with insulin response and coincided with persistently greater glucagon levels to oral glucose tolerance testing in CKD.Disruption in the incretin system and glucagon dynamics may contribute to metabolic complications in moderate-to-severe CKD. Background Incretins are regulators of insulin secretion and glucose homeostasis metabolized by dipeptidyl peptidase-4 (DPP-4). CKD may modify incretin release, metabolism, or response. Methods We performed 2-hour oral glucose tolerance testing in 59 people with nondiabetic CKD (eGFR <60 ml/min per 1.73 m2) and 39 matched controls. We measured total area under the curve and incremental area under the curve (iAUC) of plasma total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic polypeptide (GIP). Fasting DPP-4 levels and activity were measured. Linear regression was used to adjust for demographic, body composition, and lifestyle factors. Results Mean (SD) eGFR was 38±13 and 89±17 ml/min per 1.73 m2 in patients with CKD and controls, respectively. GLP-1 total area under the curve and GIP iAUC were higher in patients with CKD than controls with a mean of 1531±1452 versus 1364±1484 pM×min and 62,370±33,453 versus 42,365±25,061 pg×min/ml, respectively. After adjustment, CKD was associated with 15,271 pM×min/ml greater GIP iAUC (95% confidence intervals [CIs], 387 to 30,154) compared with controls. Adjustment for covariates attenuated associations of CKD with higher GLP-1 iAUC (adjusted difference, 122; 95% CI, −619 to 864). Plasma glucagon levels were higher at 30 minutes (mean difference, 1.6; 95% CI, 0.3 to 2.8 mg/dl) and 120 minutes (mean difference, 0.84; 95% CI, 0.2 to 1.5 mg/dl) in patients with CKD compared with controls. There were no differences in insulin levels or plasma DPP-4 activity or levels between groups. Conclusions Overall, incretin response to oral glucose is preserved or augmented in moderate-to-severe CKD, without apparent differences in circulating DPP-4 concentration or activity. However, neither insulin secretion nor glucagon suppression is enhanced....

中文翻译：

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非糖尿病中度至重度 CKD 的肠促胰岛素稳态受损


伴有胰岛素反应，并且与 CKD 患者口服葡萄糖耐量试验的胰高血糖素水平持续升高相吻合。肠促胰岛素系统和胰高血糖素动力学的破坏可能导致中度至重度 CKD 的代谢并发症。背景 肠促胰岛素是胰岛素分泌和葡萄糖稳态的调节剂，由二肽基肽酶-4 （DPP-4） 代谢。CKD 可能会改变肠促胰岛素的释放、代谢或反应。方法 我们对 59 例非糖尿病 CKD 患者 （eGFR <60 ml/min / 1.73 m2） 和 39 例匹配对照者进行了 2 小时口服葡萄糖耐量试验。我们测量了血浆总胰高血糖素样肽-1 （GLP-1） 和总葡萄糖依赖性促胰岛素多肽 （GIP） 的总曲线下面积和增量曲线下面积 （iAUC）。测量空腹 DPP-4 水平和活动。线性回归用于调整人口统计学、身体成分和生活方式因素。结果 CKD 患者和对照组的平均 （SD） eGFR 分别为 38±13 和 89±17 ml/min/1.73 m2。CKD 患者的 GLP-1 总曲线下面积和 GIP iAUC 高于对照组，平均值分别为 1531±1452 对 1364±1484 pM×min 和 62,370±33,453 对 42,365±25,061 pg×min/ml。调整后，与对照组相比，CKD 的 GIP iAUC 高出 15,271 pM×min/ml （95% 置信区间 [CIs]，387 至 30,154）。协变量调整减弱了 CKD 与较高 GLP-1 iAUC 的关联 （调整后的差异，122;95% CI，-619 至 864）。与对照组相比，CKD 患者在 30 分钟（平均差，1.6;95% CI，0.3 至 2.8 mg/dl）和 120 分钟（平均差，0.84;95% CI，0.2 至 1.5 mg/dl）血浆胰高血糖素水平更高。 两组之间胰岛素水平或血浆 DPP-4 活性或水平无差异。结论 总体而言，在中度至重度 CKD 中，肠促胰岛素对口服葡萄糖的反应保留或增强，循环 DPP-4 浓度或活性没有明显差异。然而，胰岛素分泌和胰高血糖素抑制都没有增强。