Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

* INCLUSION CRITERIA: * Provision of signed and dated informed consent form * Male or female, aged \> 5 years * Clinically significant, severe insulin resistance caused by a known or suspected defect in the insulin receptor * Presence of at least one of the following metabolic abnormalities: * Fasting insulin \>30 micro U/ml, or * Presence of diabetes as defined by the 2006 American Diabetes Association (ADA) criteria: * Fasting plasma glucose \>= 126 mg/dL * 2 hour plasma glucose \>= 200 mg/dL following a 75 gram (1.75g/kg if less than 40kg) oral glucose load, or * Diabetic symptoms with a random plasma glucose \>= 200 mg/dL EXCLUSION CRITERIA: * Pregnant at time of enrollment, women in their reproductive years who do not use an effective method of birth control, and women currently nursing or lactating within 6 weeks of having completed nursing. * Known infectious liver disease * Known HIV infection * Current alcohol or substance abuse * Active tuberculosis * Use of anorexigenic drugs * Other conditions which in the opinion of the clinical investigators would impede completion of the study. * Subjects who have a known hypersensitivity to E. Coli derived proteins.