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. The objective of the study was to investigate the relationship between insulin administration, leptin levels, and weight gain in subjects with type 2 diabetes. This was a post hoc analysis of two randomized, controlled trials. The study was conducted at an outpatient clinic. Subjects included 35 (study 1) and 32 (study 2) poorly controlled oral hypoglycemic agent (OHA)-treated type 2 diabetic subjects. 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. Changes in serum leptin levels during clamp and during 1 yr of treatment in relationship to changes in body weight. 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. Significant correlations were observed between insulin's effect on serum leptin levels and the increase in weight that accompanied insulin therapy.
