The main mechanism associated with progression of glucose intolerance in older patients with cystic fibrosis is insulin resistance and not reduced insulin secretion capacity

Abstract

BackgroundAging cystic fibrosis (CF) patients are at high risk of developing CF-related diabetes (CFRD). Decrease in insulin secretion over time is the main hypothesis to explain this increasing prevalence but mechanisms are still not well elucidated. The objective is to assess evolution of glucose tolerance and insulin secretion/sensitivity in aging CF patients. MethodsThis is a retro-prospective observational analysis in the older adult CF patients from the Montreal Cystic Fibrosis Cohort (n = 46; at least 35 years old at follow-up) and followed for at least 4 years. Baseline and follow-up (last visit to date) 2-h oral glucose tolerance test (OGTT with glucose and insulin measurements every 30 min) were performed. Pulmonary function test (FEV1) and anthropometric data were measured the same day. Insulin sensitivity was measured by the Stumvoll index. ResultsAfter a mean follow-up of 9.9 ± 2.6 years, mean age at follow-up was 43.5 ± 8.1 years old. An increase of body weight (+2.6 ± 6.5 kg, p = 0.01) and a decrease in pulmonary function (FEV1; 73.4 ± 21.2% to 64.5 ± 22.4%, p ≤ 0.001) were observed. Overall, insulin secretion is maintained at follow-up but all OGTT glucose values increased (for all values, p ≤ 0.028). At follow-up, 28.3% of patients had a normal glucose tolerance while 71.7% had abnormal glucose tolerance (AGT). AGT patients decreased their insulin sensitivity over time (p = 0.029) while it remained the same in NGT patients (p = 0.917). ConclusionIn older CF patients, the progression of impaired glucose tolerance is occurring with stable insulin secretion but reduced insulin sensitivity.