Insulin-secretion abnormalities and clinical deterioration related to impaired glucose tolerance in cystic fibrosis

Abstract

Objective: To evaluate insulin-secretion kinetics and insulin sensitivity in cystic fibrosis (CF) patients with normal glucose tolerance (CF-NGT), impaired glucose tolerance (CF-IGT) or CF-related diabetes (CFRD), and the potential effects of moderate hyperglycemia on clinical and nutritional status. Design and methods: Cross-sectional study including 50 outpatients with CF. Patients underwent both oral (OGGT) and intravenous (IVGTT) glucose tolerance tests in order to assess insulin secretion and peripheral insulin sensitivity. Homeostasis assessment model and OGGT were used to investigate insulin sensitivity. Forced expiratory volume in the first second (FEV 1 ) and forced vital capacity (FVC) were measured to evaluate pulmonary function. Body mass index (BMI) was determined to assess nutritional status. Results: Insulin secretion was significantly decreased (and delayed at OGTT) in the CFRD group (n ¼ 9) versus the CF-IGT group (n ¼ 10) and the CF-IGT versus the CF-NGT group (n ¼ 31). Insulin sensitivity was significantly different in the CF-IGT and CFRD groups versus the CF-NGT group. FEV 1 , FVC and BMI presented a significant linear correlation with plasma glucose value at 120 min at OGTT and were significantly lower in both CF-IGT and CFRD versus the CF-NGT group, whereas no differences were found between the CF-IGT and CFRD groups. Conclusions: CF patients with IGT present diminished insulin secretion and increased peripheral insulin resistance, correlating with a worse clinical status, undernutrition and impaired pulmonary function. These findings open the question of whether early treatment of mild alterations of glucose metabolism with insulin secretagogues or short-action insulin may lead to improvement of clinical status in CF patients.European Journal of Endocrinology 152 241-247

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

“…These may be related to increased glucose production and gluconeogenesis during fasting (34,35). Heterogeneous data on insulin sensitivity spanning from increased (36), normal (37,38), and decreased (11,39,40) insulin sensitivity were obtained similarly using surrogate techniques.…”

Cystic fibrosis related diabetes—a new perspective on the optimal management of postprandial glycemia

“…Measurement of insulin and C-peptide responses to an OGTT may aid in detecting abnormalities in carbohydrate metabolism and progression. A delayed and reduced insulin peak and first phase insulin response to oral and intravenous glucose tolerance tests are evident in CF subjects with impaired, compared with those with normal glucose tolerance [20]. This information may facilitate identification of those at high risk of progressing to CFRD however more studies are required.…”

Coming of age in cystic fibrosis – transition from paediatric to adult care

“…Decline in weight and lung function precede the diagnosis of CFRD by current criteria by months to years. [12][13][14] Early insulin initiation delays a decline in lung function by an average of 34 months. 15 The biggest problem facing CF physicians is the lack of a satisfactory screening tool to facilitate the early diagnosis of CFRD.…”