David M. Nathan, MD, is the founder of the Massachusetts General Hospital Diabetes Center, directed the Mass General Hospital Clinical Research Center from 1991 to 2025, and is a professor of medicine at Harvard Medical School. He is also the 2026 winner of the Association for Diagnostics & Laboratory Medicine’s (ADLM’s) Wallace H. Coulter Lectureship Award. He received this award in recognition of his pioneering studies on the treatment and prevention of diabetes — groundbreaking work that Nathan humbly attributes to his collaborations with numerous fellow clinical investigators, trainees, and bench scientists, as well as to the study participants who volunteered their time and effort to advance this research.
Clinical Laboratory News recently spoke with Nathan ahead of his upcoming
plenary session at ADLM 2026 to reflect on the touchstones of his career and look to the future of diabetes testing and treatment.
What led you to go into diabetes research?
It was somewhat happenstance. Medical science in the late 60s and 70s was advancing because of the development of the radioimmunoassay by Solomon Berson, MD, and Rosalyn Sussman Yalow, PhD. I had some contact with them when I was a medical student. The radioimmunoassay that they introduced allowed the very accurate measurement of small quantities of substances circulating in biological fluids, and the very first assay developed was for insulin. It drew me to endocrinology and diabetes specifically because we were starting to understand pathways and I very much like to solve puzzles. Understanding that these small substances had numerous downstream effects was of great interest to me.
What specific areas of diabetes care and testing are you currently studying?
Keeping in mind that I’m moving towards retirement, the studies that I continue to work on as I close down my career are expanding the information from what were huge investments by the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases in particular.
One of these is the Diabetes Control and Complications Trial (DCCT), which ran from 1982-1993 and has continued through its long-term observational follow-up called the Epidemiology of Diabetes Interventions and Complications (EDIC) study, which started in 1994 and is still ongoing today. The DCCT demonstrated the critical role of intensive therapy aimed at lowering the hemoglobin A1c (HbA1c) level for people with type 1 diabetes. Specifically, the trial showed that reducing A1c as much as clinically possible led to myriad benefits for this patient population. This finding underlies modern-day treatment of type 1 diabetes.
The vast majority of our living participants are still in the EDIC study — an invaluable population that we’ve collected data on for 95% of the time that they’ve had diabetes and over 65% of their lifespans. Since the DCCT results have extended the lifespan of people with type 1 diabetes, we now have a type 1 population that is living longer than at any time in history. However, with no prior experience with type 1 diabetes in older people, we don't know what happens to them. How do we help take care of them and, of course, help them take care of themselves? It’s still a complicated disease and I'm pleased to continue contributing with my collaborators to the knowledge base that should improve the health of people with type 1 diabetes over their lifetime.
The second major trial, which began after the end of the DCCT and which I have chaired for the past 30 years, is the Diabetes Prevention Program (DPP). Type 2 diabetes was quickly increasing in the 1990s, having almost doubled in prevalence over the preceding 10-20 years. Prediabetes, which represents a group at particularly high risk for developing diabetes, currently affects more than 100 million people in the U.S. In 1994, again, with the support of the NIH, we began to plan a study to determine whether we could slow or stop this epidemic borne of the increasing prevalence of overweight and obesity in the population. The DPP ended in 2002, about a year ahead of schedule, after demonstrating that lifestyle interventions that reduce weight and increase activity levels and the medication metformin reduce diabetes development by an impressive 58% and 31%, respectively.
We continue to follow almost 1,700 of the original DPP population, exploring the long-term durability of the original interventions and other benefits associated with diabetes delay or prevention. Their average age is now 74. In this respect, both the DPP and DCCT/EDIC are looking at similar themes: How do aging and associated characteristics interact with diabetes? What is the best way to take care of these patients over the course of their whole lives?
What’s one interesting thing you’ve found from your research comparing HbA1c testing with continuous glucose monitoring?
I’m old enough that I was beginning my research around the time that self-monitoring of blood glucose was born. The first glucose monitors became available in the late 70s, early 80s. So now, fast forwarding 40 years, continuous glucose monitoring (CGM) has come about. And to me, the real importance of these devices is that they provide the ability to “close the loop” on insulin pumps.
The major downside of intensive therapy in type 1 diabetes was hypoglycemia. In the DCCT, the cost of lowering the risk of diabetes complications by 39%-76% with intensive therapy was a three-fold increased risk of severe hypoglycemia. So, the ability to lower HbA1c to <7% (which had been adopted as the international standard of treatment based on DCCT/EDIC results) with less hypoglycemia was a major goal. CGM allows patients with type 1 diabetes to achieve goal A1c levels with less hypoglycemia. It accomplishes this by serving either as critical feedback in insulin pumps or as an early warning system in patients treated with injections. We shouldn’t lose sight that that is the reason why CGM was developed.
But then, of course, there are commercial interests involved, and type 1 diabetes is a relatively rare disease compared with the 20-fold more people who have type 2 diabetes. Understandably, companies started looking at how CGM could be used in this larger population as well. I think the best justification for using CGM with type 2 diabetes is for people who are insulin-treated where, again, you want to make sure that their blood sugar isn’t drifting low without them realizing it.
However, despite my strong feelings against these devices being used in populations without demonstrated benefit, they are now being promoted for use in nondiabetic populations. Whether this increasing use of technology improves health in most people with type 2 diabetes — or in people without diabetes — remains to be demonstrated.
Regarding the question of CGM versus A1c, the A1c is incredibly affordable and it’s easy to measure and rarely wrong. Some of the work that I’ve done has established the relationship between average glucose levels and A1c. Improving on the generally excellent correlation between measured average glucose and HbA1c values is still important. A colleague of mine at Mass General named John Higgins, MD, and I have worked on such projects for the last decade.
What are other exciting emerging trends in diabetes care today?
You know, the glucagon-like peptide-1 receptor agonist medications (GLP-1s) have captured everyone’s imagination. I was the first person to ever give a GLP-1 to a person with diabetes back in the late 1980s. And that’s because of propinquity — my colleague Joel Habener, MD, who really was the father of GLP-1s, was down the hall from my laboratory. Joel and colleagues were identifying the differential processing of pre-proglucagon in different organs, isolating and synthesizing GLP-1, and figuring out what it did in animal models. I started working on measuring GLP-1 levels in fed and non-fed persons with both type 1 and type 2 diabetes and along the way was able to administer GLP-1, 7-37 to human volunteers. The major effect we noted was the stimulation of insulin secretion, and we shouldn't lose sight that lowering glucose and HbA1c levels was the stimulus for the development of GLP-1s.
Now, the major commercial benefit of GLP-1s is that they are highly effective for weight loss. The drugs decrease your appetite through a combination of central and gastrointestinal effects. Another benefit of GLP-1s is that they decrease heart disease and kidney disease. This was an entirely accidental finding. In 2008, the Food and Drug Administration began requiring the pharmaceutical industry to demonstrate that new diabetes drugs were safe for heart disease, because there was a drug for type 2 diabetes called Rezulin, or troglitazone, which appeared to increase the risk for heart disease. So, the manufacturers of the new diabetes medications, such as the GLP-1s, were required to do cardiovascular safety studies and, lo and behold, not only were they shown to be safe, they actually appeared to be protective.
If we can determine how to keep patients on these medications long-term, we may have made a major step in addressing the rampant prevalence of overweight and obesity and the consequent diabetes and heart disease that affect public health.
One thing you’ll be discussing at ADLM 2026 is the importance of funding from the NIH throughout your career. What’s one thing you would not have been able to accomplish without NIH funding?
My entire career wouldn’t have been possible without NIH funding. I’ve chaired three highly impactful, NIH-sponsored multicenter studies and participated in several others. I think it’s fair to say that none of them would have been supported by industry. Nothing against industry, but its primary focus is developing drugs for diseases rather than for prevention. Similarly, studying interventions that don't involve medications and comparing available therapies in comparative effectiveness studies is not in industry's wheelhouse. There’s no financial incentive for companies to erase a disease or compare their medication against competitors.
NIH funding is critical on several levels beyond the support of large studies that are important to public health, and I fear that it’s under threat. NIH is really the lifeblood of training young investigators and supporting biomedical research. Without NIH funding, the pipeline of investigators will slow to a trickle. The large-scale, long-term projects that have shown how to reduce the chronic morbidity and mortality associated with diabetes and how to prevent — or at least delay — the onset of diabetes would never have been conducted without the NIH.
Will you be presenting any new research or findings during your talk at ADLM 2026?
I was asked to provide a retrospective of my career, weaving my laboratory work into my clinical research because, frankly, the laboratory elements were foundational. If we didn’t have A1c, we couldn’t have done many of these studies. If we didn’t have basic scientists developing GLP-1s, we wouldn’t have those drugs and the studies that rely on them. So, the major themes I will focus on will be the interdependence of clinical and basic laboratory work being at the heart of major advances in diabetic research, and my concern about the future.
David M. Nathan, MD, will present the plenary talk, “Diabetes prevention and treatment: A personal odyssey from bench to bedside” on Sunday, July 26 at ADLM 2026 in Anaheim, California. You can learn more about his talk here and you can register for the meeting here.
Moriah Sellers is a writer based in the Lexington, Kentucky area.
