diabetes and the current american diabetes association

8/12/2019 Diabetes and the Current American Diabetes Association

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Diabetes and the Current American Diabetes Association Guidelines

Au tho r: M a ry Elle n Koe nn , MS, MT(ASCP), C LS(NC A)

Re view e r: Le slie Lo ve tt, M S, M T(ASCP)

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Course Instructions

Please proc eed through the course by clicking on the blue arrows or text links. Use the table of contents to monitor

your progress. Your progress will be saved automatically as you proceed through the course, and you may later

continue where you left off even if you use a different computer. You may encounter practice questions within the

course, which are not graded or recorded.

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Course Info

This course carries the following continuing educa tion credits:

P.A.C.E. Contact Hours: 1.50 hour(s)

Course Number: 578-007-10

Florida Board of C linical Laboratory Science CE -General (Clinical Chemistry/UA/Toxicology): 1.50 hour(s)

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Diabetes and the Current ADA Guidelines

Introduction

Diabetes is a metabolic disorder caused by impaired pancreatic function, resulting in decreased insulin concentration

and ac tivity. This causes the patient with diabetes to have elevated blood glucose concentrations (hyperglycemia).

Hyperglycemia leads to serious risk factors and life-threatening complications for the individua l. Bec ause of these risks

and the ensuing c hronic illness for diabetic patients, ongoing med ical care a nd education for self-management are

required. Diabetes is a national and international healthcare issue due to its high incidence and healthcare costs.

Ac cording to the World Health Organization (WHO) in 2000, there were 171 million individuals worldwide with diabetes. That

number is projected to increase to 366 million by 2030.


Case Studies

The following describes three patients with a history relating to diabetes and pertinent laboratory results. As this study

proceeds, you will be asked if they meet the c riteria for diagnosis of diabetes, are at risk for diagnosis of diabetes,

and/or whether they are a type 1 or type 2 diabetic.


Organizations and Agencies

This course will primarily focus on recommendations made by the American Diabetes Assoc iation (ADA) that are related

to the d iagnosis and monitoring of diabetes. The ADA states on its website, "Our mission is to prevent and cure d iabetes

and to improve the lives of all people affec ted by diabetes."*

Other important agencies and studies referred to in this course are:

International Diabetes Federation (IDF): An alliance of 200 diabetes associations; acts as a global advocate for

individuals with diabetes.

World Health Organization (WHO): An arm of the United Nations; provides programs for prevention, treatment, and

care of those with diabetes worldwide.

Diabetes Control and C omplications Trial (DCCT): A major clinica l study 1983-1993; proved the correlation between

control of glucose blood level and lowered onset and severity of the complications of diabetes.

*Reference: American Diabetes Association. Available at: http://www.diabetes.org/about-us/. Accessed April 14, 2010.

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Case A

A 50-year-old male with a family history of diabetes visits his physician for routine physical. He reports that he feels his

health is excellent. He exercises regularly, but often his diet is high in calories and fat.

Physica l Examination: Slightly overweight; blood pressure and pulse normal.

A basic metabolic panel and PSA are ordered. All results are within reference range except the plasma glucose. The

patient's physician orders a hemoglobin A1C

(HbA1C

) the following week.

Laboratory results:

Fasting plasma glucose (FPG)= 110 mg/dL (Reference interval 75 -100 mg/dL)

One Week Later:

Hb A1C

= 6.0% (Reference interval 4 -6%)


Case B

A 14-year-old male sees his pediatrician bec ause of fatigue, weight loss, increased appetite, thirst, and frequent

urination. There is a family history of diabetes. The physican orders the following laboratory assays:

Laboratory Results:


Serum Ketones= Positive, 1+ (Reference Negative)

FPG repeated one week later= 170 mg/dL (Reference interval 75 -100 mg/dL)


Case C

A 55-year-old female is seen for a routine physicial. She has gained 20 pounds since her last physical two years ago,

which she attributes to lack of exercise and a high-fat diet. She also reports increased stress in her life because of work

and additional responsibility of caring for her elderly father. Suspecting that the patient has developed diabetes, her

physician orders a Hb A1C

test, which is repeated two weeks later.

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Initial Hb A1C


Repeat Hb A1C

(two weeks later)= 6.7% (4 -6%)

Carbohydrate Metabolism

Ungraded Practice Question

Which of the following hormones is mainly responsible for the entry of glucose into the c ell for energy production?

Plea se selec t the sing le b est answer



Which of the following hormones is mainly responsible for the entry of glucose into the c ell for energy production?

nmlkj Epinephrine

nmlkj Glucagon

nmlkj Cortisol

nmlkj Insulin


Feedback

Insulin is the hormone that is mainly responsible for the entry of g lucose into the cell for energy production

Glucagon and epinephrine promote glycogenolysis, conversion of glycogen to g lucose, which increases plasma glucose.

Cortisol, along with glucagon, increases gluconeogenesis, formation of glucose from noncarbohydrates, which a lso raises

plasma glucose concentration.

nmlkj Epinephrine

nmlkj Glucagon

nmlkj Cortisol

nmlkj Insulin

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Blood Glucose and Hormonal Control

Several hormones regulate blood glucose concentration. Insulin, the main regulatory hormone, is produced by and

secreted from the pancreatic beta-cells. Insulin stimulates the uptake of glucose and the movement of glucose from

blood to c ells for energy produc tion. Insulin also stimulates glycogenesis, inhibits glycogenolysis, and regulates protein

synthesis.

Other hormones that a re also involved in ca rbohydrate metabolism include:

Pancreatic glucagon-stimulates glycogenolysis and gluconeogenesis

Adrenal gland c ortisol-promotes gluconeogenesis

Epinephrine-a neurotransmitter that increases glycogenolysis



Which of the following hormones increase p lasma glucose concentration by converting glycogen to glucose?

More t han one a nsweris c orrec t. Plea se selec t a l l c orrec t a nsw ers



Which of the following hormones increase p lasma glucose concentration by converting glycogen to glucose?

gfedc Cortisol

gfedc Glucagon

gfedc Epinephrine


Feedback

gfedc Cortisol

gfedc Glucagon

gfedc Epinephrine

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Glucagon and epinephrine promote glycogenolysis, conversion of glycogen to g lucose, which increases plasma glucose.

Cortisol along with glucagon increases gluconeogenesis, formation of g lucose from noncarbohydrates which a lso raises

plasma glucose concentration.

Diabetes

Diabetes - A Metabolic Disorder

Diabetes results when insulin c onc entrations are

absent, reduced, or when insulin ac tion is

impaired (referred to as insulin resistanc e).

Without cellular uptake of blood glucose for

energy, the balance of metabolizing

carbohydrates, fats, and proteins for energy is

lost. Hyperglycemia and excess use of fats and

proteins for energy result. The latter causes excess

acetyl-CoA which is converted to ketone bodiesor to cholesterol.

Polydipsia, polyuria, and unexplained weight loss

are symptoms of diabetes. Polydipsia and

polyuria oc cur as the body tries to lower blood

glucose concentrations with increased urinary

excretion of glucose. Weight loss results from

increased utilization of proteins and fats for

energy.

The image on the right represents impaired

metabolism in diabetes. The thicker arrows

represent the pathways that are imbalanced. In

normal carbohydrate metabolism, the opposing

arrows would be of the same size, representing a

normal pathway and a balanced metabolism.

Diabetes

Hemoglobin A1C

and Diabetes Diagnosis

The addition of hemoglobin A1C

(HbA1C

) measurement to the diagnosis of diabetes is a significant change. HbA1C

assay is currently the standard biomarker for glycemic management. Mainly due to lack of standardization, HbA1C

measurement had not been a component for diagnosis of diabetes. HbA1C

assays are now highly standardized and

recommended usage expanded.

Impaired_metabolism_diabetes2_edit

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The 2010 ADA C linical Prac tice Recommendations specifically states that the HbA1C

measurement be a National

Glycohemoglobin Standardization Program (NGSP) method and traceable to the Diabetes Control and Complications Trial

(DCCT) reference assay. Note that po int-of-care HbA1C

methods do not currently meet this standardization criteria for

diagnostic use.

Diabetes

HbA1C

versus Blood Glucose Measurement

Advantages of utilization of HbA1C

over blood glucose mea surement include:

Fasting is not required

Greater specimen stability

Less fluctua tions in day-to-day levels caused by stress and illness

Disadvantages of utilization of HbA1Cover blood glucose mea surement include:

Cost per test is higher than blood glucose.

Conditions that shorten red blood cell (RBC) survival e.g., hemolytic anemia, homozygous sickle cell trait, pregnancy,

or rec ent significant blood loss, will reduce exposure of RBCs to glucose, thereby lowering the HbA1C

test value.

Specimens with >10% fetal hemoglobin (HbF) may have a falsely decreased HbA1C

test result.

If onset of diabetes is rapid, blood glucose levels will more correc tly reflect glycemia than HbA1C

levels.

Diabetes

Diagnosis of Diabetes

In 1997, the ADA recommended significant changes in the diagnosis of diabetes. The poorly reproducible oral glucose

tolerance test (OGTT) was replaced with easier to use and more patient-friendly diagnostic c riteria. An elevated fasting

plasma glucose (FPG) was the preferred test to document hyperglycemia acc ording to the 1997 ADA Clinical Practice

Recommendations. An elevated c asual plasma glucose with symptoms of diabetes and 2-hour plasma glucose after

an ingestion of 75 grams of dissolved glucose were also used for diagnosis.

In 2010, the ADA affirmed the decision of an international expert committee's rec ommendation to use the HbA1c

test to

diagnose diabetes with a threshold > 6.5%.

Any one of the four criteria can be used. The hyperglycemia should be demonstrated a second time by any of the four

criteria unless the glucose level is significantly high and diabetes is unquestionab le. The table below lists the diagnostic

assays and criteria.

Assay DescriptionCriteria for

Diabetes

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These criteria are reviewed regularly by ADA, WHO, and IDF.

Diabetes

Case Studies

Review Case A, Case B, and Case C by clicking on each one. Which of these patients do you think would bediagnosed with diabetes according to the c riteria for diagnosis? Proceed to the next page to provide your response.

Diabetes

Ungraded Practice QuestionWhich patients would be diagnosed with diabetes according to the criteria for diagnosis?

HbA1C

Performed in laboratory by method NGSP c ertified and standardized to

DCCT assay

> 6.5 %

Fasting plasma glucose At least 8 hour fast > 126 mg/dL

Casual plasma glucose Symptoms of diabetes;

Blood glucose measured at any time of day

> 200 mg/ dL

Two -hour plasma

glucose

Following a glucose load of 75g anhydrous glucose dissolved in water > 200 mg/dL


Diabetes


nmlkj Case A, Case B, and C ase C

nmlkj Case B only

nmlkj Case B and C

nmlkj Case C only

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Which patients would be diagnosed with diabetes according to the criteria for diagnosis?


Feedback

Case A has elevated FPG and HbA1C

, but the current criteria for diagnosis of d iabetes using FPG is FPG >/=126 mg/dL and

A1C >/= 6.5% . Both Ca se B and Case C meet the c urrent criteria.

Diabetes

Categories of Increased Risk for Diabetes

Categories of increased risk for diabetes is the new designation for individua ls whose glucose or HbA1C

levels are higher

than reference ranges but lower than the diagnostic criteria for diabetes (ADA 2010 Clinical Practice

Recommendations). These individuals are at increased risk for development of diabetes and should have intervention

initiated.

Formerly individuals at increased risk for development of diabetes were called pre -diabetic; the 2010 rec ommendations

recommend use of this new category designation but also state that the term pre -diabetic may still be used. Besides risk of

diabetes, these individua ls have higher risk for cardiovascular disease.

Diabetes

Categories of Increased Risk for Diabetes

These are the ranges that are recommended by the 2010 ADA Clinical Prac tice Guidelines for determining increased risk

for diabetes:

nmlkj Case A, Case B, and C ase C

nmlkj Case B only

nmlkj Case B and C

nmlkj Case C only

Glucose test Range indicating increased risk for diabetes

Fasting plasma glucose 100 -125 mg/dL

2-hour plasma glucose following 75g glucose load 140 -199 mg/dL

HbA1C 5.7 -6.5%

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Diabetes

Reference Ranges

Diabetes


Case A (continued)





patient's physician orders a HbA1C

the following week.

Laboratory results:


One Week Later:

HbA1C


Which of the following statements is most accurate regarding the patient in Case A?

Plasma Glucose Level Designation

75-100 mg/dL Referencerange for Fasting Plasma Glucose

< 100 mg/dL 2003 ADANormal Fasting Plasma Glucose

100 mg/dL to 125 mg/dL ADAImpaired Plasma Glucose (IFG)

140 mg/dL to 199 mg/dL ADAand WHO Impaired Glucose Tolerance (IGT)

HbA1C

4-6% ADA Recommended

Due to limited A1C

assay availability worldwide, WHO

does not publish A1C

recommended levels


nmlkj The patient in Ca se A should be c lassified as at increased risk for diabetes.

nmlkj The patient in Ca se A has diabetes.

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Diabetes


Case A (continued)





patient's physician orders a HbA1C

the following week.

Laboratory results:


One Week Later:

HbA1C


Which of the following statements is most accurate regarding the patient in Case A?


Feedback

The FPG for Case A is less than 126 mg/dL but above 100 mg/dL; the HbA1C

is 6.0 %. According to the current criteria, this

pa tient is at increased risk for diabetes.

Classification of Diabetes


In 1997, the ADA also revised the classification of diabetes. The new designations are based upon the cause, not

treatment, for each class of diabetes. Where numbers are used for type classification, Arabic numerals have replaced

Roman numerals for greater clarity and ease.

There are four clinical classes of diabetes:

Type 1

Type 2

nmlkj The patient in Ca se A should be c lassified as at increased risk for diabetes.

nmlkj The patient in Ca se A has diabetes.

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Gestational Diabetes

Other


Type 1 Diabetes

Type 1 diabetes is caused by an absolute deficiency of insulin from an autoimmune destruction of pancreatic beta cells

or degeneration of these cells. The infiltration of mononuc lear cells can be prec ipitated by environmental factors such

as viruses, chemica ls, and cow's milk or caused by unknown or idiopathic reactions. Ordinarily the individua l has an

inherited susceptibility to this autoimmune reaction and diabetes develops suddenly. Most often this onset occurs in

childhood or young adult years. Type 1 diabetes encompasses about 10% of diabetes cases.

Because of the beta-cell destruction, type 1 diabetic pa tients require insulin to prevent ketosis and reduce complications of

this disease.

This class was formerly Type I Insulin Dependent Diabetes Mellitus (IDDM) and referred to as juvenile-onset diabetes. The ADA

has abo lished using these designations but are noted in this review to correlate previously learned information with newrecommendations.


Type 2 Diabetes

The cause of type 2 diabetes is more complicated. The hyperglycemia can result from insulin resistance, insulin

deficiency, or a defect in insulin secretion.

Insulin resistance is probably the primary dysfunction. The insulin is present; however, due to other metabolic processes,

it is unable to ac t on peripheral cells and tissue. The pancreas is unable to increase insulin production to c ompensate

for the resistance and therefore, insulin activity is deficient.

The insulin resistance and deficiency result from a c ombination of genetic and environmental factors. Common among

these are obesity, family history, and d istribution of body fat. Trunca l obesity is assoc iated with insulin resistance. Increased

calorie intake, weight gain, duration of obesity, and decreased physical activity are other factors contributing to type 2

diabetes onset.


Type 2 Diabetes Continued

Often with change in environmental factors (diet changes, weight loss, and exercise), a type 2 diabetic can rega in

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Case Studies (continued)

Case B and Case C

These pa tients have now been diagnosed with diabetes. Review the cases by clicking on each one and consider the

material that was presented regarding classifications. Then, determine which is the most likely classification for eac h

patient. Proceed to the next page to provide your answer.



Case B and C ase C have been diagnosed with diabetes. Select the correct statements rega rding the c lassification of

these diabetic patients.




Case B and C ase C have been diagnosed with diabetes. Select the correct statements rega rding the c lassification of

these diabetic patients.

gfedc Case B is type 1


gfedc Case C is type 1


Case Studies.pdf[click to view / print]

Adobe Ac roba t PDF file






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Feedback

Case B is 14 years old and a t initial visit, ketones are positive. His history typifies type 1 diabetes. Case C is an adult, physica lly

unac tive, consumes an unhealthy diet, and has gained weight recently. Type 2 diabetes occurs in individuals with this

lifestyle and history.

Risks and Complications of Diabetes


The diabetic patient is at risk for many serious complications and often experiences a diminished quality of life.

Angiopathy, damage to basement membranes of vessels, injures the linings of blood vessels and leads to

microvascular and macrovascular damage.


Microvascular Damage

Injury to tiny vessels is more often assoc iated with type 1 diabetes but a lso oc curs in other classes of diabetes.

Damaged vessels lead to retinopathy, nephropathy, and neuropathy. Diminished eyesight, blindness, renal disease and

renal failure can occur in a diabetic patient who does not maintain good carbohydrate control and can occur in a

diabetic with good control because of the harm done to the vessel linings. Neuropathy results in pain, numbness,

tingling, dizziness, decreased nerve conduction and can progress to cardiac disease and failure.


Macrovascular Complications

These complications can oc cur in either type 1 or type 2. Heart disease, stroke, and peripheral vascular disease resultfrom damage to larger vessels. Type 2 diabetic patients often have hyperlipidemia and atherosclerosis leading to a

greater risk of heart disease a nd heart failure.

Case Studies.pdf[click to view / print]

Adobe Ac roba t PDF file

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Other Complications

Ketoacidosis is always a serious complication for type 1 diabetics. Due to lack of uptake of glucose into cells by insulin,

proteins and fats are utilized as energy sources. This results in excess acetyl CoA which is converted to ketone bodies. A

serious acidosis results and if untreated or not resolved by the body, coma and death can occur.

Most often the acetyl CoA in a type 2 patient is converted to cholesterol and results in hyperlipidemia and heart

disease in these patients.

The elderly type 2 diabetic is at risk for a hyperosmolar nonketotic coma. The patient becomes dehydrated due to increased

urine excretion to lower the blood glucose. If reduced renal or cardiac function is also present, glucose excretion is impaired

and blood glucose concentrations can become extremely high. Ketones are not produced in excess, thus the pa tient

remains nonketotic. Insufficient hydration, elevated blood glucose, and decreased renal excretion of waste products result

in an increased osmolality and total concentration of a ll plasma components.



Which of the following patients is most at risk for hyperosmolar nonketotic coma?




Which of the following patients is most at risk for hyperosmolar nonketotic coma?

nmlkj A 70-year-old type 1 diabetic patient








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Feedback

Ordinarily ketones are negative in a type 2 diabetic patient. Because the elderly often have reduced renal excretion and

impaired cardiac function, a type 2 elderly diabetic is at risk for developing a hyperosmolar nonketotic coma.

Screening for Diabetes


The ADA guidelines include recommendations for screening for diabetes. It is recommended to screen asymptomatic

persons for diabetes or their risk of diabetes. Screening is recommended for all individuals age 45 years and older; a

negative screen should be repeated every three years. Screening is essential for individuals who are overweight,

defined as a body mass index (BMI) > 25 kg/ m2.

The ADA also recommends earlier screening for many individuals. Among these are individuals who are overweight and

have additiona l risk factors. Additional risk factors include:

Physica l inactivity

Family history of diabetes

A member of a high-risk ethnic group

Women who have had a large birth weight baby or gestational diabetes diagnosis should have earlier screening. Also

included for earlier screening are individuals who are hypertensive or have lipidemia, vascular disease, or other clinica l

conditions assoc iated with insulin resistanc e. Individuals who in previous testing had impaired glucose toleranc e (IGT),

impa ired fasting glucose (IFG), or HbA1C

in the range of 5.7-6.5% should be screened for diabetes regularly.


Benefits of Earlier Screening

Screening for diabetes of all adults over 45 years of age is recommended. Upon diagnosis of diabetes, many already

have experienced some of the c omplications assoc iated with diabetes. For those with no complications at diagnosis,

earlier diabetes treatment delays onset of complications.



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The American Diabetes Assoc iation (ADA) guidelines recommend screening all asymptomatic individuals age 45 and

older for diabetes. If the screen is negative, this pa tient will never require another screening.

Selec t true or fa lse



The American Diabetes Assoc iation (ADA) guidelines recommend screening all asymptomatic individuals age 45 and

older for diabetes. If the screen is negative, this pa tient will never require another screening.

nmlkj True

nmlkj False


Feedback

The ADA guidelines recommend screening all asymptomatic individuals age 45 and older. If the screen is negative, it should

be repeated every three years.

Laboratory Assays in Evaluating Diabetic Patients

Clinical Testing

A large number of assays related to carbohydrate management and d iabetes monitoring a re performed in clinical

laboratories, hospital nursing units, nursing homes, physician offices, c linics, and by patients at home, school, or work.

Assays that will be d iscussed are:

Blood G lucose

Urine Glucose

Ketones

Microalbuminuria

Insulin and C -Peptide

Insulin Antibodies

Glycosylated Proteins

nmlkj True

nmlkj False

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Blood Glucose

Serum, plasma, and whole b lood glucose levels are among the most common laboratory assays. Due to self-monitoring of blood glucose (SMBG), blood glucose is also the most common assay performed by patients themselves

or their caretakers.

Fasting, timed, and casual serum or plasma specimens are run in hospital laboratories for screening, diagnosis, and

monitoring of patients.


Whole Blood Glucose Testing

In the past twenty years there have been significant improvements in the

accuracy of handheld glucose meters. Patient use has resulted in

substantial improvements in diabetic c ontrol and insulin therapy.

Capillary whole blood is easily obtained and glucose c oncentration is

derived on simple to use, portable meters. Since whole blood glucose is

lower than plasma glucose, the meters are programmed to correc t the

value before presenting the result; therefore, the whole blood glucose

meter result correlates to serum or plasma results.

C linica l and Laboratory Standards Institute (CLSI) has set standards for

correlation between g lucose meter and laboratory measured glucoselevels. If the laboratory measured glucose is > 75 mg/ dL, the glucose

meter result should be within 20%. For laboratory measured values < 75

mg/dL, the glucose meter result should be within 15 mg/dL.

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A clinica l laboratory scientist is reviewing the results of comparison studies between laboratory plasma glucose results

and patients' self-monitoring (whole-blood) blood glucose (SMBG) results. Which SMBG results are acceptable?




A clinica l laboratory scientist is reviewing the results of comparison studies between laboratory plasma glucose results

and patients' self-monitoring (whole-blood) blood glucose (SMBG) results. Which SMBG results are acceptable?

gfedc SMBG 195 mg/dL; laboratory 150 mg/dL





Feedback

If the laboratory measured plasma glucose is > 75 mg/ dL, the patient's glucose meter result should be within 20%. For

laboratory measured va lues < 75 mg/dL, the patient's glucose meter result should be within 15 mg/ dL.

For a laboratory result of 150 mg/dL, SMBG of 120 to 180 mg/dL would be acceptable. For a laboratory results of 70 mg/dL,

SMBG of 55 to 85 mg/dL would be acceptable.

Note that most hospital-approved glucose meters report whole blood glucose results in plasma -equivalent values (ie, the

calculation is done by the instrument) so that the whole blood glucose result from a glucose meter used within a health

care facility should correlate directly with the plasma glucose result reported by the laboratory instrument within the

reportable range of the glucose meter.





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Urine Glucose

Before glucose meters were available, urine glucose was frequently used to approximate diabetic glucose levels. Blood

glucose levels can be related to urine glucose concentration because of urinary excretion of glucose. Physician offices,

clinics, and patients at home tested urine with reagent strips for a semi-quantitative measurement of urine glucose andadjustments in insulin therapy were made. Monitoring a diabetic carbohydrate management is seldom performed this

way today. Portable meter measurement of blood glucose is a much better management method. Urine glucose

measurement is neither sensitive nor specific and does not give information about blood glucose below the renal

threshold (usually 180 mg/dL).

As a semiquantitative measurement, urine glucose is a routine assay on urinalysis test and an abnormal result would be

investigated with blood levels. If quantitative measurements are needed, a timed urine specimen is collected and

measured for glucose by blood glucose methods.


Urinary Albumin

Beca use of the risk of nephropathy, monitoring renal function is critical in diabetes management. Renal failure occurs

more often in type 1 diabetes but because of the greater incidence of type 2 diabetics, a larger number of type 2

individuals are among those with diabetic nephropathy. Diabetic urinary albumin levels are monitored with urinary

albumin excretion (UAE); these assays are referred to as microalbuminuria testing.


Urinary Albumin Excretion

Screening for early occurrence and low amounts of albumin in urine detects microvascular disease before impaired

renal function and insufficiency occur. Regular screening of urinary albumin excretion (UAE) is recommended for

individuals with both type 1 diabetes and type 2 diabetes as an early indicator of renal disease. It is recommended at

the time of initial diagnosis and annually thereafter for patients with type 2 diabetes, and c ommenc ing annually 5 years

after the initial diagnosis of type 1 diabetes.

Control of blood pressure and blood glucose c oncentrations can slow the rate of renal function decline.


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Microalbuminuria

Microalbumin is not a measurement of a small size albumin molecule but measurement of low concentrations of

urinary albumin in diabetes to identify early renal impairment. Microalbuminuria tests measure conc entrations of

albumin that are lower than levels that can be detected with routine urine dipstick tests for protein.

Timed, overnight, and first morning specimens can be screened for microa lbuminuria. Quantitative measurements are

also utilized for screening of renal impairment and for monitoring treatment.


Ketones

Acetyl CoA is converted to acetone, acetoac etate, and beta-hydroxybutyrate. These are ac ids and when dissolved in

body fluids in excess lower the blood pH. Increased ketones can result in a metabolic acidosis referred to as ketosis,

ketoacidosis or diabetic acidosis. Type 1 diabetic pa tients are espec ially at risk for ketoacidosis. Urine and serum

ketones are measured semiquantitatively and a diabetic in ketosis is monitored for ketones and blood pH.


Insulin and C-Peptide

Insulin is secreted by the pancreatic beta-cells as a prohormone composed of fragments: C-peptide and insulin. The C -

peptide fraction is cleaved off the prohormone. The insulin frac tion becomes active. C -peptide is inactive but provides

structure to the prohormone and has a much longer half-life. Both of these hormones can be quantitated in blood.

Insulin levels are not measured to diagnose or monitor diabetes but can give information about a pa tient and is an

important assay in hypoglycemia. C -peptide is also measured in evaluating hypoglycemia and is used to distinguish

between endogenous and exogenous insulin; it would be present in circulation in endogenous insulin sec retion. It is also

often used to monitor pancreatic surgery and transplant because of its longer half-life.

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Insulin Antibodies

Since type 1 diabetes is caused by an autoimmune destruction of pancreatic tissue, sometimes antibody measurements

are used to ga in more information about a type 1 diabetic. Like insulin and C -peptide, insulin antibodies are not

measured to diagnose or monitor a diabetic patient.


Glycated Proteins

There are many possible post-translational mod ifications to proteins after ribosomal synthesis. Glycated proteins are

examples of modified proteins and are formed by the addition of glucose molecules to amino acid chains.

Hemoglobin A1C

is an important glycated protein assayed to diagnose and monitor diabetes. Fructosamine is another

less assayed modified protein.

Insulin

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HbA1C

Hemoglobin A comprises the majority of normal adult hemoglobin (Hb) and includes the minor hemoglobins, Hb A1a

,

Hb A1b

, and Hb A1c

. Sometimes these three are referred to as Hb A1but A

1Cis the major fraction and c omposes 80% of

Hb A1. Following synthesis of Hb A, a nonenzymatic reaction adds glucose to the N -terminal valine on either beta chain

forming glycated Hb. The pre-A1C

molec ule is a labile Schiff base and this reaction is reversible.

As the red blood c ells circulate, an irreversible Amadori rearrangement of the pre-A1C

base occurs forming a stable

ketoamine, A1C

. Over the life span of the red blood cells (120 days) this process continues and the concentration of A1C

is

proportional to the concentration of the blood glucose. The concentration of A1C

then relates to an individual's average

glucose over time and c an be used as an index relating to the extent of carbohydrate control during a 2 -3 month period.

There is also a direct relationship between the concentration of HbA1C

and risk of complications in diabetic patients.

Therefore, the ADA has recommended using HbA1C

measurements to monitor glycemic control.


Monitoring Diabetic Glycemic Control

A HbA1C

that is


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of d iabetes (i.e., gestational diabetes), long life expectancy, and no significant c ardiovascular disease.

Less stringent HbA1c

goals than the general goa l of


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What is the role of microalbuminuria testing?




What is the role of microalbuminuria testing?

nmlkj Monitor diabetic patient carbohydrate management

nmlkj Detect small-sized urinary albumin molecules in ea rly rena l disease

nmlkj Detect small urinary concentrations of albumin before there is irreparable renal damage

nmlkj Diagnose renal failure in a type 1 diabetic patient


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HbA1C

is the recommended test for monitoring diabetic c arbohydrate management. Microalbuminuria, low concentrations

of urinary albumin, is measured to detect early renal impairment, at a stage where it is reversible with treatment.



HbA1C

measurements areNOTordinarily used to monitor long-term diabetic control in a diabetic with sickle c ell

anemia.

nmlkj Monitor diabetic patient carbohydrate management

nmlkj Detect small-sized urinary albumin molecules in ea rly rena l disease

nmlkj Detect small urinary concentrations of albumin before there is irreparable renal damage

nmlkj Diagnose renal failure in a type 1 diabetic patient


nmlkj True

nmlkj False

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HbA1C

measurements areNOTordinarily used to monitor long-term diabetic control in a diabetic with sickle c ell

anemia.


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In sickle cell anemia, rapid hemoglobin turnover may be present. HbA1C

and other glycated hemoglobin assays are not

valid in rapid hemoglobin turnover and in abnormal hemoglobin conditions. Fructosamine measurements can be used

because of shorter half life of albumin.

Estimated Average G lucose (eAG)

Estimated Average Glucose

Estimated average glucose (eAG) is a glucose c oncentration level calculated from a patient's HbA1C

result. In 2008, the

ADArecommended the use of this new term and that this calculation be performed and reported routinely with themeasured A

1Cresult.

The formula for conversion of HbA1C

to glucose in mg/ dL is eAG = 28.7 x A1C 46.7.

A web c alculator is located at:

ht tp : / / p ro fessiona l.d iab ete s.org / g luco sec a l cu la tor .a spx. Accessed J anuary 11, 2010.


Relationship Between HbA1C

and eAG

nmlkj True

nmlkj False

HbA1C

(%) eAG (mg/dL)

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The formula for conversion of HbA1Cto g lucose in mg/dL is eAG = (28.7 x A1

C) 46.7.

The HbA 1Cmeasured on a patient is reported as 7.5%. What would be reported as the estimated average glucose

(eAG) for this % A1C(rounded to the nearest whole number)?

5.5 111

6.5 140

7.5 169

8.5 197

9.5 226




The formula for conversion of HbA1Cto g lucose in mg/dL is eAG = (28.7 x A1

C) 46.7.

The HbA 1Cmeasured on a patient is reported as 7.5%. What would be reported as the estimated average glucose

(eAG) for this % A1C(rounded to the nearest whole number)?

nmlkj 142 mg/dL

nmlkj 169 mg/dL

nmlkj 200 mg/dL


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nmlkj 142 mg/dL

nmlkj 169 mg/dL

nmlkj 200 mg/dL

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The eAG for a HbA1C

of 7.5% would be reported as 169 mg/dL eAG. Remember, the formula for conversion of HbA1Cto

glucose in mg/dL is eAG = (28.7 x A1C

) 46.7. So, in this case, the calculation is: eAG = (28.7 x 7.5) -46.7 = 168.55 mg/ dL.

Diabetes and the Role of the Laboratory

The Laboratory's Role in Diagnosis and Monitoring of Diabetes

Even though most diabetics, physician offices, clinics, nursing homes, and nursing units use glucose meters for

monitoring g lucose levels, the laboratory's role in diagnosis is vital. The func tion of the laboratory is crucial in diagnosis,

monitoring, and management of diabetes.

Diabetic patients can go into severe metabolic imbalances that a re life threatening. These metabolic conditions

include: diabetic ketoacidosis, hyperosmolar nonketotic coma, and hypoglycemia. Laboratory testing is essential in

diagnosing and monitoring these conditions.

Laboratory blood glucose and HbA1C

levels are used to demonstrate the level of hyperglycemia required for diagnosis. If an

OGTT is needed for classification or charac terization of hyperglycemia, a patient is sent to a hospital or clinica l laboratory

for the test. Detection of elevated microalbumin levels that can signal early stages of renal impairment is accomplished

through laboratory testing.

There are many other disease states and complications assoc iated with diabetes. Clinical laboratories detect these diseases

and monitor the complications that result. Important among these assays are urea , crea tinine, and serum lipids. If a

diabetic does have a pancreatic transplant, serum C -peptide and insulins levels monitor transplant success and viability of

transplanted organ.

Diabetes and the Role of the Laboratory

References

American Diabetes Assoc iation. Standards of medical c are in diabetes -2010. Diab etes Care; J anuary 2010;33:S11-S61.

American Diabetes Assoc iation. Diagnosis and classification of diabetes mellitus. Dia be tes Ca re. J anuary 2010;33:S62-

S69.

Anderson SA, Cockayne S. Cl in ic a l Chem ist ry Conc ep ts a nd Ap p lic a t ions. Long Grove, Illinois: Waveland Press, Inc,

2003.

Bell J R. The new glycohemoglobin standard. Cl in La b Ne ws, American Assoc iation of C linical Chemistry; Oc tober 2008; 34:1,

3-4.

Burtis CA, Ashwood ER, Burns DE, eds. Tietz Fund am en ta ls of Cl in ica l Che m ist ry, 6th ed. St. Louis: Saunders, an imprint of

Elsevier, Inc, 2008.

Charles MA. Diabetes and the laboratorian: Opportunities for a new role. M LO. May 2001, 16-24.

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Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia WHO 2006. World Hea lth Publica tions.

Available at http://www.who.int/topics/diabetes_mellitus/en/Accessed 1/11/10.

Estimated average glucose, eAG. Available at:

http://professional.diabetes.org/glucosecalculator.aspx

Accessed 1/11/10.

Kaplan LA, Pesce AJ , eds.Clinic a l Che m istry The ory, An a lysis, Co rrela t ion. St. Louis: Mosby Inc, a n affiliate of Elsevier Inc, 2010.

Rollin G. A new role for hemoglobin A1C. Cl in La b Ne ws, American Assoc iation for C linical Chemistry. December 2008; 34:1,

3.

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diabetes and the current american diabetes association

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