAD (21%), and diabetes (19%). The severity of PTSD symptoms

correlated with increasing various parameters of CMR. Similar to increases in BP, when compared with

data from NHANES, military veterans also tended to have:

Higher mean triglycerides (189.5 mg/dL versus 132.3 mg/dL in women; 164.0 mg/dL in men from

NHANES).

Higher FPG (106.4 mg/dL versus 98.8 mg/dL [women] and 103.4 mg/dL [men])

Lower HDL (42.7 mg/dl versus 55.8 mg/dL [women] and 45.3 mg/dL [men]).

Reference(s):

Loucks EB, Magnusson KT, Cook S, Rehkopf DH, Ford ES, Berkman LF. Socioeconomic position and

the metabolic syndrome in early, middle, and late life: evidence from NHANES 1999–2002. Ann

Epidemiol. 2007;17:782–790.

Jakovljević M, Babić D, Crncević Z, Martinac M, Maslov B, Topić R. Cardiovascular manifestations of

posttraumatic stress disorder. Psychiatr Danub. 2008;20:406-410.

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Heppner PS, Crawford EF, Haji UA, et al. The association of posttraumatic stress disorder and metabolic

syndrome: a study of increased health risk in veterans. BMC Med. 2009;7:1.

Institutes of Medicine of the National Academies. Treatment for posttraumatic stress disorder in military

and veteran populations: Initial assessment. Available at www.iom.edu/militaryptsd. Accessed

November 7, 2013.

Levine AB, Levine LM, Levine TB. Posttraumatic stress disorder and cardiometabolic disease.

Cardiology. 2013;127:1-19.

62. Which of the following statements is CORRECT regarding the relationship between PTSD,

CMR, and depression or psychiatric disorders?

A. There is no relationship between PTSD and CMR on the development of depression.

B. PTSD is associated with increased rates of affective disorders, anxiety disorders, and substance abuse.

C. Women who have PTSD are twice as likely to develop a major depression.

D. Men who have PTSD are three times as likely to develop depression.

E. CMR was present in 25% of war veterans with PTSD, and approximately half had co-morbid

depression.

Answer: B

Rationale:

PTSD is associated with increased rates of affective disorders, anxiety disorders, and substance abuse.

Results of the National Comorbidity Survey indicate that at least one additional psychiatric disorder is

present in 88.3% of men and 79.0% of women who have a history of PTSD. In addition, 59% of men and

44% of women who have PTSD meet the criteria for three or more psychiatric diagnoses. Women who

have PTSD are approximately 4 times as likely to develop a major depression and greater than 4 times as

likely to develop mania as women who do not have PTSD. Men who have PTSD are approximately 7

times as likely to develop depression and more than 10 times as likely to develop mania as men who do

not have PTSD.

In military personnel, a variety of factors predispose these individuals to increased risk of developing

CMR. High levels of stress, depression, poor sleep quantity and quality as well as unhealthy lifestyle

habits such as tobacco use and restricted physical exercise, have all been linked to increased CV disease.

Despite growing evidence, there is a lack of awareness of the roles of these additional risk factors among

physicians treating military patients. Increasing knowledge of the relationship between these conditions

and CMR will enable physicians to initiate a multi-targeted approach to impact outcomes in a positive

nature.

Psychological factors are independently associated with an increased risk of both diabetes and CV

disease. These factors include depressive and anxiety symptoms, hostility, anger, and pessimism. Rates

of CMR in patients with a psychiatric disorder is remarkably high, with 72% in patients with PTSD, 60%

in those with schizophrenia, 58% in those with mood disorder, and 56% in those with dementia. This

relationship can be partially correlated to PTSD and its effects on increasing those psychological factors.

http://www.iom.edu/militaryptsd


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The relationship between PTSD and CMR in military service personnel is multifaceted and the

mechanisms seem to be associative rather than direct. However, a study identified CMS in 25% of war

veterans with PTSD, and approximately half of these patients had co-morbid depression (47.8%).

Reference(s):

Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National

Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048–60.

Brady KT, Killeen TK, Brewerton T, Lucerini S. Comorbidity of psychiatric disorders and post-traumatic

stress disorder. J Clin Psychiatry. 2000;61(suppl 7):22–32.

Phillips B. Sleep-disordered breathing and cardiovascular disease. Sleep Med Rev. 2005;9:131-140.

Jakovljević M, Babić D, Crncević Z, Martinac M, Maslov B, Topić R. Cardiovascular manifestations of

posttraumatic stress disorder. Cohen BE, Panguluri P, Na B, Whooley MA. Psychological risk factors

and the metabolic syndrome in patients with coronary heart disease: findings from the Heart and Soul

Study. Psychiatry Res. 2010;175:133-137.

63. Individuals who use tobacco should be reminded that:

A. No matter how long they’ve smoked, their health will improve upon quitting.

B. Smoking aggravates cardiometabolic problems.

C. The risk of heart disease remains the same if they are long-time smokers.

D. Both a and b

E. All of the above

Answer: D

Rationale:

The deleterious effects of smoking are well known. About one in five deaths from CV diseases is

attributable to smoking. And approximately 35,000 to 40,000 non-smokers die each year from CV

disease as a result of exposure to environmental tobacco smoke. Research shows smoking aggravates

cardiometabolic problems and doubles the risk for CV disease in patients with diabetes and increases the

risk of neuropathy, nephropathy and possibly retinopathy in people with diabetes. The risk of heart

disease is cut in half just one year after quitting. After 5 to 15 years without smoking, the patient’s CV

risk is comparable to someone who never smoked.

Reference(s):

Ockene JK, Kuller LH, Svendsen KH, Meilahn E. The relationship of smoking cessation to coronary

heart disease and lung cancer in the Multiple Risk Factor Intervention Trial (MRFIT). Am J Public

Health. 1990;80:954–958.

American Heart Association. “Cigarette Smoking and Cardiovascular Disease” Fact Sheet. Available at:

http://www.heart.org/HEARTORG/GettingHealthy/QuitSmoking/QuittingResources/Smoking-

Cardiovascular-Disease-Heart-Disease_UCM_305187_Article.jsp. Accessed November 21, 2013.

Saudek CD, Margolis S. Diabetes. Johns Hopkins White Paper. Johns Hopkins Medical Institutions,

2003.

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Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and

lipoprotein profiles: a meta-analysis. Prev Med. 2003;37:283–290.

Case 5 Continuation

Based upon recommendations from the Association’s Standards of Care, you refer GRL to a mental

health specialist. Although he does not have diabetes, he has CMR factors that could predispose him to

develop type 2 diabetes. Indications for referral to a mental health specialist (familiar with diabetes

management) may include gross disregard for the medical regimen (by self or others), depression,

possibility of self-harm, debilitating anxiety (alone or with depression), indications of an eating disorder,

or cognitive functioning that significantly impairs judgment.

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Case Study #6

JH is a 54-year-old female who presents to you with complaints of a severe skeletomuscular shoulder pain

secondary to surgical repair of an AC separation and broken collarbone.

Family history: Mother is alive and has type 2 diabetes; underwent CABG at age 56 and a PCI with stent

placement at age 72. Father died at age 76 from an M.I.

Social history: Denies tobacco use, exercises only occasionally, and does not pay attention to her

nutrition.

Physical exam: blood pressure, 135/77 mmHg; BMI, 27 kg/m2; height, 5’4” (162.5 cm); waist

circumference, 36 inches (91.4 cm).

Laboratory results: total cholesterol level, 210 mg/dL; LDL-C, 156 mg/dL; HDL-C, 39 mg/dL;

triglyceride, 145 mg/dL; FPG, 104 mg/dL; A1c, 6.2%.

Current medications: none

Assessment: female with skeletomuscular shoulder pain and newly diagnosed dyslipidemia and

prediabetes; a family history of type 2 diabetes and coronary artery disease.

Questions 64-71

64. JH has lipid levels that have increased significantly since her last appointment 18 months ago.

You discuss with her prescribing medication to manage her cholesterol levels. When evaluating

this patient’s target goal in the management of cholesterol, which of the following is/are true?

A. LDL-C goals are different depending on category of risk (e.g., 0–1 risk factors, multiple risk factors,

people with CHD or risk equivalent like diabetes)

B. Cholesterol should be checked every year for patients >20 years of age

C. Ordering a non-fasting lipid panel is preferred to gauge the patient’s total cholesterol, LDL-C, HDL-

C and triglycerides

D. A normal triglyceride level is <100 mg/dL

E. All of the above

Answer: A

Rationale:

JH has CMR based upon her physical exam and lab results. Patients with at CMR or type 2 diabetes have

an increased prevalence of lipid abnormalities, contributing to their high risk of CV disease. Thus it is

important to monitor lipids to minimize adverse outcomes. For patients >20 years of age, cholesterol

should be checked every 5 years. Ordering a fasting lipid panel is preferred to gauge the patient’s total

cholesterol, LDL-C, HDL-C and triglycerides, and monitor for risk factors, which include SBP/DBP

>140/90 mmHg; HDL-C <40 mg/dL (in men); family history of myocardial infarction before age 55: in

males, >45 years; in females, >55 years.

Number of Risk Factors Recommended LDL-C Level

0-1 risk factor <160 mg/dL

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Multiple (2+) risk factors <130 mg/dL

People with overt CV disease <100 mg/dL

According to the ATP-III and the Association’s Standards of Care, aggressive lowering of LDL-C is

recommended for patients with known risk of CV disease to achieve levels <100 mg/dL, or if very high

risk, as low as 70 mg/dL; target HDL-C >40 mg/dl for men, >50 mg/dL for women; and triglycerides

<150mg/dL. Conversely, the recent ACC/AHA guidelines on the management of cholesterol do not

recommend titrating therapies to a specific LDL-C target level. Rather, they recommend monitoring

overall patient risk score once prescribed lipid-lowering therapy, specifically a statin.

The ACC/AHA guidelines recommend for individuals with diabetes who are 40 to 75 years of age, a

moderate-intensity statin (a drug that lowers LDL-C by 30% to 49%) should be used, whereas a high-

intensity statin is a reasonable choice if the patient also has a 10-year risk of atherosclerotic CV disease

>7.5%.

Reference(s):

Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol In Adults (Adult Treatment


(NCEP). JAMA. 2001:2486–2497.


2014;37:S14-S80.


cholesterol to reduce atherosclerotic CV risk in adults: A report of the American College of


65. Based upon JH’s waist circumference and waist-to-height ratio, she has visceral obesity. Which

of the following proinflammatory markers can be measured to determine level of CMR?

A. Adiponectin

B. hs-CRP

C. IL-6

D. Plasminogen activator inhibitor-1

E. All of the above

Answer: E

Rationale:

Inflammation is a potential mechanism linking obesity and CMR. Excess abdominal fat is believed to

increase blood levels of free fatty acids, which can inhibit the regulation of glucose by insulin. Visceral

obesity is also characterized by a proinflammatory, prothrombotic state with elevated levels of CRP,

cytokines and other proteins that may promote heart disease. CRP concentrations are elevated

predominantly in obese individuals who are also insulin resistant.


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An unfavorable inflammatory status has been shown to be negatively associated with metabolic health in

obese (BMI >30 kg/m2) and overweight (BMI <30 kg/m2) individuals. Other molecules thought to play a

role in development of insulin resistance and increased risk of CV disease include PAI-1 and fibrinogen.

Research shows metabolically unhealthy obese and non-obese individuals present with higher

concentrations of these various cytokines, including CRP, TNF-α, IL-6, and PAI-1, and lower levels of

adiponectin compared to their metabolically healthy counterparts.

Reference(s):

Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–126.


2005;6:21–29.

McLaughlin T et al. Differentiation between obesity and insulin resistance in the association with C-

reactive protein. Circulation. 2002;106:2908–2912.

McLaughlin T, Lamendola C, Coghlan N, Liu TC, Lerner K, Sherman A, Cushman SW. Subcutaneous

adipose cell size and distribution: Relationship to insulin resistance and body fat. Obesity (Silver

Spring). 2012 Nov 29:NA. doi: 10.1002/oby.20209. [Epub ahead of print]

Davidson MH. Emerging therapeutic strategies for the management of dyslipidemia in the patients with

the metabolic syndrome. Am J Cardiol. 2004;93(11):3–11.

Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese

adults? J Clin Endocrinol Metab. 2013;98:E1610-1619.

66. CRP is an emerging marker of inflammation and may provide useful information to assess the

risk of CV disease. Which of the following statements is/are true?

A. CRP is an independent predictor of inflammation, insulin resistance and future CV disease events in

patients with and without established CV disease.

B. Patients with low CRP levels have 1.5 to 4 times the risk of myocardial infarction than those with

high CRP levels.

C. Elevated CRP levels are not influenced by smoking, chronic inflammation, obesity and estrogen.

D. All of the above


Answer: A

Rationale:

Studies have consistently found CRP to be an independent predictor of inflammation, insulin resistance

and future CV disease events in patients with and without established CV disease. Individuals with

elevated CRP levels (>2.0 mg/L) have 1.5 to 4 times the risk of myocardial infarction than those with low

CRP levels. Some studies suggest that high CRP levels in the setting of low LDL-C impart the same

level of CVD risk as high LDL-C levels in the setting of low CRP. CRP levels are more likely to be

elevated in obese, insulin resistant patients.

The updated guidelines on atherosclerotic CV risk use CRP as a differentiator for assessing individuals

with higher risk assessments to determine management strategies.



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Reference(s):

Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–126.


2005;6:21–29.

McLaughlin T et al. Differentiation between obesity and insulin resistance in the association with C-

reactive protein. Circulation. 2002;106:2908–2912.

Davidson MH. Emerging therapeutic strategies for the management of dyslipidemia in the patients with

the metabolic syndrome. Am J Cardiol. 2004;93:3–11.




67. Which of the following statements is CORRECT regarding adiponectin?

A. Is important because of its anti-inflammatory, anti-diabetic and anti-atherogenic properties

B. Higher adiponectin levels are associated with insulin resistance.

C. Is not important in mediating CMR factors.

D. None of the above

E. All of the above

Answer: A

Rationale:

Adiponectin is the only known anti-inflammatory protein whose circulating levels are decreased before

type 2 diabetes. Insulin resistance and obesity are both associated with lower plasma adiponectin

concentrations. Results of one study showed insulin-resistant subjects had significantly lower adiponectin

concentrations (p < .001), in both obese and non-obese subjects as compared with either obese or non-

obese insulin-sensitive subjects.

Reference(s):

Abbasi F, Chu JW, Lamendola C, et al. Discrimination between obesity and insulin resistance in the

relationship with adiponectin. Diabetes. 2004;53:585-590.

Case 6 Continuation

68. You order a CRP level; results come back as 3.4 mg/L (high). Which intervention(s) would you

recommend for JH?

A. Aspirin

B. Statins

C. Increased physical activity

D. All of the above


Answer: D


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Rationale:

Despite ongoing uncertainty about the value of assessing markers of inflammation or hypercoagulation,

interventions that target these abnormalities have been shown to reduce CMR. Aspirin therapy has a

strong role in CV disease prevention, especially in men, older women, and people with multiple CV

disease risk factors. Guidelines recommend increased physical activity because evidence shows

consistent exercise can reduce risk of CV disease by improving lipid levels, lowering blood pressure,

reducing inflammation and decreasing visceral fat accumulation, positively impacting inflammatory

markers, such as CRP. And statins are recommended for individuals with diabetes aged 40 to 75 years

with LDL–C levels between 70 to189 mg/dL, with or without evidence of clinical atherosclerotic CV

disease, which includes acute coronary syndromes, or a history of MI, stable or unstable angina, coronary

or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of

atherosclerotic origin.

Reference(s):

USPSTF. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale.

Ann Inter Med. 2002;136:157-160.

Thompson PD, Buchner D, Pina IL, et al; American Heart Association Council on Clinical Cardiology

Subcommittee on Exercise, Rehabilitation, and Prevention; American Heart Association Council on

Nutrition, Physical Activity, and Metabolism Subcommittee on Physical Activity. Exercise and physical

activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the

Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the

Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity).

Circulation. 2003;107:3109–3116.

Poirier P et al. Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight

Loss. An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart

Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.

Circulation. 2006;113:898–918.

Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary

prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized

controlled trials. JAMA. 2006;295:306-313.


2014;37:S14-S80.




69. JH has prediabetes and a family history of diabetes. Which of the following statements

regarding aspirin is CORRECT for individuals at high risk for CV events?

A. Aspirin is beneficial for primary prevention of CV events in individuals with no previous history of

vascular disease and a low risk of CV disease.

B. Aspirin is recommended only for women with prediabetes who are not at increased risk for

gastrointestinal tract, intracranial, or other bleeding.


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C. The use of aspirin in the primary prevention of vascular events should be considered on a case by

case basis depending upon absolute risks of the patient (i.e., age, gender, family history of premature

vascular disease).

D. The appropriate aspirin dose for primary prevention is 325 mg once daily.

E. Aspirin may reduce cerebrovascular events in persons with diabetes irrespective of CRP level.

Answer: B

Rationale:

Aspirin has been shown to be effective for secondary prevention of CV morbidity and mortality in high-

risk patients. However, two randomized controlled trials investigated the beneficial effects of aspirin

specifically in patients with diabetes failed to show a significant reduction in CV disease endpoints.

These results raise further questions about the efficacy of aspirin for primary prevention in people with

diabetes.

Based upon results from the Antithrombotic Trialists’ Collaboration study, aspirin significantly reduced

coronary heart disease events in men but not in women; however, it had no effect on stroke in men but

significantly reduced stroke in women. For secondary prevention, gender differences on the effects of

aspirin have not been observed. The Association’s Standards of Care recommend the use of aspirin

therapy (75–162 mg/day) as a secondary prevention strategy in those with diabetes who have a history of

CV disease; however, aspirin not recommended for those at low CV disease risk, as the low benefit is

likely to be outweighed by the risks of significant bleeding. The American Association of Clinical

Endocrinologists’ guidelines recommend aspirin for all persons with prediabetes who are not at increased

risk for gastrointestinal tract, intracranial, or other bleeding.

In a subanalysis of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD)

study, results revealed for those not taking aspirin, the incidence of cerebrovascular events was higher in

those individuals with diabetes who had an elevated CRP level (>0.1 mg/L) versus those with a low CRP

level (<0.1 mg/L). However, for those taking aspirin, no significant difference was noted in the incidence

of the cerebrovascular events between the high CRP group and the low CRP group. Thus, aspirin therapy

may reduce cerebrovascular events in persons with diabetes who have an elevated CRP level.

Advanced glycation end products (AGE) and/or their receptors are significantly positively correlated with

adiposity, inflammation, dyslipidemia, and insulin resistance in adults. In the Targeting Inflammation

Using Salsalate for Type-2 Diabetes (TINSAL-T2D) study, salsalate, a non-acetylated salicylate, lowed

plasma glucose levels in participants with type 2 diabetes and positively influence markers of

inflammation, decreasing levels of AGE (e.g., CRP and TNF-α) and increasing levels of adiponectin.

Reference(s):

Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet

therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ.

2002;324:71-86.

Berger JS, et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-

specific meta-analysis of randomized controlled trials. JAMA. 2006;295:306-313.

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Ogawa H, Nakayama M, Morimoto T, et al; Japanese Primary Prevention of Atherosclerosis with Aspirin

for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic

events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300:2134–2141

Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes

(POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients

with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840.

Pignone M, Alberts MJ, Colwell JA, et al; American Diabetes Association; American Heart Association;

American College of Cardiology Foundation. Aspirin for primary prevention of cardiovascular events in

people with diabetes: a position statement of the American Diabetes Association, a scientific statement

of the American Heart Association, and an expert consensus document of the American College of

Cardiology Foundation. Diabetes Care. 2010;33:1395-1402.


2014;37:S14-S80.

Soejima H, Ogawa H, Morimoto T, et al; JPAD Trial Investigators. Aspirin possibly reduces

cerebrovascular events in type 2 diabetic patients with higher C-reactive protein level: subanalysis from

the JPAD trial. J Cardiol. 2013;62:165-170.

Rosenzweig JL, Ferrannini E, Grundy SM, et al; Endocrine Society. Primary prevention of cardiovascular

disease and type 2 diabetes in patients at metabolic risk: an endocrine society clinical practice guideline.

J Clin Endocrinol Metab. 2008;93:3671-3689.

Barzilay JI, Jablonski KA, Fonseca V, et al; the TINSAL T2D Research Consortium. The impact of

salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes. Diabetes

Care. 2013 Nov 19. [Epub ahead of print]

70. JH asks about the risk of bleeding with aspirin. Which of the following statements is correct

regarding the risk of MAJOR bleeding (gastrointestinal or intracranial) from aspirin use, especially

in persons with diabetes?

A. Major bleeding is observed only at doses greater than 325 mg per day.

B. There is no significant increase in major bleeding in individuals with diabetes who take aspirin.

C. Major bleeding is not an issue in patients at high risk of a CV event

D. Diabetes is associated with an increased risk of major bleeding episodes only in those taking aspirin.


Answer: B

Rationale:

Therapy with low-dose aspirin is used for the treatment of CV disease. It is recommended as a secondary

prevention measure for individuals with moderate to high risk of CV events, that is, for patients with

multiple risk factors such as hypertension, dyslipidemia, obesity, diabetes, and family history of ischemic

heart disease. However, any benefit may be outweighed by the risks of significant bleeding. But is this

true for individuals with diabetes when compared to those without?

In a population-based cohort that compared individuals being treated with low-dose aspirin (<300

mg/day) versus matched controls without aspirin use, results showed aspirin use was associated with a






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greater risk of major bleeding in most of the subgroups investigated; however, there was no significant

increase in major bleeding in individuals with diabetes. For participants with diabetes, there was an

associated increase risk of major bleeding episodes irrespective of aspirin use. Thus, those with diabetes

had a high rate of bleeding that was not independently associated with aspirin use.

Reference(s):

Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet

therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ.

2002;324:71-86.

Pignone M, Alberts MJ, Colwell JA, et al; American Diabetes Association; American Heart Association;

American College of Cardiology Foundation. Aspirin for primary prevention of cardiovascular events in

people with diabetes: a position statement of the American Diabetes Association, a scientific statement

of the American Heart Association, and an expert consensus document of the American College of

Cardiology Foundation. Diabetes Care. 2010;33:1395-1402.


2014;37:S14-S80.

71. Matching Question.

In discussing the management of her cholesterol levels, JH asks what are the different types of

medications and how do they work. Match the class of drugs with the appropriate mechanism of

action.

Drug Class Mechanism

A. Statins ___ Activates an enzyme that enhances the

breakdown of triglyceride-rich lipoproteins while

increasing HDL-C

B. Cholesterol absorption inhibitors ___ Reduces the liver’s ability to produce VLDL

C. Fibrates ___ Lowers LDL-C by reducing the amount of

cholesterol absorbed in the intestines and increases

LDL receptor activity.

D. Niacin ___ Binds to bile acids in the intestines and prevent

their reabsorption, leading to increased hepatic

LDL-C removal from the blood.

E. Resins ___ Increasing hepatic LDL-C removal from the

blood.

Answer: C, D, B, E, A

Rationale:

Niacin reduces the liver’s ability to produce VLDL. At a dose of 1 to 2 g per day it has been shown to

increase HDL-C levels by 15% to 30% and decrease triglycerides. However, evidence from clinical

of 69

outcome trials, which included concomitant statin therapy, failed to show any benefit with niacin. The

AIM-HIGH trial, a secondary prevention trial in patients with low HDL-C and elevated triglycerides that

added extended-release niacin to simvastatin (and ezetimibe as needed to achieve LDL-C goals), was

stopped owing to the clinical futility for demonstrating event reduction, despite significant HDL-C

increases and a significant event rate.

Fibrates activate an enzyme that enhances the breakdown of triglyceride-rich lipoproteins while

increasing HDL-C. These drugs lower triglycerides while raising HDL-C approximately 10% to 20%,

effects thought to occur via peroxisome proliferator-activated receptor alpha activation. However, in the

lipid arm of ACCORD, adding fenofibrate to simvastatin did not improve the primary CV end point.

Cholesterol absorption inhibitors lower LDL-C by reducing the amount of cholesterol absorbed in the

intestines and increase LDL receptor activity.

Resins bind to bile acids in the intestines and prevent their reabsorption, leading to increased hepatic

LDL-C removal from the blood.

Statin therapy has proven risk reduction in both primary and secondary prevention of cardiovascular

disease. Statin monotherapy has been shown to reduce LDL cholesterol and triglycerides by 18–55% and

7–30%, respectively, and increase HDL by 5–15%. Currently, statins remain the first-line therapy among

individuals with low HDL-C levels and significant CV risk who warrant intervention.

Reference(s):

Expert Panel on Detection, Evaluation, Treatment of High Blood Cholesterol In Adults (Adult Treatment

Panel III) Executive Summary of The Third Report of the National Cholesterol Education Program

(NCEP). JAMA. 2001:2486–2497.

Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients

with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298:1180–1188.

Ginsberg HN, Elam MB, Lovato LC, et al; ACCORD Study Group. Effects of combination lipid therapy

in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–1574.

Mihaylova B, Emberson J, Blackwell L, et al; Cholesterol Treatment Trialists’ (CTT) Collaborators. The

effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-

analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–590.

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