Recombinant Human Leptin Therapy Effects on Insulin Action

The Washington University

Status: Completed

Conditions: Type Two Diabetes Mellitus

Treatments: Drug: high-dose leptin; Dietary Supplement: placebo; Drug: low-dose leptin

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT01207934

98-0643

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 25 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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18 participants in 3 patient groups, including a placebo group

placebo

Placebo Comparator group

Description:

saline placebo for fourteen days

Treatment:

Dietary Supplement: placebo

low-dose leptin

Experimental group

Description:

30mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days

Treatment:

Drug: low-dose leptin

high-dose leptin

Experimental group

Description:

80mg per day of recombinant methionyl human (r-met hu) leptin for fourteen days

Treatment:

Drug: high-dose leptin