Moderation of the effect of glycemia on the risk of cardiovascular disease in type 1 diabetes: The DCCT/EDIC study.

Objective: We assessed whether and to what extent established cardiovascular disease (CVD) risk factors moderate (enhance/reduce) the effect of hyperglycemia on CVD outcomes in the long-term follow-up of the Diabetes Control and Complications Trial type 1 diabetes (T1D) cohort (N = 1441).

Methods: Moderation of the effect of glycemia on subsequent risk of major adverse cardiovascular events (MACE: fatal or non-fatal myocardial infarction or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure) was assessed separately using interaction terms between HbA1c and other risk factors in Cox proportional hazards models.

Results: Over a median follow-up of 29 years, there were 120 MACE cases and 239 any-CVD cases. Higher pulse, higher triglycerides, use of calcium channel blockers, and presence of neuropathy individually enhanced (p < 0.01) the effect of glycemia on any-CVD. Higher pulse and triglyceride levels, albumin excretion rate, hypertension, and no family history of type 2 diabetes enhanced (p < 0.01) the effect of glycemia on MACE.

Conclusions: Such moderation analyses identify subgroups with increased CVD risk who might especially benefit from earlier and/or more intensive glycemic control. Interventions treating modifiable moderating factors may independently reduce the risk of CVD and also reduce the risk associated with a higher HbA1c.