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.
Subject(s)
Atherosclerosis/chemically induced , Cardiovascular Diseases/chemically induced , Diabetes Mellitus, Type 2/drug therapy , Diabetic Angiopathies/chemically induced , Insulin/adverse effects , Aged , Atherosclerosis/epidemiology , Atherosclerosis/physiopathology , Blood Glucose/analysis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/physiopathology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/physiopathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/etiology , Neoplasms/physiopathology , Prevalence , Randomized Controlled Trials as Topic , Risk AssessmentABSTRACT
Cardiovascular disease is a leading cause of death in the United States and across the world, and better therapies are constantly being sought to improve patient outcomes. Recent studies have brought our attention to the mechanisms of glucagon-like peptide 1 (GLP-1). Not only does it demonstrate beneficial effects in regard to cardiovascular risk factors (i.e., diabetes, lipid management, and weight control), but it also has been shown in animal studies to have positive cardiac effects irrespective of its effects on glucose control and weight loss. This review discusses the biology of GLP-1 and its effects on cardiovascular risk factors, and it also elaborates on the positive direct cardiovascular outcomes of GLP-1 in animal studies.
