Association Between 7 Years of Intensive Treatment of Type 1 Diabetes and Long-Term Mortality | Journal Scan

Study Questions:

What are the differences in all-cause and cause-specific mortality between the original treatment groups that received 6.5 years of intensive versus conventional therapy during the DCCT (Diabetes Control and Complications Trial) study?

Methods:

After the DCCT (1983-1993) ended, participants were followed up in a multisite (27 US and Canadian academic clinical centers) observational study (EDIC [Epidemiology of Diabetes Control and Complications]) until December 31, 2012. Participants were 1,441 healthy volunteers with diabetes mellitus who, at baseline, were 13-39 years of age with 1-15 years of diabetes duration and no or early microvascular complications, and without hypertension, pre-existing cardiovascular disease, or other potentially life-threatening disease. 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. Total and cause-specific mortality was assessed through annual contact with family and friends, and through records over 27 years of mean follow-up.

Results:

Vital status was ascertained for 1,429 (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% confidence interval [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 = 0.045). 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 < 0.001), as well as the development of albuminuria (HR, 2.20; 95% CI, 1.46-3.31; p < 0.001).

Conclusions:

The authors concluded that 6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause mortality rate when compared with conventional therapy in patients with type 1 diabetes.

Perspective:

This study reports that over an average of 27 years of follow-up in the DCCT/EDIC cohort with type 1 diabetes mellitus, overall mortality risk in the intensive group was lower than that in the conventional group (p = 0.045), although the absolute risk reduction was small at approximately 1/1,000 patient-years. These results appear to provide reassurance that adoption of 6.5 years of intensive therapy in type 1 diabetes does not incur increased risk of overall mortality, but are in contrast to findings from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial in type 2 diabetes. At this time, it seems prudent to follow recommendations from the American Diabetes Association, which suggest a target HbA1c of 7% for most nonpregnant adults with diabetes.

Keywords: Accidents, Albuminuria, Canada, Cause of Death, Diabetes Complications, Cardiovascular Diseases, Diabetes Mellitus, Type 1, Healthy Volunteers, Hemoglobin A, Glycosylated, Hyperglycemia, Hypoglycemia, Risk Factors, United States


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