Irisin and leptin concentrations in relation to obesity, and developing type 2 diabetes: A cross sectional and a prospective case-control study nested in the Normative Aging Study

Objective. To investigate the associations between irisin and leptin levels in obesity and insulin resistance in a cross sectional study. To assess the potential role of irisin and leptin as a predictive marker of T2DM using a nested case-control study. Methods. Both studies were designed within the longitudinal VA NAS cohort. The cross sectional study involved 111 non obese and 105 obese subjects who were subdivided into two groups based on their fasting glucose tolerance. In the nested 1:3 case-control study, 47 subjects with T2DM and 140 non-diabetic controls were selected. Serum samples collected 3-5 years before the diagnosis of T2DM were analyzed. Irisin and leptin concentrations were measured using a validated ELISA and radioimmunoassay respectively. Results. In the cross-sectional study, irisin did not differ between groups based on their fasting glucose tolerance. When subjects were grouped based on obesity status, both irisin and leptin concentrations were significantly higher in obese compared to the non-obese group (p = 0.03 and <0.001, respectively). Irisin concentrations positively correlated with leptin concentrations (r = 0.392, P < 0.001). In the nested case control study, leptin concentrations were a significant predictor of developing diabetes (p = 0.005) in unadjusted models, but not after correcting for BMI, whereas irisin concentrations did not play a role of comparable significance. Conclusions. Leptin concentrations are higher in the obese group irrespective of their glucose tolerance. Obese individuals with impaired fasting glucose have higher concentrations of circulating irisin compared to non-obese subjects with normal glucose tolerance. Irisin concentrations do not predict risk of developing diabetes prospectively. (C) 2017 Elsevier Inc. All rights reserved.