Secretion of Glucose-Dependent Insulinotropic Polypeptide in Patients With Type 2 Diabetes

Abstract

OBJECTIVETo investigate glucose-dependent insulinotropic polypeptide (GIP) secretion in patients with type 2 diabetes and nondiabetic control subjects during oral glucose or meal tests.RESEARCH DESIGN AND METHODSEligible trials were identified by The Cochrane Library, MEDLINE, Embase, and Web of Science. Data were retrieved and random-effects models for the primary meta-analysis, random-effects meta-regression, and subgroup and regression analyses were applied.RESULTSRandom-effects meta-analysis of GIP responses in 23 trials during 28 different stimulation tests showed that patients with type 2 diabetes (n = 363) exhibited no significant differences (P = not significant) in peak plasma GIP, total area under the curve (tAUC), time-corrected tAUC (tAUC × min−1), and time-corrected incremental area under the curve (iAUC × min−1) in comparison with nondiabetic control subjects (n = 325) but had lower GIP responses as evaluated from iAUC (weighted mean difference, −648 pmol/L × min; 95% CI, −1,276 to −21). Fixed-effects models meta-analyses confirmed most of the results of the primary meta-analysis but showed iAUC × min−1 to be reduced and showed tAUC and tAUC × min−1 to be higher in diabetic patients. Random-effects meta-regression of the primary meta-analysis showed that age (peak GIP, tAUC, iAUC, and iAUC × min−1), BMI (tAUC, iAUC, and iAUC × min−1), and HbA1c (iAUC and iAUC × min−1) predicted some of the GIP outcomes. Post hoc subgroup analysis showed a negative influence of age and of HbA1c on GIP responses and showed a positive influence of BMI on GIP responses.CONCLUSIONSOur results suggest that patients with type 2 diabetes are characterized by preserved GIP secretion in response to oral glucose and meal tests. They also suggest that high BMI is associated with increased GIP responses but increasing age and HbA1c are associated with reduced GIP secretion.

Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB

“…Many of the early discrepancies can be explained by differences in the assays used (57) but also by indistinctly referring to incremental (i.e., secreted after a standard oral glucose tolerance test or meal test), nonfasting unstimulated, and fasting GIP concentrations. In a recent meta-analysis of 22 studies including 688 patients, the authors concluded that patients with type 2 diabetes (n = 363), in general, exhibit normal GIP secretion in response to oral glucose tolerance tests or meal tests but have elevated fasting plasma GIP concentrations compared with healthy control subjects (58). The latter is in agreement with our data (Fig.…”

Enteroendocrine K and L cells in healthy and type 2 diabetic individuals

“…the reduced insulinotropic effect of GIP observed in individuals with type 2 diabetes [23,24]. In line with this, fasting GIP levels have been demonstrated to be higher in participants with type 2 diabetes compared with non-diabetic control participants [25,26], and, furthermore, it has been proposed that GIP contributes to the hyperglycaemia seen in type 2 diabetes (primarily due to the glucagonotropic effect of GIP) [27]. However, data regarding GIP responses following oral glucose or mixed meals in individuals with type 2 diabetes have been inconsistent, and a systematic review with meta-analysis has suggested that postprandial GIP responses are similar in those with type 2 diabetes and healthy individuals [26].…”

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

“…immediately degraded by dipeptidyl peptidase-4 (DPP-4), consequently only approximately 25% reaches the hepatoportal circulation and less than 10% reaches the systemic circulation 21,24 .…”