title: Insulin treatment and cardiovascular disease; friend or foe? A point of view.
abstract: BACKGROUND
  Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature.
  
  
  RESULTS
  Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk.
  
  
  CONCLUSIONS
  Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Muis
authors.forename: M L
authors.initials: ML
authors.lastname: Bots
authors.forename: D E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: R P
authors.initials: RP
authors.lastname: Stolk
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000139:chemically induced*; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin