Metabolic Syndrome:

Risk factors for different populations

Akhtar Hussain MD; Ph.D; D.Sc

Vice President IDF

Professor, UiO

What is metabolic Syndrome

• Metabolic Syndrome is not a disease, but rather a cluster of disorders of our body’s metabolism, including:

o High blood pressure

o High insulin levels

o Excess body weight

o Abnormal cholesterol levels

• Each of these disorders is by itself a risk factor for other diseases.

• In combination, however, these disorders should identify people at their highest risk for developing potentially life-threatening illnesses, such as diabetes, heart disease or stroke.

• Does it?? And equally applicable in all populations?? Which definition??

What is the definitions of MS??

• Its applicability to identify risk in different

populations

• Which definition and components?

• Predictability for CVD and DM in different

populations especially Asian Indians

Definitions and concept developments of Metabolic Syndrome?

The concept has existed for more than 80 years

The Metabolic Syndrome: An Evolving Concept

Other features of

insulin resistanceMicroalbuminuriaOther

≥100 mg/dl (5.6

mmol/l) (includes

diabetes)

IGT or IFG (but not

diabetes)

>110 mg/dl (6.1

mmol/l) (includes

diabetes)

IGT or IFG (but not

diabetes)IGT, IFG, or T2DMGlucose

≥130 mmHg systolic

or ≥85 mmHg

diastolic or on

hypertension Rx

≥130/85 mmHg≥130/85 mmHg≥140/90 mmHg or

on hypertension Rx≥140/90 mmHg

Blood

pressure

HDL-C <40 mg/dl

(1.03 mmol/l) in men

or <50 mg/dl (1.29

mmol/l) in women or

on HDL-C Rx

HDL-C <40 mg/dl

(1.03 mmol/l) in

men or <50 mg/dl

(1.29 mmol/l) in

women

HDL-C <40 mg/dl

(1.03 mmol/l) in

men or <50 mg/dl

(1.29 mmol/l) in

women

HDL-C <39 mg/dl

(1.01 mmol/l) in

men or women

HDL-C <35 mg/dl

(0.90 mmol/l) in

men or <39 mg/dl

(1.01 mmol/l) in

women

TG ≥150 mg/dl (1.7

mmol/l) or on TG Rx

TG ≥150 mg/dl

(1.7 mmol/l)and

TG ≥150 mg/dl

(1.7 mmol/l)

TG ≥150 mg/dl

(1.7 mmol/l) and/or

TG ≥150 mg/dl (1.7

mmol/l) and/or Lipid

Increased WC

(population specific)

plus any 2 of the

following

BMI ≥25 kg/m2

WC ≥102 cm in

men or ≥88 cm in

women

WC ≥94 cm in men

or ≥80 cm in

women

Men: waist-to-hip

ratio >0.90; women:

waist-to-hip ratio

>0.85 and/or BMI

>30 kg/m2

Body

weight

None

IGT or IFG plus

any of the

following based on

clinical judgment

None, but any 3 of

the following 5

features

Plasma insulin

>75th percentile

plus any 2 of the

following

IGT, IFG, T2DM, or

lowered insulin

sensitivity plus any

2 of the following

Insulin

resistance

IDF (2005)Int. Diabetes Federation

AACE (2003)Am.Assoc.of Clin.Endo

ATP III (2001)National Cholesterol Education Program

EGIR(1999)Eur.Gr for the study IR

WHO (1998)World Health Organization

Clinical measure

Global cardiometabolic risk*

Gelfand EV et al, 2006; Vasudevan AR et al, 2005* working definition

Prevalence of MeS in different Countries

Prevalence (%)SampleYear Country

235422003Arab Americans

2114192001Oman

3611212002Jordan

20.822502004Saudi Arabia

17*1998Palestine

27.68172007Qatar

33.4*16372004Turkey

33.710368?Iran

* Crude rates Mussallam et al. Int J Food Safety and PH 2008

Rational: 90% of Type 2 diabetes : IR and MS

Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota.

The Continuum of CV Risk in Type 2 Diabetes

Adapted from American Diabetes Association. Diabetes Care. 2003;26:3160-3167.

Tsao PS, et al. Arterioscler Thromb Vasc Biol. 1998;18:947-953.

Hsueh WA, et al. Am J Med. 1998;105(1A):4S-14S.

American Diabetes Association. Diabetes Care. 1998;21:310-314.

Fat Topography In

Type 2 Diabetic Subjects

Intramuscular

Intrahepatic

Subcutaneous

Intra-abdominal

FFA*

TNF-alpha*

Leptin*

IL-6 (CRP)*

Tissue Factor*

PAI-1*

Angiotensinogen*

Abdominal obesity and increased risk of

cardiovascular events

Dagenais GR et al, 2005

Adju

sted r

ela

tive r

isk

1 1 1

1.17 1.16 1.14

1.29 1.27

1.35

0.8

1

1.2

1.4

CVD death MI All-cause deaths

Tertile 1

Tertile 2

Tertile 3

Men Women

<95

95–103

>103

<87

87–98

>98

Waist

circumference (cm):

The HOPE study

Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-C; CVD:

cardiovascular disease; MI: myocardial infarction; BMI: body mass index; DM: diabetes

mellitus; HDL: high-density lipoprotein cholesterol

IDF Criteria: Abdominal Obesity and Waist Circumference Thresholds

Men Women

Europid ≥ 94 cm (37.0 in) ≥ 80 cm (31.5 in)

South Asian ≥ 90 cm (35.4 in) ≥ 80 cm (31.5 in)

Chinese ≥ 90 cm (35.4 in) ≥ 80 cm (31.5 in)

Japanese ≥ 85 cm (33.5 in) ≥ 90 cm (35.4 in)

• AHA/NHLBI criteria: ≥ 102 cm (40 in) in men, ≥ 88 cm (35 in) in women

• Some US adults of non-Asian origin with marginal increases should benefit

from lifestyle changes. Lower cutpoints (≥ 90 cm in men and ≥ 80 cm in

women) for Asian Americans

Alberti KGMM et al. Lancet 2005;366:1059-1062. | Grundy SM et al. Circulation 2005;112:2735-2752.

Insulin Resistance: Associated

Conditions

Approximately Half of Patients with Acute Myocardial Infarction Have Metabolic Syndrome (RICO AMI France)

• Metabolic syndrome defined by NCEP ATP III criteria

• 633 patients with confirmed myocardial infarction

Diabetes and Metabolic Syndrome Worsen Long-term Prognosis in Patients with Acute Myocardial Infarction

G Levantesi G, et al. (GISSI-Prevenzione). J Am Coll Cardiol 2005;46:277-283.

Whatever The Definition, The Metabolic Syndrome Increases 1.5 to 2-fold The Risk of CV Events

Dekker JM, et al. (Hoorn study). Circulation 2005;112:666-673.

MS by Different Definitions in Relation to CVD Mortality in European Men and Women

Criteria MS (%) HR for CVD

Male Female Male Female

WHO 27.0 19.7 2.09 1.60

NCEP 25.9 23.4 1.74 1.39

NCEP-revised 32.2 28.5 1.72 1.09

IDF 35.9 34.1 1.51 1.53

Source: The DECODE Study groupDiabetologia,2006; 49: 2837-2846

Translation

• Can the concept/s of MS be translated into

different population and gender equally?

The Metabolic Syndrome is Significantly Associated with the Prevalence of CHD in the ARIC Study (NCEP ATP III criteria)

McNeill AM, et al. Am J Cardiol 2004;94:1249-1254.

Prevalence of the metabolic syndrome in developing countries (IDF)

Source: The metabolic syndrome in developing countries, Diabetic Voice, May 2006 Volume 51

Prevalence of the metabolic syndrome in Asians

Tan et al. Diabetes Care 2004;Misra et al. Diabetes Care 2005; Fan et al. J Hepatol 2005; Oh et al. Diabetes Care 2004; Ford et al. JAMA 2002.

Preva

lenc

e, %

Men Women

White

African American

Mexican American

Other

25%

16%

28%

21%23%

26%

36%

20%

Ford ES et al. JAMA 2002;287:356-359. Used with permission of the American Medical Association.

Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/Ethnicity

26

MS among SA,AC and White in UK

Source: P. M. McKeigue. Diabetologia (2005) 48: 649–656

Men Women

49,0%

34,8%

16,9%15,2%

7,4%

0 %

10 %

20 %

30 %

40 %

50 %

60 %

WHO EGIR AACE IDF ATP-III

0

10

20

30

40

50

60

Prevalence of Metabolic Syndrome

According to Different Definitions- Pakistan

Temporal change of MS in rural Bangladesh: 1999-2009

0.9 0.8 2.5

8.611.2

20.7

9.9

23.7

29.1

0

5

10

15

20

25

30

35

WHO IDF ATP

1999 2004 2009

Modified ATP III criteria kappa

Metabolic syndrome

IDF criteria

Metabolic Syndrome Present Absent Total

0.65Present 444 0 444

Absent 382 3155 3537

Total 826 3155 3981

WHO criteria kappa

Metabolic syndrome

IDF criteria

Metabolic Syndrome Present Absent Total

0.20Present 110 334 444

Absent 231 3306 3537

Total 341 3640 3981

Modified ATP III criteria kappa

Metabolic syndrome

WHO criteria

Metabolic Syndrome Present Absent Total

0.45Present 304 37 341

Absent 522 3118 3640

Total 826 3155 3981

Agreement between the modified ATP III, IDF and WHO criteria in diagnosing of Metabolic Syndrome - Bangladesh

30

MS: India, Pakistan, Bangladesh and China

Sources:

India- Deepa M, Diab Metab Res and Rev: 2007;23:127-134

Bangladesh- Rahim MA, Diabetes & Metabolic Syndrome: Clinical Research & Reviews (2007)

Pakistan: Basit A, Annual Meetings Athens, Greece,2005; 10-15

China: GTC Ko. DRCP 73,2006, 58-64

Prevalence of MS among Normal, IGR & Type2 DM individual in rural Bangladeshi population: 2009

Prevalence of MS (with 95% CI)

WHO IDF ATP

Normal 0 63.9% (61.74-66.05) 61.1% (58.92-63.28)

IGR 33.8% (27.19-40.40) 16.6% (11.40-21.79) 17.1% (11.84-22.36)

DM 66.2% (59.31-73.09) 19.5%(13.73-25.27) 21.9% (15.87-27.92)

Total 9.9% (8.67-11.12) 23.7% (21.95-25.44) 29.1% (27.24-30.96)

Giovanni de S et al. Diabetes Care, 2007; vol. 30 no. 7 1851-1856 Adjusted cumulative hazard in

participants with (—) or without () metabolic syndrome, in nondiabetic or diabetic participants, according to

diagnostic criteria issued by the WHO (top panel), ATP III (middle panel), or IDF (bottom panel).

Determinants of the metabolicsyndrome in developing countries

Economic Transition:Urbanisation, open marketeconomy, increasing affluence

Epidemiological Transition:Low level of infant mortality,Survival of LBW children

Demographic Changes:increasing elderly population, Rural-urban migration, Mechanization

Decreasing food scarcity andEconomic Changes: famine, laborintensive work

Improved food supply, Increased foodavailability (longer shelf life, 24-hoursupermarkets), Competitive prices ofenergy-dense foods

Increased intake of fat, salt and sugar Dietary liberalization and ‘westernization’

Pattern 4: Rise of Obesity, the metabolic syndrome and Non-communicable diseases

Shortcomings of definitions for Metabolic syndrome

• WHO definition: difficult to measure insulin sensitivity by euglycaemicclamp, lack of standardization of assays for microalbuminuria.

• ATP III definition: cut-point for waistline is high and no consideration ofethnic differences; no consideration of receiving treatment for metabolicdisorders.

• IDF definition: low cutoff value for waistline leads to inclusion of patientswith a relatively lower level of risk (especially in Europids).The mandatorystatus of the waistline criterion results in a relatively lower prevalence ofother metabolic syndrome risk factors (especially in Asians).

Analogy for the diverse prevalence of MS in different

populations and gender following different definitions

• Possible sources for disagreement for MS

in different populations and definitions:

- Body structure

- Fat deposition pattern

- Different levels of IR and lipids given the same BMI in

different populations

- Diverse components and cutoffs included in different

definitions

- Can we still apply the MS for the prediction of CVD??

Underlying Risk Factors of the Metabolic Syndrome

• Overweight/obesity (esp. abdominal obesity)

• Insulin resistance

• Additional underlying factors

– Physical inactivity

– Aging

– Endocrine dysfunction

– Genetic factors

Take Home Points

• Metabolic syndrome is a cluster of risk factors for cardiovascular disease (CVD) that includes abdominal obesity, dyslipidemia, elevated blood pressure, and impaired glucose tolerance.

• CVD is considered the principal clinical end point of the metabolic syndrome, while type 2 diabetes mellitus is considered another important sequelae.

• The principal determinant of the syndrome is obesity, particularly visceral/abdominal obesity.

• There is wide range of variations across ethnicity, gender and applied definitions for the assessment of MS.

• We need large scale cohort studies of MS based on different definitions for its sensetivity to assess the risk of DM or CVD to identify suitable definition for Asians

• Whether MS is a myth or fact remains open to discussion

THANKS