Oscar B. Crofford: Clinician, Scientist, Educator, Advocate for People With Diabetes, and Godfather of Diabetes Control and Complications Trial

It is not often that one individual is gifted with leadership skills encompassing basic science, clinical trials, diabetes clinical care, and political lobbying for diabetes. Oscar B. Crofford, MD, at various stages in his career, was a master in each of these disciplines. Although each endeavor required a somewhat unique skill set with different short-term goals, his singular overarching aim was always to improve the lives of people with diabetes. In this context, it is not difficult to weave together his major role in the establishment of the National Commission on Diabetes in the U.S., the development of diabetes research and training centers, and, ultimately, the planning and implementation of the Diabetes Control and Complications Trial (DCCT), one of the most highly cited type 1 diabetes studies, which set a new standard of care for the management of this condition.

Oscar B. Crofford was born in Chickasha, Oklahoma, in 1930, attended high school in Memphis, Tennessee, and obtained an undergraduate degree at Vanderbilt University where he also completed his medical degree in 1955. He met his wife, Jane Long Crofford, on a blind date in 1955, and they were married in 1957. Jane had just graduated from nursing school at Vanderbilt, and he was midway through his residency training. He and Jane have three children: daughter Leslie who is a distinguished rheumatologist and Professor of Medicine at Vanderbilt, son David is in the construction business, and son Stephen is a trial lawyer.

To fulfill military obligations, Oscar entered the U.S. Navy Medical Corps immediately following his marriage to Jane and served 2 years as a medical officer. In 1959, he returned to Vanderbilt for a postdoctoral fellowship, training in clinical investigative physiology under the direction of Dr. Elliott V. Newman, a physician-scientist who had established a clinical research center at Vanderbilt University. At that time, Vanderbilt was already recognized as one of the leading centers of excellence in metabolism research, breaking new ground particularly as it related to understanding the pathophysiology and molecular biology of metabolic disease.

Another internationally recognized center of excellence in diabetes/metabolism research was the Institut de Biochimie Clinique at the University of Geneva, in Switzerland, directed by Dr. Albert Renold. So it was not a surprise that Oscar chose to do a fellowship with Dr. Renold. Oscar’s work at that time was focused on understanding more basic metabolic phenomenon in preclinical models (1). He returned to Nashville in 1965 as Vanderbilt’s first full-time diabetes clinician scientist specialist and ultimately became the director of the Division of Diabetes and Metabolism. Using his research training from Geneva, he continued to investigate hormonal and metabolic mechanisms in preclinical studies publishing his results in high-impact journals (2–4).

Taking on a more national role in diabetes research, he was appointed Vice Chair of the American Diabetes Association (ADA) research committee. In this capacity, he was called to Washington, DC, to testify in support of increased federal funding for diabetes research, and, ultimately, this led to the establishment of the National Commission on Diabetes, with the principal goal of developing a long-range plan to combat diabetes and its complications. Consulting widely, Crofford and colleagues developed a strategy that focused on both the clinical needs and the research agenda required to advance the understanding and management of diabetes. As chair of the National Commission on Diabetes, Oscar was able to obtain support from various diabetes organizations, including the Juvenile Diabetes Foundation (currently JDRF), the ADA, and diabetes centers such as the Joslin Diabetes Center, for a common purpose. As a consequence, the U.S. Congress passed legislation resulting in an initial $5 million dollars being directed to establish a program of Diabetes Research and Training Centers. Indeed, Oscar is rightly proud of the fact that 10 years after its establishment, the majority of the National Commission on Diabetes recommendations have been adopted.

One particularly noteworthy recommendation of the National Commission on Diabetes was to determine whether it was feasible to conduct a trial to answer the glucose hypotheses question. At the time, it was hotly debated whether hyperglycemia was the principal cause of long-term complication or, as other researchers believed, whether it was due to other unrelated factors such as genetic susceptibility.

Although Crofford was not a clinical trialist, he quickly understood that the glucose hypothesis could only be tested in the context of a randomized, controlled clinical trial. However, was a trial of glucose control actually feasible in 1982? The National Institutes of Health (NIH) issued a request for applications. Twenty-one centers from the U.S. and Canada would be selected to design and implement the feasibility phase of the DCCT. The leadership of the NIH, and specifically the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), recognized Dr. Crofford’s unique talent in bringing people together and motivating excellence in collaborative research and appointed him as Chair of the DCCT Research Group. The twenty-one centers selected to participate in the DCCT planning phase, and subsequent feasibility study, met monthly for 1 year in Bethesda to craft the final feasibility protocol and manual of operations (5). This planning phase represented a unique approach to collaborative research and, under Crofford’s leadership, became a research family dedicated to achieving the goals of the feasibility study.

The successful completion of the feasibility phase of the DCCT (6) allowed the study group to proceed to the large-scale study with the addition of eight new centers and the recruitment of 1,441 participants to the primary prevention and secondary intervention components of the DCCT. Half of the patients were randomized to intensive therapy (multiple daily injections or insulin pumps with targeted self-monitoring of blood glucose and HbA_1c goals) and half to conventional therapy equivalent to the standard of diabetes care at the time. Dr. Crofford continued to chair the study group and was able to provide the outstanding leadership necessary to motivate physician investigators, clinical trial coordinators, and other study personnel to achieve incredible success in study recruitment and compliance with a demanding protocol. The Data Safety and Monitoring Board overseeing the DCCT recommended that it be stopped early, after a mean follow-up of 6.5 years. This was indeed an exciting time, and the study group would have the opportunity to present for the first time the results of this long-awaited trial at the 1993 Scientific Sessions of the ADA in Las Vegas. The study group had completed an intensive planning exercise designed to develop the best protocol, and it successfully demonstrated that two levels of glycemic control could be achieved in the 278 feasibility study participants and ultimately recruited 1,441 patients to the expanded 29 DCCT centers with incredible participant retention and adherence to the study protocol. The diabetes community was anxiously awaiting the DCCT results, which were expected to finally resolve the glucose hypothesis debate. Consistent with his leadership style, Crofford wanted the spotlight to shine on his DCCT family and not himself. Thus, although he worked diligently with the study group to craft a polished presentation, he chose to allow his younger colleagues to present these results to a packed ADA DCCT-dedicated symposium with simultaneous publication in the New England Journal of Medicine (7). Under his leadership, he also insisted that prior to the scientific presentation at the ADA and the subsequent announcement in the lay press, each center would have to convene a study participant meeting with family members to present the DCCT findings to them, our partners in this research. These events were scheduled 2–3 days before the ADA presentation, and remarkably not a single participant broke the embargo on the study results before the ADA presentation.

Although the DCCT answered the key study question pertaining to the glucose hypothesis and the development of complications, much was still to be learned by following these patients in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. The impact of intensive therapy on more advanced complications and the demonstration of the phenomenon of metabolic memory are major outcomes from EDIC. The incredible DCCT participant loyalty to the study has been fundamental to obtaining continued NIH support.

Recently, DCCT/EDIC celebrated its 30th anniversary with a symposium at both the ADA and the EASD. The summary of these presentations has been published in a series of articles in Diabetes Care (8–13) and a perspective published in Diabetes (14). The DCCT research group demonstrated that chronic glycemia and the duration of diabetes are the major factors in the development and progression of complications in people with type 1 diabetes and that early intervention is most effective in achieving these goals. Another measure of the impact and legacy of the DCCT/EDIC study is the large number of annual citations that continues to increase over time (Fig. 1) and was well over 20,000 by 2013.

By 1995, Crofford had been working in the diabetes field for 40 years. He regarded the completion of the DCCT as the culmination of his academic and clinical diabetes mission and made the difficult choice not to continue with the DCCT/EDIC journey. It was time to retire.

During his medical career, awards included the ADA’s Outstanding Scientific Achievement Award in 1970, the Charles H. Best Medal for Distinguished Service in the Cause of Diabetes in 1976, the Banting Medal for Service (to President, Medicine and Science) in 1982, and the Addison B. Scoville Award for Outstanding Volunteer Service in 1987, and in 1999, he was presented with the Novartis Long-standing Achievement Award. Although retired, he still attends the ADA Scientific Sessions every other year and the EASD meeting on alternate years.

After leaving Vanderbilt in 1995, the Croffords relocated from Nashville to the family farm in the Ozarks of North Central Arkansas to take up cattle ranching. Today Crofford describes it as “. . . the most beautiful farm in the Ozarks in north Arkansas.”

The farm was originally purchased by Oscar’s parents in 1950 as a family retreat. Today, Oscar and Jane raise Black Angus cattle on their Rocky Bayou Angus and Timber Farm. Retirement has not been without its own obstacles. Disaster struck in February 2008 in the form of a CF5 tornado. With driving rains and high winds, their home, outbuildings, and vehicles were destroyed and, as Oscar stated, “200 acres of timber were reduced to toothpicks.” After the tornado, Crofford wrote in a letter to family and friends that “surviving was the easy part.” Deciding what to do in the aftermath, when most all was gone, was the challenge (15). It was their love for the area that kept them there.

Among some of the salvageable items, they were able to save the tractor, which they used for another 5 years before replacing it in 2013. In a recent interview, Oscar pointed out that, “tractors are an essential part of any farming operation.” At 84 years of age, he still grows, cuts, cures, fluffs, rakes, bales, and hauls Bermuda grass hay for feed for the animals, supplementing with a small amount of grain during the wintertime. The cattle farm is “semi-sustainable,” using mostly forage for feed.

Today, the Croffords have 1,000 acres: 200 for the cows, 300 planted in loblolly pine trees, and 500 in natural woodlands and wildlife habitat. The house has been rebuilt, along with two barns and a guest house (which they refer to as the “bunkhouse”). Fences, fields, and pastures have been restored. The farm’s end product is registered Black Angus breeding bulls. Oscar commented, “having a pasture full of 16-month-old bulls is like a house full of teenage boys…trouble, but entertaining.” Someone recently asked him if he was making any money. His answer was, “no, but we are losing less.”

It would still appear that Oscar Crofford does not consider personal gain as the value of what he does but rather how his actions can encourage and inspire others.

For those of us involved in diabetes, we will always regard Oscar Crofford’s diabetes research accomplishments as having a seminal impact on diabetes care, education, and research that continues to have far-reaching effects on the millions of people affected by diabetes.