Age- and sex-dependent distribution of OGTT-related variables in a population of cystic fibrosis patients

Context: Cystic fibrosis (CF) causes an exceptionally high prevalence of diabetes that increases with age, especially in females. The glucose tolerance defect is progressive, but a cystic fibrosis transmembrane conductance regulator-dependent insulin secretory defect cannot be excluded. The age and sex dependence of the secretory defect is unclear. Objective: The objective of the study was to analyze the age and sex dependency of insulin secretory and sensitivity parameters in CF. Design: This was a cross-sectional analysis in an observational ongoing cohort (mean follow-up duration 7.5 y). Setting: The study was conducted at the CF Center of Milan. Patients: The study included 187 patients aged 8-30 years. Intervention: Interventions included 3-hour oral glucose tolerance tests (n = 478) with 30-minute insulin and c-peptide sampling. Main Outcome Measures: Model-derived insulin secretory and sensitivity parameters were measured. Results: Age was associated with a progressive decrement in insulinemia (at 30 min) and a subsequent increment in glycemia (at 60-90 min), returning at or below baseline (at 180 min). These changes are explained by a progressive reduction in ?-cell sensitivity to glucose and a progressive increment in insulin clearance. Fasting and postprandial insulin sensitivity do not seem to be involved. Compared with males, females display higher glucose, insulin, and c-peptide responses with greater insulin secretion, ?-cell sensitivity to glucose, insulin clearance, and equal insulin sensitivity. Conclusions: A defect in ?-cell sensitivity to glucose progressively develops with age, but it is not sex specific and does not explain the worse glucose tolerance reported in females. In contrast, insulin clearance increases with age, especially in females, contributing to the deterioration in glucose tolerance. The effects of age and sex should be considered when evaluating oral glucose tolerance test results in CF patients.