title: Vasculotoxic effects of insulin and its role in atherosclerosis: what is the evidence?
abstract: As a result of ambiguous results from several recent trials in diabetes, scrutiny has focused on the potential effects of insulin and its role in atherosclerosis. This article reviews the premise that anti-diabetes therapy (type 2 diabetes) with insulin causes vascular impairment that leads to atherothrombosis and compromises vascular integrity, which may further potentiates cardiovascular morbidity and mortality. Underlying mechanisms are discussed, including metabolic derangements (blood pressure, lipids, body weight, and glucose) and how these factors trigger insulin-like growth factor (IGF) receptors, leading to cancer. Cellular and molecular mechanisms are discussed, as well as whether the negative results seen in recent glucose trials support this premise. As with most drug therapy, aggressive therapies designed to reach glucose control targets trigger multiple and inter-related mechanisms that, in many cases, go far beyond the pre-determined physiologic targets. From a clinical perspective, physicians should always stress lifestyle modifications, including physical exercise and diet, to their patients who show the first signs of metabolic impairment. Yet even within this context, diet and exercise should be the cornerstone of good therapy when pharmacotherapy is necessary. Given the amount of evidence seen to date with existing agents and the amount of information we do not yet know, patient-centered approaches to modifying behavior before intensive drug therapy are needed should be stressed.
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. shailesh0123@gmail.com
authors.forename: Shailesh
authors.initials: S
authors.lastname: Nandish
authors.forename: Oscar
authors.initials: O
authors.lastname: Bailon
authors.forename: Jamison
authors.initials: J
authors.lastname: Wyatt
authors.forename: John
authors.initials: J
authors.lastname: Smith
authors.forename: Adrienne
authors.initials: A
authors.lastname: Stevens
authors.forename: Mike
authors.initials: M
authors.lastname: Lujan
authors.forename: Robert
authors.initials: R
authors.lastname: Chilton
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D003925:Diabetic Angiopathies / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin