Effects of small intestinal glucose on glycaemia, insulinaemia and incretin hormone release are load-dependent in obese subjects

Abstract

BACKGROUND/OBJECTIVES: Studies concerning the glycaemic response to oral glucose, or meals in obesity have usually failed to account for gastric emptying. It has been suggested that the incretin effect may be diminished in obesity as a result of a reduction in glucagon-like peptide-1 (GLP-1) secretion. We sought to determine the effect of two different rates of intraduodenal glucose infusions on glycaemic, insulinaemic and incretin hormone responses in lean and obese subjects and compare the effects of oral and intraduodenal glucose in obese subjects. SUBJECTS/METHODS: Eleven obese subjects (age 37.5±4.1 years, body mass index (BMI) 35.7±1.4 kg m(-)(2)) and 12 controls (age 34.7±4.0 years, BMI 23.9±0.7 kg m(-)(2)) received intraduodenal infusions of glucose at 1 or 3 kcal min(-1), or saline for 60 min (t=0-60 min), followed by intraduodenal saline (t=60-120 min). In obese subjects, an oral glucose tolerance test was performed. Blood glucose, serum insulin, plasma total GLP-1 and total gastric inhibitory polypeptide (GIP) were measured. RESULTS: In both the groups (P<0.001), the incremental areas under the curve (iAUC)0-60 min for glucose was greater with the 3 kcal min(-1) than the 1 kcal min(-1) infusion; the iAUC0-120 min for glucose during 3 kcal min(-1) was greater (P<0.05), in the obese. Insulin responses to 1 kcal min(-1) and, particularly, 3 kcal min(-1) were greater (P<0.001) in the obese. Stimulation of GLP-1 and GIP were greater (P<0.001) in response to 3 kcal min(-1), compared with 1 kcal min(-1) and saline, without any difference between the groups. In the obese, glycaemic, insulinaemic and GIP, but not GLP-1, responses to oral and intraduodenal glucose were related (P<0.05). CONCLUSIONS: The rate of duodenal glucose delivery is a major determinant of glycaemia, insulinaemia and incretin hormone release in obese subjects. Obesity is not apparently associated with impaired GLP-1 secretion.International Journal of Obesity advance online publication, 6 December 2016; doi:10.1038/ijo.2016.202.