Editorial

According to the International Diabetes Federation World Atlas the frequency of diabetes is increasing at an alarming rate, with 246 million people worldwide affected, and a projected figure of 380 million by 2025 if the current situation is not rectified. More than 90% of this epidemic is of type 2 diabetes, the causes relating in large part to ageing of the population, diet and obesity, and a sedentary lifestyle. This gives rise to enormous direct and indirect costs for healthcare systems, people with diabetes and their families, and society in general. At no time there has been a greater impetus for research in to the causes and treatment of diabetes and its complications. This issue contains several insightful reviews on aspects of diabetes and metabolic syndrome, and potential therapeutic intervention. Jay and Ren, and Stojanovska et al. examined the role of peroxisome proliferator-activated receptors (PPARs) in insulin resistance and type 2 diabetes, and review results of trials with PPAR agonists on diabetes management. Evidence for reducing the cardiovascular risks of diabetes is considered, particularly in terms of blood pressure control, effects on smooth muscle and endothelial function, and the anti-atherogenic effects of thiazolidinediones. Saraceni and Broderick review the potential benefits of exercise in diabetes, with a particular focus on data from animal models. They consider the actions of exercise to increase myocardial and skeletal muscle glucose homeostasis, increase insulin sensitivity, and improve autonomic nervous system control and vascular endothelium function. The glucagon-like peptide (GLP) signalling system is of current interest in treatment of type 2 diabetes. The review by Salvatore et al. give an overview of the incretin system and examines the therapeutic potential of GLP-1 and small molecule inhibitors of the enzymes that degrade this gut peptide. Fukui et al. consider effects of lowered endogenous androgen levels in men with type 2 diabetes on insulin resistance and atherosclerosis, and discuss the potential clinical implications and side effect profile of androgen replacement therapy in these patients. The renal complications of diabetes are addressed in two specialist reviews. Nordquist and Palm review the important effects of diabetes on renal medulla microcirculation and metabolism. The research that the normally low medullary oxygen tensions are further reduced in diabetes is likely to have great significance for total kidney function. The potential roles of glucose-driven mechanisms such as oxidative stress, polyol pathway activity, protein kinase C and advanced glycation are discussed. It is well established that the angiotensin converting enzyme (ACE) inhibition is renoprotective in diabetes. The review by Lely et al. examines evidence for genetic and environmental factors that increase ACE levels, their role in the pathogenesis of renal damage, and potential relevance to treatment of nephropathy. Capillary occlusion is an early sign of problems in non-proliferative diabetic retinopathy. Chibber and co workers review the evidence for leukocyte entrapment as a cause of capillary non-perfusion in man and experimental models. This is an area of great current interest. The review examines potential endothelial and leukocyte mechanisms, and the therapeutic potential of drug therapy to inhibit leukostasis. A particular novel target identified by these workers is the leukocyte adhesion molecule core 2 GlcNAc-T. These states of the art reviews in this issue of CDR were a pleasure to work with, and I hope readers will find them stimulating and highly informative.