Diabetology International

, Volume 5, Issue 1, pp 1–20

Identifying and interpreting novel targets that address more than one diabetic complication: a strategy for optimal end organ protection in diabetes

Review Article

DOI: 10.1007/s13340-013-0148-5

Cite this article as:
Hagiwara, S., Jha, J.C. & Cooper, M.E. Diabetol Int (2014) 5: 1. doi:10.1007/s13340-013-0148-5


It is increasingly appreciated that subjects with diabetes who develop one vascular complication are more likely to also suffer from another complication. For example, those with diabetic nephropathy will often have concomitant retinopathy and a much higher risk of macrovascular disease leading to increased cardiovascular morbidity and mortality. It is considered that haemodynamic and metabolic factors interact to activate signaling pathways that then result in upregulation of a range of well-characterized cytokines and growth factors leading to various pathological processes including angiogenesis, inflammation and extracellular matrix accumulation. As the various mediators of end-organ injury in diabetes are identified, new targets for intervention are being explored. Some of these targets such as enzymes implicated in oxidative stress such as nicotinamide adenine dinucleotide phosphate oxidase (Nox) 1 and Nox 4, various growth factors such as transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) as well as their cognate receptors are increasingly being investigated first in preclinical studies and now in early phase clinical trials.


Diabetic complications Diabetic nephropathy Diabetic retinopathy Diabetic neuropathy AGEs Oxidative stress Growth factors PKC ROCK Renin-angiotensin-aldosterone system 

Copyright information

© The Japan Diabetes Society 2013

Authors and Affiliations

  1. 1.JDRF Danielle Alberti Memorial Centre for Diabetes Complications, Diabetes DivisionBaker IDI Heart and Diabetes InstituteMelbourneAustralia