'Huge Impact' From 40 Years of DCCT/EDIC Trials Celebrated

Akshay B. Jain, MD; Bruce A. Perkins, MD, MPH; Mark Harmel, MPH, CDCES


August 04, 2023

This transcript has been edited for clarity.

Akshay B. Jain, MD: Welcome, from San Diego. We are at the 83rd American Diabetes Association Scientific Sessions. I'm Akshay Jain, an endocrinologist from Surrey, British Columbia. With me is Professor Perkins from the University of Toronto.

There's been some good information shared here, particularly about the Diabetes Control and Complications (DCCT) Trial which came out 40 years ago. It showed us that intensive control of glucose in type 1 diabetes leads to really good outcomes. We see a reduction in microvascular complications by almost 40%. Following DCCT were the data from the Epidemiology of Diabetes Interventions and Complications (EDIC) trial, which also came out 40 years ago.

Professor Perkins, what have you learned in these 40 years?

Bruce A. Perkins, MD, MPH: We've learned a great deal. It was nice to have this 40th anniversary symposium because we celebrated participants who've committed to participation in a trial and an observational follow-up for 40 years, which is a big deal, as well as our huge network of investigators and coordinators across North America.

It's not news that intensive treatment, which involved simple things like more than two injections a day or an insulin pump, had a huge impact. In fact, it was like 70% reductions in primary outcomes, like retinopathy, depending on primary and secondary prevention. There's a huge impact.

Now, we can look back to see whether it actually influenced care: Did it is just itemizing intensive treatments' importance or did it really change the way we manage diabetes? Actually, it's changed fundamentally how we think about coaching people around type 1 diabetes and patient self-management.

Imagine going to three or more injections; this opens the possibility of basal insulin vs bolus and more stable basal insulins that allow lower insulin between meals. People are less likely to have hypoglycemia, less likely to gain weight. Rapid-acting analogs have faster offsets reducing hypoglycemia and weight gain between meals. There's also been automation of insulin.

It's not like DCCT tested those innovations, but it opened the floodgates for their development. We called it the domino effect. There are many other implications. It set the standards for screening, for screening frequency, and it is our main source to help us understand the glucose hypothesis in cardiovascular disease. It also introduced this concept of metabolic memory that's forced us to help adolescents and young adults who, on average, really struggle with glycemic control but also to offer hope for someone who has had higher glycemic exposure for some years that it's never too late to improve it.

We really wanted to highlight the impact that DCCT had on future trials. It also opened the floodgates for National Institute of Diabetes and Digestive and Kidney Diseases–sponsored research, large projects in prediabetes and type 2 diabetes, and all the ancillary studies and collaborations.

I'll just finish by saying that it's these 5 years of funding we're in now and that in these next years, we have amazing objectives, such as understanding things associated with aging, cognitive function, this interaction between essentially weight gain and insulin resistance in type 1 diabetes, things like fatty liver disease, and sleep apnea.

We're doing some amazing techniques and examinations, including cardiopulmonary testing, for example. It is really exciting. When I joined DCCT/EDIC over these past 5 or 10 years, I was always afraid this is going to be the last 5 years of funding, but I honestly feel very encouraged that this is going to be a very long-term, observational follow-up of the trial.

Jain: It has given us so much more information. Funding is one important aspect of a long-term trial. The really impressive part in the EDIC 40-year data is that you have 90% of patients recruited and still retained. That must be very gratifying to see these patients want to continue, share their information, and participate in our understanding of diabetes.

Perkins: Even though the word wasn't coined decades ago when DCCT was being designed and implemented, it's patient-engaged research. There's very close communication with coordinators and principal investigators with patients. Patients are determining research objectives, how protocols are being set out, do they make sense, and they are very engaged in the results. I love it because I'm very much dedicated to patient-oriented research. Honestly, I think DCCT is a perfect example even though it was not officially named as patient-oriented research.

Jain: If you had to look in your crystal ball and see the next few years for clinicians out in the trenches, what are the things they can look forward to from further learnings from DCCT/EDIC?

Perkins: I'm afraid that about all the data in the general population in type 2 diabetes is about the impact of fatty liver disease: steatosis and fibrosis. Apparently, we're going to be running into a pandemic of liver disease, and we're going to be studying this. We've started and we're already seeing that there's this phenotype of fatty liver disease, even in type 1 diabetes, that we didn't think would be there.

We're going to solve that problem. We're going to understand it much better. How big of an issue is that in type 1 diabetes? I think that might open the door to considering drugs for fatty liver, which are essentially type 2 diabetes drugs in people with type 1 diabetes.

Jain: After 40 years, the average age of a person enrolled in EDIC is now 63 years. As you're looking at the diabetes aspect, we also have to factor in the physiology of aging. What are the key points you'll be looking at for this population that's now much older compared with when they entered EDIC?

Perkins: A big part of it is cognition and the brain. What type 1 diabetes–specific therapies or complications may push issues with the brain and cognition? We're starting to understand things like that. We don't see the Alzheimer's disease–like patterns in the brain, but more this phenotype of brain aging. We're going to do repeat imaging and further cognitive testing along with functional capacity. How are people struggling with activities of daily living? We're going to understand these older adult issues really well in the development of type 1 diabetes.

Jain: Thank you, Professor Perkins. There has been many learnings gained from the 40-year data, and hopefully, we will continue to gain more information from you and the trial participants. Thanks for joining us today.

Perkins: Thank you.

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