Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China.
Diabetes Metab Res Rev. 2018 Feb;34(2). doi: 10.1002/dmrr.2964. Epub 2017 Dec 14.
Lipotoxicity plays an important role in the pathogenesis of β-cell dysfunction. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that exerts beneficial effects on the number and function of islet β cells. However, the effect of lipotoxicity on GLP-1 secretion is still unknown.
Twenty-five patients who were newly diagnosed with diabetes were recruited from 400 subjects based on 75-g Oral Glucose Tolerance Test. Patients were divided into diabetes (DM) and DM combined with hypertriglyceridaemia (DM + HTG) groups according to their serum triglyceride (TG) levels. Seventy-one normal controls and 17 patients with isolated hypertriglyceridaemia were matched by age and gender.
Total and active fasting GLP-1 and 2-hour GLP-1 levels were not significantly altered among the 4 groups. However, total and active ΔGLP-1 levels (the difference between 2-hour GLP-1 and fasting GLP-1 levels) were significantly reduced in the isolated HTG, DM, and DM + HTG groups, particularly the DM + HTG group. The ratio of serum active GLP-1 (AGLP-1) to total GLP-1 (TGLP-1) levels was also decreased in patients with isolated HTG, suggesting that active GLP-1 secretion may be more seriously impaired. Both ΔTGLP-1 and ΔAGLP-1 levels were negatively correlated with serum TG levels, body mass index and fasting plasma glucose (FPG) levels and positively correlated with HDL-C levels. According to the multivariate linear regression analysis, only TG and FPG levels were independently associated with ΔTGLP-1 and ΔAGLP-1 levels.
Impaired GLP-1 secretion was associated with hypertriglyceridaemia and diabetes, and a more obvious association was noted in hypertriglyceridaemic patients with diabetes.
脂毒性在β细胞功能障碍的发病机制中起重要作用。胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素激素，对胰岛β细胞的数量和功能有有益的影响。然而，脂毒性对 GLP-1 分泌的影响尚不清楚。
根据 75g 口服葡萄糖耐量试验，从 400 名受试者中招募了 25 名新诊断为糖尿病的患者。根据血清甘油三酯（TG）水平，患者被分为糖尿病（DM）和糖尿病合并高甘油三酯血症（DM+HTG）组。匹配了 71 名正常对照者和 17 名单纯高甘油三酯血症患者的年龄和性别。
4 组间空腹和 2 小时 GLP-1 水平以及总 GLP-1 和活性 GLP-1 差值（2 小时 GLP-1 与空腹 GLP-1 水平之差）均无明显差异。然而，单纯 HTG、DM 和 DM+HTG 组的总 GLP-1 和活性 GLP-1 差值明显降低，DM+HTG 组尤为明显。血清活性 GLP-1（AGLP-1）与总 GLP-1（TGLP-1）的比值在单纯 HTG 患者中也降低，提示活性 GLP-1 分泌可能受到更严重的损害。ΔTGLP-1 和 ΔAGLP-1 水平与血清 TG 水平、体重指数和空腹血糖（FPG）水平呈负相关，与高密度脂蛋白胆固醇（HDL-C）水平呈正相关。根据多元线性回归分析，只有 TG 和 FPG 水平与 ΔTGLP-1 和 ΔAGLP-1 水平独立相关。
GLP-1 分泌受损与高甘油三酯血症和糖尿病有关，在合并糖尿病的高甘油三酯血症患者中更为明显。
