Weiss Ram, Caprio Sonia, Trombetta Maddalena, Taksali Sara E, Tamborlane William V, Bonadonna Riccardo
Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., P.O. Box 208064, New Haven, CT 06520, USA.
Diabetes. 2005 Jun;54(6):1735-43. doi: 10.2337/diabetes.54.6.1735.
The profile of insulin secretion and the role of proinsulin processing across the spectrum of glucose tolerance in obese youth have not been studied. The aims of this study were to define the role of insulin secretion and proinsulin processing in glucose regulation in obese youth. We performed hyperglycemic clamps to assess insulin secretion, applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration data. Thirty obese youth with normal glucose tolerance (NGT), 22 with impaired glucose tolerance (IGT), and 10 with type 2 diabetes were studied. The three groups had comparable anthropometric measures and insulin sensitivity. The glucose sensitivity of first-phase secretion showed a significant stepwise decline from NGT to IGT and from IGT to type 2 diabetes. The glucose sensitivity of second-phase secretion was similar in NGT and IGT subjects yet was significantly lower in subjects with type 2 diabetes. Proinsulin-to-insulin ratios were comparable during first- and second-phase secretion between subjects with NGT and IGT and were significantly increased in type 2 diabetes. Obese youth with IGT have a significant defect in first-phase insulin secretion, while a defect in second-phase secretion and proinsulin processing is specific for type 2 diabetes in this age-group.
肥胖青少年糖耐量范围内胰岛素分泌情况及胰岛素原加工的作用尚未得到研究。本研究的目的是确定胰岛素分泌和胰岛素原加工在肥胖青少年血糖调节中的作用。我们进行了高血糖钳夹试验以评估胰岛素分泌，将葡萄糖刺激胰岛素分泌模型应用于葡萄糖和C肽浓度数据。研究了30名糖耐量正常（NGT）的肥胖青少年、22名糖耐量受损（IGT）的肥胖青少年和10名2型糖尿病患者。三组的人体测量指标和胰岛素敏感性相当。第一相分泌的葡萄糖敏感性从NGT到IGT以及从IGT到2型糖尿病呈显著的逐步下降。第二相分泌的葡萄糖敏感性在NGT和IGT受试者中相似，但在2型糖尿病患者中显著降低。NGT和IGT受试者在第一相和第二相分泌期间胰岛素原与胰岛素的比率相当，而在2型糖尿病患者中显著升高。IGT肥胖青少年在第一相胰岛素分泌方面存在显著缺陷，而第二相分泌和胰岛素原加工缺陷在该年龄组中是2型糖尿病所特有的。
