title: Insulin and atherosclerosis: how are they related?
abstract: The relationship between insulin and atherosclerosis is complex. People with type 2 diabetes are affected by three main glycaemic disorders: chronic hyperglycaemia; glycaemic variability; and iatrogenic hypoglycaemia. In addition to this triumvirate, the diabetic condition is characterized by lipid disorders, chronic low-grade inflammation and activation of oxidative stress. All these associated disorders reflect the insulin-resistant nature of type 2 diabetes and contribute to the development and progression of cardiovascular (CV) diseases. By both lowering plasma glucose and improving the lipid profile, insulin exerts beneficial effects on CV outcomes. In addition, insulin has several pleiotropic effects such as anti-inflammatory, antithrombotic and antioxidant properties. Insulin per se exerts an inhibitory effect on the activation of oxidative stress and seems able to counteract the pro-oxidant effects of ambient hyperglycaemia and glycaemic variability. However, insulin actions remain a subject of debate with respect to the risk of adverse CV events, which can increase in individuals exposed to high insulin doses. Evidence from the large-scale, long-term ORIGIN trial suggests that early implementation of insulin supplementation therapy in the course of glycaemic disorders, including type 2 diabetes, has a neutral impact on CV outcomes compared with standard management. Thus, the answer to the question "What impact does insulin have on atherosclerosis?" remains unclear, even though it is logical to deduce that insulin should be initiated as soon as possible and that small doses of insulin early on are better than higher doses later in the disease process.
authors.affiliation: Laboratory of Human Nutrition, University Montpellier I, Institute of Clinical Research, 641, avenue du Doyen-Giraud, 34093 Montpellier cedex 5, France. louis.monnier@inserm.fr
authors.forename: L
authors.initials: L
authors.lastname: Monnier
authors.forename: M
authors.initials: M
authors.lastname: Hanefeld
authors.forename: O
authors.initials: O
authors.lastname: Schnell
authors.forename: C
authors.initials: C
authors.lastname: Colette
authors.forename: D
authors.initials: D
authors.lastname: Owens
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D018797:Cell Cycle Proteins; D002784:Cholesterol / Q000097:blood; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood* / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D016328:NF-kappa B / Q000097:blood; D009687:Nuclear Proteins / Q000097:blood; D018384:Oxidative Stress; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002784:Cholesterol; D004268:DNA-Binding Proteins; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D020782:Matrix Metalloproteinases; D016328:NF-kappa B; D009687:Nuclear Proteins; D014280:Triglycerides; C535048:PAGR1 protein, human; C517652:hemoglobin A1c protein, human