"Anti-inflammatory" drugs and their effects on type 2 diabetes.
There is a growing body of evidence for the role of inflammation in type 2 diabetes. In addition to the evidence presented elsewhere, evidence is emerging that many drugs that have apparent "anti-inflammatory" properties may reduce the incidence and/or delay the onset of type 2 diabetes. Statins have been found to lower inflammatory markers, and a post hoc analysis of the West of Scotland Coronary Prevention Study (WOSCOPS) suggested that pravastatin may reduce the risk of developing diabetes, although the Lipid Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) found no statistically significant effect of atorvastatin on risk of developing diabetes. Fibrates have been found to lower some markers of inflammation, and a prospective trial found that bezafibrate reduces risk of developing diabetes. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers appear to reduce some markers of inflammation, and a meta-analysis concluded that ACE inhibitors and angiotensin receptor blockers reduce risk of developing type 2 diabetes. Metformin is known to reduce the risk of developing diabetes, and more recent evidence suggests it also lowers C-reactive protein, in part because of its modest weight-reducing effect. Thiazolidinediones reduce risk of developing diabetes, and consistently lower inflammatory markers independent of adiposity effects. High-dose aspirin inhibits cyclooxygenase and IkappaB kinase-beta and reduces fasting plasma glucose concentration, although there has not, as yet, been a large-scale trial to examine the effect of aspirin on the risk of developing diabetes. We conclude that although many drugs with potential anti-inflammatory properties reduce the risk of developing diabetes, it is difficult to prove that such anti-inflammatory properties contribute to their diabetes prevention since nearly all drugs have other, often more pronounced, actions. Studies with more specific inhibitors of inflammatory pathways (e.g., interleukin- 6 blockers) and mendelian randomization (genetic studies) will help determine whether targeting the inflammation axis is a fertile mechanism to treat or prevent type 2 diabetes.
Deans
Kevin A
KA
University Department of Clinical Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom.
Sattar
Naveed
N
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation
D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D002316:Cardiotonic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D001241:Aspirin