Disparities in GLP-1 and GIP responses to small intestinal glucose infusion in individuals with well- and poorly-controlled type 2 diabetes

Aims: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are key regulators of glucose homeostasis in health and type 2 diabetes (T2D). Whether their secretion is influenced by antecedent glycaemic control in T2D remains unclear. This study compared GLP-1 and GIP responses to intraduodenal glucose infusion between individuals with well- and poorly-controlled T2D. Methods: 24 diet-controlled participants with T2D (n = 12 with HbA1c < 7.0% and n = 12 with HbA1c > 8.5%) received an intraduodenal infusion of 30 g glucose with 3 g 3-O-methylglucose (3-OMG; a marker of intestinal glucose absorption) over 30 min. Blood glucose was maintained comparably (6.4 ± 0.4 vs. 6.1 ± 0.3 mmol/L) by intravenous insulin. Plasma GIP, GLP-1 and C-peptide and serum 3-OMG were measured at frequent intervals. Results: Basal hormone concentrations were comparable between groups. In response to intraduodenal glucose infusion, the GIP response was greater in the poorly-controlled group (P = 0.02 for time*group interaction), with a trend for higher iAUC_0-60min compared with well-controlled group (1329.9 ± 163.7 vs. 1009.5 ± 108.3 pmol/L*min, P = 0.12 unadjusted; P = 0.09 adjusted for age, sex and BMI). GLP-1 responses were lower in the poorly-controlled group (P = 0.007 for time*group interaction), with lower iAUC_0-60min (453.3 ± 110.6 vs. 1037.5 ± 177.1 pmol/L*min, P = 0.01), but this difference became non-significant after adjustment for age, sex and BMI. C-peptide and 3-OMG responses were comparable. Conclusions: Poor glycaemic control in T2D is associated with a greater GIP, and lower GLP-1, response to small intestinal glucose, independent of intestinal glucose absorption. However, differences in GLP-1 may be influenced by age, sex and BMI, so should be interpreted cautiously and validated in larger cohorts.