Metabolic syndrome is a cluster of disorders including high blood pressure, high insulin levels, excess body weight, and abnormal cholesterol that increases the risk of diseases like diabetes and heart disease. There is wide variation in the reported prevalence of metabolic syndrome across populations and definitions, and questions remain about its applicability and predictive power equally in all groups. Key determinants include obesity, especially abdominal obesity, and insulin resistance, but genetic and lifestyle factors also contribute to risk.

1. Metabolic Syndrome:
Risk factors for different populations
Akhtar Hussain MD; Ph.D; D.Sc
Vice President IDF
Professor, UiO

2. 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??

3. 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

4. Definitions and concept developments of
Metabolic Syndrome?
The concept has existed for more than 80 years

5. The Metabolic Syndrome: An Evolving Concept

6. Other features of
insulin resistance
MicroalbuminuriaOther
≥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

7. Global cardiometabolic risk*
Gelfand EV et al, 2006; Vasudevan AR et al, 2005
* working definition

8. Prevalence of MeS in different Countries
Prevalence (%)SampleYearCountry
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

9. Rational: 90% of Type 2 diabetes : IR and MS
Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota.

10. 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.

11. Fat Topography In
Type 2 Diabetic Subjects
Intramuscular
Intrahepatic
Subcutaneous
Intra-
abdominal
FFA*
TNF-alpha*
Leptin*
IL-6 (CRP)*
Tissue Factor*
PAI-1*
Angiotensinogen*

12. Abdominal obesity and increased risk of
cardiovascular events
Dagenais GR et al, 2005
Adjustedrelativerisk
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

13. 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.

14. Insulin Resistance: Associated
Conditions

15. 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

16. 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.

17. 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.

18. 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 group
Diabetologia,2006; 49: 2837-2846

19. Translation
• Can the concept/s of MS be translated into
different population and gender equally?

20. 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.

21. Prevalence of the metabolic syndrome in developing countries (IDF)
Source: The metabolic syndrome in developing countries, Diabetic Voice, May 2006 Volume 51

22. 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.

23. Prevalence,%
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

24. 26
MS among SA,AC and White in UK
Source: P. M. McKeigue. Diabetologia (2005) 48: 649–656
Men Women

25. 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

26. Temporal change of MS in rural Bangladesh: 1999-2009
0.9 0.8 2.5
8.6
11.2
20.7
9.9
23.7
29.1
0
5
10
15
20
25
30
35
WHO IDF ATP
1999 2004 2009

27. 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

28. 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

29. 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)

30. 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).

31. Determinants of the metabolic
syndrome in developing countries
Economic Transition:
Urbanisation, open market
economy, 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 and
Economic Changes: famine, labor
intensive work
Improved food supply, Increased food
availability (longer shelf life, 24-hour
supermarkets), Competitive prices of
energy-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

32. Shortcomings of definitions for Metabolic syndrome
• WHO definition: difficult to measure insulin sensitivity by euglycaemic
clamp, lack of standardization of assays for microalbuminuria.
• ATP III definition: cut-point for waistline is high and no consideration of
ethnic differences; no consideration of receiving treatment for metabolic
disorders.
• IDF definition: low cutoff value for waistline leads to inclusion of patients
with a relatively lower level of risk (especially in Europids).The mandatory
status of the waistline criterion results in a relatively lower prevalence of
other metabolic syndrome risk factors (especially in Asians).

33. 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??

34. Underlying Risk Factors of
the Metabolic Syndrome
• Overweight/obesity (esp. abdominal obesity)
• Insulin resistance
• Additional underlying factors
– Physical inactivity
– Aging
– Endocrine dysfunction
– Genetic factors

35. 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

36. THANKS