Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents.
Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents.
复制标题
DOI：
10.2337/dc08-1274
复制
发表时间：
2009-03
期刊：
影响因子：
16.2
通讯作者：
Caprio S
中科院分区：
文献类型：
--
作者：
Cali AM;Man CD;Cobelli C;Dziura J;Seyal A;Shaw M;Allen K;Chen S;Caprio S
目的：糖耐量受损（IGT）是一种糖尿病前期状态，在肥胖青少年中越来越普遍。本研究的目的是确定肥胖青少年从正常糖耐量（NGT）到IGT进展的自然历史。研究设计和方法：在大约30个月的时间里，我们确定了60名多种族肥胖青少年的β细胞功能、胰岛素敏感性（SI）和葡萄糖耐量的演变。每个受试者进行三次连续的3小时口服葡萄糖耐量试验。通过口服c肽和葡萄糖最小模型评估动态、静态和总β细胞反应性（分别为Φd、Φs和Φtot）和Si。计算了调节胰岛素分泌Si的处置指数（DI）。结果：在基线时，所有60名受试者都有NGT。77%（46名受试者）在三个测试期间（非进展者）维持了NGT，而23%（14名受试者）随着时间的推移发展了IGT（进展者）。在基线时，两组之间的脂肪百分比和BMI Z评分具有可比性。两组空腹血糖、2小时血糖、180分钟曲线下葡萄糖面积、Φd在基线时差异有统计学意义，而Si在两组间具有可比性。随着时间的推移，虽然Si在非进展者中保持不变，但在进展者中稳步恶化约45% （P > 0.04）。β-细胞反应性在进展者中下降20%，而在非进展者中保持稳定。进展者的DI逐渐下降，而非进展者的DI略有改善（P = 0.02）。结论：发展为IGT的肥胖青少年可能表现为β细胞功能的原发性缺陷。此外，Si的进行性下降进一步加重β细胞功能，导致葡萄糖耐受不良的恶化。
OBJECTIVE—Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing prevalence among obese adolescents. The purpose of this study was to determine the natural history of progression from normal glucose tolerance (NGT) to IGT in obese adolescents. RESEARCH DESIGN AND METHODS—We determined the evolution of β-cell function, insulin sensitivity (SI), and glucose tolerance in a multiethnic group of 60 obese adolescents over the course of approximately 30 months. Each subject underwent three serial 3-h oral glucose tolerance tests. Dynamic, static, and total β-cell responsivity (Φd, Φs, and Φtot, respectively) and Si were assessed by oral C-peptide and glucose minimal models. The disposition index (DI), which adjusts insulin secretion for Si, was calculated. RESULTS—At baseline, all 60 subjects had NGT. Seventy-seven percent (46 subjects) maintained NGT over the three testing periods (nonprogressors), whereas 23% (14 subjects) developed IGT over time (progressors). At baseline, percent fat and BMI Z score were comparable between the groups. Fasting plasma glucose, 2-h glucose, glucose area under the curve at 180 min, and Φd were significantly different between the two groups at baseline, whereas Si was comparable between the two groups. Over time, although Si remained unchanged in nonprogressors, it steadily worsened by ∼45% (P > 0.04) in progressors. β-Cell responsivity decreased by 20% in progressors, whereas it remained stable in nonprogressors. The DI showed a progressive decline in progressors compared with a modest improvement in nonprogressors (P = 0.02). CONCLUSIONS—Obese adolescents who progress to IGT may manifest primary defects in β-cell function. In addition, progressive decline in Si further aggravates β-cell function, contributing to the worsening of glucose intolerance.
登录
查看更多内容
影响因子：
8.2
作者：
Walker, M;Mari, A;Ferrannini, E
通讯作者：
Ferrannini, E
影响因子：
4.2
作者：
Steppel, Jeanne H;Horton, Edward S
通讯作者：
Horton, Edward S
影响因子：
5.8
作者：
Cali, Anna M. G.;Bonadonna, Riccardo C.;Caprio, Sonia
通讯作者：
Caprio, Sonia
影响因子：
7.7
作者：
Goran MI;Lane C;Toledo-Corral C;Weigensberg MJ
通讯作者：
Weigensberg MJ
影响因子：
15.9
作者：
Weyer, C;Bogardus, C;Pratley, RE
通讯作者：
Pratley, RE