Intensive therapy and tight glycemic controls carry long-term benefits for patients with type 1 diabetes, according to the latest results of the Epidemiology of Diabetes Interventions and Complications (EDIC) trial, the long-term follow-up study to the 10-year landmark Diabetes Control and Complications Trial (DCCT).
People with type 1 diabetes who maintain long-term intensive therapy and HbA1c values close to normal values of 6% or less slash their risk of developing severe eye disease, impaired kidney function, and limited hand and shoulder flexibility, reported Lloyd P. Aiello, MD, PhD, head of the Joslin Diabetes Center’s Section on Eye Research in Boston and DCCT/EDIC investigator.
In the DCCT, 1,441 patients were randomly assigned to intensive therapy or to conventional therapy. Intensive therapy included either an external insulin pump or 3 or more daily insulin injections guided by frequent blood glucose monitoring. Conventional therapy involved 1 or 2 daily insulin injections.
As first reported in 1993, intensive therapy reduced the early stages of retinopathy, nephropathy, and neuropathy by as much as 76% compared to conventional therapy, which at the time set HbA1c goals of 9%. Yet the potential benefits of long-term intensive therapy were not known, spurring researchers to continue their work in the EDIC by following 95% of the surviving members of the original DCCT cohort for close to two decades.
Dr. Aiello reported that tight control cut the long-term risk of new diabetic retinopathy by 47% and new macular edema by 35%. Participants who maintained intensive therapy experienced a 46% risk reduction in retinopathy progression, and were 39% less likely to need scatter or focal laser therapy, 48% less likely to require any ocular surgery, 44% less likely to undergo vitrectomy, 48% less likely to need cataract extraction, and 50% less likely to experience what Dr. Aiello referred to as “severe retinal outcomes” such as blindness.
“Although we have means of treating severe eye disease to prevent vision loss, it is always better to reduce its development in the first place in order to avoid the need for expensive and only partly effective late-stage therapies. Intensive diabetes therapy effectively accomplishes this goal,” said Dr. Aiello.
Participants with long-term intensive therapy had a 39% lower risk of developing microalbuminuria and a 61% lower risk of developing macroalbuminuria, reported Ian de Boer, MD, MS, associate professor of medicine in the Division of Nephrology at the University of Washington in Seattle and a DCCT/EDIC researcher. As of 2011, participants with tight diabetes control also had a 50% lower risk of developing impaired glomerular filtration.
“Early intensive therapy is effective for preventing and delaying diabetes-related kidney disease,” said Dr. de Boer. “The reduction in impaired kidney function represents a major finding since kidney failure increases the risk of subsequent heart disease and death more than any other complication.”
Mary Larkin, RN, MSN, CDE, a DCCT/EDIC investigator at Massachusetts General Hospital’s Diabetes Research Center in Boston, reported on cheiroarthropathy, a complication that has traditionally not received as much attention as the others. She said that 33% of patients experienced at least one form of the condition, most commonly adhesive capsulitis, followed by carpal tunnel, prayer sign, and trigger finger. Roughly 20% of participants had two forms of cheiroarthropathy, 10% had three forms, and 3% had four. Ms. Larkin added that progressive stiffening around the hands and shoulders affected two-thirds of DCCT participants who had diabetes for 30 years or more, and noted that the benefits of tight blood glucose control can extend to cheiroarthropathy.
“A lower glucose level was associated with reduced risk of these complications as it was for the other, better recognized complications,” she said. “Surveillance of musculoskeletal disorders should be considered in the routine care of patients with type 1 diabetes.”
The results demonstrate the necessity of tight diabetes control, said Judith Fradkin, MD, director of the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD), National Institutes of Health (NIH).
“The long-term results of the DCCT/EDIC further reinforce the importance of early, intensive therapy over the lifetime of people with type 1 diabetes,” Dr. Fradkin told EndocrineWeb. “Our challenge now is to ensure that all patients with type 1 diabetes are able to take advantage of these remarkable findings and to make intensive therapy as convenient and safe as possible.”
Dr. Aiello is on the advisory panel of Genzyme Corporation and a consultant for KalVista Pharmaceuticals, Merck, and Thrombogenics. Dr. Fradkin and Ms. Larkin disclosed no conflicts of interest. Dr. de Boer receives research support from AbbVie. The DCCT was funded by the NIH/NIDDKD, trial #NCT00360815. The EDIC trial was funded by the NIH/NIDDKD, trial #NCT00360893.