Impaired secretion of active GLP-1 in patients with hypertriglyceridaemia: A novel lipotoxicity paradigm?

Diabetes Metab Res Rev. 2018 Feb;34(2). doi: 10.1002/dmrr.2964. Epub 2017 Dec 14.

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.

Keywords: diabetes mellitus; glucagon-like peptide 1; hypertriglyceridaemia; lipotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood*
  • Blood Glucose / analysis
  • Body Mass Index
  • Case-Control Studies
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide 1 / blood*
  • Glucose Tolerance Test
  • Humans
  • Hypertriglyceridemia / physiopathology*
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Young Adult

Substances

  • Biomarkers
  • Blood Glucose
  • Glucagon-Like Peptide 1