New Hope For People With Dysglycemia and Cardiovascular Disease Manifestations
Reduction of Acute Coronary Events With Pioglitazone
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Article, see p 1882
The 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 and11.0 mmol/L), compromises cardiovascular prognosis.2,3 The 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.4 This 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.5 It 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.6
Based 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.7 Disappointingly 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 …