Introduction: The incretin effect (IE), which accounts for 50-70% of the postprandial insulin release in health, and is reduced in type 2 diabetes (T2D), reflects a) an amplified insulin secretory response (ISR) and b) reduced insulin clearance to oral, compared with intravenous, glucose. We previously reported, using intraduodenal (ID) glucose infusions as a surrogate, that gastric emptying (which ranges between 1-4 kcal/min in health) is a major determinant of the magnitude of both ISR and IE in health and T2D, such that at higher rates of duodenal glucose delivery, both ISR and IE are substantially greater. The impact on insulin clearance is, however, not known.
Objective: We evaluated the impact of ID glucose infusions at 2 kcal/min (ID2) and 4kcal/min (ID4) (equating to two rates of gastric emptying within the physiological range) on insulin clearance.
Methods: 10 healthy men (age 47±3 years; BMI 29.3±1 kg/m2) received ID glucose infusions at ID2 or ID4 for 120 min in random order following an overnight fast, on two separate days. Blood glucose, serum insulin and C-peptide were measured at baseline and regular intervals and total areas under the curve (AUC) during 120 min of glucose infusion estimated. Insulin clearance was estimated from molar ratios of C-peptide and insulin and the relative reduction in insulin clearance calculated as: [AUC120min (C-peptide) / AUC120min (insulin)] - (C-peptide baseline / insulin baseline) / [AUC120min (C-peptide) / AUC120min (insulin)] and expressed in %.
Results: There was no difference in the glycaemic responses to ID2 and ID4 but insulin and C-peptide secretory responses to ID4 were much greater (P<0.01 for both). Importantly, there was a greater reduction in insulin clearance to ID4 (-68% for ID4 vs. -52% for ID2, P=0.04).
Conclusions: Gastric emptying affects the magnitude of the IE by impacting both insulin secretion and clearance.