Recombinant Human Leptin Therapy Effects on Insulin Action

Recombinant Human Leptin Therapy Effects on Insulin Action

Leptin therapy improves insulin sensitivity in people with leptin-deficiency but it is not known whether it improves insulin action in persons who are not leptin deficient. The purpose of the present study was to determine whether leptin therapy has effects on insulin action in obese subjects with type 2 diabetes mellitus (T2DM). A randomized, placebo controlled trial was conducted in obese subjects with newly-diagnosed T2DM. Subjects were randomized to treatment with placebo, low-dose, or high-dose leptin. Insulin sensitivity was measured.

Leptin therapy improves insulin sensitivity in people with leptin-deficiency but it is not known whether it improves insulin action in persons who are not leptin deficient. The purpose of the present study was to determine whether leptin therapy has weight loss-independent effects on insulin action in obese subjects with type 2 diabetes mellitus (T2DM). A randomized, placebo controlled trial was conducted in obese subjects with newly-diagnosed T2DM. Subjects were randomized to treatment with placebo (saline), low-dose (30 mg/d), or high-dose (80 mg/d) recombinant methionyl human (r-met hu) leptin for 14 days. Multi-organ insulin sensitivity before and after treatment was evaluated by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labelled tracer infusions to measure glucose, glycerol and fatty acid kinetics.

Inclusion Criteria:

• diagnosed with type 2 diabetes for less than ten years
• Body mass index 25 - 40
• hemoglobin A1C 7.5% - 12.0%
• fasting blood glucose between 90 and 240mg/dL

Exclusion Criteria:

• smoking
• pregnancy
• diabetes medications
• regular exercise (more than 3 hours per week)
• uncontrolled hypertension: systolic blood pressure greater than 160 or diastolic blood pressure greater than 95