Department of Paediatrics, University Hospital of Parma, Parma, Italy.
J Endocrinol Invest. 2012 Mar;35(3):246-53. doi: 10.3275/7628. Epub 2011 Apr 6.
To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD).
One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic β-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR).
The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMAIR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the agegroup, and to the HOMA-IR and insulinogenic indexes.
IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, β-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.
评估年龄、基因型和临床状态在囊性纤维化（CF）患者葡萄糖耐量中的主要决定因素，并研究胰岛素分泌和胰岛素敏感性缺陷是否与 CF 相关糖尿病（CFRD）的发生有关。
对 119 名处于稳定临床状态的患者进行了研究。根据年龄将他们分为 3 组，并根据 Schwachman-Kulczycki 临床评分将他们分为 2 组。所有患者均进行了基因分型，并随后分为 3 组。还研究了 94 名健康、体重正常的对照组，这些对照组在性别和年龄上具有可比性。所有受试者均采集基础血样进行血糖和胰岛素、C 肽和糖化血红蛋白检测。稳态模型评估的胰岛素抵抗（HOMA-IR）、空腹血糖/胰岛素比值（FGIR）作为胰岛素抵抗和胰岛素原指数的指标来计算，作为胰腺β细胞功能的标志物。所有患者均进行口服葡萄糖耐量试验，57 例患者进行静脉葡萄糖耐量试验以计算第一时相（FPIR）和急性胰岛素反应（AIR）。
纯合 F508del 患者发生糖耐量受损（IGT）的几率增加，且 FPIR 明显降低，HOMA-IR 和胰岛素原指数降低。杂合 F508del 患者发生糖耐量正常的几率增加。HOMA-IR、FGIR 和胰岛素原指数不随年龄或临床评分而变化。HOMA-IR 与 FPIR 相关。FPIR 与胰岛素原指数呈正相关。AIR 与 FGIR 呈负相关，与 C 反应蛋白呈正相关。在多元线性回归分析中，血糖耐量与年龄组以及 HOMA-IR 和胰岛素原指数相关。
IGT 和 CFRD 主要与基因型有关，但正如预期的那样，随着年龄的增长，患病率增加。数据表明，胰岛素缺乏、β细胞功能和胰岛素敏感性降低可能共同导致 CFRD 的发生；然而，需要进一步的研究来更好地阐明这一方面。
