Abstract：
BACKGROUND: The pathophysiological mechanisms underlying the natural history of glucose intolerance and its fluctuations in subjects with cystic fibrosis (CF) are still unclear.
OBJECTIVE: To investigate the relationship between longitudinal changes in glucose tolerance and concomitant changes in the main parameters of insulin secretion/metabolism/action determining glucose regulation in CF subjects.
METHODS: Insulin sensitivity and glucose-stimulated insulin secretion (GSIS, a biomarker of beta cell functional mass), as estimated by the Oral Glucose Sensitivity Index (OGIS) and by a sophisticated mathematical model, respectively, and insulin clearance were assessed in 127 CF subjects, aged 10-25 years, who underwent two OGTT tests over at least 1-year follow-up period. Subjects were classified a posteriori as regressors (improved glucose tolerance), stable, or progressors (worsened glucose tolerance). The interplay between beta cell compensatory action and insulin sensitivity over time was analyzed by vector plots of insulin clearance adjusted GSIS (PCadj) versus OGIS.
RESULTS: OGIS decreased in progressors and stable. Insulin clearance decreased in both regressors and progressors. GSIS (beta cell functional mass) improved in regressors and worsened in progressors, whereas it did not change in stable. Vector plot analysis confirmed that glucose regulation changed differently in each group. Multinomial logistic regression analysis showed that baseline glucose tolerance and GSIS changes were the only significant predictors of the changes in glucose tolerance (p<0.02, R2Nagelkerke=0.55), whereas age, gender, z-BMI, CF genotypes, and baseline PCadj were not.
CONCLUSIONS: In CF subjects, changes in beta cell functional mass are associated with favorable or detrimental changes of glucose tolerance over time.
OBJECTIVE: To investigate the relationship between longitudinal changes in glucose tolerance and concomitant changes in the main parameters of insulin secretion/metabolism/action determining glucose regulation in CF subjects.
METHODS: Insulin sensitivity and glucose-stimulated insulin secretion (GSIS, a biomarker of beta cell functional mass), as estimated by the Oral Glucose Sensitivity Index (OGIS) and by a sophisticated mathematical model, respectively, and insulin clearance were assessed in 127 CF subjects, aged 10-25 years, who underwent two OGTT tests over at least 1-year follow-up period. Subjects were classified a posteriori as regressors (improved glucose tolerance), stable, or progressors (worsened glucose tolerance). The interplay between beta cell compensatory action and insulin sensitivity over time was analyzed by vector plots of insulin clearance adjusted GSIS (PCadj) versus OGIS.
RESULTS: OGIS decreased in progressors and stable. Insulin clearance decreased in both regressors and progressors. GSIS (beta cell functional mass) improved in regressors and worsened in progressors, whereas it did not change in stable. Vector plot analysis confirmed that glucose regulation changed differently in each group. Multinomial logistic regression analysis showed that baseline glucose tolerance and GSIS changes were the only significant predictors of the changes in glucose tolerance (p<0.02, R2Nagelkerke=0.55), whereas age, gender, z-BMI, CF genotypes, and baseline PCadj were not.
CONCLUSIONS: In CF subjects, changes in beta cell functional mass are associated with favorable or detrimental changes of glucose tolerance over time.
摘要：
背景：囊性纤维化（CF）患者的葡萄糖耐受不良自然史及其波动的病理生理机制尚不清楚。
目的：研究CF受试者中葡萄糖耐量的纵向变化与胰岛素分泌/代谢/决定葡萄糖调节的主要参数的伴随变化之间的关系。
方法：胰岛素敏感性和葡萄糖刺激的胰岛素分泌（GSIS，β细胞功能质量的生物标志物)，根据口服葡萄糖敏感性指数(OGIS)和复杂的数学模型估计，分别,在127名CF受试者中评估了胰岛素清除率，10-25岁,在至少1年的随访期内接受了两次OGTT测试。受试者被后验分类为回归因子（改善的葡萄糖耐量），稳定,或进展者（葡萄糖耐量恶化）。通过胰岛素清除率调整的GSIS（PCadj）与OGIS的矢量图分析了β细胞代偿作用与胰岛素敏感性之间随时间的相互作用。
结果：OGIS在进步者中下降且稳定。回归者和进展者的胰岛素清除率均降低。GSIS（β细胞功能质量）在回归因子中改善，在进展因子中恶化，而它并没有稳定的变化。矢量图分析证实，各组的葡萄糖调节变化不同。多项logistic回归分析表明，基线糖耐量和GSIS变化是糖耐量变化的唯一显着预测因子（p<0.02，R2Nagelkerke=0.55），而年龄,性别,z-BMI,CF基因型，和基线PCadj没有。
结论：在CF受试者中，β细胞功能量的变化与葡萄糖耐量随时间的有利或不利变化有关。
目的：研究CF受试者中葡萄糖耐量的纵向变化与胰岛素分泌/代谢/决定葡萄糖调节的主要参数的伴随变化之间的关系。
方法：胰岛素敏感性和葡萄糖刺激的胰岛素分泌（GSIS，β细胞功能质量的生物标志物)，根据口服葡萄糖敏感性指数(OGIS)和复杂的数学模型估计，分别,在127名CF受试者中评估了胰岛素清除率，10-25岁,在至少1年的随访期内接受了两次OGTT测试。受试者被后验分类为回归因子（改善的葡萄糖耐量），稳定,或进展者（葡萄糖耐量恶化）。通过胰岛素清除率调整的GSIS（PCadj）与OGIS的矢量图分析了β细胞代偿作用与胰岛素敏感性之间随时间的相互作用。
结果：OGIS在进步者中下降且稳定。回归者和进展者的胰岛素清除率均降低。GSIS（β细胞功能质量）在回归因子中改善，在进展因子中恶化，而它并没有稳定的变化。矢量图分析证实，各组的葡萄糖调节变化不同。多项logistic回归分析表明，基线糖耐量和GSIS变化是糖耐量变化的唯一显着预测因子（p<0.02，R2Nagelkerke=0.55），而年龄,性别,z-BMI,CF基因型，和基线PCadj没有。
结论：在CF受试者中，β细胞功能量的变化与葡萄糖耐量随时间的有利或不利变化有关。
