Initial intensive therapy associated with lower all-cause mortality in type 1 diabetes

Patients in the intensive treatment group of the Diabetes Control and Complications Trial (DCCT) appeared to have modestly lower all-cause mortality over long-term follow-up than those in the conventional treatment group, according to a new study.

Researchers looked at participants in the DCCT and its follow-up observational study, Epidemiology of Diabetes Control and Complications (EDIC), to examine whether a mortality difference existed between the original treatment groups. The DCCT took place from 1983 to 1993, and participants were then followed in EDIC until Dec. 31, 2012. During the DCCT, participants with type 1 diabetes who were 13 to 39 years of age were randomly assigned to receive intensive glucose-lowering therapy or conventional therapy. Intensive therapy was recommended for and taught to all participants when the DCCT ended, after a mean of 6.5 years. From that point, participants were cared for by their personal physicians. The current study's primary outcome measures were total and cause-specific mortality as ascertained by annual contact with family and friends and by medical records. Follow-up was a mean of 27 years. The study results appear in the Jan. 6 Journal of the American Medical Association.

In the DCCT, 711 patients were randomly assigned to the intensive therapy group and 730 were randomly assigned to the conventional therapy group. The goal of intensive therapy was to achieve glycemia as close to the nondiabetic range as safely possible, and the goal of conventional therapy was to avoid symptomatic hypoglycemia and hyperglycemia. In the current study, the researchers determined the vital status of 1,429 participants (99.2%). One hundred seven had died, 64 in the conventional group and 43 in the intensive therapy group. There was an absolute risk difference of −109 per 100,000 patient-years, and all-cause mortality risk per 100,000 patient-years was lower in the intensive therapy group (hazard ratio, 0.67; 95% CI, 0.46 to 0.99; P=0.045). No difference in mortality was seen between the groups until the first 15 years of follow-up had passed. Cardiovascular disease caused the most deaths (24%), followed by cancer (19.6%), acute diabetes complications (17.8%), and accidents or suicide (16.8%). Higher HbA1c levels were associated with higher all-cause mortality (hazard ratio, 1.56; 95% CI, 1.35 to 1.81 per 10% relative increase; P<0.001) and with albuminuria (hazard ratio, 2.20; 95% CI, 1.46 to 3.31; P<0.001).

The authors noted that the number of deaths was small and that racial diversity among participants was lacking, among other limitations. However, they concluded that although the absolute risk reduction was small, overall mortality risk appeared to be lower in the intensive group than in the conventional group. “The current data suggest net mortality benefit from intensive therapy, even when the controlled clinical trial comparing intensive with conventional therapy was implemented over less than 25% of the 27-year follow-up time,” the authors wrote.