Conditions: Type 1 Diabetes
Keywords: Type 1 Diabetes Mellitus
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 8
Healthy volunteers: no

Brief summary:
This study will add leptin therapy to the current insulin therapy of Type 1 Diabetics with the aim of lowering the total insulin requirements and suppressing the steep fluctuations typically associated with Type 1 Diabetes.

Detailed description:
The adipocyte hormone, leptin, has been shown to restore the health and glucoregulation of near-death, insulin deficient diabetic rodents. This makes leptin the only hormone, since the discovery of insulin in 1922, with this capability. Leptin normalizes the hyperglucagonemia of diabetes and reduces lipogenesis and cholesterologenenesis. Treatment of diabetic rodents with a combination of leptin and insulin, leads to a stable pattern of glucose control with reduced insulin requirements, as opposed to the high glucose variability that characterizes the treatment of type 1 diabetes with supraphysiologic doses of insulin alone. As such, we will initiate a pilot clinical trial to test combination leptin and insulin therapy in type 1 diabetes. Fifteen leptin sensitive patients (body mass index \<27 kg/m²) with uncontrolled diabetes (HbA1c 7.0 to 10.0 %) will be treated with slightly supraphysiologic doses of recombinant human leptin (Amylin Pharmaceuticals). Subjects will be compared to themselves before and after treatment with leptin. Endpoint variables include HbA1c, change in daily insulin dose, mean and standard deviation of blood glucose from inpatient glucose monitoring and glucose meter download. We will also assess effects of leptin therapy on energy intake as assessed by 3-day food record and body weight and fat by DEXA. Intramyocellular and intrahepatic lipid concentration by 1H-MRS will be assessed before and after 3 months of metreleptin therapy. A satiety analysis will be employed. In addition, plasma hormones and inflammatory biomarkers will be assayed during the course of this study.

Arms:
arm 1: Active open label Leptin for type 1 Diabetes

Interventions: intervention 1: Leptin
Intervention descriptions: intervention 1: weight based sub-cutaneous injection twice daily of Leptin

Protocol document: