Trevor Orchard: Fruitful Contributions to Diabetes Epidemiology

In EDC, a well-characterized long-term cohort of people with type 1 diabetes started in 1986, Orchard has followed nearly 800 participants identified within 1 year of diagnosis between 1950 and 1980 at Children’s Hospital of Pittsburgh (1). Orchard gives credit for inspiration and guidance to Professor Ronald Klein of the long-running Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR); Klein continues to this day to grade the retinal fundal photographs from EDC. EDC was also preceded by the Allegheny County Type 1 Diabetes Registry (2), which still contributes data on longevity (3). Unlike a registry, EDC offers regular follow-up, data on censoring, and the ability to characterize multiple exposures. EDC generates vital statistics to verify life expectancy (4), descriptive statistics to monitor incidence of complications (1), and relational statistics to test associations between patient characteristics and subsequent complications. Orchard and coworkers have identified associations, but have also identified when associations do not exist, for example, between BMI and the complications of diabetes (5). Orchard and colleagues (6) have used EDC to develop a model for type 1 diabetes that accounts simultaneously for risk factors and extrapolates the incidence of complications into the future. Through dedication and finesse, Orchard has kept EDC going; the longer the study runs, the more valuable it becomes.

Others have established cohorts of people with type 1 diabetes, including, among others, WESDR, started in 1979, and EURODIAB, started in 1989 (7). This has offered Orchard the opportunity to collaborate and combine data from different populations. Ongoing projects include characterizing phenotypes and studying novel biomarkers to identify those at highest risk of diabetes complications. Of existing cohorts, Orchard considers the Finnish Diabetic Nephropathy Study, also known as FinnDiane, to be among the most important.

Orchard was born in the northern coal-mining center of Gateshead, England, in 1951, the son of Dorothy, a nurse, and Donald, a civil servant, whom the Queen honored with Commander of the Most Excellent Order of the British Empire for his contributions to the retraining of the unemployed. In 1958, Orchard moved to Brighton, on the south coast, where starting in 1962 he attended an English grammar school, a state-supported school for England’s brightest students. His main interest outside of school was cricket, a game he continues to follow enthusiastically. Per British tradition, he went straight from high school to medical school in 1969; he chose to study in Cardiff, Wales. He dates his interest in diabetes to his summer break in 1970. He and some friends had purchased an old ambulance they intended to drive to Greece for the summer; unfortunately, it broke down before the trip began. Forced to abandon his holiday, Orchard chose instead to volunteer as a counselor with the Camp America program. As he was a medical student, he was assigned to a camp organized for children with diabetes by the New York Diabetes Association. His summer was fun but also revelatory; he decided to make it his life’s goal to “investigate or cure” diabetes.

Previously, Orchard had become interested in research after working during a summer on the Brighton ambulance where he met Professor Douglas Chamberlain. Chamberlain had shown for the first time in England that automatic defibrillators saved lives in patients with out-of-hospital cardiac arrest. According to Orchard, the notion that the speed with which a patient receives defibrillation rather than the medical qualifications of the person holding the paddles “caused total uproar.” The idea that new unassailable evidence could rock entrenched medical practice excited Orchard and clinched his decision to pursue medical research.

Following his calling to research, Orchard’s transition to epidemiology seemed inevitable. According to Orchard, “epidemiology just grew on me.” His Brighton experience impressed upon him that observational evidence could change clinical practice. He also realized that to prevent an illness was better than to treat an illness. He acknowledges the major influence his Cardiff professor Archibald “Archie” Cochrane had on him, under whose guidance he wrote up a comparative evaluation of the Brighton ambulance man–based and Belfast doctor-based coronary ambulance services. Archie Cochrane is considered the father of evidence-based medicine.

Orchard resolved to combine clinical practice with public health and chose a fellowship in Nottingham, England, where he earned a master's degree in medical sciences. Among the patients he saw in his practice, particularly memorable was a 23-year-old man who presented with chest pain that was diagnosed as (just) musculoskeletal chest pain, but in reality was an acute myocardial infarction secondary to familial hypercholesterolemia. Concerned about the implications to the patient and to the patient’s family, Orchard embarked on a life-long interest in lipid disorders.

Orchard did not intend to emigrate to the U.S., but when training in Britain, he felt the need to get a BTA degree (Been to America). His choice of job in the U.S. was based not on institutional strengths but on the manner in which he was recruited (surface mail from Cincinnati, air mail from Pittsburgh). In 1979, he left Nottingham for the Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, where he remains. Within a year, he received 5-year funding from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute, and within another year, he became an assistant professor. Since 1980, Orchard has received continuous support from the National Institutes of Health, and since 1992 has held the title of Professor of Epidemiology.

For a period following a divorce, Orchard considered moving back to England. But he chose to remain after meeting his future wife, Trish, at his local tennis club. Having lived in both countries, Orchard now appreciates that the Americans and British can teach each other important lessons. For example, he feels strongly that Americans should “learn to drink before learning to drive,” as is done in Europe. He feels American clinicians could teach their British counterparts how easy it is to e-mail, fax, or pick up the phone and talk to patients and their referring physicians. He believes fundamentally that Americans should learn from the British how to provide a publicly funded egalitarian health care system. Orchard states his view succinctly: “The competitive market system does not work for health care.”

Orchard is known for “telling it like it is” and does not sway with prevailing beliefs that vary from his own. He differs with some members of the diabetes research community with respect to the extent the role glycemia plays in accelerating the complications of diabetes. Specifically, he doubts a strong epidemiologic association between hemoglobin A_1c and coronary artery disease and considers this “both concerning and intriguing” (8). Though clearly he accepts the DCCT/EDIC results showing that intensive therapy started early in type 1 diabetes reduces cardiovascular disease risk (9), he also suggests that the clinical community would “do better to address traditional risk factors, including insulin resistance, inflammatory markers, and depressive symptomatology, rather than focus on glycemic control” (8). Of relevance, a recent Cochrane meta-analysis of interventional data offered a related conclusion—namely, that intensive glucose control does not lower the incidence of cardiovascular disease in type 1 diabetes (10). While some may consider Orchard’s beliefs iconoclastic, Orchard is not incautious; his beliefs reflect years of observation and reflection.

Orchard appreciates that if glycemia alone does not cause premature death from cardiovascular disease in type 1 diabetes, then something else must. He believes that renal disease, or more accurately increased albuminuria, accounts for most—if not all—of the increased risk of death associated with diabetes. Orchard has shown that in the absence of albuminuria, mortality risk over 20 years in type 1 diabetes is comparable to that of the general population (11), confirming the earlier observations of the FinnDiane study (12).

He summarizes his approach to work as taking the “broad look” and avoiding “traditional lines.” His studies have addressed such diverse topics as the influence of socioeconomic status on diabetes complications (13), noninvasive means to determine hemoglobin A_1c (14), and whether preventing diabetes makes economic sense (15).

Alongside his métier as epidemiologist, Orchard practices medicine, attending in lipid clinics. (When asked why he chooses not to do diabetes clinics, he remarked, “clinical diabetes is too complicated.”) He understands firsthand how clinical trials can influence patient care. Having participated in the major trials in diabetes, he has helped foreshadow step changes in care. These changes include, from the DCTT, lowering blood glucose to lower the risk of diabetes complications in people with type 1 diabetes and, from the DPP, losing weight and increasing physical activity to delay—if not prevent—the onset of type 2 diabetes. The DPP had operationalized long-standing epidemiologic knowledge into an intervention. Orchard led the Pittsburgh field site as both trials evolved into epidemiologic studies: the DCCT into the EDIC study and the DPP into the DPPOS. The BARI 2D (16) trial addressed questions including whether in a population with type 2 diabetes and coronary disease revascularization of patients was better at reducing cardiovascular events than medical therapy alone and whether drugs that sensitize the body to insulin were better than those that provide insulin (endogenously or exogenously). The trial’s findings were negative, and, if real, then they are as important to clinical care as had the trials been positive.

From a personal standpoint, Orchard identifies his most interesting work as his projects in Africa. He works closely with the Life for a Child Program of the International Diabetes Federation and the Association Rwandaise des Diabetiques. Both provide care to youth with diabetes. In conjunction with the National University of Rwanda and through the University of Pittsburgh, he also leads a trial funded by the National Institutes of Health that compares, among youth with type 1 diabetes, a basal insulin approach to care versus the current standard of care (NPH/regular twice daily). Orchard’s prior belief is that this will provide better care—especially fewer episodes of hypoglycemia—than current treatment. Orchard and colleagues (17) have also contributed to the epidemiology of diabetes in Rwanda, documenting disturbing figures that one-third of young people with type 1 diabetes have hemoglobin A_1c values over 14% and nearly half have hypertension. Orchard wants to learn more about the interplay between African culture and health. From a scientific standpoint, Orchard declares his most interesting work as his projects that characterize the “very poor understanding of gene-environment interaction” and is particularly interested, along with his colleague Tina Costacou, in the role of haptoglobin and its potential association with the complications of diabetes (18,19).

When questioned in what professional role other than doctor he would excel, he suggested “a curmudgeon.” He admires postmen because “like surgeons,” postmen have defined tasks and see immediate results at the end of each day. This sentiment is unsurprising for a man who runs studies that require decades to get definitive results.

Among the commendations he has received are the Kelly West Award (1993) and the Charles Best Medal (1994) from the American Diabetes Association. Informal praise includes remarks on his dedication to graduate students who now number more than 60, and he has received formal praise with his recent University of Pittsburgh Provost Award for excellence in mentoring. Orchard oversees fellows in clinic and is principal investigator of a National Heart, Lung, and Blood Institute Cardiovascular Epidemiology Training grant. Kind and patient, he is well liked by his trainees to the extent that some never leave his company.

He balances work with family, which includes his wife, Trish; their combined three children; and seven grandchildren. He plays tennis and golf. When not at home in Pittsburgh, among the most livable of U.S. cities, he spends time hiking, boating, and boogie boarding at his home on the northern California coast. Orchard attends scientific meetings and is a fixture at the European Diabetes Epidemiology Group, where he fraternizes with old acquaintances and is gracious to young new researchers. He does not talk of retirement. But, with research funding to at least 2019, he does not need to.

Trevor Orchard is dedicated and has a strong sense of social commitment. He identifies “thoughtful” and “persistent” as (the kinder) adjectives his family might choose to describe him. Others describe his self-deprecatory style and understated sense of humor. He is popular with colleagues at all stages of their careers. Being modest in the setting of substantial accomplishments makes him an ideal role model. Fortunately, he shows no signs of slowing.

Duality of Interest. No potential conflicts of interest relevant to this article were reported.