Declining beta-cell function relative to insulin sensitivity with increasing fasting glucose levels in the nondiabetic range in children.
Declining beta-cell function relative to insulin sensitivity with increasing fasting glucose levels in the nondiabetic range in children.
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DOI：
10.2337/dc09-2292
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发表时间：
2010-09
期刊：
影响因子：
16.2
通讯作者：
Arslanian S
中科院分区：
文献类型：
--
作者：
Tfayli H;Lee S;Arslanian S
在成年人中，较高的空腹血糖(FPG)水平，即使在正常血糖范围内，也与糖尿病风险增加有关。这项研究验证了这一假设，即β细胞功能与胰岛素敏感性的关系随着青年空腹血糖的增加而降低。共有223名患有空腹血糖126 mg/dl的青年患者接受了双能X线骨密度仪和计算机断层扫描，评估了2小时高血糖(∼225 mg/dl)钳夹期间的第一和第二时相胰岛素分泌、3小时高胰岛素-正常血糖钳夹期间的胰岛素敏感性、身体成分和腹部肥胖症。以第一时相胰岛素与胰岛素敏感性的乘积即葡萄糖处置指数计算β细胞功能与胰岛素敏感性的关系。受试者被分成三个空腹血糖类别：≤90、90-lt；100和≥100--126 mg/dl。血糖指数随空腹血糖升高而显著降低(1,086±192vs.814±67和454±57 mg/kg/min，P=0.002)。在对种族、性别、BMI和体脂或内脏脂肪百分比进行调整后，这一下降仍然显著。在每个空腹血糖类别中，GDI随着BMI百分位数的增加而下降。即使在儿童非糖尿病空腹血糖范围内，与胰岛素敏感性相关的β细胞功能损害也是明显的。在目前空腹血糖受损的临界值为100毫克/分升时，与肥胖和种族无关，血糖指数∼下降了49%。这一观察结果可能反映了这些儿童中β细胞功能障碍和进展为糖尿病的风险增加。考虑到在1999-2000年和2005-2006年全国健康和营养检查调查期间，年轻人中IFG的患病率几乎翻了一番，我们的发现具有重要的公共卫生意义。
In adults, higher fasting plasma glucose (FPG) levels, even within the normoglycemic range, are associated with increased diabetes risk. This investigation tested the hypothesis that β-cell function relative to insulin sensitivity decreases with increasing FPG in youth. A total of 223 youth with FPG <126 mg/dl underwent evaluation of first- and second-phase insulin secretion during a 2-h hyperglycemic (∼225 mg/dl) clamp, insulin sensitivity during a 3-h hyperinsulinemic-euglycemic clamp, body composition, and abdominal adiposity with dual-energy X-ray absorptiometry and computed tomographic scan. β-Cell function relative to insulin sensitivity was calculated as the product of first-phase insulin and insulin sensitivity, i.e., glucose disposition index (GDI). The subjects were divided into three FPG categories: ≤90, >90–<100, and ≥100–<126 mg/dl. GDI decreased significantly across the three categories as FPG increased (1,086 ± 192 vs. 814 ± 67 and 454 ± 57 mg/kg/min, P = 0.002). This decline remained significant after adjustment for race, sex, BMI, and percent body fat or visceral fat. Within each FPG category, GDI declined with increasing BMI percentiles. The impairment in β-cell function relative to insulin sensitivity is apparent even within the nondiabetic FPG range in children. At the current cutoff of 100 mg/dl for impaired fasting glucose (IFG), there is an ∼49% decline in the GDI independent of obesity and race. This observation may reflect a heightened risk of β-cell dysfunction and progression to diabetes in these children. Considering the near doubling of IFG prevalence among youth between National Health and Nutrition Examination Survey 1999–2000 and 2005–2006, our findings have important public health implications.
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