Insulin-Stimulated Increase in Serum Leptin Levels Precedes and Correlates with Weight Gain during Insulin Therapy in Type 2 Diabetes

Context: Infusion of insulin acutely stimulates leptin production and chronic insulin treatment is associated with elevated serum leptin levels and body weight in subjects with type 2 diabetes. Objective: The objective of the study was to investigate the relationship between insulin administration, leptin levels, and weight gain in subjects with type 2 diabetes. Design: This was a post hoc analysis of two randomized, controlled trials. Setting: The study was conducted at an outpatient clinic. Subjects: Subjects included 35 (study 1) and 32 (study 2) poorly controlled oral hypoglycemic agent (OHA)-treated type 2 diabetic subjects. Intervention: Study 1: subjects were investigated during a hyperinsulinemic, euglycemic glucose clamp and 12 months after being randomly allocated to start insulin or continue on OHAs. Study 2: 1 yr treatment with either OHAs and lifestyle intervention or insulin with or without concomitant lifestyle intervention. Main outcome measure: Changes in serum leptin levels during clamp and during 1 yr of treatment in relationship to changes in body weight. Results: Study 1: during acute insulin infusion leptin levels increased by 10% (P < 0.001). During 1 yr of insulin therapy, mean body weight increased by 6%, whereas the fasting leptin levels increased by 108% (both P < 0.001). The weight gain observed at 1 yr correlated with the increase in leptin levels observed during the clamp (r = 0.62, P = 0.003). Study 2: mean body weight increased by 4% (P < 0.01), whereas leptin levels increased by 56% (P < 0.001) during 1 yr of insulin treatment and the increase in leptin preceded the increase in body weight. Conclusions: Significant correlations were observed between insulin's effect on serum leptin levels and the increase in weight that accompanied insulin therapy. (J Clin Endocrinol Metab 94: 2900-2906, 2009)