Hyperglycemia alters perception of rectal distention and blunts rectoanal inhibitory reflexes in normal controls: Implications for diabetic constipation

Abstract

HYPERGLYCEMIA ALTERS PERCEFl’ION OF RECTAL DISTENTION AND BLUNTS RECI-OANAL INHIBITORY REFLEXES IN NORMAL CONTROLS: IMPLICATIONS FOR DIABETIC CONSTIPATION. qYD Cheq M Kim, W Hasler, C &yang. Dept of Int Med. Univ of Michigan, Ann Arbor, MI. The pathogenesis of constipation in diabetes mellitus is unclear. We have shown that hyperglycemia blunts gastrocolonic reflex and colonic peristaltic reflex contractions in normal volunteers, documenting inhibitory effects of elevated plasma glucose on efferent neural function. In this study, we tested if hyperglycemia alters rectal afferent neural function and local rectoanal reflex activity in 7 healthy volunteers using anotectal manometry, and if any inhibitory effects are due to hyperglycemia itself or to secondary hypcrinsulinemia. Subjects rated perception of graded rectal balloon inflation under control, hyperglycemic clamp, and euglycemic, hypcrinsulinemic clamp conditions. Hyperglycemic clamping to 255f 10 mg/dl increased volumes of inflation needed to elicit different levels of perception from basal values of 35*7 ml (threshold), 71fl3 ml (mild discomfort), 129+28 ml (moderate discomfort), 221f48 ml (severe discomfort), and 287&54 ml (maximal toler-ated pain) to 66&7 ml, 122*28 ml, 19lf45 ml, 252f57 ml, and 317f65 ml respectively. Differences were significant for all levels of perception except maximal tolerated pain (PcO.05). Rectal volume thresholds for detection of the rectoanal inhibitory reflex increased from lOzl2 ml under basal conditions to 28f6 ml with hyperglycemia (P<O.O38). In contrast, euglycemic (65+4 mg/dl), hypetinsulinemic clamping to produce insulin levels (75* 8 uU/ml) similar to those during acute hyperglycemia (77+9 @J/ml) had no effect on perception of rectal distention or rectoanal inhibitory reflexes, confirming that hyperglycemia itself, not hyperinsulinemia, is responsible for the observed inhibitory effects. Rectal pressure-volume relationships and maximal anal squeeze pressures were not affected by hyperglycemic or hyperinsulinemic clamping. m: Acute hyperglycemia, but not secondary hyperinsulinemia, blunts perception of rectal distention without increasing rectal compliance, indicating inhibitory effects on afferent neural pathways projecting from the rectum. Rectoanal inhibitory reflex activity is also altered, suggesting effects on local neural arcs involved in defecation, These findings provide further potential roles for hyperglycemia Intht:nathoPeneslsstioation in diabetes.