Endocrine Abstracts

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 1–16%), 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 2288–98.

2. Gerstein HC. Nat Rev Endocrinol 2009 5 270–275.

3. BARI 2D Study Group. N Engl J Med 2009 360 2503–15.

4. Origin Trial Investigators. Am Heart J 2008 155 26–32.