Insulin-stimulated increase in serum leptin levels precedes and correlates with weight gain during insulin therapy in type 2 diabetes

J Clin Endocrinol Metab. 2009 Aug;94(8):2900-6. doi: 10.1210/jc.2008-1005. Epub 2009 Jun 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucose / metabolism
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / pharmacology*
  • Insulin / therapeutic use
  • Leptin / blood*
  • Male
  • Middle Aged
  • Signal Transduction
  • Weight Gain*


  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Leptin
  • hemoglobin A1c protein, human
  • Glucose