Higher Insulin Doses Do Not Increase Adverse CV Outcomes in T1D

insulin, diabetes
The use higher insulin doses in patients with type 1 diabetes can alter several cardiovascular risk factors without increasing cardiovascular outcomes.

The use of higher insulin doses in patients with type 1 diabetes (T1D) can alter several cardiovascular (CV) risk factors without increasing negative CV outcomes, according to study results published in Diabetes Care. Moreover, maintaining a high dose of insulin may reduce the risk for microvascular and CV complications by approximately 50%.

The investigators studied 1441 patients with T1D from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study who were enrolled and followed for up to 30 years. The investigators randomly assigned patients to receive either conventional or intensive insulin therapy. During follow-up, the researchers recorded participant medical history, performed physical examinations, and took laboratory measurements of fasting lipids and glycated hemoglobin (HbA1c). The relationships between the dose of insulin used and cardiometabolic risk factors were studied using generalized linear mixed models and Cox proportional hazard regression models.

When comparing results between groups, women in the group receiving conventional insulin dosing weighed less than those in the intensive group (mean difference, 2.7 kg; P =.0037). However, individuals in the conventional group also had higher mean pulse rate, higher triglycerides (75.1 ± 27.4 mg/dL vs 73.9 ± 27.0 mg/dL; P =.0002), lower insulin dose requirements (0.65 ± 0.18 units/kg/day vs 0.67 ± 0.17 units/kg/day; P =.0069), and higher HbA1c values (8.4 ± 1.0% vs 7.9 ± 1.0%; P <.0001). In models assessing the relationship between insulin dose and CV risk factors, a high dose of insulin was associated with increased systolic blood pressure, triglycerides, and HbA1c as well as decreased diastolic blood pressure and high- and low-density lipoprotein cholesterol.

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During the study, a total of 366 CV events were recorded in 184 participants. Using a minimally adjusted model, an increase of insulin by 0.1 unit/kg body weight/day was associated with a 6% increased risk for CV disease of any kind (hazard ratio [HR], 1.06; 95% CI, 1.03-1.09). However, after adjustment for risk factors identified as significant predictors of any CV disease and major adverse CV event, the health risk was attenuated and no longer significant (HR, 1.03; 95% CI, 0.99-1.08; Z =1.39 and HR, 0.99; 95% CI, 0.92-1.08; Z =-0.13, respectively).

Based on these findings, despite being associated with several negative effects in CV risk factors, it is recommended to maintain and intensify insulin therapy to reduce the risk for microvascular and CV complications in patients with T1D. “Given the adverse impact of weight gain, adjunctive lifestyle regimens that minimize weight gain would be advisable for patients receiving insulin therapy,” added the researchers.

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Braffett BH, Dagogo-Jack S, Bebu I, et al. Association of insulin dose, cardiometabolic risk factors, and cardiovascular disease in type 1 diabetes during 30 years of follow-up in the DCCT/EDIC study [published online February 6, 2019]. Diabetes Care. doi:10.2337/dc18-1574