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Effect of Variations in Small Intestinal Glucose Delivery on Plasma Glucose, Insulin, and Incretin Hormones in Healthy Subjects and Type 2 Diabetes

Department of Medicine (D.G.O., S.D., C.F.-B., K.L.J., J.H.M., J.M.W., M.H.), University of Adelaide, Royal Adelaide Hospital; and Division of Clinical Biochemistry (H.A.M.), Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia, 5000

Address all correspondence and requests for reprints to: Professor Michael Horowitz, University of Adelaide, Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia. E-mail: michael.horowitz{at}adelaide.edu.au.

The determinants of postprandial blood glycemia are controversial. We assessed the effects of variations in the initial rate of small intestinal glucose delivery on blood glucose, plasma insulin, and incretin responses in both health and type 2 diabetes. Eight controls and eight patients with type 2 diabetes managed by diet alone underwent paired studies. On both days subjects received an intraduodenal glucose infusion (t = 0–120 min); on one day the infusion rate was variable, being more rapid initially (3 kcal/min) between t = 0 and 15 min and slower (0.71 kcal/min) subsequently (t = 15–120 min), whereas on the other day, the infusion rate was constant (1 kcal/min) from t = 0 to 120 min (i.e. on both days 120 kcal of glucose were administered). Between t = 0–180 min blood glucose, plasma insulin and plasma glucose-dependent insulin-releasing polypeptide were greater with the variable, compared with the constant, infusion. Between t = 0 and 30 min the magnitude of the rise in plasma glucagon-like peptide-1 was greater with the variable, compared with the constant infusion (P < 0.01, both groups). We conclude that modest variations in the initial rate of duodenal glucose entry may have profound effects on subsequent glycemic, insulin, and incretin responses.

This work was supported by project grants from the Royal Adelaide Hospital and the National Health and Medical Research Council (NH&MRC) of Australia. K.L.J.’s salary is derived from a fellowship jointly awarded by the NH&MRC and Diabetes Australia. C.F.-B.’s salary is provided by a Career Development Award from the NH&MRC.

Abbreviations: GIP, Glucose-dependent insulin-releasing polypeptide; GLP-1, glucagon-like peptide-1; TMPD, transmucosal potential difference.

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