Diabetes is a strong risk factor for cardiovascular (CV) events, and large epidemiologic studies have repeatedly shown that higher fasting or post-load glucose levels predict a higher incidence of CV events regardless of whether or not diabetes is present. In the UKPDS, targeting near-normal fasting glucose levels in newly diagnosed diabetes with a strategy starting with basal insulin or sulfonylurea reduced the 20-year risk of myocardial infarction and mortality by 15% and 13%, respectively. However, this strategy did not maintain stable glucose levels, possibly because it was reactive in nature.
In more recent large clinical trials of different degrees of glucose-lowering in people with advanced type 2 diabetes, stable glucose levels were achieved using a proactive strategy but with more mixed effects on CV outcomes. Indeed, a recent meta-analysis of the major CV outcomes trials in 27 049 people with type 2 diabetes including 5-year data from the UKPDS, the ACCORD trial, VA Diabetes Trial and the ADVANCE trial reported that a strategy of intensive control (which was largely based on insulin therapy) vs conventional glycaemic control reduced the composite CV outcome of myocardial infarction, stroke or cardiovascular death by 9% (95% CI 116%), with most of the effect attributable to a 15% reduction in myocardial infarction and no effect on CV death or stroke1. However, there was evidence of a mixed effect on mortality with higher deaths in the ACCORD trial.
In addition to these trials of glucose-lowering degrees (i.e. more vs less) several other trials of different glucose-lowering strategies have also been reported or are underway2. These include the recently published BARI 2D trial showed that in patients receiving medical therapy for documented coronary artery disease, a strategy of glucose lowering based on insulin-providing therapies had CV effects that were similar to those observed with a strategy based on insulin-sensitizing therapies3. To date no clearly effective strategy has been identified however other trials are underway4.
1. Turnbull FM et al. Diabetologia 2009 52 228898.
2. Gerstein HC. Nat Rev Endocrinol 2009 5 270275.
3. BARI 2D Study Group. N Engl J Med 2009 360 250315.
4. Origin Trial Investigators. Am Heart J 2008 155 2632.