For patients with type 1 diabetes who received 6.5 years of intensive therapy in the late 1980s and early 1990s, all-cause mortality decades later was modestly lower than that for patients who had received usual diabetes therapy, according to a report published online Jan. 6 in JAMA.
Intensive diabetes therapy was shown to prevent renal and cardiovascular complications in the Diabetes Control and Complications Trial (DCCT) in 1983-1993 and its successor, the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up trial in 1994-2012. The intensive approach became the recommended standard of care, but it was never determined whether a period of intensive therapy improved mortality outcomes, while other studies have reported that it does not. In particular, hypoglycemia is more frequent with intensive therapy and may contribute to car accidents and other trauma that raises mortality risk, said Dr. Trevor J. Orchard of the University of Pittsburgh, chair of the DCCT/EDIC writing group, and his associates.
Dr. Trevor Orchard
They assessed mortality outcomes in an extended follow-up study involving 711 of the DCCT/EDIC participants who had received intensive diabetes therapy and 730 who had received conventional diabetes therapy an average of 27 years earlier. During the treatment phase of the DCCT, patients given intensive therapy achieved a mean hemoglobin A1c level of 7% and those given usual therapy achieved a mean HbA1c level of 9%; however, this benefit soon disappeared during follow-up, most likely because many patients found it difficult to maintain intensive therapy on their own, Dr. Orchard and his associates said (JAMA 2015 Jan. 6 [doi:10.1001/jama.2014.16107]). At the present extended follow-up, there were 43 deaths (6.0%) in the intensive-therapy group and 64 (8.8%) in the usual-therapy group. Mortality per 100,000 patient-years was modestly lower in the intensive-therapy group, with a hazard ratio of 0.67. The absolute risk reduction was “small,” at about 1 death per 1,000 patient-years, the researchers noted.
The slightly lower mortality with intensive therapy was consistent across all causes of death except for the category of accident/suicide. A history of severe hypoglycemia was associated with greater mortality (HR, 1.63), but none of the accidental or suicidal deaths in this study were clearly associated with hypoglycemia. And the small numbers of accidental and suicidal deaths (13 in the intensive group and 5 in the conventional group) “preclude any definitive conclusions” regarding intensive therapy’s potential to raise mortality risk through this mechanism, the investigators said.
The DCCT/EDIC study established that tight glycemic control reduces microvascular and macrovascular complications, “and we now show its association with subsequent mortality. Although the numbers are small, there were fewer diabetic renal deaths (1 vs. 6) and cardiovascular deaths (9 vs. 15) with intensive compared with conventional therapy, causes for which glycemia might be expected to play a major role,” they added.