Department of Endocrinology and Diabetology, Angiology, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, University of Tübingen, Tübingen, Germany.
Nephrol Dial Transplant. 2017 Apr 1;32(4):670-676. doi: 10.1093/ndt/gfx018.
Renal function is known to affect glucose metabolism. The aim of this study was to assess glucose metabolism in end-stage renal disease (ESRD) patients and in matched controls with normal renal function and to delineate its underlying pathophysiology.
ESRD patients without diabetes mellitus on the active kidney transplant waiting list of a large European university hospital were metabolically phenotyped by an oral glucose tolerance test (OGTT) and by calculating insulin sensitivity and secretion indices. Matched controls with normal renal function were derived from the TUEF (Tuebingen Family) study cohort, which includes healthy non-diabetic individuals with an increased risk of developing type 2 diabetes. Matches were made for (i) gender, age and body mass index (BMI) (cohort 1) and for (ii) gender, age, BMI, fasting plasma glucose (FPG) and 2-h glucose in OGTT (cohort 2).
A total of 107 patients (90 on haemodialysis and 17 on peritoneal dialysis) and two cohorts, each comprising 107 matched controls, were investigated. ESRD patients had significantly lower FPG. Additional matching for OGTT glucose concentrations revealed significantly lower insulin sensitivity in ESRD patients than in controls. This finding was abrogated after adjustment for triglyceride levels. Insulin secretion, however, was significantly higher in ESRD patients. Insulin kinetics during OGTT as well as C-peptide levels demonstrate higher insulin secretion to be a compensation for lower insulin sensitivity and not to result from impaired insulin clearance.
Our study is the first to provide metabolic phenotyping in patients with ESRD and to compare them with matched controls with normal renal function. Glucose metabolism differs substantially between cohorts, with insulin resistance and a compensatory increase in insulin secretion in ESRD patients.
已知肾功能会影响葡萄糖代谢。本研究旨在评估终末期肾病（ESRD）患者和肾功能正常的匹配对照者的葡萄糖代谢情况，并阐明其潜在的病理生理学机制。
在一家大型欧洲大学医院的活跃肾移植等待名单上，没有糖尿病的 ESRD 患者通过口服葡萄糖耐量试验（OGTT）和计算胰岛素敏感性和分泌指数进行代谢表型分析。匹配的肾功能正常对照者来自于 Tuebingen 家族（TUEF）研究队列，其中包括患有 2 型糖尿病风险增加的健康非糖尿病个体。匹配基于（i）性别、年龄和体重指数（BMI）（队列 1）和（ii）性别、年龄、BMI、空腹血糖（FPG）和 OGTT 中 2 小时血糖（队列 2）。
共研究了 107 例患者（90 例血液透析和 17 例腹膜透析）和两个队列，每个队列包括 107 例匹配对照者。ESRD 患者的 FPG 显著降低。进一步根据 OGTT 葡萄糖浓度进行匹配，发现 ESRD 患者的胰岛素敏感性明显低于对照组。这一发现在调整甘油三酯水平后得到了纠正。然而，胰岛素分泌明显更高。OGTT 期间的胰岛素动力学和 C 肽水平表明，高胰岛素分泌是对低胰岛素敏感性的补偿，而不是由于胰岛素清除受损所致。
我们的研究首次提供了 ESRD 患者的代谢表型分析，并将其与肾功能正常的匹配对照者进行了比较。两组之间的葡萄糖代谢存在显著差异，ESRD 患者存在胰岛素抵抗和代偿性胰岛素分泌增加。
