High Iron Feeding Modulates Glucose Metabolism in Duodenal-Jejunal Bypass Surgery but Not in Vertical Sleeve Gastrectomy in Mice

Abstract

High dietary iron intake is associated with impaired islet-cell function and increased risk of type 2 diabetes mellitus (T2DM) while iron chelation leads to improved glucose tolerance. Bariatric surgery has multiple metabolic benefits but iron-deficiency anemia is a common occurrence following surgery, presumably because of preferential iron absorption in the upper intestine. We hypothesized that a duodenal-jejunal bypass (DJB) procedure that bypasses the proximal small bowel and vertical sleeve gastrectomy (VSG) that eliminate 80% of the stomach without altering the intestine would have differential effects on iron metabolism and glucose homeostasis. C57BL6J mice were fed either high- (2000 ppm) or low-iron diet (4 ppm) for 16 weeks before DJB (n=6 per diet group), VSG (n=6/7 per diet group) or sham surgery (n = 11 per diet group). Intraperitoneal glucose, and insulin, tolerance tests were performed at Day 0, 10 and 20 after surgery. Compared to animals given a low-iron diet, 4 months of high-iron diet significantly impaired glucose tolerance (p<0.05) and decreased insulin and glucagon secretion, but had no effect on body weight or insulin sensitivity prior to surgery. Compared to sham controls neither VSG nor DJB affected glucose or insulin tolerance at day 10 after surgery. However, 20 days after surgery, VSG significantly improved glucose tolerance in both the high- and low-iron diet groups, with increased secretion of islet hormones in in vivo test. In contrast, DJB surgery only improved glucose tolerance in the low-iron-fed mice, this response was not present in the high-iron-fed animals. In sum, these findings indicate that high-iron intake modulates the benefits of DJB, but not VSG on glucose metabolism. This is consistent with an important contribution of GI tract handling of dietary iron to the metabolic effect of surgery to improve glucose tolerance. Disclosure J. Niu: None. J.D. Douros: None. J. Campbell: None. M. Capozzi: None. S.M. Gray: None. F. Lorenzo: None. D. D'Alessio: Consultant; Self; Intarcia Therapeutics, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S. D. McClain: None. J. Tong: None.