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 CFTR-dependent insulin secretory defect cannot be excluded. The age and sex dependence of the secretory defect is unclear. OBJECTIVE: To analyze the age and sex dependency of insulin secretory and sensitivity parameters in CF. DESIGN: Cross-sectional analysis in an observational ongoing cohort (mean follow-up duration 7.5yr). SETTING: CF Center of Milan. PATIENTS: 187 patients aged 8-30yr. INTERVENTION: 3-hour Oral Glucose Tolerance Tests (OGTT, n=478) with 30-min insulin and c-peptide sampling. MAIN OUTCOME MEASURES: model-derived insulin secretory and sensitivity parameters. RESULTS: Age was associated to a progressive decrement in insulinemia (at 30min) and a subsequent increment in glycemia (at 60-90min) returning at or below baseline (at 180min). These changes are explained by a progressive reduction in beta-cell sensitivity to glucose and a progressive increment in insulin clearance. Fasting and postprandial insulin sensitivity do not seem to be involved. Compared to males, females display higher glucose, insulin and c-peptide responses with greater insulin secretion, beta-cell sensitivity to glucose, insulin clearance and equal insulin sensitivity. CONCLUSIONS: A defect in beta-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 deterioration in glucose tolerance. The effects of age and sex should be considered when evaluating OGTT results in CF patients.