More than 30 years after the end of the DCCT study for type 1 diabetes, the benefits persist.
Participants who were taught intensive therapy for type 1 diabetes during the Diabetes Control and Complications Trial (DCCT) experienced clinically beneficial effects on cardiovascular outcomes at 30 years of follow-up, according to research published online Feb. 9 in Diabetes Care.
The DCCT/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group assessed whether intensive therapy compared with conventional therapy during the DCCT (mean, 6.5 years) had an effect on the incidence of cardiovascular disease (CVD) over 30 years of follow-up.
The researchers found 149 CVD events had occurred in 82 former participants from the intensive treatment group versus 217 CVD events in 102 of those from the conventional treatment group. For those in the intensive therapy group, the incidence of any cardiovascular disease was reduced by 30 percent (95 percent confidence interval, 7 to 48 percent; P = 0.016), and the incidence of major cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) was reduced by 32 percent (95 percent confidence interval, −3 to 56 percent; P = 0.07).
As a reminder, during the DCCT, intensive therapy consisted of three or more daily insulin injections or use of an external insulin infusion pump, with dose adjustments based on at least four self-monitored glucose measurements per day. Daily glucose goals were 70–120 mg/dL before meals and 180 mg/dL peak levels after meals. The HbA1c goal was a value of 6.05% (42.6 mmol/mol). Conventional therapy used one or two daily injections of insulin and had no glucose goals beyond prevention of hyper- and hypoglycemia.
The primary outcome was the time to the first of any of the following types of cardiovascular events: nonfatal myocardial infarction or stroke; death judged to be secondary to CVD; subclinical (silent) myocardial infarction detected on an annual electrocardiogram; angina confirmed by ischemic changes with exercise tolerance testing or by clinically significant obstruction on coronary angiography; congestive heart failure (CHF) with paroxysmal nocturnal dyspnea, orthopnea, or marked limitation of physical activity caused by heart disease; or revascularization with angioplasty and/or coronary artery bypass. The occurrence of any CVD event was routinely documented during annual participant study visits, with additional medical records sought to verify all self-reported events. To ensure complete capture of all known CVD events before year end, staff efforts were escalated in early 2013 to ensure full reporting of all known CVD events irrespective of completion of the annual visit.
The beneficial effects of an average of 6.5 years of intensive versus conventional diabetes therapy on the risk of any CVD and also on the standardized MACE outcome was previously demonstrated. This was based on analysis of events when at least 50 conventional subjects had experienced a CVD event (mean of 17 years of follow-up). The current analysis (mean of 26 years of follow-up) was performed after at least 100 cases (184 total events) in the former conventional group had occurred.
As noted, the incidence estimates beyond 25 years are less precise owing to the declining numbers at risk. These suggest that the beneficial metabolic memory effect on the underlying incidence of any CVD and MACE may be diminishing with longer follow-up.
The current analyses have strengths and weaknesses. The DCCT/EDIC includes a well-characterized cohort of individuals with type 1 diabetes monitored for up to 30 years, with entry criteria designed to address the development and progression of the complications of type 1 diabetes. The CVD adjudication process ensures capture of valid and verifiable CVD events. Over time, the occurrence of CVD events has increased, reflective of the increasing duration of type 1 diabetes and advancing age of the cohort. However, the mean age (56 years) of the cohort remains relatively young when considering CVD events. In addition, the exclusion of individuals with pre-existing hypertension, hyperlipidemia, or CVD, coupled with the continued relatively small number of CVD events, may limit applicability of these results to the population with type 1 diabetes as a whole.
In summary, intensive diabetes therapy during the DCCT (6.5 years) has long-term, clinically beneficial effects on the incidence of CVD in this cohort with type 1 diabetes. Efforts to make intensive diabetes management attainable at a young age must continue so as to reduce the rates of life-threatening CVD over the life span for patients with diabetes.
- Intensive diabetes therapy during the DCCT (6.5 years) has long-term beneficial effects on the incidence of cardiovascular disease in type 1 diabetes that persist for up to 30 years, so far.
- The researchers found 149 CVD events had occurred in 82 former participants from the intensive treatment group versus 217 CVD events in 102 of those from the conventional treatment group.
- The research will continue for those original DCCT participants.
Researched and prepared by Steve Freed, BPharm, Diabetes Educator, Publisher and reviewed by Dave Joffe, BSPharm, CDE
Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up, Diabetes Care February 9, 2016