Table of Contents
Advances in Endocrinology
Volume 2014 (2014), Article ID 503846, 11 pages
http://dx.doi.org/10.1155/2014/503846
Review Article

Endogenous Glucagon-Like Peptide-1 as a Potential Mediator of the Resolution of Diabetic Kidney Disease following Roux en Y Gastric Bypass: Evidence and Perspectives

1Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland
2Gastrosurgical Laboratory, University of Gothenburg, Sweden
3Investigative Science, Imperial College London, UK

Received 27 April 2014; Revised 1 August 2014; Accepted 25 August 2014; Published 18 September 2014

Academic Editor: James M. Lenhard

Copyright © 2014 Neil G. Docherty and Carel W. Le Roux. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetic kidney disease in patients with type 2 diabetes strongly correlates with the incidence of major cardiovascular events and all-cause mortality. Pharmacological and lifestyle based management focusing on glycaemic, lipid, and blood pressure control is the mainstay of treatment but efficacy remains limited. Roux en Y gastric bypass is an efficacious intervention in diabetes. Emerging evidence also supports a role for bypass as an intervention for early diabetic kidney disease. This paper firstly presents level 1 evidence of the effects of bypass on hyperglycaemia and hypertension and then summarises emerging data on its effects on diabetic kidney disease. Glucagon-like peptide-1 is implicated as a central mediator of diabetes resolution following bypass through the incretin effect. It has been ascribed vasodilatory, pronatriuretic, and antioxidant properties and its exogenous administration or optimisation of its endogenous levels via dipeptidyl peptidase IV inhibition results in antioxidant and antiproteinuric effects in preclinical models of DKD. Some evidence is emerging of translation of coherent effects in the clinical setting. These findings raise the question of whether pharmacotherapy targeted at optimising circulating hormone levels may be capable of recapitulating some of the effects of bypass surgery on renal injury.