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Impaired secretion of active GLP‐1 in patients with hypertriglyceridaemia: A novel lipotoxicity paradigm?
Author(s) -
Wang Xiangxiang,
Liu Jia,
Li Chaolin,
Zhao Meng,
Liu Lu,
Guan Qingbo,
Zhang Haiqing,
Zhang Xu,
Gao Ling,
Zhao Jiajun,
Song Yongfeng
Publication year - 2018
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2964
Subject(s) - medicine , lipotoxicity , endocrinology , incretin , triglyceride , diabetes mellitus , glucagon like peptide 1 , body mass index , pathogenesis , islet , type 2 diabetes , insulin resistance , cholesterol
Background 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. Methods 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. Results 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. Conclusion Impaired GLP‐1 secretion was associated with hypertriglyceridaemia and diabetes, and a more obvious association was noted in hypertriglyceridaemic patients with diabetes.