This research project is supported by a multicentric network of collaborators whose goal is to assess the efficacy of transplanting allogenic pancreas islets to restore insulin secretion in patients with brittle type 1, insulin-dependent diabetes mellitus and to improve their metabolic control.

The general objective is to demonstrate the beneficial effect of islet allotransplantation in patients with brittle type 1 diabetes with no endogenous insulin secretion, for whom the risk of the spontaneous course of the disease is judged to be worse than the transplantation-related risk. The specific objective is to establish reference data for islet transplantation in non-uremic patients with brittle diabetes, in a multicentric network setting, using the Edmonton protocol.

Inclusion criteria:

• Type 1 diabetes mellitus
• Disease duration > 5 years
• Despite intensive insulin therapy with tight endocrinologist supervision, persistence of the following conditions : hypoglycemia unawareness (< 54 mg/dl) ; brittleness with at least two episodes of severe hypoglycemia ((defined by the need for assistance to correct the blood glucose level) or ketoacidosis per year , or often enough that the diabetologist judges the frequency to be life-threatening, the risk of transplantation and immunosuppression being judged to be less than the risk of the spontaneous course of uncontrolled diabetes
• Basal and stimulated plasma C-peptide < 0.2 ng/ml
• Creatinine clearance ≥ 50 ml/min/1.73 m2 and proteinuria < 0.5 g/24h

Exclusion criteria:

• Severe cardiovascular disease (recent myocardial infarction, unstable coronaropathy…)
• Severe systemic infection, including hepatitis C or B viral infection, HIV infection or tuberculosis
• Past or present neoplasia (with the exception of non melanoma skin cancers)
• Body weight > 70 kg in women and BW > 75 kg in men or BMI > 26
• Stimulated C-peptide ≥ 0.3 ng/ml upon Glucagon or Arginine stimulation
• Age < 18 years or > 65 years
• Creatinine clearance < 50 ml/min/1.73 m2
• Albuminuria > 300 mg /24h or proteinuria > 0.5 g/24h
• Hemoglobinemia < 120 g/l in women or < 130 g/l in men
• Liver disease (enzymes > 1.5 N) such as cirrhosis or hepatitis
• Liver hemangioma
• Untreated proliferating diabetic retinopathy
• Pregnancy, lactation, pregnancy project or absence of efficient contraception
• Previous transplantation or immunization as judged by anti-HLA antibodies (> 20%)
• Insulin needs > 0.7 IU/kg/d or > 50 IU
• HbA1c > 12 %
• Any medical condition needing the chronic use of steroids
• Addison disease
• Any hemostasis disorder needing a prolonged treatment with anticoagulation drugs. Low-dose aspirin is permitted. coagulation disorders contraindicating the procedure, such as platelet count < 100000/mm3.
• Serious life-threatening disease
• Medical or surgical history potentially influencing the absorption, distribution, metabolism and clearance of drugs
• Uncontrolled hypercholesterolemia (> 350 mg/dl, 9.1 mmol/l) or hypertriglyceridemia (> 500 mg/dl, 5.6 mmol/l)
• Leukocytes < 4500/mm3, neutrophils < 2000/mm3, platelets < 100000/mm3
• Any medical or psychosocial condition susceptible to interfere with the study, such as drug abuse or recent alcohol abuse
• Poor therapeutic observance
• Failure to communicate or cooperate with the investigator