Mechanisms of diabetic complications

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Authors: Forbes,J. M.;Cooper,M. E.

Publication: Physiological Reviews

Year: 2013

Volume: 93

Issue: 1

Start Page: 137


It is increasingly apparent that not only is a cure for the current worldwide diabetes epidemic required, but also for its major complications, affecting both small and large blood vessels. These complications occur in the majority of individuals with both type 1 and type 2 diabetes. Among the most prevalent microvascular complications are kidney disease, blindness, and amputations, with current therapies only slowing disease progression. Impaired kidney function, exhibited as a reduced glomerular filtration rate, is also a major risk factor for macrovascular complications, such as heart attacks and strokes. There have been a large number of new therapies tested in clinical trials for diabetic complications, with, in general, rather disappointing results. Indeed, it remains to be fully defined as to which pathways in diabetic complications are essentially protective rather than pathological, in terms of their effects on the underlying disease process. Furthermore, seemingly independent pathways are also showing significant interactions with each other to exacerbate pathology. Interestingly, some of these pathways may not only play key roles in complications but also in the development of diabetes per se. This review aims to comprehensively discuss the well validated, as well as putative mechanisms involved in the development of diabetic complications. In addition, new fields of research, which warrant targets of the future, will be highlighted. © 2013 the American Physiological Society.

  • Listing ID: 4596
  • Author/s: Forbes,J. M.;Cooper,M. E.
  • Publication: Physiological Reviews
  • Year: 2013
  • Volume: 93
  • Issue: 1
  • Start Page: 137
  • Article Keywords: 2,4 thiazolidinedione derivative;acetylsalicylic acid;angiotensin II;angiotensin receptor antagonist;antilipemic agent;antithrombocytic agent;apolipoprotein E;C peptide;dipeptidyl carboxypeptidase inhibitor;erythropoietin;fibric acid derivative;glucagon like peptide 1 derivative;glucose;hemoglobin A1c;high density lipoprotein;HLA DQB1 antigen;HLA DRB1 antigen;hydroxymethylglutaryl coenzyme A reductase inhibitor;insulin;lipid;low density lipoprotein;low density lipoprotein receptor;metformin;nitric oxide;streptozocin;sulfonylurea derivative;triamcinolone;unindexed drug;vasculotropin inhibitor;vitamin D;adipose tissue;amputation;atherosclerosis;blindness;blood glucose monitoring;cardiovascular disease;cerebrovascular accident;clinical research;cohort analysis;coronary artery disease;dementia;depression;diabetes mellitus;diabetic ketoacidosis;diabetic nephropathy;diabetic neuropathy;diabetic patient;diabetic retinopathy;diastolic heart failure;dyslipidemia;echocardiography;environmental factor;epidemiological data;glomerulus filtration rate;glucose blood level;glucose metabolism;glucose transport;glycemic control;heart failure;heart infarction;hemoglobin blood level;human;hyperalgesia;hyperglycemia;hypertension;hypoglycemia;incidence;insulin dependent diabetes mellitus;insulin release;insulin resistance;insulin sensitivity;insulin treatment;laser coagulation;lipid blood level;non insulin dependent diabetes mellitus;nonhuman;obesity;pancreas islet beta cell;pathophysiology;prevalence;priority journal;prognosis;proteinuria;quality of life;renin angiotensin aldosterone system;review;risk factor;risk reduction;sexual dysfunction;streptozotocin-induced diabetes mellitus;aspirin