Impaired secretion of glucagon-like peptide 1 during oral glucose tolerance test in patients with newly diagnosed type 2 diabetes mellitus

Objectives:

To assess glucagon-like peptide 1 (GLP-1) secretion after oral glucose tolerance tests (OGTTs) in subjects with newly diagnosed type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) to clarify changes in GLP-1 secretion during the course of T2DM.

Methods:

In this cross sectional study, 80 subjects were divided into the NGT, IGT, and T2DM groups after undergoing a 75 g OGTT from March to December 2014 at the School of Medicine, First Affiliated Hospital, Shihezi University, Xinjiang, China. Plasma total GLP-1 was measured at 0, 30, 60, 120, and 180 minutes. Homeostasis model assessment of insulin resistance (HOMA-IR), islet β-cell function (HOMA-β), Gutt index, Matsuda index, incremental GLP-1 (ΔGLP-1), and areas under the curves of GLP-1 (AUC_glp-1), glucose (AUC_g), and insulin (AUC_ins) were calculated.

Results:

Plasma total GLP-1 at 30-120 minutes and ΔGLP-1 at 30-120 minutes were lower in the T2DM group than in the IGT and NGT groups (p<0.05). Peak GLP-1 levels were 35% lower in the T2DM group than in the NGT group. Plasma total GLP-1, ΔGLP-1, and AUC_glp-1 correlated negatively with HOMA-IR and AUC_g, and positively with HOMA-β, Gutt index, Matsuda index, and AUC_ins (p<0.05).

Conclusion:

The GLP-1 secretion after 75 g OGTT was impaired in newly diagnosed T2DM patients, inversely proportional to IR and hyperglycemia, and positively correlated with β-cell function and insulin sensitivity.Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with multiple pathophysiological abnormalities. Currently, T2DM is one of the most common chronic diseases in almost every country. China has the largest population of diabetes patients. The prevalence of diabetes among adults in China is 11.6%, which is equivalent to 114 million patients.1 Glucagon-like peptide-1 (GLP-1) is secreted by L-cells in the distal parts of the intestines in response to nutrient ingestion.2 The GLP-1 regulates blood glucose levels deriving from several mechanisms. It stimulates insulin secretion from the pancreatic β-cells in a glucose-dependent manner and suppresses glucagon secretion.3,4 The GLP-1 also affects gastrointestinal motility, enhances satiety, promotes weight loss, and increases β-cell mass.5-9 Therefore, impaired GLP-1 secretion may contribute to the initiation and development of DM. As a consequence of these properties, GLP-1 based therapies (GLP-1 agonists and dipeptidyl peptidase-4 inhibitors) are currently playing a cornerstone role in the treatment of T2DM. Since GLP-1 plays an important role in the pathophysiology of DM, the assessment of GLP-1 secretory responses in individuals with different glycometabolism states is of great interest. The outcomes of GLP-1 secretion after the administration of an oral glucose load in individuals with and without diabetes are controversial. Toft-Nielsen et al10 reported a 53% reduction in integrated incremental GLP-1 concentrations in T2DM patients relative to healthy controls, while participants with impaired glucose tolerance (IGT) had an intermediate GLP-1 response. However, other studies11,12 have reported that GLP-1 secretion was not reduced in response to an oral glucose tolerance test (OGTT), or meal test in patients with T2DM. The mode of GLP-1 secretion in Asians may be different. Thus far, limited data are available on comparisons of GLP-1 levels among Chinese individuals with newly diagnosed T2DM, IGT, and normal glucose tolerance (NGT). Therefore, this study was conducted to measure GLP-1 levels during a standard OGTT in Chinese subjects with newly diagnosed T2DM, IGT, and NGT, in order to characterize the changes in GLP-1 secretion during the course of T2DM development. We also investigated the relationship between GLP-1 secretion, insulin resistance (IR), and insulin β-cell function.