Feasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosis-related diabetes-PIM study: A multicenter phase 1-2 trial.

Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF), and restoring metabolic control in these patients may improve their management after lung transplantation. In this multicenter, prospective, phase 1-2 trial, we evaluate the feasibility and metabolic efficacy of combined pancreatic islet-lung transplantation from a single donor in patients with CFRD, terminal respiratory failure, and poorly controlled diabetes. Islets were infused via the portal vein under local anesthesia, 1 week after lung transplantation. At 1 year, the primary outcome was transplant success as evaluated by a composite score including four parameters (weight, fasting glycemia, HbA1c, and insulin requirements). Ten participants (age: 24 years [17-31], diabetes duration: 8 years [4-12]) received a combined islet-lung transplant with 2892 IEQ/kg [2293-6185]. Transplant success was achieved in 7 out of 10 participants at 1-year post transplant. Fasting plasma C-peptide increased from 0.91 µg/L [0.56-1.29] to 1.15 µg/L [0.77-2.2], HbA1c decreased from 7.8% [6.5-8.3] (62 mmol/mol [48-67]) to 6.7% [5.5-8.0] (50 mmol/mol [37-64]), with 38% decrease in daily insulin doses. No complications related to the islet injection procedure were reported. In this pilot study, combined pancreatic islet-lung transplantation restored satisfactory metabolic control and pulmonary function in patients with CF, without increasing the morbidity of lung transplantation.

DPP4 inhibitor-induced polyarthritis: a report of three cases.

Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel therapy widespread used in type 2 diabetes mellitus. We describe 3 cases of polyarthritis which delay of appearance strongly suggests a link with DPP4 inhibitors. Three patients presented with bilateral, symmetrical, seronegative polyarthritis after introduction of DPP4 inhibitors (sitagliptine (n = 2) and vildagliptine (n = 1)). Two patients also developed xerostomia and xerostomia, and laboratory test results showed normal values of CRP and erythrocyte sedimentation rate. Joints X-rays were normal. One patient was diagnosed with primary Sjögren's syndrome and treated with hydroxychloroquine, methotrexate and prednisone, with a poor efficacy. When sitagliptine was stopped, all symptoms disappeared, leading to methotrexate and prednisone discontinuation within a month. There were no immunological abnormalities in the 2 other patients, but a chronic viral hepatitis B was found in one patient. Eventually, discontinuation of DPP4 inhibitors led to resolution of symptoms in 1 and 3 weeks for both patients. DPP4 inhibitors seemed to trigger bilateral, non-erosive, seronegative polyarthritis in our 3 patients. DPP4, also known as CD26, is expressed on many cells including lymphocytes and fibroblasts, and its inhibition may lead to immunomodulating effect as suggested by clinical and in vitro studies.