CHICAGO -- Benefits seen with intensive therapy for type 1 diabetes in a large epidemiological study persist through extended follow-up, according to the latest data from the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) trial.
Over 18 years, patients who had intensive management -- hitting a glycated hemoglobin (HbA1c) target of 7% -- had a 46% lower risk of retinopathy, a 39% reduced risk of microalbuminuria, and a 61% lower risk of macroalbuminuria (P<0.0001 for all), several investigators involved in the trial reported during a special symposium at the American Diabetes Association (ADA) meeting here.
"As we follow this population longer, we've been able to show that early benefits with regard to early complications has extended," study co-chair David Nathan, MD, of Massachusetts General Hospital (MGH) in Boston, told MedPage Today. "We've demonstrated that loss of kidney function is reduced, people develop less severe eye complications, and we see a host of other benefits on long-term severe complications that we didn't see during the initial trial because the patients were too young and had diabetes for a relatively short period of time."
The 10-year DCCT was followed by the ongoing EDIC trial, and has now been running for a total of 30 years.
The DCCT revealed that intensive therapy -- lowering HbA1c to 7% rather than the 9% which was standard practice at the time -- in patients with type 1 diabetes diminished a range of complications about 35% to 75%, establishing intensive therapy as the standard of care.
The trial was extended into EDIC and Judith Fradkin, MD, director of diabetes at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) said during a press briefing that 95% of trial patients who are still alive continue to participate in the trial.
At the meeting, several researchers presented updated data on complications including retinopathy, nephropathy, and musculoskeletal complications.
Lloyd Paul Aiello, MD, PhD, of the Joslin Diabetes Center at Harvard Medical School, reported a 46% reduced risk of retinopathy after 18 years of follow-up in the EDIC study with intensive therapy compared with the standard of care (P<0.0001).
He noted that 86.7% of that risk reduction was explained by between-group differences in HbA1c levels.
Aiello also reported a reduction in severe diabetic retinopathy with intensive management, with a 47% reduced risk of proliferative diabetic retinopathy and a 35% reduced risk of clinically significant macular edema (P<0.0001 for both).
During the 18 years of EDIC follow-up, the researchers also saw a 39% lower risk of focal laser therapy and a 48% lower risk of any ocular surgery (P<0.0001).
"Further EDIC follow-up has demonstrated a consistent beneficial effect on severe eye disease," Aiello said. "Although the risk reduction has decreased with time, the effect is still substantial."
Ian de Boer, MD, of the University of Washington in Seattle, reported nephropathy findings that pointed to a "continued separation of microvascular and macrovascular complications" over 18 years of EDIC data.
Specifically, the researchers saw a 39% reduced risk of microalbuminuria and a 61% reduced risk of macroalbuminuria with intensive therapy through that time (P<0.0001 for both).
Once again, the vast majority of risk reduction -- between 91% and 100% -- was explained differences in HbA1c levels, de Boer said.
Earlier analyses that had been previously reported also showed that intensive therapy delayed the development of hypertension and preserved estimated glomerular filtration rate (eGFR), he added.
"The kidney findings speak volumes about the long-term benefits of intensive therapy," de Boer said during a press briefing. "It's demonstrated that intensive therapy can have a sustained, long-term impact on mini manifestations of this microvascular and macrovascular disease."
The researchers also reported new data on musculoskeletal complications, particularly cheiroarthropathy, which is periarticular skin thickening of the hands and limited joint mobility. It typically results from the accumulation of advanced glycation end-products in collagen, and includes carpal tunnel syndrome, adhesive capsulitis, Dupuytren's contracture, flexor tenosynovitis (or "trigger finger"), and prayer sign (or trouble holding the hands flat when palm-to-palm).
Mary Larkin, RN, of MGH, and colleagues conducted a cross-sectional analysis of EDIC data during years 18 and 19.
They found that a third of of about 1,200 patients (33%) had at least one type of this complication, with the most common being adhesive capsulitis, followed by carpal tunnel and then prayer sign.
Another 20% of patients had at least two complications, and another 10% had at least three, Larkin said. About 3% had four or more complications.
Only 34% were free of these complications, Larkin reported.
Risk factors for these conditions included older age, female gender, longer duration of disease, and higher HbA1c over time. It was also associated with neuropathy and retinopathy, but not with nephropathy, she reported.
"Cheiroarthropathy represents an important constellation of long-term complications worthy of further clinical and research attention," Larkin said. "Surveillance of musculoskeletal disorders should be considered in routine care of patients with type 1 diabetes."
Nathan said these conditions may have been under-recognized in type 1 diabetes in the past.
John Lachin, MD, of George Washington University in Washington, D.C., said longer term EDIC data also show a reduced risk of cardiovascular effects with intensive management, as well as cardiovascular mortality -- a finding that somewhat departs from recent findings in type 2 diabetes.
"This is a little different from type 2 diabetes, where there's been a question as to whether intensive therapy is important or not," Nathan told MedPage Today.
Lachin said the mortality data are in press and therefore embargoed and could not be released at the time of his ADA presentation.
But he noted that, as with other complications, the long-term benefits of intensive therapy on cardiovascular outcomes are largely mediated by HbA1c levels.
The study was supported by the NIDDK.
The researchers reported no conflicts of interest.
Primary source: American Diabetes Association
Source reference:
Nathan DM, et al "DCCT/EDIC 30th anniversary symposium -- contributions and progress" ADA 2013.
Source reference:
Nathan DM, et al "DCCT/EDIC 30th anniversary symposium -- contributions and progress" ADA 2013.
Graham
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