Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality

Abstract

Importance: Whether mortality in type 1 diabetes mellitus is affected following intensive glycemic therapy has not been established.

Objective: To determine whether mortality differed between the original intensive and conventional treatment groups in the long-term follow-up of the Diabetes Control and Complications Trial (DCCT) cohort.

Design, setting, and participants: After the DCCT (1983-1993) ended, participants were followed up in a multisite (27 US and Canadian academic clinical centers) observational study (Epidemiology of Diabetes Control and Complications [EDIC]) until December 31, 2012. Participants were 1441 healthy volunteers with diabetes mellitus who, at baseline, were 13 to 39 years of age with 1 to 15 years of diabetes duration and no or early microvascular complications, and without hypertension, preexisting cardiovascular disease, or other potentially life-threatening disease.

Interventions and exposures: During the clinical trial, participants were randomly assigned to receive intensive therapy (n = 711) aimed at achieving glycemia as close to the nondiabetic range as safely possible, or conventional therapy (n = 730) with the goal of avoiding symptomatic hypoglycemia and hyperglycemia. At the end of the DCCT, after a mean of 6.5 years, intensive therapy was taught and recommended to all participants and diabetes care was returned to personal physicians.

Main outcomes and measures: Total and cause-specific mortality was assessed through annual contact with family and friends and through records over 27 years' mean follow-up.

Results: Vital status was ascertained for 1429 (99.2%) participants. There were 107 deaths, 64 in the conventional and 43 in the intensive group. The absolute risk difference was -109 per 100,000 patient-years (95% CI, -218 to -1), with lower all-cause mortality risk in the intensive therapy group (hazard ratio [HR] = 0.67 [95% CI, 0.46-0.99]; P = .045). Primary causes of death were cardiovascular disease (24 deaths; 22.4%), cancer (21 deaths; 19.6%), acute diabetes complications (19 deaths; 17.8%), and accidents or suicide (18 deaths; 16.8%). Higher levels of glycated hemoglobin (HbA1c) were associated with all-cause mortality (HR = 1.56 [95% CI, 1.35-1.81 per 10% relative increase in HbA1c]; P < .001), as well as the development of albuminuria (HR = 2.20 [95% CI, 1.46-3.31]; P < .001).

Conclusions and relevance: After a mean of 27 years' follow-up of patients with type 1 diabetes, 6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause mortality rate when compared with conventional therapy.

Trial registration: clinicaltrials.gov Identifiers: NCT00360815 and NCT00360893.

Figure 1

Cumulative incidence of mortality from the date of randomization in the DCCT (starting in 1983) to December 31, 2012 with estimates of the Hazard Ratio, 95% confidence limits and p-value obtained from a Cox Proportional Hazards model. A) For males versus females, HR = 1.61 (1.09, 2.39), p = 0.02. B) For the intensive versus conventional treatment groups (intent-to-treat analysis), HR = 0.67 (0.46, 0.99), p = 0.045.

Figure 1

Cumulative incidence of mortality from the date of randomization in the DCCT (starting in 1983) to December 31, 2012 with estimates of the Hazard Ratio, 95% confidence limits and p-value obtained from a Cox Proportional Hazards model. A) For males versus females, HR = 1.61 (1.09, 2.39), p = 0.02. B) For the intensive versus conventional treatment groups (intent-to-treat analysis), HR = 0.67 (0.46, 0.99), p = 0.045.