Recombinant Human Leptin Therapy Effects on Insulin Action

Not Applicable

Completed

Interventions: Dietary Supplement: placebo
Drug: high-dose leptin
Drug: low-dose leptin

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
placebo	placebo	saline placebo for fourteen days
high-dose leptin	high-dose leptin	80mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days
low-dose leptin	low-dose leptin	30mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days

Primary Outcome Measures

Name	Time	Method
Post-treatment Glucose Disposal. I.e. Glucose Disposal After Treatment With Leptin or Placebo.	fourteen days	This is a measure of the body's ability to metabolize sugar after treatment with either leptin or a placebo. We compare the effect of leptin therapy on insulin-mediated stimulation of glucose disposal with that of placebo. In general, a high glucose disposal rate is a marker of healthy metabolic function. Glucose disposal is measured by tracking the amount of tagged glucose in the bloodstream over time. It is adjusted to subject body weight.
Baseline Glucose Disposal - a Measure of the Body's Ability to Process Sugars.	baseline	pre-treatment glucose disposal. In general, a high glucose disposal rate is a marker of healthy metabolic function. Glucose disposal is measured by tracking the amount of tagged glucose in the bloodstream over time. It is adjusted to subject body weight.

Secondary Outcome Measures

Name	Time	Method
Post-treatment Plasma Leptin Levels	fourteen days	plasma leptin levels after fourteen days ingestion of either leptin or placebo.
Baseline Plasma Leptin Concentrations	baseline	Leptin is an endogenous hormone. Here we measure the pre-treatment concentration of naturally-occurring leptin in the blood.