1. Waist circumference, hip circumference, body index (BMI), and ratios: Which best predicts type 2 diabetes mellitus in men and women? 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, PhD Susan Grandy, PhD for the SHIELD Study Group NAASO – The Obesity Society Annual Scientific Meeting, New Orleans October 24, 2007

2. 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

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

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

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

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

7. 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 (T2DM) and those at high risk for its development This analysis assessed anthropometric measures in predicting type 2 diabetes in men and women

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

9. 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: –T2DM and other metabolic diseases –Varying numbers of risk factors (0-5) associated with T2DM 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), T2DM (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

10. Risk Factor Definitions Risk FactorDefinition Abdominal obesityMen: waist circumference > 97cm Women: waist circumference >89 cm BMI  28 kg/m 2 DyslipidemiaDiagnosed with cholesterol problems of any type HypertensionDiagnosed with high blood pressure CV eventOne 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

11. 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

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

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

14. Results – T2DM Women Quintile n=10466 women BMI kg/m 2 N (%) n=2212 T2DM women Quintile n=9707 WC cmN (%) n=2013 T2DM women 1 n=2093 <24.4162 (7.3) 1 n=1942 <83.8173 (8.6) 2 n=2093 24.4 to 28.3361 (16.3) 2 n=1941 83.8 to 94.0264 (13.1) 3 n=2094 28.4 to 32.3425 (19.2) 3 n=1941 94.1 to 104.1354 (17.6) 4 n=2093 32.4 to 37.8536 (24.2) 4 n=1942 104.2 to 116.8529 (26.3) 5 n=2093 ≥37.8728 (32.9) 5 n=1941 ≥116.8693 (34.4) The highest percent of women with T2DM occurred at the highest BMI and at the highest WC.

15. Results – T2DM Women Quintile n=9623 women WC:BMI ratio N (%) n=1998 T2DM women Quintile n=9558 WC:HC ratio N (%) n=1985 T2DM women 1 n=1925 <2.93484 (24.2) 1 n=1912 <0.81217 (10.9) 2 n=1925 2.93 to 3.17413 (20.7) 2 n=1911 0.81 to 0.86295 (14.9) 3 n=1924 3.18 to 3.38369 (18.5) 3 n=1911 0.87 to 0.90384 (19.3) 4 n=1924 3.39 to 3.64363 (18.2) 4 n=1912 0.91 to 0.95473 (23.8) 5 n=1925 >3.64369 (18.5) 5 n=1912 ≥0.95616 (31.0) The highest percent of women with T2DM occurred at the lowest WC:BMI ratio, and the highest WC:HC ratio.

16. Results – T2DM Men Quintile n=6686 men BMI kg/m 2 N (%) n=1613 T2DM men Quintile n=6418 WC cmN (%) n=1565 T2DM men 1 n=1337 <25.1161 (10.0) 1 n=1284 <91.442 (2.7) 2 n=1337 25.1 to 28.2408 (25.3) 2 n=1284 91.4 to 101.6208 (13.3) 3 n=1338 28.3 to 30.8399 (24.7) 3 n=1283 101.7 to 109.2 394 (25.2) 4 n=1338 30.9 to 34.7366 (22.7) 4 n=1283 109.3 to 119.4 461 (29.5) 5 n=1337 ≥34.7279 (17.3) 5 n=1284 ≥119.4460 (29.4) The highest percent of men with T2DM occurred at the highest WC.

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

18. Results – T2DM Men Quintile n=6357 men WC:BMI ratio N (%) n=1548 T2DM men Quintile n=6031 WC:HC ratio N (%) n=1470 T2DM men 1 n=1271 <3.2499 (6.4) 1 n=1206 <0.9021 (1.4) 2 n=1272 3.24 to 3.46156 (10.1) 2 n=1206 0.90 to 0.9546 (3.1) 3 n=1272 3.47 to 3.64257 (16.6) 3 n=1207 0.96 to 1.00147 (10.0) 4 n=1271 3.65 to 3.87414 (26.7) 4 n=1206 1.01 to 1.05357 (24.3) 5 n=1271 ≥3.87622 (40.2) 5 n=1206 ≥1.05899 (61.2) The highest percent of men with T2DM occurred at the highest WC:BMI ratio and the highest WC:HC ratio.

19. Summary In univariate analyses of women, the number of patients with T2DM 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 T2DM 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.

20. Back up slides

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

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

23. Adiposopathy: Treatment Adiposopathy treatments and their effects upon select parameters that promote type 2 diabetes mellitus InterventionVisceral fat Free fatty acids LeptinAdiponectinTumor 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)

24. Adiposopathy: Treatment Adiposopathy treatments and their effects upon select parameters that promote hypertension InterventionVisceral fat Free fatty acids LeptinAdiponectinRenin- angiotensin - aldosterone 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)

25. Adiposopathy: Treatment Adiposopathy treatments and their effects upon select parameters that promote dyslipidemia InterventionVisceral fat Free fatty acids LeptinAdiponecti n Androgen s Estrogen s 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)

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

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