Postprandial hypoglycaemia after gastric bypass in type 2 diabetes: pathophysiological mechanisms and clinical implications – published online 29/11/2024

Domenico Tricò, Luca Sacchetta, Eleni Rebelos, Noemi Cimbalo, Martina Chiriacò, Diego Moriconi, Lorenzo Nesti, Giulia Nesti, Silvia Frascerra, Maria T. Scozzaro, Giuseppe Daniele, Simona Baldi, Andrea Mari, Monica Nannipieri, Andrea Natali

Postprandial hypoglycaemia (PPHG) is a frequent complication of Roux-en-Y gastric bypass and is associated with negative health consequences. In this issue, Tricò et al (https://doi.org/10.1007/s00125-024-06312-3) report findings from a case–control clinical study, which identified excessive glucose clearance as the main determinant of post-bypass hypoglycaemia in people with type 2 diabetes. This was driven by high insulin sensitivity and early glucose-stimulated hyperinsulinaemia, the latter being dependent on low insulin clearance and enhanced beta cell function. PPHG was also characterised by defective counterregulatory hormone responses that hinder the compensatory increase in endogenous glucose production, and prevent the appearance of symptoms and signs of sympathetic cardiovascular activation and neuroglycopenia. The latter makes the individual unaware of hypoglycaemia and vulnerable to recurrent hypoglycaemic episodes. Consistently, the authors found that OGTT-induced hypoglycaemia was associated with more hypoglycaemic events, as assessed using continuous glucose monitoring, and with potentially (mal)adaptive dietary habits, which may repeatedly trigger PPHG. In summary, Tricò et al state that by implementing an integrated physiology approach, this study exposes the complex pathogenetic mechanisms underlying post-bypass PPHG, as well as the clinical relevance of this pathological condition in individuals with type 2 diabetes, and reveals potential therapeutic targets.