Impaired Secretion of Total Glucagon-like Peptide-1 in People with Impaired Fasting Glucose Combined Impaired Glucose Tolerance

Abstract

Objective: We assessed the serum glucagon-like peptide-1 (GLP-1) levels for Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus (NDDM) during oral glucose tolerance test (OGTT). The relationships between total GLP-1 level and islet β cell function, insulin resistance (IR) and insulin sensitivity (IS) were also investigated.Methods: A 75g glucose OGTT was given to 531 subjects. Based on the results, they were divided into groups of normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP-1 levels were measured at 0- and 2-hour during OGTT. Homeostasis model assessment of β cell function (HOMA-β), HOMA of insulin resistance (HOMA-IR), Gutt and Matsuda indexes were calculated. The relationships between GLP-1 level and β cell function, IR and IS were analyzed.Results: The levels of total fasting GLP-1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 increments (∆GLP-1) following OGTT reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-β , HOMA-IR, Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG, isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation analysis and multivariable linear regression model suggested that some levels of correlation between GLP-1 levels, ∆GLP-1 and β cell function, IR (P<0.05).Conclusions: The total GLP-1 levels and its response to glucose load decreased significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were even similar to that of NDDM group. Moreover, there were observable correlations between impaired GLP-1 secretion and β cell function, IR and IS.

GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study

“…with previous studies of response to an OGTT in men and women with i-IGT, IFG&IGT, and type 2 diabetes (6,(9)(10)(11)(12). Differences in circulating GLP-1 levels were particularly observed after 120 min, which supports previous observations of reduced late GLP-1 response in diabetes and prediabetes (11).…”

“…It has been controversial whether the impaired incretin effect observed in type 2 diabetes and obesity may result from a reduction in the release of incretin hormones and, if so, whether this reduction occurs prior to the development of type 2 diabetes and obesity (4)(5)(6)(7)(8)28,29). A general belief has been that impaired GLP-1 release in overt type 2 diabetes and obesity is a phenomenon secondary to other metabolic abnormalities (4,30).…”

“…Systematic reviews and meta-analyses have found that GLP-1 release is generally unaltered in type 2 diabetes (4,5). However, single studies have found a reduced (6,7) or even upregulated (8) GLP-1 response to oral glucose in patients with type 2 diabetes, indicating variation among subsets of populations with type 2 diabetes. Information obtained from individuals with prediabetes may contribute to a better understanding of the timing of a potential alteration in GLP-1 response in type 2 diabetes pathogenesis.…”

Mechanisms and Clinical Efficacy of Lixisenatide for the Management of Type 2 Diabetes

“…proline deletion [61]. Lixisenatide is unique in that it is "short-acting," but administered as a once-daily dose; this is believed to be partly due to its marked ability to delay gastric emptying (Table 1) secretion may be impaired [62][63][64].…”

Glucagon-like peptide-1 profile during oral glucose tolerance test in young people

“…Reduction of the incretin, i.e. decreased GLP-1 secretion with normal GIP secretion, is observed in subjects with concomitant impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT) and in patients with type 2 diabetes [9].…”