Patients with end-stage cystic fibrosis (CF) and severe CF-related diabetes (CFRD) may benefit from combined lung-pancreatic islet transplantation. A recent case series showed that combined bilateral lung and pancreatic islet transplantation is a viable therapeutic option for patients with end-stage CF and CFRD. The use of different organs from a single donor may lead to reduced immunogenicity. As the prevalence of CFRD has increased dramatically with the improved life expectancy of patients with CF, islet transplantation should be considered at the end-stage CF. By restoring metabolic control, the investigators hypothesize that islet transplantation may improve the management of CF patients undergoing lung transplant and decrease the complication rate in the early postoperative period.

Inclusion criteria:

• Patient with cystic fibrosis
• Patient able to respect the protocol procedures
• Patient with end-stage respiratory insufficiency indicating a lung transplant
• Clinical history of cystic fibrosis related diabetes and/or insulin-dependent diabetes, with no residual insulin secretion (C-peptide < 0,5 ng/mL) and/or no response to IV glucagon stimulation: [peak stimulated C-peptide (T6min)/basal plasma C-peptide(T0)] < 2. The absence of insulin secretion will be verified 2 times before inclusion
• Evolution of diabetes for over 3 years
• Patient whose glycaemic control obtained with insulin therapy is not satisfactory and could significantly alter quality of life (HbA1c > 7% and/or MAGE index > 1,25). This situation is assessed by a diabetologist.
• Social Security membership or benefit from Social Welfare
• Patient who received the results of the medical evaluation required

Non-inclusion criteria:

• Patient with contra-indication for undergo a lung transplant
• Patient with an indication of heart, liver or kidney transplantation
• Patient for which poor therapeutic compliance is expected
• Patient under oral antidiabetic drug
• In women of childbearing potential: pregnancy test (urine and / or blood) positive, lactation, or unwilling to use effective contraception for the duration of the study until 3 months after the end . Men: procreation project during the study period up to 3 months after its end, or unwilling to use effective contraception patient.
• Active infection, including hepatitis B, hepatitis C, HIV
• Any history of malignancy within the past 5 years, with the exception of cutaneous basal cell carcinomas completely resected. The history of breast or melanoma cancers are an absolute contraindication
• Alcoholic intoxication or drug addiction
• Anemia (hemoglobin Hb <10g / dL in women and Hb <11 g / dL in men), lymphopenia (<1000 / uL), neutropenia (<1500 / uL) or thrombocytopenia (<100,000 / uL).
• Persistent elevated liver enzymes at baseline
• Portal hypertension identified by oesophageal varice and/or hypersplenism (platelets < 120 000 /mm3) or Child-Pugh score > 6.
• Use of a medical treatment under investigation within 4 weeks before inclusion
• All medical situation assessed by an investigator which could interfere with the good management of the project
• Patient restricted of freedom or unable to give his consent
• Patient has been included in another study that could interfere with the results of the study
• Contraindications to the use of experimental drugs (Cellcept®, prednisone, Prograf, prednisolone, methylprednisolone, and pancreatic islets)