Recombinant Human Leptin Therapy Effects on Insulin Action

Study Overview
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Brief Summary
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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
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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.

Official Title
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Recombinant Human Leptin Therapy Effects on Insulin Action

Conditions
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Type Two Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: placebo
* Drug: low-dose leptin
* Drug: high-dose leptin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>saline placebo for fourteen days | Dietary Supplement: placebo<br>* saline placebo<br>|
| Experimental: low-dose leptin<br>30mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days | Drug: low-dose leptin<br>* 30mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days<br>|
| Experimental: high-dose leptin<br>80mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days | Drug: high-dose leptin<br>* 80mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Glucose Disposal - a Measure of the Body's Ability to Process Sugars. | 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. | baseline | 
| Post-treatment Glucose Disposal. I.e. Glucose Disposal After Treatment With Leptin or Placebo. | 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. | fourteen days | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, obesity