Diabetes and Cardiovascular Disease: Is intensive glucose control beneficial or deadly? Lessons from ACCORD, ADVANCE, VADT, UKPDS, PROactive, and NICE-SUGAR.

Type 2 diabetes is a rather complex metabolic disorder still associated with a 2-fold increased cardiovascular (CV) mortality despite a dramatic improvement in CV risk reduction by multifactorial intervention strategies. Intensive glucose control can also reduce CV morbidity, but this effect seems to be limited to younger patients with shorter duration of disease and no CV disease. Intensive glucose control--in particular when complex insulin strategies are used--is associated with a 5-fold increased risk for severe hypoglycemia, which could induce harm in some patients. In contrast to blood pressure and lipid-lowering interventions a reduction of CV mortality cannot be seen before 10-20 years after the start of the glucose-lowering intervention (metabolic memory, legacy effect). Future ongoing outcome studies in more than 50,000 patients will clarify whether new antidiabetic drugs--not inducing hypoglycemia or weight gain--will further improve the prognosis of T2DM patients.