* Note that 1999 WHO uses hyperinsulinemic euglycemic clamp
whereas 1998 WHO and EGIR use HOMA-IR.
WHO. Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Geneva: WHO, 1999.
Inflammation is the underlying cause of the metabolic syndrome
–
Treatment:
a) reduce obesity and increase activity b) insulin sensitizers c) statins, ACE Inhibitors, ARBs
Reaven G. Diabetes. 1988;37:1565-1607.
The Metabolic Syndrome: Current Perspective
Body Size BMI Central Adiposity
Insulin Resistance
+
Hyperinsulinemia
Glucose Metabolism
Novel Risk Factors
CRP PAIPAI-1 Fibrinogen
CORONARY HEART DISEASE
Adapted from Reaven G. Drugs. 1999;58 (suppl):19-20
ATP III: The Metabolic Syndrome*
*Diagnosis is established when >3 of these riБайду номын сангаасk factors are present Risk Factor
Elevated BP (>140/90 or drug Rx) Plasma TG >150 mg/dl HDL <35 mg/dl (men); <40 mg/dl (women) BMI >30 and/or W/H >0.9 (men), >0.85 (women) Urinary albumin >20 mg/min; Alb/Cr >30 mg/g
Prevalence of CHD by the Metabolic Syndrome and Diabetes in the NHANES Population Age 50+
25%
19.2%
CHD Prevalence
20%
13.9%
15% 10% 5% 0%
8.7% 7.5%
% of Population =
n = 2,815 (age 25-64) – Both NCEP and WHO metabolic syndrome, 509 – NCEP alone, n=197 – WHO alone, n=199 12.7 year follow-up (229 deaths) Three populations considered – Overall population – No CVD at baseline – No CVD or diabetes at baseline (primary prevention)
Prevalence of the NCEP Metabolic Syndrome: NHANES III by Age
50% 40%
Men Women
24% 23%
44% 44%
Prevalence, %
30% 20% 10% 0%
8% 6%
20 70+ 20–29 20–70+
30 39 30–39
30
Prevalence of CHD (%)
Metabolic Syndrome P<.001 27.1% P<.001 21.4%
Yes
25 20 15 10 5 0
P=.04 9.2%
No
P=.06 11.0% 4.1% 5.3% 13.5%
5.5%
NGT
(n=1,808)
IFG/IGT
(n=685)
40–49
50–59
60 69 60–69
≥70
Age, years
Ford ES et al. JAMA 2002;287:356-359.
Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/Ethnicity
IRS: AACE Criteria – Parameters (Choose 2)
Triglycerides >150 mg/dl HDL cholesterol – Men <40 mg/dl – Women <50 mg/dl Blood pressure >135/85 Blood glucose – 2-hour >140 mg/dl, OR – Fasting 110 – 125 mg/dl
DM
(n=1,430)
All
(n=3,928)
Isomaa B et al. Diabetes Care. 2001;24:683-689.
Cardiovascular Disease Mortality Increased in the Metabolic Syndrome: Kuopio Ischemic Heart Disease Risk Factor Study
The Metabolic Syndrome: Historical Perspective
1988: Syndrome X
Insulin Resistance
Glucose Intolerance
Hyperinsulinemia
TG
HDL-C
Hypertension
CORONARY HEART DISEASE
–
Treatment:
reduce obesity and increase activity
Insulin resistance is the underlying cause of the metabolic syndrome (WHO)
–
Treatment:
a) reduce obesity and increase activity b) insulin sensitizers
WHO Metabolic Syndrome Definition 1999: Based on Clinical Criteria
Insulin resistance (type 2 diabetes, IFG, IGT)* Plus any 2 of the following:
– – – – –
Abdominal obesity (Waist circumference) Men Women TG HDL-C Men Women Blood Pressure Fasting glucose
Defining Level
>102 cm (>40 in) >88 cm (>35 in) >150 mg/dL <40 mg/dL <50 mg/dL >130/>85 mm Hg >110 (>100)**mg/dL
BMI >25 kg/m2 Waist circumference – Men >40" – Women >35" Sedentary Lifestyle Age >40 Non-Caucasian ethnicity Family History of DM, HTM, or CVD History of glucose intolerance or gestational diabetes Personal Dx of HTN, TGL, low HDL or CVD Acanthosis nigricans Polycystic ovarian syndrome (PCOS) Nonalcoholic fatty liver disease (NAFLD) Cancer (obesity related)
** 2003 New ADA IFG criteria (Expert Panel…,Diabetes Care 26:3160-3167, 2003)
* The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. **The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160-3167, 2003
Obesity and Metabolic Syndrome
Steven M. Haffner, MD
Conceptual Framework for the Metabolic Syndrome
Environmental causes are responsible for the epidemic of the metabolic syndrome (NCEP)