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Cardiovascular Mortality Not Associated with Insulin Dosage

Patient history of CVD, higher A1C factored into risk.

The study Action to Control Cardiovascular Risk in Diabetes (ACCORD), conducted in 2008, suggested that intensive treatment of patients with T2DM and high cardiovascular risk was linked to increased mortality. However, no further studies were performed to determine reasons regarding this finding. Therefore, researchers at the Lewis Katz School of Medicine at Temple University in Philadelphia conducted a post-hoc analysis to further investigate this issue.

Researchers analyzed data from the large-scale ACCORD study involving 10,000 subjects. An analysis was performed to examine whether insulin dosage was a responsible factor for increased CV mortality. Initially, researchers believed that insulin was the offending agent.

Analysis of the unadjusted results of the study suggested that an increase in insulin dose by 1 unit/kg of body weight increased the risk of CV death by 83% to 236% (HR 1.83; 95% CI, 1.45-2.31; P<0.001). Furthermore, insulin-treated patients had greater CV risk at baseline with higher mean HbA1c, and majority of subjects had history of CV disease, congestive heart failure, and peripheral neuropathy. However, once the data was adjusted for potential factors and medical conditions, researchers found no observable association between insulin dosage and death from CV risk (HR 1.21; 95% CI, 0.92-1.60; P=0.173).

Authors believe that insulin-treated patients were at greater CV risk because people on insulin tend to be sicker, and they tend to have a higher risk of heart disease. The findings of this study that insulin dose is not an independent factor is reassuring for clinicians; however, since there are limitations to a post-hoc analysis study, further prospective clinical trials are warranted for a definitive answer.

Practice Pearls:

  • Taking higher doses of insulin is not associated with a higher risk of cardiovascular death.
  • Insulin dosage was not an independent factor for the risk CV death, as four key variables had the greatest effect on reducing the hazard ratio; HbA1c, history of CHF, peripheral neuropathy, and history of CVD.
  • Further studies are warranted to validate the findings of this post-hoc analysis.

Siraj, Elias S., et al. “Insulin Dose and Cardiovascular Mortality in the ACCORD Trial.” Diabetes Care, (October 13, 2015): dc15-0598.