Efficacy of Lisosan G (fermented wheat) on post-prandial hypoglycemia after bariatric surgery

Introduction: post-bariatric hypoglycemia (PBH) is considered a chronic complication after bariatric surgery that increase cardiovascular risk. Changes in gut microbiota and a dysregulated inflammatory response to a glucose load seems to be the conditions favoring the development of PBH. Lisosan G (LG) is a fermented powder obtained from whole grains (Triticum aestivum), rich in polyphenols and flavonoids with antioxidant, anti-inflammatory and prebiotic properties. Aims: The aims of the study were 1) to evaluate the effectiveness of using LG added to the diet in reducing PBH events in patients undergoing RYGB, 2) investigate the mechanism by which LG acts on the gut-pancreas axis. Methods: Twenty patients self-reporting symptoms/signs of PBH, who had undergone gastric bypass between 2015 and 2018, were enrolled. At baseline, patients underwent clinical examination, blood test and 4-hour oral glucose load test (OGTT). After that, the patients were kept on a free diet with 15 days of continuous glucose monitoring (CGM). The CGM was then repeated for another 15 days, adding LG to the same dietary regimen (5 g LG-powder, bid). At the end of the treatment period, patients repeated the 4-hours OGTT and blood test. Plasma insulin and C-peptide were measured by electrochemiluminescence on a Cobas e411 instrument. Plasma total glucose-like peptide-1 (GLP 1) concentrations were measured by ELISA (Millipore). Insulin sensitivity was assessed by the oral glucose insulin sensitivity index (OGIS). PBH was defined as a plasma glucose level of ≤ 60 mg/dl in presence of typical symptoms. Results: a marked reduction in PBH episodes recorded by CGM was observed after LG administration (6.5 [5-11] vs 2.5 [2-3], p= 0.009), as well as a reduction in the overall length of hypoglycemia (410 [129-633] vs 39 [20-89], minutes, p=0.003). During OGTT, a marked increase in the blood glucose nadir (44 ± 11 vs 56 ± 10, mg/dl, p= 0.038) was found after LG treatment. Conversely, no difference were observed in fasting glycemia, in the time-to-nadir, as well as in the blood glucose zenith nor the time-to-zenith. After treatment, the peak of GLP-1 was attenuated and total GLP-1 AUC significantly decrease (7.6 ± 4.1 vs 6.5 ± 3.8, nmol/L*min, p= 0.043), as well as potentiation factor ratio (1.5 ± 0.5 vs 0.8 ± 0.4, p= 0.038) and total insulin AUC (57±12 vs 49±9, nmol/m2 , p= 0.041). Conclusion: LG is effective on reducing frequency, overall duration and severity of PBH episodes. The main mechanism by which LG acts appears to be the attenuation of GLP-1 peak and, consequently, the second phase of insulin secretion in response to the glucose load. Further specific studies are necessary to evaluate the effects of LG on the microbiota and inflammation to better understand the mechanisms of action of this precious supplement.