Prepuberal insulin secretory indices are long term predictors of short adult stature in Cystic Fibrosis

Objective: Diabetes is a frequent comorbidity in cystic fibrosis (CF), related to multiple unfavorable outcomes. During the progression of beta-cell dysfunction to diabetes, insulin deficiency could possibly reduce the anabolic support to grow even in the absence of significant glycemic derangements. To test this hypothesis, we evaluated whether prepuberal insulin secretory indices are independent predictors of adult height. Design: Observational cohort study. Research design and methods: A longitudinal analysis of 66 CF patients (33 females) from an ongoing cohort received at prepuberal age (median age of 12 years) modified 3-h oral glucose tolerance tests with 30-min insulin and C-peptide sampling, modeling of insulin secretory and sensitivity parameters, anthropometric evaluation. The latter was repeated when adults after a median follow-up of 9 years. Results: In alternative models, we found a positive association with either basal insulin secretion (mean 0.22, 95% CI 0.01, 0.44 z-scores) or prepuberal beta-cell glucose sensitivity (mean 0.23, 95% CI 0.00, 0.46 z-scores) and adult height, while total insulin secretion was negatively related to adult height (mean -0.36, 95% CI -0.57, -0.15 z-scores or mean -0.42, 95% CI -0.69, -0.16 z-scores, respectively). The high total insulin secretion of low adult height patients was mainly due to late (>60 min) secretion and was associated with a worse glucose response during OGTT. Conclusions: Abnormal insulin secretion associated with high glucose response during OGTT predicts a decrease in adult height z-score. Our results suggest that insulin secretory defects in CF affect growth prior to the development of fasting hyperglycemia.