Abstract 19867: Fasting Ghrelin, Body Mass Index and Risk of Incident Diabetes in Women
Background: Ghrelin is a ligand of the growth hormone secretagogue receptor. Synthesized mostly by gastric cells, ghrelin may play a role in the hypothalamic regulation of appetite and body weight. While cross-sectional data indicate low ghrelin levels in obesity and overt type 2 diabetes (T2D), with elevated levels occurring during diet-induced weight loss, prospective data pertaining to new onset T2D are sparse.
Methods: This study sought to assess whether baseline ghrelin levels relate to body mass index (BMI) and associate with incident T2D. Using a prospective case-cohort approach in the Women's Health Study, total fasting ghrelin levels were measured in baseline samples among 490 non-diabetic women (HbA1c < 6.5%) who later developed T2D and a representative subcohort (n=561). Median ghrelin levels were compared by WHO BMI categories and hazard ratios (HRs) estimated from Cox proportional hazard models, with variance adjustment for the case-cohort design.
Results: Ghrelin levels were strongly inversely related to BMI in the subcohort as well as in cases of incident T2D (p<0.0001 in both). In the subcohort, for each BMI category (<25, 25.0-29.9, ≥ 30 kg/m2), median ghrelin levels were 691.2, 523.1 and 420.2 ng/L (P <0.0001). Ghrelin levels were also lower in women who later developed T2D than in the subcohort (429.1 vs. 579.3 ng/L, P<0.001). In models that adjusted for age and race, there was a decreasing risk of T2D with increasing quartile of ghrelin (HRs 1.00, 0.70, 0.49, 0.26, P-trend <0.0001). This relationship, while modestly attenuated, persisted in models that additionally adjusted for BMI as well as other T2D risk factors including smoking, hypertension, cholesterol, hormone therapy, exercise, alcohol use, and family history of T2D (HRs 1.00, 1.09, 0.71, and 0.49, P-trend 0.01).
Conclusion: Total ghrelin levels are inversely associated with BMI and with T2D in these prospective data, supporting a potential biologic role for ghrelin in obesity and diabetes.
- © 2010 by American Heart Association, Inc.