Battezzati Alberto, Foppiani Andrea, Alicandro Gianfranco, Bisogno Arianna, Biffi Arianna, Bedogni Giorgio, Bertoli Simona, De Carlo Giulia, Nazzari Erica, Colombo Carla
International Center for the Assessment of Nutritional Status, DeFENS, University of Milan, Milan, Italy.
Cystic Fibrosis Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Endocr Connect. 2022 May 10;11(5):e220056. doi: 10.1530/EC-22-0056.
Diabetes is a frequent comorbidity in cystic fibrosis (CF), related to multiple unfavorable outcomes. During the progression of β-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.
Observational cohort study.
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.
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 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) secretion and was associated with a worse glucose response during OGTT.
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.
糖尿病是囊性纤维化（CF）常见的合并症，与多种不良结局相关。在β细胞功能障碍进展为糖尿病的过程中，即使在无明显血糖紊乱的情况下，胰岛素缺乏也可能减少对生长的合成代谢支持。为验证这一假设，我们评估了青春期前胰岛素分泌指标是否为成人身高的独立预测因素。
观察性队列研究。
对来自一个正在进行的队列中的66例CF患者（33例女性）进行纵向分析，这些患者在青春期前（中位年龄12岁）接受改良的3小时口服葡萄糖耐量试验，每30分钟采集胰岛素和C肽样本，建立胰岛素分泌和敏感性参数模型，并进行人体测量评估。在中位随访9年后患者成年时重复进行人体测量评估。
在替代模型中，我们发现基础胰岛素分泌（平均0.22，95%CI 0.01，0.44 z评分）或青春期前β细胞葡萄糖敏感性（平均0.23，95%CI 0.00，0.46 z评分）与成人身高呈正相关，而总胰岛素分泌与成人身高呈负相关（分别为平均-0.36，95%CI -0.57，-0.15 z评分或平均-0.42，95%CI -0.69，-0.16 z评分）。成年身高较低患者的高总胰岛素分泌主要归因于晚期（>60分钟）分泌，且与口服葡萄糖耐量试验期间较差的葡萄糖反应相关。
口服葡萄糖耐量试验期间与高血糖反应相关的异常胰岛素分泌预示着成人身高z评分降低。我们的结果表明，CF患者的胰岛素分泌缺陷在空腹高血糖发生之前就影响生长。
