Insulin resistance, β-cell dysfunction and differences in curves of plasma glucose and insulin in the intermediate points of the standard glucose tolerance test in adults with cystic fibrosis

Background: diabetes has become a co-morbidity with a negative impact on nutritional status, lung function and survival in cystic fibrosis. Objective: To identify any changes in intermediate points after a 2-hour oral glucose tolerance test (OGTT), pancreatic beta-cell dysfunction, and insulin resistance in cystic fibrosis-related diabetes. Methods: It was carried out a retrospective analysis in a cohort of 64 patients affected of cystic fibrosis, older than 14 years, using the first pathological OGTT. Peripheral insulin resistance was measured using the homeostasis model assessment for insulin resistance (HOMA -IR), and pancreatic beta-cell function was calculated according to Wareham. Time to maximum plasma insulin and glucose levels and area under the curve (AUC(0-120)) were also measured. Results: Twenty-eight women and 36 men with a mean age of 26.8 years were enrolled, of whom 26.7% had normal glucose tolerance (NGT), 18.3% cystic fibrosis-related diabetes without fasting hyperglycemia (CFRD w/o FPG), 10% indeterminate (INDET), and 45% impaired glucose tolerance (IGT). HOMA-IR values were not significantly different between the diagnostic categories. Patients with any pathological change had worse beta-cell function, with a significant delay in insulin secretion, although there were no differences in total insulin production (AUC(0-120)). Time to maximum glucose levels was significantly shorter in NGT patients as compared to other categories, with glucose AUC(0-120) being higher in the different diagnostic categories as compared to NGT. Conclusions: In over half the cases, peak blood glucose levels during a standard OGTT are reached in the intermediate time points, rather than at the usual time of 120 minutes. Patients with cystic fibrosis and impaired glucose metabolism have a delayed insulin secretion during the standard OGTT due to loss of first-phase insulin secretion, with no differences in total insulin production. Absence of significant changes in HOMA-IR suggests that beta-cell dysfunction is the main pathogenetic mechanism. (C) 2014 SEEN. Published by Elsevier Espana, S.L.U. All rights reserved.