In the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, people with type 2 diabetes who received intensive blood glucose-lowering treatment were found to have a higher risk of all-cause and cardiovascular (CV) mortality than those who received standard treatment. Post hoc analyses to date have failed to implicate rapid glucose reductions, hypoglycaemia or specific antidiabetes drugs in this excess risk. Given that some studies have shown an association between hyperinsulinaemia or insulin therapy and CV mortality, and given that insulin’s action at the cellular level has been proposed to cause vascular changes that could increase the risk of CV events, it is possible that higher doses of insulin in the intensive treatment arms could account for the higher CV risk in ACCORD.
However, a new post hoc evaluation by the ACCORD investigators suggests that this was not the case. The authors explored the associations between CV mortality and total, basal, and prandial insulin doses over time, adjusting for both baseline and on-treatment covariates, in 10 163 ACCORD participants. While higher insulin dose was associated with an increased risk of CV death, after adjustment for baseline covariates there was no significant difference. Further adjustment for severe hypoglycaemia, weight change and achieved HbA1c, which would be expected as a result of insulin treatment, did not alter the results.
The authors conclude that insulin exposure was not independently associated with CV risk in ACCORD. The explanation for the unexpected mortality risk in the study remains unknown.
The study can be read in full here.
