Daily insulin dose unlikely contributor to CV mortality in ACCORD
Higher daily insulin dose does not appear to be correlated with an increase in cardiovascular mortality found in patients with type 2 diabetes undergoing intensive treatment in the ACCORD trial, according to a recent subanalysis.
In the study, researchers evaluated data from 10,163 participants in ACCORD, a randomized clinical trial in which type 2 diabetes patients at high CV risk were allocated to standard glycemic therapy or intensive treatment.
For the current analysis, researchers assessed participants’ insulin exposure data, calculating insulin dose from randomization until CV death or the end of follow-up, with a mean follow-up of 5 years. Researchers used Cox proportional hazards models to investigate the relationships between CV mortality and total, basal and prandial insulin doses over time. They adjusted for baseline and on-treatment covariates, including randomization allocation.
A total of 328 CV deaths occurred during ACCORD. Univariate analysis demonstrated an association between the following baseline characteristics and increased risk for CV death: older age; male sex; longer diabetes duration; previous history of CVD, myocardial infarction, congestive heart failure and diabetes-related complications; use of insulin prior to randomization; and higher HbA1c, serum creatinine and urine albumin-to-creatinine ratio.
Compared with those assigned standard therapy (62%), more of the participants assigned to intensive treatment (79%) used insulin at some point in the follow-up period, and the intensive-treatment group had a higher mean total daily insulin dose compared with the standard-therapy group (0.41 units per kg of body weight vs. 0.30 units per kg of body weight; P < .001).
Prior to adjustment for covariates, there was an association between 1 unit/kg increase in average daily insulin dose and significant elevations in CV mortality risk for all three insulin characterizations (total insulin, HR: 1.83; 95% CI, 1.45-2.31; basal insulin, HR: 2.29; 95% CI, 1.45-2.31; bolus insulin, HR: 3.36; 95% CI, 2.00-5.66). After adjustment for baseline factors, HRs did not retain statistical significance for total, basal or prandial insulin doses.
“These results fail to support the hypothesis that exposure to injected insulin is an independent risk factor for CV mortality in this population,” the researchers wrote. “However, these exploratory analyses of ACCORD do not fully lay to rest the possibility of adverse effects of insulin in particularly vulnerable individuals.” – by Jennifer Byrne
Disclosure: The study was supported by contracts from the National Heart, Lung, and Blood Institute. Other components of the National Institutes of Health and the Centers for Disease Control and Prevention contributed funding. Siraj reports serving as a consultant for Corcept Therapeutics. Please see the complete study for other researchers’ financial disclosures.