Roux en Y gastric bypass hypoglycemia resolves with gastric feeding or reversal: Confirming a non-pancreatic etiology

Abstract

Objective: Postprandial hypoglycemia is an infrequent but disabling complication of Roux-en-Y gastric bypass (RYGB) surgery. Controversy still exists as to whether the postprandial hyperinsulinemia observed is due to inherent changes in pancreatic β-cell mass or function or to reversible alterations caused by RYGB anatomy. We aimed to determine if gastric feeding or reversal of RYGB would normalize postprandial glucose and hormone excursions in patients with symptomatic hypoglycemia.

Methods: We completed a prospective study of six patients with severe symptomatic RYGB hypoglycemia who underwent RYGB reversal. An additional subject without hypoglycemia who underwent RYGB reversal was also studied prospectively. Mixed meal tolerance testing (MTT) was done orally (RYGB anatomy), via gastrostomy tube in the excluded stomach in the setting of RYGB, and several months after RYGB reversal.

Results: All subjects reported symptomatic improvement of hypoglycemia after reversal of RYGB. Weight gain after reversal was moderate and variable. Postprandial glucose, insulin, and GLP-1 excursions were significantly diminished with gastric feeding and after reversal. Insulin secretion changed proportional to glucose levels and insulin clearance increased after reversal. Glucagon/insulin ratios were similar throughout study. We further compared the impact of modified sleeve gastrectomy reversal surgery to those with restoration of complete stomach and found no significant differences in weight regain or in postprandial glucose or hormone levels.

Conclusions: Reversal of RYGB is an effective treatment option for severe postprandial hypoglycemia. The pathophysiology of this disorder is primarily due to RYGB anatomy resulting in altered glucose, gut, and pancreatic hormone levels and decreased insulin clearance, rather than inherent β-cell hyperplasia or hyperfunction.

Keywords: Bariatric surgery; Gastric bypass reversal; Glucagon-like peptide 1; Hypoglycemia; Insulin; Roux en Y gastric bypass.

Graphical abstract

Figure 1

Glucose (A) and Insulin (B) responses during 75 g oral glucose tolerance testing (GTT) via the RYGB anatomy in 6 symptomatic (solid line and closed circle) and 1 asymptomatic (dashed line and open circle) subject. Error bars represent standard error of the mean.

Figure 2

Glucose (A) and Insulin (B) responses to mixed meal tolerance testing (MMT) orally via the RYGB anatomy (black solid line and closed circle), via G-tube (black dashed line and triangle) and orally after reversal (gray solid line and open circle), *P < .05, **P < .01, ***P < .0001. Error bars represent standard error of the mean.

Figure 3

Insulin and glucagon dynamics during MTT. Insulin:glucose ratio (A), pre-hepatic insulin secretion rates (ISR) (B), time to peak of ISR (C), insulin clearance (D), glucagon (E) and insulin:glucagon ratio (F) during mixed meal testing. Oral via the RYGB anatomy (black solid line and closed circle, black bar), via G-tube (black dashed line and triangle, white bar) and orally after reversal (gray solid line and open circle, gray bar), ns not significant, *P < .05. Error bars represent standard error of the mean.

Figure 4

Gut hormone profiles during MTT. Active glucagon-like peptide 1 (GLP-1) (A), total glucose-dependent insulinotropic peptide (GIP) (B), total peptide YY (PYY) (C), and pancreatic polypeptide (PP) (D) responses during MTT. Orally via the RYGB anatomy (black solid line and closed circle), via G-tube (black dashed line and closed triangle) and orally after reversal (gray solid line and open circle), ns not significant, *P < .05, **P < .01. Error bars represent standard error of the mean.

Figure 5

Correlations between glucose (red) or glucagon-like peptide 1 (GLP-1) (blue) with insulin secretion rate (ISR) over the first 60 min of mixed meal tolerance testing (MTT) orally via the RYGB anatomy (RYGB), via G-tube and orally after reversal (Reversal). Pearson correlation r values and p values are shown on each graph in the corresponding color.

Figure 6

Glucose (A), active glucagon-like peptide 1 (GLP-1) (B), insulin (C), total GIP (D), total peptide YY (PYY) (E), and pancreatic polypeptide (PP) (F) responses in the single asymptomatic patient during mixed meal testing orally via the RYGB anatomy (black solid line and closed circle), via G-tube (black dashed line and closed triangle) and orally after reversal (gray solid line and open circle).

Figure 7

Comparison of sleeve gastrectomy to normal anatomy. Glucose (A), glucagon-like peptide 1 (GLP-1) (B), insulin (C), peptide YY (PYY) (D), glucagon (E), insulin clearance (F), time to peak insulin secretion (G) and prehepatic insulin secretion (H) during mixed meal testing after reversal to sleeve gastrectomy (black line and closed circles) and normal anatomy (gray line and open circles). Error bars represent standard error of the mean.