Glycemic control may influence incretin hormone responses in type 2 diabetes mellitus (T2DM), with potential implications for metabolic regulation. A comparative physiological study published in Diabetes Research and Clinical Practice evaluated glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) responses to intraduodenal glucose infusion in individuals with well-controlled and poorly controlled T2DM.

The study included 24 diet-controlled individuals with T2DM, stratified by glycated hemoglobin (HbA1c) levels into well-controlled (<7.0%) and poorly controlled (>8.5%) groups. Participants received a 30 g intraduodenal glucose infusion with 3 g 3-O-methylglucose (3-OMG) over 30 minutes. Blood glucose levels were maintained at comparable concentrations between groups using intravenous insulin. Plasma GLP-1, GIP, C-peptide, and serum 3-OMG were measured at multiple time points.

Basal hormone levels were similar between groups. During glucose infusion, GIP response was greater in the poorly controlled group, with a significant time-by-group interaction (P=0.02) and a trend toward higher incremental area under the curve (iAUC₀-₆₀min). GLP-1 response was lower in the poorly controlled group (P=0.007), with reduced iAUC, although this difference was not significant after adjustment for age, sex, and body mass index. C-peptide and 3-OMG responses did not differ between groups.

These findings indicate that poorer glycemic control is associated with altered incretin responses, independent of intestinal glucose absorption. The attenuation of GLP-1 differences after adjustment suggests potential confounding effects. Larger studies are required to confirm these observations and clarify their clinical relevance.