Islet Allotransplantation With Steroid Free Immunosuppression

The short term effectiveness of islet transplantation for alleviating hypoglycemia and controlling glucose homeostasis while limiting or even avoiding the nedd for exogenous insulin has been established despite protocol modifications in donor selection, islet preparation or recipient treatment, insulin independence with adequate metabolic control was however rarely prolonged beyond two years. The most frequently proposed explanations include chronic allogenic rejection, recurrence of autoimmunity and beta cell toxicity from administered immunosuppressive drugs.

Fourteen patients were enrolled in this single center phase 2 trial initiated in 2003. Eligible patients were males or females between 18 and 65 years of age, with type 1 diabeted documented for more than 5 years, arginine stimulated C-peptide lower than 0.2ng/ml, and hypoglycemia awareness or documented metabolic lability. Exclusion criteria included body mass index greater than 28Kg/m2, unstable arteriopathy or heart disease, active infection, previous transplantation, insulin daily requirements above 1.2 UI/kg, creatinin clearance below 60 ml/mn/m2 or urinary albumin excretion above 300 mg/day, malignancy, smoking, desire for pregnancy, psychiatric disorders and lack of compliance. The study primary efficacy endpoint was graft survival defined as insulin independence and HbA1c<6.5%. Secondary outcomes were graft function and metabolic control.

Inclusion criteria

• type 1 diabetes documented for more than 5 years
• arginine stimulated C-peptide lower than 0.2 ng/mL
• one of the following:hypoglycemia unawareness OR metabolic lability documented by one or more severe hypoglycemias or two or more hospital admissions for ketoacidosis within the previous year.

Exclusion criteria

• body mass index greater than 28 kg/m2
• non stable arteriopathy or heart disease
• active infection
• previous transplantation
• hyperimmunization
• insulin daily needs above 1.2 U/Kg
• creatinine clearance below 60 ml/mn or urinary albumin excretion above 300 mg/d
• malignancy
• smoking
• desire for pregnancy
• psychiatric disorders
• lack of compliance