Abstract MP015: Associations of Leptin With Incident Type 2 Diabetes and Their Interactions With Adiponectin Among African Americans: The Jackson Heart Study

Abstract

Introduction: Directly proportional to body fat leptin influences the regulation of blood glucose through several mechanisms some of them influenced by adiponectin. In population studies high leptin levels have been associated with the development of type 2 diabetes mellitus (T2D), with differences by sex. Because African Americans have high prevalence of obesity and T2D, we assessed the association of leptin with T2D and its interaction with adiponectin in a large ongoing cohort study. The hypothesis was a direct association between leptin and T2D, with differences by sex and modulated by adiponectin. Methods: We included participants who were free of T2D (ADA 2004) at the baseline examination (Exam 1) from the Jackson Heart Study (JHS), a single-site, prospective cohort of risk factors of heart disease in African Americans in Jackson, Mississippi. Incident T2D was defined as new T2D cases among Exam 2 or Exam 3 participants. Separate logistic regression models (odds ratios per log-transformed unit of biomarker) included a minimally adjusted model for age, sex and BMI; a model with addition of systolic blood pressure, antihypertension medication, triglycerides, HDL-cholesterol and antihyperlipidemic medication, smoking, alcohol intake, physical activity and education level; and a full model with addition of insulin resistance, HOMA-IR, on top of these variables. Several interactions were assessed such as by sex and glycated hemoglobin, HgA1c. Results: Among our 3083 participants (mean age 53 years, 63% women) there were 584 incident T2D cases. Significant correlations were present among women for leptin with BMI (0.64) and HOMA-IR (0.30), and for adiponectin with HOMA-IR (-0.32) and HDL-cholesterol (0.39). Among men, significant correlations were found for leptin with BMI (0.76) and HOMA-IR (0.53); and for adiponectin with HOMA-IR (-0.28) and HDL-cholesterol (0.38). Leptin was directly associated with incident T2D in the minimally adjusted model (OR= 1.46; 95% C.I. 1.21, 1.77). The association remained in the additional model (OR=1.43, 95% C.I. 1.15-1.78). However the fully adjusted model showed no association between leptin and T2D (OR=0.97, 95% C.I. 0.76-1.24), indicative of a mediation through insulin resistance. The direct association between leptin and T2D was present in men (OR=1.54, 95% C.I. 1.18-1.99; association nullified by insulin resistance), but not in women (OR=1.30, 95% C.I. 0.96-1.76); although no statistical interaction was present (p=0.96). Adiponectin did not interact with leptin in their association with incident T2D (p=0.08). Effect modification was not present for HgA1c and leptin or adiponectin. Conclusion: Among our African American participants there was an association between leptin and incident T2D, explained by insulin resistance but not modulated by adiponectin. Differences by sex were present, men showing an association nullified by HOMA-IR.