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

Abstract

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes. RESEARCH DESIGN AND METHODS A total of 1,441 participants were randomly assigned to intensive or conventional diabetes therapy during the DCCT. After an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study, which included annual visits with detailed medical history, physical examination, and laboratory testing. CVD events were adjudicated by a review committee. Generalized linear mixed models and Cox proportional hazards regression models were used to assess the association between insulin dose and cardiometabolic risk factors and CVD risk, respectively, over a total of 30 years. RESULTS Higher insulin doses were significantly associated with a less favorable cardiometabolic risk profile (higher BMI, pulse rate, and triglycerides and lower HDL cholesterol) with the exception of lower diastolic blood pressure and lower LDL cholesterol. In a minimally adjusted model, a 0.1 unit/kg body wt/day increase in insulin dose was associated with a 6% increased risk of any CVD (95% CI 3, 9). However, the association with insulin dose was no longer significant after adjustment for other CVD risk factors. CONCLUSIONS During DCCT/EDIC, higher insulin doses were associated with adverse trends in several cardiometabolic risk factors, even after multivariable adjustment, but not with incident CVD outcomes.

The bigger, the better? When multicenter clinical trials and meta-analyses do not work

“…Additionally, according to the DCCT-EDIC (Epidemiology of Diabetes Interventions and Complications) 9 years of follow-up beyond the end of the DCCT was required to become statistically significant. [30][31][32][33] You may note that although there are internationally well-known scientists who designed these huge trials, there were many unpredicted confounding factors. Although they tried to define the inclusion criteria, additional heterogeneity of their participants in other factors affected the interpretation of their results.…”

Application of Artificial Intelligence in Diabetes Education and Management: Present Status and Promising Prospect

“…Published data from the American Diabetes Control and Complication Trial (DCCT) indicated that a 1.9% decrease in HbA1c through early intensive insulin treatment could significantly decrease the risk of complications and death (36,37). Furthermore, the most recent evidence indicated that large doses of insulin may be associated with adverse cardiovascular outcomes in patients (38). Insulin is therefore a double-edged sword, and should be used in a safe and effective manner.…”

Sex-specific Mendelian randomization study of genetically predicted insulin and cardiovascular events in the UK Biobank

“…Patients switching from metformin to an insulin secretagogue, sulphonylurea, have a higher risk of myocardial infarction (MI) 19 . Higher insulin doses are also associated with an unfavorable cardiovascular risk factor profile 20 . No large randomized controlled trials (RCTs) have assessed the role of insulin in CVD, and it may not be ethical to do so.…”