Patients with mutations of the insulin receptor have diabetes that is challenging to control
withconventional therapies, leading to early morbidity and mortality. We hypothesize that
recombinant leptin (metrel eptin) in these patients will improve glycemia control.
Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in
patients with genetic defects of the insulin receptor. Secondary Objectives: To determine
mechanisms by which metreleptin improves glycemia.
Primary Endpoint: Hemoglobin A1c.
Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide,
glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.
20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at
the NIH Clinical Center.
Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:
NIH Clinical Center
Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).
The study will allow researchers to obtain blood, plasma, DNA, and RNA for genetic studies of
insulin. There will be a focus on the causes of insulin resistance and diabetes mellitus.
Insulin is a hormone found in the body that controls the level of sugar in the blood. Insulin
resistance refers to conditions like diabetes when insulin does not work properly. In this
study researchers would like to compare patients with diabetes and other forms of insulin
resistance to normal individuals. The study will investigate how insulin attaches to cells.
Researchers will take 4 to 6 ounces (100-150 ml) of blood from adult patients and may request
up to 12 ounces (one unit) of blood if necessary. Skin samples may be taken for a biopsy if
further genetic testing is necessary. In addition some patients may be asked not to eat for
up to 72 hours prior to testing.