LAUSR

Patients with type 2 diabetes mellitus (T2DM) are at higher risk of developing fatal and non-fatal cardiovascular (CV) complications, but whether this is a direct effect of hyperglycaemia or indirectly related, such that hyperglycaemia is a surrogate marker of underlying poor CV substrate, is less clear.1 Clinical trials investigating intensive glycaemic control targeting lower glycated haemoglobin levels successfully reduced microvascular complications but failed to lower CV events when compared to standard therapy.2–6 The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was halted prematurely due to higher mortality seen with tight glucose control.4 Taken together, these data suggest that targeting hyperglycaemia lowers microvascular complications but may not necessarily improve CV outcomes. According to guidelines, glycaemic goals should be personalized, which reflects the heterogeneous effects of T2DM.7 Individuals with diabetes and co-morbid heart failure (HF) are at particularly high risk for CV events.8 Risk stratification of individuals with diabetes and HF who are at increased risk for CV events is critical for prevention and management of this vulnerable population. In this issue of the Journal, Kristensen and colleagues evaluated whether microvascular complications in patients with diabetes and HF with reduced ejection fraction (HFrEF) were associated with increased risk of adverse clinical outcomes in the Beta-blocker Evaluation of Survival Trial (BEST), a clinical trial of individuals with HFrEF who were randomized to receive either bucindolol or placebo.9 Of the 2707 study participants from BEST, individuals were divided into three groups based on the presence of diabetes and, for individuals with diabetes, the presence of microvascular complications, specifically, neuropathy, retinopathy,