Prepuberal insulin secretory indices are long-term predictors of short adult stature in cystic fibrosis

Abstract

Objective: Diabetes is a frequent comorbidity in cystic fibrosis (CF), rela ted to multiple unfavorable outcomes. During the progression of β-cell dysfunction to diabetes, insulin deficiency could possibly reduce the anabolic support to grow ev en in the absence of significant glycemic derangements. To test this hypothesis, w e 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 eit her basal insulin secretion (mean 0.22, 95% CI 0.01, 0.44 z-scores) or prepuberal β-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) secretio n and was associated with a worse glucose response during OGTT. Conclusions: Abnormal insulin secretion associated with high glucose respons e during OGTT predicts a decrease in adult height z-score. Our results s uggest that insulin secretory defects in CF affect growth prior to the development of fasting hyperglycemia.

Keywords

• cystic fibrosis
• oral glucose tolerance test
• insulin secretion
• beta cell glucose sensitivity