FP18-5 Changes in Insulin Sensitivity and Cytokine Levels Following a 12-Month Weight Loss in Non-Diabetic Overweight and Obese Subjects

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP18-Diabetes: Glycemia & Insulin Sensitivity
Basic/Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:05 AM
Room 304 (Moscone Center)

Poster Board SUN-783
Thanh P Ho*1, Xiongce Zhao1, Joyce D Linderman1, Sheila Smith1, Amber B Courville2, Louis Simchowitz1 and Francesco S. Celi3
1NIDDK-NIH, Bethesda, MD, 2CC-NIH, Bethesda, MD, 3National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD
Introduction: Weight loss is associated with improvement in insulin sensitivity and reduction in markers of tissue inflammation, but little is known about the action of inflammatory mediators in modulating insulin sensitivity in non-diabetic obese subjects. The aim of the study is to identify factors that affect changes in glucose metabolism during moderate, controlled weight loss.

Methods: Overweight non-diabetic subjects (BMI≥25 Kg/m2) without cardiovascular or thyroid disease were recruited for a one-year dietary intervention weight loss program. Study participants received counseling for individualized, calorie-restricted diets and lifestyle modification. During the first 3 months education/support group sessions were offered bi-weekly, and monthly for the remainder of the study. Glucose metabolism, cytokines and anthropometric parameters were recorded at baseline and after 6 and 12 months of dietary intervention.  Insulin sensitivity (SI) was calculated with FSIVGTT and Minimal Model.

Results: Twenty-eight subjects (f. 15, m. 13, age 38.6±1.0 year, BMI 33.2±0.9 Kg/m2) completed the study, achieving a weight loss of 9.1± 0.2 kg (P<0.05) and a fat mass loss of 7.7±0.1 kg (P<0.01). At baseline a negative association was observed between SI and fat mass, waist circumference, and hip circumference (P<0.001), but no significant association was observed between SI and IL-2, IL-1b, or IL-10. The intervention resulted in a significant increase in SI (3.0±0.5 baseline, 4.4±0.5 6 months, 4.3±0.6 12 months, P<0.001). A non significant decrease in IL-2, IL-1b, and IL-10 was also observed. Using a mixed model analysis the change in SI was significantly associated with changes in waist-to-hip ratio (WHR) (P<0.02), IL-2 (P<0.05), IL-1b (P<0.03). The changes in fat mass, waist circumference, and IL-1b were independently associated with changes in SI (all P<0.05).

Discussion: Weight loss intervention in non-diabetic overweight and obese subjects resulted in an improvement in the insulin sensitivity and in a moderate, non-significant reduction of the pro-inflammatory cytokines IL-2 and IL-1b. Moreover, the decrease in central adiposity was independently associated with improvement in insulin sensitivity. The data indicate that in this study population although the changes in IL-2, IL-1b, and IL-10 likely explain some of the variability in glucose metabolism observed during controlled weight loss, the majority of the observed changes are secondary to reduction of fat mass.

1Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN. MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther. 2003;5:1003-1015.

Nothing to Disclose: TPH, XZ, JDL, SS, ABC, LS, FSC

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

Sources of Research Support: This research was supported in part by the Intramural Research Program of the NIDDK-NIH Z01-DK047057-02This research was made possible through the National Institutes of Health (NIH) Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from Pfizer Inc, The Leona M. and Harry B. Helmsley Charitable Trust, and the Howard Hughes Medical Institute, as well as other private donors.  For a complete list, please visit the Foundation website at http://www.fnih.org/work/programs-development/medical-research-scholars-program).