OR09-4 Metabolic Features of Insulin-Sensitive Obesity

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR09-Obesity: Physiologic Responses to Energy Balance Disruption
Clinical
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 12:15 PM
Room 307 (Moscone Center)
Daniel Li Tu Chen*1, Dorit Samocha-Bonet1, Carsten Liess2, Mike Trenell3, Don Chisholm1 and Jerry Richard Greenfield1
1Garvan Institute of Medical Research, Sydney, Australia, 2Philips Healthcare, Hamberg, Germany, 3Newcastle University, Newcastle, United Kingdom
Background: While insulin resistance and obesity coexist, some obese individuals remain insulin-sensitive (up to 30%). The metabolic factors that co-segregate with, and hence may explain, insulin-sensitivity in obesity have not been fully elucidated. While visceral adiposity correlates positively with insulin resistance, it remains unclear whether insulin-sensitive obesity is characterized by low visceral adiposity. Most previous studies classified obese individuals as insulin-sensitive and insulin-resistant based on surrogate measures, rather than the gold standard hyperinsulinaemic-euglycaemic clamp. The present study examined the metabolic features of insulin-sensitive obesity.

Methods: Fifty three obese subjects (34 female) aged 52 ± 11 years were studied. Anthropometric and clinical metabolic data were measured. Participants underwent hyperinsulinaemic-euglycaemic clamp (insulin infusion rate 80 mU/m2/min) with indirect calorimetry.  Subjects in the top tertile of glucose infusion rate (GIR, normalized for fat-free mass [FFM]) were deemed obese insulin-sensitive (Obsen), with separate cut-offs for men and women. Obese insulin-resistant (Obres) individuals were those in the bottom two tertiles of GIR/FFM. Body composition and abdominal fat distribution were measured by DXA and MRI (at L4/L5), respectively.

Results: Age (P=0.42) and BMI (34.9 ± 3.0 vs. 36.5 ± 4.6 kg/m2; P=0.16) were similar in Obsen and Obres groups. By definition, insulin sensitivity was higher in Obsen subjects (121 ± 26 vs. 76 ± 19 µmol/min/kgFFM). Obsen subjects had significantly lower waist-to-hip ratio (0.87 ± 0.1 vs. 0.93 ± 0.1; P=0.04), HbA1c (5.3 ± 0.3 vs. 5.5 ± 0.3 %; P=0.01) and systolic blood pressure (119 ± 10 vs. 127 ± 14 mmHg; P=0.04). Despite similar total body fat (45.8 ± 10.4 vs. 46.6 ± 10.4 kg; P=0.78) and FFM (50.2 ± 11.2 vs. 54.1 ± 11.5 kg; P=0.24), Obsen subjects had lower central abdominal fat (3.1 ± 0.6 vs. 3.6 ± 0.7 kg; P=0.02). There was no difference in subcutaneous fat (517 ± 146 vs. 524 ± 131 cm2; P=0.87) between the groups. However, Obsen had significantly lower visceral fat (213 ± 49 and 288 ± 80 cm2; P<0.001) and visceral-to-subcutaneous fat ratio (0.47 ± 0.26 vs. 0.59 ± 0.25; P=0.03) than Obres subjects. Obsen subjects were more metabolically flexible (as defined by change in respiratory quotient from baseline to clamp steady state) than Obres subjects (0.18 ± 0.05 vs. 0.14 ± 0.05; P=0.01).

Conclusions: Obese insulin-sensitive adults are characterized by lower HbA1c, systolic blood pressure, abdominal adiposity and visceral fat compared to equally-obese but insulin-resistant subjects. Whether insulin-sensitive obese humans remain insulin-sensitive life-long, and whether their insulin-sensitive phenotype reduces their risk of developing diabetes, cardiovascular disease and certain cancers, is yet to be determined.

Nothing to Disclose: DLTC, DS, CL, MT, DC, JRG

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Australian Research Council NHMRC St Vincen'ts Clinic Foundation, Australia