HYPERGLYCEMIA INHIBITS MECHANORECEPTOR-MEDIATED GASTROCOLONIC RESPONSES AND COLONIC PERISTALTIC REFLEXES IN HEALTHY HUMANS

Background/Aims: The effects of hyperglycemia on colonic motor function are unknown. Therefore, colonic neuromuscular function was tested in normal volunteers as a model for constipation in diabetes. Methods: Extended (gastrocolonic response) and local (peristaltic reflex) neural responses and colonic muscle contractility were tested under control, hyperglycemic clamp, and euglycemic, hyperinsulinemic cramp conditions with placement of barostat-regulated balloons in the descending colon to measure changes in tone as differences in balloon volume. Results: Hyperglycemic clamping to 274 +/- 3 mg/dL blunted increases in colon tone evoked by gastric distention (gastrocolonic response) (100-300 mL) but did not affect gastric tone. Three descending colonic balloons in series assessed the peristaltic reflex. Inflation of the middle stimulus balloon increased proximal tone, an increase that was blunted by hyperglycemia, but produced distal relaxation followed by increases in tone that were unaffected by hyperglycemia. Euglycemic, hyperinsulinemic clamping had no effect on the gastrocolonic response or peristaltic reflex. Tonic increases evoked by bethanechol (5 mg administered subcutaneously) were unaffected by hyperglycemic clamping. Conclusions: Hyperglycemia blunts mechanoreceptor-mediated gastrocolonic responses and ascending contractions but not descending components of the peristaltic reflex in humans, effects not caused by hyperinsulinemia or direct muscle actions. These inhibitory effects on long and short neural reflexes that modulate colonic motility may contribute to constipation in diabetes.