口服葡萄糖耐量试验期间葡萄糖反应曲线的形态： TODAY 中血糖衰竭率升高和β细胞功能加速下降的先兆。
The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in β-Cell Function in TODAY.
机构信息
Children's Hospital of Pittsburgh, Pittsburgh, PA.
George Washington University Biostatistics Center, Rockville, MD
出版信息
Diabetes Care. 2019 Jan;42(1):164-172. doi: 10.2337/dc18-1122. Epub 2018 Nov 19.
OBJECTIVE
Obese youth without diabetes with monophasic oral glucose tolerance test (OGTT) glucose response curves have lower insulin sensitivity and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function.
RESEARCH DESIGN AND METHODS
OGTTs ( = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, insulin sensitivity (1/fasting insulin), C-peptide index (△C/△G), and β-cell function relative to insulin sensitivity (oral disposition index [oDI]) were compared among the three groups.
RESULTS
At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar insulin sensitivity but significantly lower C-peptide index and lower oDI, despite similar diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus the biphasic group (39.1%) ( < 0.0001). The 6-month decline in C-peptide index (32.8% vs. 18.1% vs. 13.2%) and oDI (32.2% vs. 11.6% vs. 9.1%) was greatest in incessant increase versus monophasic and biphasic with no difference in insulin sensitivity.
CONCLUSIONS
In the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 diabetes.
目的
与具有双相 OGTT 葡萄糖反应曲线的肥胖非糖尿病青少年相比，单相 OGTT 葡萄糖反应曲线的青少年胰岛素敏感性较低，β细胞功能受损。尚未研究过青少年发病的 2 型糖尿病患者的 OGTT 葡萄糖反应曲线。在这里，我们假设 TODAY（青少年和儿童 2 型糖尿病的治疗选择）研究中随机分组时的 OGTT 葡萄糖反应曲线可以预测更高的血糖失败率和加速β细胞功能下降。
研究设计和方法
对随机分组时进行的 OGTT（=662）进行分类，分为单相、双相或持续增加。比较三组之间的人口统计学、胰岛素敏感性（1/空腹胰岛素）、C 肽指数（△C/△G）和相对于胰岛素敏感性的β细胞功能（口服处置指数[oDI]）。
结果
在随机分组时，21.7%的人有持续增加，68.6%的人有单相，9.7%的人有双相葡萄糖反应曲线。尽管糖尿病持续时间相似，但持续增加组的胰岛素敏感性相似，但 C 肽指数和 oDI 明显较低，与其他两组相比。血糖失败率在持续增加组（58.3%）高于单相组（42.3%）高于双相组（39.1%）（<0.0001）。6 个月时 C 肽指数（32.8%比 18.1%比 13.2%）和 oDI（32.2%比 11.6%比 9.1%）的下降幅度在持续增加组中最大，而在单相和双相组中则没有差异。
结论
在 TODAY 研究队列中，随机分组时 OGTT 葡萄糖反应曲线的持续增加反映了β细胞功能的降低，并预示着血糖失败率的增加，与单相和双相曲线相比，β细胞功能的恶化速度更快，与糖尿病持续时间和治疗分配无关。OGTT 葡萄糖反应曲线的形状可能是预测青少年 2 型糖尿病患者对治疗反应的代谢生物标志物。
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