Xiangxiang Wang1,2, Jia Liu1,2, Chaolin Li1,2,3, Meng Zhao1,2, Lu Liu1,2, Qingbo Guan1,2, Haiqing Zhang1,2, Xu Zhang1,2, Ling Gao1,4, Jiajun Zhao1,2, Yongfeng Song1,2. 1. Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. 2. Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China. 3. Department of Endocrinology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China. 4. Scientific Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Abstract
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.
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.