Mechanisms of post-prandial hypoglycaemia after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (LSG)

Background and aims: Symptomatic hypoglycaemia (Hypo) is a well recognised complication of RYGB surgery. Data on the development of postprandial Hypo after LSG are scanty. We investigated the mechanisms of postprandial Hypo in patients undergoing RYGB or LSG. Materials and methods: 32 obese non-diabetic subjects treated with RYGB and 39 with LSG received a 3-h OGTT before and 12-18 months after surgery. Hypo was defined as plasma glucose ≤2.7 mmol/L. Insulin sensitivity was assessed by OGIS index and ß-cell function by modelling analysis of the C-peptide response to glucose load. Results: Postprandial Hypo occurred in 20 of 32 RYGB patients and in 13 of 39 LSG patients. Age did not discriminate Hypo from non-Hypo (NH) subjects. Presurgery BMI was lower in RYGB-Hypo than RYGB-NH (43.8±5.2 vs 49.7±6.1 kg/m2, p=0.004), but not in in LSG-Hypo vs LSG-NH patients. Similarly, baseline insulin sensitivity was higher in RYGB-Hypo than RYGBNH (386±53 vs 325±44 ml.min-1.m-2, p=0.004), but was similar in LSGHypo and LSG-NH subjects. After either operation, insulin sensitivity improved (p<0.0001) to the same extent in Hypo and NH subjects. Pre-surgery fasting glycaemia was lower in both RYGB-Hypo and LSG-Hypo compared to the respective NH group (5.0±0.4 vs 5.7±0.9 mM, p<0.001, and 5±0.3 vs 5.6±0.7 mM, p<0.02 in LSG). Similarly, before surgery mean OGTT glycaemia was lower in Hypo than NH subjects (6.9±0.9 vs 8.4±1.3 mM, p=0.001), as was the plasma glucose nadir (4.7±1.3 vs 6.4±1.6 mM, p=0.005) similarly in the two groups. Pre-surgery fasting plasma insulin and insulin secretion rate were similar at baseline in all four groups, and were similarly reduced after surgery (p<0.0001). In contrast, total insulin secretion was reduced in NH, but not in Hypo after either intervention (79 ± 23 vs 59 ± 27 and 71 ± 28 vs 72 ± 30 nmol.m-2, p<0.01 for the timexgroup interaction). ß-cell glucose sensitivity was negatively correlated with glucose nadir values in both surgeries (p=0.02 in RYGB and p=0.0009 in LSG). Likewise, insulin sensitivity was inversely correlated with the glucose nadir (p<0.0001 in RYGB and p=0.009 in LSG). Conclusion: Baseline lower plasma glucose concentrations during an OGTT are associated with a higher risk of post-surgery reactive hypoglycaemia after both RYGB and LSG. Mechanistically, inherently higher insulin output and better ß-cell glucose sensitivity and peripheral insulin sensitivity are responsible for postprandial Hypo in surgically weight-reduced patients.