New Hope For People With Dysglycemia and Cardiovascular Disease Manifestations
Authors: Lars Rydén, Linda Mellbin
Journal: Circulation (2017)

T he enhanced risk for cardiovascular disease induced by dysglycemia starts already well below the diagnostic threshold that, according to the World Health Organization, defines type 2 diabetes mellitus, ie, ≥126 mmol/dL (7.0 mmol/L) in the fasting state, or ≥200 mg/dL (11.1 mmol/L) after a 75 g oral glucose tolerance test. 1 Impaired glucose tolerance as defined by the World Health Organization, ie, a postload glucose between 140 and 199 mg/dL (7.8 and11.0mmol/L), compromises cardiovascular prognosis. 2,3The dysglycemic condition may remain unknown for many years, silently promoting atherosclerosis that precedes the acute cardiovascular event, which not infrequently is the first manifestation of the glucose perturbation. 4This time course is substantiated by the observation that lifestyle interventions normalizing or counteracting the progression of impaired glucose tolerance to type 2 diabetes mellitus reduce cardiovascular morbidity and mortality. 5t is also underscored by the fact that a majority of patients with coronary, cerebrovascular, and peripheral artery disease without a history of glucose perturbations in fact are dysglycemic if appropriately screened. 6ased on the assumption that if hyperglycemia causes cardiovascular complications, glucose lowering should be counteractive, many trials with glucose-lowering agents have been and are being conducted in patients with established type 2 diabetes mellitus over the years.In the beginning, it seemed to be a reasonable hypothesis.Early trials during the 1990s, eg, the UKPDS trial (United Kingdom Prospective Diabetes Study) and the DIGAMI 1 study (the first Diabetes Insulin Glucose in Myocardial Infarction) succeeded in reducing cardiovascular mortality and morbidity through intensified glucose control. 7Disappointingly enough, this was not verified by subsequent trials, eg, the ADVANCE study (Action in Diabetes and Vascular Disease), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and VADT (Veterans Administration Diabetes Trial), each of which failed to show that further reduction of hyperglycemia improved cardiovascular prognosis. 8The discrepant outcomes may relate to the fact that dysglycemia was the only risk factor that could be efficiently modified before the invention and widespread clinical use of statins and modern blood pressure-reducing drugs.The benefits of glucose lowering became considerably less apparent in the presence of contemporary lipid and blood pressure control.Thus, beyond lifestyle adjustments, lipid and blood pressure control became the most effective tools for preventing cardiovascular disease in people with type 2 diabetes mellitus.This assumption is not contradicted by the encouraging results of recent clinical trials with the 2 glucagon-like peptide 1 receptor agonists, liraglutide and semaglutide, and the sodium glucose cotransporter 2 inhibitor, empagliflozin.The favorable impact of these compounds on cardiovascular outcomes cannot be explained solely by glucose control, but relate to other, so-called pleiotropic effects still not clearly identified, as outlined in a recent review by Standl et al. 9New Hope For People With Dysglycemia and Cardiovascular Disease Manifestations Reduction of Acute Coronary Events With Pioglitazone