Waist circumference hip circumference body mass index BMI

Waist circumference, hip circumference, body mass index (BMI) , and ratios: Which best predicts type 2 diabetes mellitus in men and women? Harold E. Bays, MD Kathleen M. Fox, Ph. D Susan Grandy, Ph. D for the SHIELD Study Group NAASO – The Obesity Society Annual Scientific Meeting, New Orleans October 24, 2007

Background Adiposopathy is defined as pathogenic adipose tissue: • Promoted by positive caloric balance and sedentary lifestyle in genetically and environmentally susceptible patients • Anatomically manifested by adipocyte hypertrophy, adipose tissue accumulation (adiposity) in the visceral region, as well as ectopic fat (triglyceride) deposition in peripheral organs such as liver, muscle, and pancreas • Whose adverse metabolic and immune consequences result in clinical metabolic disease Bays HE et al. Future Cardiology. 2005; 1(1): 39 -59 Bays HE. Expert Rev Cardiovas Ther. 2005; 3(3): 395 -404

Background Bays H, Ballantyne C. Future Lipidology. 2006; 1(4): 389 -420

Background EFRMD=excessive fat-related metabolic diseases Bays H, Ballantyne C. Future Lipidology. 2006; 1(4): 389 -420

Background Bays H, Ballantyne C. Future Lipidology. 2006; 1(4): 389420

Adiposopathy: Visceral and Peripheral Adipose Tissue Bays H, Blonde L, Rosenson R. Expert Rev Cardiovas Ther. 4(6), 871– 895 (2006)

SHIELD • Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) • 5 -year, national, longitudinal survey of diabetes, CVD, and cardiometabolic risk in US adults • Purpose: To better understand patterns of health behavior, knowledge and attitudes of people living with type 2 diabetes (T 2 DM) and those at high risk for its development • This analysis assessed anthropometric measures in predicting type 2 diabetes in men and women

Objective • To assess gender-specific associations between type 2 diabetes and adipose tissue parameters

Methods: Identifying Cohorts • Screening questionnaire mailed to 200, 000 nationally representative US households – Part of the TNS* (formerly National Family Opinion) consumer panel – Responses for 211, 097 adults from 127, 420 households (64% response rate) • Used to identify individuals who self-reported: – T 2 DM and other metabolic diseases – Varying numbers of risk factors (0 -5) associated with T 2 DM diagnosis • Follow up 64 -item survey was sent to 22, 001 people, along with tape measure and instructions for use • Type 1 diabetes (n=1000), T 2 DM (n=5000), History of gestational diabetes (n=1000), Control/at risk (n=15, 000, ~2400 in each risk level) • Responses from 17, 640 adults (80% response rate; 10, 466 women & 6, 686 men) *TNS = Taylor Nelson Sofres

Risk Factor Definitions Risk Factor Definition Abdominal obesity Men: waist circumference > 97 cm Women: waist circumference >89 cm BMI 28 kg/m 2 Dyslipidemia Diagnosed with cholesterol problems of any type Hypertension Diagnosed with high blood pressure CV event One or more CV problems or events (heart disease/myocardial infarction, narrow or blocked arteries, stroke, coronary artery bypass graft surgery/angioplasty/stents/surgery to clear arteries) BMI= body mass index; CV=cardiovascular

Adipose Tissue Measures • Waist circumference (WC): assesses “pathogenic” visceral adipose tissue • Body mass index (BMI): assesses overall obesity, with most of total fat being “protective” subcutaneous adipose tissue • Hip circumference: “protective” gluteal subcutaneous adipose tissue • WC-BMI ratio: pathogenic / ”protective” adipose tissue ratio • WC-HC ratio: pathogenic / “protective” adipose tissue ratio

Statistical Analyses • Distribution of measured and reported adipose tissue parameters by quintiles of all respondents • Analyses stratified by gender

NHLBI Treatment Guidelines for Adult Obesity Bays H, Dujovne C. Curr Atheroscler Rep. 2006; 8(2): 144 -156

Results – T 2 DM Women Quintile n=10466 women BMI kg/m 2 N (%) n=2212 T 2 DM women 1 n=2093 <24. 4 162 (7. 3) 2 n=2093 24. 4 to 28. 3 3 n=2094 Quintile n=9707 WC cm N (%) n=2013 T 2 DM women 1 n=1942 <83. 8 173 (8. 6) 361 (16. 3) 2 n=1941 83. 8 to 94. 0 264 (13. 1) 28. 4 to 32. 3 425 (19. 2) 3 n=1941 94. 1 to 104. 1 354 (17. 6) 4 n=2093 32. 4 to 37. 8 536 (24. 2) 4 n=1942 104. 2 to 116. 8 529 (26. 3) 5 n=2093 ≥ 37. 8 728 (32. 9) 5 n=1941 ≥ 116. 8 693 (34. 4) The highest percent of women with T 2 DM occurred at the highest BMI and at the highest WC.

Results – T 2 DM Women Quintile n=9623 women WC: BMI ratio N (%) n=1998 T 2 DM women 1 n=1925 <2. 93 484 (24. 2) 2 n=1925 2. 93 to 3. 17 Quintile n=9558 WC: HC ratio N (%) n=1985 T 2 DM women 1 n=1912 <0. 81 217 (10. 9) 413 (20. 7) 2 n=1911 0. 81 to 0. 86 295 (14. 9) 0. 87 to 0. 90 384 (19. 3) 3 n=1924 3. 18 to 3. 38 369 (18. 5) 3 n=1911 4 n=1924 3. 39 to 3. 64 363 (18. 2) 4 n=1912 0. 91 to 0. 95 473 (23. 8) 369 (18. 5) 5 n=1912 ≥ 0. 95 616 (31. 0) 5 n=1925 >3. 64 The highest percent of women with T 2 DM occurred at the lowest WC: BMI ratio, and the highest WC: HC ratio.

Results – T 2 DM Men Quintile n=6686 men BMI kg/m 2 N (%) n=1613 T 2 DM men 1 n=1337 <25. 1 161 (10. 0) 2 n=1337 25. 1 to 28. 2 3 n=1338 Quintile n=6418 WC cm N (%) n=1565 T 2 DM men 1 n=1284 <91. 4 42 (2. 7) 408 (25. 3) 2 n=1284 91. 4 to 101. 6 208 (13. 3) 28. 3 to 30. 8 399 (24. 7) 3 n=1283 101. 7 to 109. 2 394 (25. 2) 4 n=1338 30. 9 to 34. 7 366 (22. 7) 4 n=1283 109. 3 to 119. 4 461 (29. 5) 5 n=1337 ≥ 34. 7 279 (17. 3) 5 n=1284 ≥ 119. 4 460 (29. 4) The highest percent of men with T 2 DM occurred at the highest WC.

ATP III: The Metabolic Syndrome Diagnosis is established when 3 of these risk factors are present. Risk Factor Defining Level Abdominal obesity (Waist circumference) Men Women TG HDL-C Men Women Blood pressure Fasting glucose >102 cm (>40 in) >88 cm (>35 in) 150 mg/d. L <40 mg/d. L <50 mg/d. L 130/ 85 mm Hg 110 mg/d. L Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001; 285: 2486 -2497.

Results – T 2 DM Men Quintile n=6357 men WC: BMI ratio N (%) n=1548 T 2 DM men Quintile n=6031 WC: HC ratio N (%) n=1470 T 2 DM men <0. 90 21 (1. 4) 1 n=1271 <3. 24 99 (6. 4) 1 n=1206 2 n=1272 3. 24 to 3. 46 156 (10. 1) 2 n=1206 0. 90 to 0. 95 46 (3. 1) 3 n=1272 3. 47 to 3. 64 257 (16. 6) 3 n=1207 0. 96 to 1. 00 147 (10. 0) 4 n=1271 3. 65 to 3. 87 414 (26. 7) 4 n=1206 1. 01 to 1. 05 357 (24. 3) 5 n=1271 ≥ 3. 87 622 (40. 2) 5 n=1206 ≥ 1. 05 899 (61. 2) The highest percent of men with T 2 DM occurred at the highest WC: BMI ratio and the highest WC: HC ratio.

Summary • In univariate analyses of women, the number of patients with T 2 DM gradually increased with increasing BMI, WC, and WC: HC ratio, but not WC: BMI, indicated that total peripheral, subcutaneous adipose tissue may not always be “protective” • In men, univariate analyses indicated that WC: HC ratio was a better predictor of T 2 DM than WC: BMI, WC, or BMI, possibly reflecting the pathogenic effects of having both increased visceral adipose tissue & relative lack of “protective” gluteal and peripheral, subcutaneous adipose tissue.

Back up slides

Six “Faces” of Adiposopathy Bays H, Blonde L, Rosenson R. Expert Rev Cardiovas Ther. 4(6), 871– 895 (2006)

Adiposopathy: Treatment “Finally, an emerging concept is that the development of antiobesity agents must not only reduce fat mass (adiposity) but must also correct fat dysfunction (adiposopathy)” Bays HE. Obesity Research 2004; Vol. 12 No. 8: 1197 -1211.

Adiposopathy: Treatment Adiposopathy treatments and their effects upon select parameters that promote type 2 diabetes mellitus Intervention Visceral fat Free fatty acids Leptin Adiponectin Tumor necrosis factor alpha Diet/Exercise ↓ ↓ ↓ ↑ ↓ PPAR gamma agonists ↓/- ↓ ↓/- ↑ ↓ Orlistat ↓ ↓ ↓ ↑ ↓ Sibutramine ↓ ↓ ↓ ↑/- ? Cannabinoid receptor antagonists ↓ ↓ ↓ ↑ ↓ Bays H, Blonde L, Rosenson R. Expert Rev Cardiovas Ther. 4(6), 871– 895 (2006)

Adiposopathy: Treatment Adiposopathy treatments and their effects upon select parameters that promote hyperte Intervention Visceral fat Free fatty acids Leptin Adiponectin Reninangiotensinaldosterone enzymes Diet/Exercise ↓ ↓ ↓ ↑ ↓ PPAR gamma agonists ↓/- ↓ ↓/- ↑ - Orlistat ↓ ↓ ↓ ↑ ? Sibutramine ↓ ↓ ↓ ↑/- ? Cannabinoid receptor antagonists ↓ ↓ ↓ ↑ ? Bays H, Blonde L, Rosenson R. Expert Rev Cardiovas Ther. 4(6), 871– 895 (2006)

Adiposopathy: Treatment Adiposopathy treatments and their effects upon select parameters that promote dyslipidemia Intervention Visceral fat Free fatty acids Leptin Adiponectin Androgens Estrogens Diet/Exercise ↓ ↓ ↓ ↑ ↓ (women) ↑ (men) ↓/(men) PPAR gamma agonists ↓/- ↓ ↓/- ↑ ↓ ↓/(men) Orlistat ↓ ↓ ↓ ↑ ↓ (women) ? Sibutramine ↓ ↓ ↓ ↑/- ↓ (women) ? Cannabinoid receptor antagonists ↓ ↓ ↓ ↑ ? ? Bays H, Blonde L, Rosenson R. Expert Rev Cardiovas Ther. 4(6), 871– 895 (2006)

Bays H, Ballantyne C. Future Lipidology. 2006; 1(4): 389 -420; Bays H et al. Expert Rev Cardiovasc Ther. 2005; 3(5): 789 -820

Bays H, Ballantyne C. Future Lipidology. 2006; 1(4): 389 -420