Waist circumference, hip Waist circumference, hip circumference, body circumference, body mass index index

(BMI) , and ratios: Which best (BMI) , and ratios: Which best predicts type 2 diabetes mellitus in predicts type 2 diabetes mellitus in

men and women?men and women?Harold E. Bays, MD

Kathleen M. Fox, PhDSusan Grandy, PhD

for the SHIELD Study GroupNAASO – The Obesity Society Annual Scientific

Meeting, New OrleansOctober 24, 2007

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

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):389420

Background

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 (T2DM) 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:– 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

Risk Factor Definitions

Risk Factor Definition

Abdominal obesity Men: waist circumference > 97cmWomen: waist circumference >89 cm

BMI 28 kg/m2

Dyslipidemia Diagnosed with cholesterol problems of any type

Hypertension Diagnosed with high blood pressure

CV event One or more CV problems or events (heartdisease/myocardial infarction, narrow or blockedarteries, stroke, coronary artery bypass graftsurgery/angioplasty/stents/surgery to cleararteries)

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

Bays H, Dujovne C. Curr Atheroscler Rep. 2006;8(2):144-156

NHLBI Treatment Guidelines for Adult Obesity

Results – T2DM WomenQuintilen=10466 women

BMI kg/m2 N (%)n=2212 T2DM women

Quintilen=9707

WC cm N (%)n=2013 T2DM women

1n=2093

<24.4 162 (7.3) 1n=1942 <83.8 173 (8.6)

2n=2093

24.4 to 28.3 361 (16.3) 2n=1941 83.8 to 94.0 264 (13.1)

3n=2094

28.4 to 32.3 425 (19.2) 3n=1941 94.1 to 104.1 354 (17.6)

4n=2093

32.4 to 37.8 536 (24.2) 4n=1942 104.2 to 116.8 529 (26.3)

5n=2093

≥37.8 728 (32.9) 5n=1941 ≥116.8 693 (34.4)

The highest percent of women with T2DM occurred at the highest BMI and at the highest WC.

Results – T2DM WomenQuintilen=9623 women

WC:BMI ratio

N (%)n=1998 T2DM women

Quintilen=9558

WC:HC ratio

N (%)n=1985 T2DM women

1n=1925 <2.93 484 (24.2)

1n=1912 <0.81 217 (10.9)

2n=1925 2.93 to 3.17 413 (20.7)

2n=1911 0.81 to 0.86 295 (14.9)

3n=1924 3.18 to 3.38 369 (18.5)

3n=1911 0.87 to 0.90 384 (19.3)

4n=1924 3.39 to 3.64 363 (18.2)

4n=1912 0.91 to 0.95 473 (23.8)

5n=1925 >3.64 369 (18.5)

5n=1912 ≥0.95 616 (31.0)

The highest percent of women with T2DM occurred at the lowest WC:BMI ratio, and the highest WC:HC ratio.

Results – T2DM MenQuintilen=6686 men

BMI kg/m2 N (%)n=1613

T2DM men

Quintilen=6418

WC cm N (%)n=1565

T2DM men

1n=1337

<25.1 161 (10.0) 1n=1284 <91.4 42 (2.7)

2n=1337

25.1 to 28.2 408 (25.3) 2n=1284 91.4 to 101.6 208 (13.3)

3n=1338

28.3 to 30.8 399 (24.7) 3n=1283

101.7 to 109.2 394 (25.2)

4n=1338

30.9 to 34.7 366 (22.7) 4n=1283

109.3 to 119.4 461 (29.5)

5n=1337

≥34.7 279 (17.3) 5n=1284 ≥119.4 460 (29.4)

The highest percent of men with T2DM occurred at the highest WC.

ATP III: The ATP III: The Metabolic Syndrome SyndromeDiagnosis 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 Factor Defining LevelAbdominal obesity(Waist circumference)

Men Women

>102 cm (>40 in)>88 cm (>35 in)

TG 150 mg/dLHDL-C

Men Women

<40 mg/dL<50 mg/dL

Blood pressure 130/85 mm Hg

Fasting glucose 110 mg/dL

Results – T2DM MenQuintilen=6357 men

WC:BMI ratio

N (%)n=1548

T2DM men

Quintilen=6031

WC:HC ratio

N (%)n=1470

T2DM men

1n=1271 <3.24 99 (6.4)

1n=1206 <0.90 21 (1.4)

2n=1272 3.24 to 3.46 156 (10.1)

2n=1206 0.90 to 0.95 46 (3.1)

3n=1272 3.47 to 3.64 257 (16.6)

3n=1207 0.96 to 1.00 147 (10.0)

4n=1271 3.65 to 3.87 414 (26.7)

4n=1206 1.01 to 1.05 357 (24.3)

5n=1271 ≥3.87 622 (40.2)

5n=1206 ≥1.05 899 (61.2)

The highest percent of men with T2DM occurred at the highest WC:BMI ratio and the highest WC:HC ratio.

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.

Back up slides

Six “Faces” of Adiposopathy

Bays H, Blonde L, Rosenson R. Expert Rev Cardiovas Ther. 4(6), 871–895 (2006)

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)”

Adiposopathy: TreatmentAdiposopathy treatments and their effects upon select parameters that promote type 2 Adiposopathy treatments and their effects upon select parameters that promote type 2

diabetes mellitusdiabetes 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: TreatmentAdiposopathy treatments and their effects upon select parameters that promote hypertension

Intervention

Visceral fat

Free fatty acids

Leptin Adiponectin

Renin-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)

Adiposopathy: TreatmentAdiposopathy 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