Alterations in small intestinal physiology are proposed to play a causative role in the beneficial impact of Roux-en-Y gastric bypass on type 2 diabetes mellitus. The present article describes the key proposed mechanisms implicated with an emphasis on some of the newer findings in the field.
Augmented incretin and diminished anti-incretin effects postsurgery are explored and a model proposed that reconciles the hindgut and foregut hypotheses of improved glycaemic control as being complementary rather than mutually exclusive. Synthesis of recent findings on postbypass changes in intestinal glucose handling then follows. Finally an updated view of the role of distal bile diversion and changes in the microbiota on enteroendocrine signalling is presented.
A series of nonmutually exclusive changes in small intestinal physiology likely make a significant contribution to improved glycaemic control postgastric bypass. Longitudinal data indicate that these effects do not translate into a long-term cure. A number of surgery-induced changes, however, are amenable to device-based and pharmacology-based mimicry, and this is an area for prioritization of future research focus.
aMetabolic Medicine Laboratory, Diabetes Complications Research Centre, Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland
bGastrosurgical Laboratory, University of Gothenburg, Gothenburg, Sweden
cInvestigative Science, Imperial College London, London, UK
Correspondence to Neil G. Docherty, Metabolic Medicine Laboratory, MetabolicMed Diabetes Complications Research Centre, Conway Institute School of Medicine University College Dublin, Dublin 4, Ireland. Tel: +0353 1 716 6877; e-mail: firstname.lastname@example.org