Aging and Type 1 Diabetes: 'Complete Picture' 40 Years On

SAN DIEGO – The landmark Diabetes Control and Complications Trial (DCCT) follow-up study has entered a new phase, focusing on a relatively recent phenomenon: aging in type 1 diabetes.

New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.

The original randomized DCCT clinical trial results, published September 30, 1993, in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.

And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the recent American Diabetes Association 83rd Scientific Sessions. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.

Together, DCCT and EDIC — both funded by the National Institutes of Health at 27 sites in the United States and Canada — have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.

"All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important — continuous glucose monitoring (CGM), new insulins, better [insulin] pumps…I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all," Nathan told Medscape Medical News.

And now, "what we still have yet to contribute is what happens to type 1 diabetes as people get older," added Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital in Boston.

'Something That Heretofore None of Us Could Have Imagined'

The 1441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal healthcare teams. The 1075 participants in EDIC today are an average age of 63 years.

Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of this year, said study coordinator co-chair Gayle Lorenzi, RN, who is a Certified Diabetes Care and Education Specialist (CDCES) at the University of California, San Diego.

"DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s," Lorenzi commented.

About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean A1c of 7.3%.

According to Barbara H. Braffett, PhD, co-principal investigator at the DCCT/EDIC data coordinating center, "The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences."

Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, 2D Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.

Nathan commented that although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, "now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything."

Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the FIB-4 index, a quantification of liver enzymes and platelet count.

Nathan noted that the study participants have had "this kind of funny metabolic milieu in their liver for decades. They don't make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?"

Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Braffett said.

DCCT/EDIC Over 40 Years: "Incredibly Complete Picture"

As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Braffett noted.

During the EDIC 2017-2022 cycle, Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.

Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease (CVD) risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.

Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.

Nathan told Medscape Medical News: "Today, the number with horrible complications is very few, but we haven't erased complications entirely...We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That's the value of this research."

The speakers quoted have reported no relevant financial relationships.

ADA Scientific Sessions. Symposium presented June 25, 2023.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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