Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies

Abstract

Aims/hypothesis We carried out a systematic review of clinical studies investigating glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test. Methods Random effects models for the primary meta-analysis and random effects meta-regression, subgroup and regression analyses were applied. Results Random effects meta-analysis of GLP-1 responses in 22 trials during 29 different stimulation tests showed that patients with type 2 diabetes (n=275) and controls without type 2 diabetes (n=279) exhibited similar responses of total GLP-1 (p=NS) as evaluated from peak plasma concentrations (weighted mean difference [95% CI] 1.09 pmol/l [−2.50, 4.67]), total AUC (tAUC) (159 pmol/l×min [−270, 589]), time-corrected tAUC (tAUC min−1) (0.99 pmol/l [−1.28, 3.27]), incremental AUC (iAUC) (−122 pmol/l×min [−410, 165]) and time-corrected iAUC (iAUC min−1) (−0.49 pmol/l [−2.16, 1.17]). Fixed effects meta-analysis revealed higher peak plasma GLP-1 concentrations in patients with type 2 diabetes. Subgroup analysis showed increased responses after a liquid mixed meal test (peak, tAUC and tAUC min−1) and after a 50 g OGTT (AUC and tAUC min−1), and reduced responses after a solid mixed meal test (tAUC min−1) among patients with type 2 diabetes. Meta-regression analyses showed that HbA1c and fasting plasma glucose predicted the outcomes iAUC and iAUC min−1, respectively. Conclusions/interpretation The present analysis suggests that patients with type 2 diabetes, in general, do not exhibit reduced GLP-1 secretion in response to an OGTT or meal test, and that deteriorating glycaemic control may be associated with reduced GLP-1 secretion.

Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and relationships with triglycerides and ALT

“…Although the reduced incretin effect among diabetic patients has been well characterized for some time (1), a potential defect in incretin secretion may only be present in patients with long-standing diabetes (5,6). This study demonstrates higher GLP-1 response (tAUC) after oral glucose among patients with diabetes when compared with persons with NGM, while no altered GLP-1 response after mixed meal is observed.…”

“…Despite this well-established reduced incretin effect among diabetic patients, whether a defect in incretin secretion exists is still not fully resolved (5,6). Secretion of the incretins GLP-1 and GIP following meal intake or oral glucose has been described in a number of studies and was reviewed by Calanna et al and Nauck et al (5,6).…”

“…Secretion of the incretins GLP-1 and GIP following meal intake or oral glucose has been described in a number of studies and was reviewed by Calanna et al and Nauck et al (5,6). These authors concluded that patients with type 2 diabetes, in general, do not exhibit reduced GLP-1 secretion (5,6).…”

Modulation of Glucagon-like Peptide-1 (GLP-1) Potency by Endocannabinoid-like Lipids Represents a Novel Mode of Regulating GLP-1 Receptor Signaling

“…Finally, deterioration in GLP-1 signaling response in type 2 diabetes rather than reduced GLP-1 secretion is associated with the pathogenesis of the disease (47). Such patients have impaired incretin effect, despite normal GLP-1 secretion (48) and normal GLP-1 secretion in response to oral glucose or meal tests (47).…”

“…Such patients have impaired incretin effect, despite normal GLP-1 secretion (48) and normal GLP-1 secretion in response to oral glucose or meal tests (47). Clinically, the administration of GLP-1 analog has been successful in ameliorating reduced GLP-1 signaling in type 2 diabetes; likewise, similar therapeutic effects may be achieved with positive modulators for GLP-1 peptide, which may restore the function of GLP-1 signaling that is more in line with physiological demands.…”