Abbas E. Kitabchi, PhD, MD: An Exemplary Mentor and Clinical Researcher

The word “mentor” was first used in Homer’s epic poem The Odyssey. When Odysseus, the king of Ithaca, went to fight the Trojan War, he asked Mentor to serve as a teacher and overseer to his son Telemachus. Mentor failed in his duties, and it was Athena, goddess of war and patroness of the arts and industry, who assumed the form of Mentor and served as Telemachus’ wise and trusted adviser and counselor. The first recorded modern usage of the term can be traced to the 18th century book entitled Les Aventures de Télémaque, by the French writer Fénelon. Since then, the word “mentor” has evolved to mean trusted adviser, a wise and responsible tutor who shares knowledge with and inspires, challenges, and serves as a role model to a less experienced person. Dr. Abbas E. Kitabchi exemplifies all the attributes of a great mentor, as can be attested by the large number of health care professionals that have benefited from his mentoring during the past four decades.

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Abbas E. Kitabchi at the Clinical Research Unit, UTHSC, Memphis, TN

Dr. Kitabchi, or Abbie as his friends and relatives call him, was born in Teheran, Iran, in 1933. He was the third among seven siblings and the first in his family to receive a high school education. His father, Hossein Eqbal Kitabchi, was a publisher and his mother was a housewife. After completing high school, he immigrated to the U.S. at 17 years of age to attend Cornell College in Mount Vernon, IA, to follow his father’s dream for Abbie to become a heart surgeon. He remembers:As a young immigrant with almost no ability to speak English and only $600 in my pocket, it was indeed uncomfortable and challenging at first. I was scared and lonely living in this new country by myself. When I first arrived at Cornell College, I lived in one of the barracks originally built for soldiers during World War II. Living conditions were less than ideal, the weather in Iowa was very cold in the winter and hot in the summer; with no form of transportation I had to walk 2 miles to and from class. After the first year, wonderful friends helped me find private boarding with an elderly lady who provided me with a room in her home. In exchange for her hospitality, I helped her with daily household chores and taught her how to cook Persian food.

He completed his bachelor of science in chemistry in 1954 and then began his graduate studies at the Graduate College, University of Oklahoma Medical Center in Oklahoma City, OK, where he received his master of science in 1956 and a PhD degree in chemistry and biological sciences in 1958.

During his postgraduate training in the Department of Physiology in Oklahoma, he joined the laboratory of Dr. Ranwel Caputto. He was the first to isolate the product of lipid peroxidation, malondialdehyde, from the liver of vitamin E–deficient animals. He reported that liver preparations from rats fed a diet deficient in vitamin E have a lower rate of synthesis of ascorbic acid than from animals receiving vitamin E. He also reported that changes in the concentrations of ascorbic acid and cholesterol were related to steroid secretion in the adrenal glands (1) and described the role of ascorbic acid in steroidogenesis on lipid peroxidation and free fatty acid content in the adrenal gland. He reported that high concentrations of ascorbic acid could prevent steroidogenesis through peroxidation of unsaturated lipids (2).

At the end of his doctorate training, he was accepted to medical school at the University of Oklahoma Medical Center and received his medical degree in 1965. As a medical student, he received his first R01 grant from the National Institutes of Health (NIH) to study the role of vitamin E on lipid peroxidation. Dr. Kitabchi remembers that it was not easy to fulfill the demanding chores of medical school and run his research grant. He spent most evenings and weekends in the laboratory completing experiments and crunching data, leaving weekdays for his clinical work as a medical student. After completing medical school, he moved to Seattle in 1966 to join the endocrinology fellowship program at the University of Washington under the supervision of Dr. Robert H. Williams. He continued to work on lipid peroxidation and vitamin E as a proinflammatory agent. During his fellowship, he became distressed by the high mortality rate of patients with diabetic ketoacidosis (DKA), which led to his profound interest in the physiology and management of patients with hyperglycemic crises.

After completion of his endocrinology training in 1973, he accepted the position of associate chief of staff and the director of research at the Veterans Administration Medical Center at the University of Tennessee Health Science Center (UTHSC) in Memphis, TN. Shortly after that, he became section chief of endocrinology and director of the General Clinical Research Center at UTHSC. In this position, he designed a series of prospective randomized clinical trials in the management of DKA. Our current knowledge and practice of treatment of hyperglycemic crises is based on his seminal work in patients with hyperglycemic crises. Prior to his work, treatment of DKA was complicated, and protocols required large doses of insulin (∼100 units/h) to be given intravenously (IV), subcutaneously (SC), or intramuscularly (IM). This was thought to be necessary because of fears of insulin resistance. In 1973, he reported that a low-dose (7–10 units/h) was as effective as large-dose IM insulin therapy in the treatment of DKA without significant differences in the time of resolution of hyperglycemia and ketoacidosis (3). In addition, he reported that high-dose insulin therapy was associated with ∼25% incidence of hypoglycemia and hypokalemia compared with less than 5% of patients treated with a low-dose insulin regimen (4).

In subsequent trials, he studied the differences in the route of insulin administration given IV, IM, or SC in patients with DKA (5). His research team reported that all routes of administration were effective but that the IV infusion resulted in a more rapid resolution of hyperglycemia and ketonemia compared with the IM or SC routes. He also investigated the need for a “loading or bolus” insulin dose to improve the resolution of hyperglycemia and hyperketonemia in DKA (6). He reported that recovery parameters were similar between groups, indicating that the priming IM dose followed by intermittent IM or SC injections was as effective as the continuous IV infusion of regular insulin in resolution of ketoacidosis. In two randomized studies, he investigated the benefits of phosphate and bicarbonate therapy in patients with DKA. He reported that the phosphate-treated patients had higher levels of 2,3-diphosphoglyceric acid but that phosphate administration had no demonstrable effect on tissue oxygenation or any parameter of clinical response (7). Similarly, the benefit of bicarbonate administration was assessed by repeated lumbar punctures at baseline, at 6–8 h, and at 12–24 h during therapy with analysis of the cerebrospinal fluid for glucose, bicarbonate, pH, total ketones, and osmolality (8). His group reported no significant differences in the rate of glucose or ketone body decline between groups. These studies led to the conclusion that the routine administration of phosphate and bicarbonate is not associated with improved recovery in patients with DKA.

The availability of rapid-acting insulin analogs, with an onset of action resembling IV dose, let his research team postulate that this new insulin formulation could be used as an alternative route to the IV infusion of regular insulin in patients with DKA. In two randomized studies, his team compared the efficacy and safety of SC lispro every hour (9) and aspart every 2 h (10) with that of a standard IV infusion of regular insulin. Patients treated with SC insulin analogs were treated in the emergency department or in regular medicine wards, and those treated with IV protocol were managed in the intensive care unit. He reported no differences in mean duration of treatment until correction of hyperglycemia and ketoacidosis between groups. In addition, treatment with SC insulin analogs outside the intensive care unit was associated with a 39% lower hospitalization costs.

Teaming with researchers in Atlanta, he reported on the high prevalence of overweight and obesity in newly diagnosed patients with DKA and their unique clinical course resembling type 2 diabetes. These studies showed that the majority of obese patients with unprovoked DKA have type 2 diabetes, as indicated by measurable insulin reserve, a strong family history of diabetes, an absence of autoimmune markers, and the ability to discontinue insulin therapy and go through a period of near-normoglycemia remission. Studies in these patients showed that, at presentation, patients with ketosis-prone type 2 diabetes have markedly decreased pancreatic insulin secretion, which is lower than in obese patients with comparable hyperglycemia but significantly greater than in lean patients with type 1 diabetes (11). Aggressive management with insulin significantly improves glucose toxicity and β-cell function, allowing for the discontinuation of insulin therapy (12). In recent years, he also reported that hyperglycemia and ketoacidosis are associated with a severe inflammatory state characterized by an elevation of proinflammatory cytokines, reactive oxygen species, and cardiovascular risk factors (13). Circulating levels of tumor necrosis factor-α, interleukin [IL]-6, IL-1β, IL-8, C-reactive protein, plasminogen activator inhibitor-1, free fatty acids, cortisol, and growth hormone are significantly increased on admission, and levels return to normal after resolution of the hyperglycemic state. Similar to hyperglycemia, he also reported that insulin-induced hypoglycemia results in increased inflammation, oxidative stress, cytokine activation, and counterregulatory hormones (14).

In addition to his seminal studies in hyperglycemic crises, Dr. Kitabchi has made important and long-lasting contributions to the science and practice of endocrinology and diabetes. He served as the principal investigator or co-investigator of several landmark NIH trials, including Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC), Diabetes Prevention Program (DPP)/Diabetes Prevention Program Outcomes Study (DPPOS), Look AHEAD (Action for Health in Diabetes), Actos Now for Prevention of Diabetes (ACT NOW), and two studies supported by the American Diabetes Association (ADA) on the role of macromolecules (high protein or high carbohydrate) on various metabolic parameters in subjects without diabetes and in people with impaired glucose tolerance. He has published more than 300 original articles and over 100 book chapters and reviews. He states that each one of his publications brings a unique sense of accomplishment—each article has an important message and a personal satisfaction.

Dr. Kitabchi has been the recipient of numerous teaching and clinical awards. He was elected as member of The American Society for Clinical Investigation in 1972, was appointed as Maston K. Callison Professor of Medicine and Molecular Sciences for UTHSC in 2009, and was elected Master of the American College of Endocrinology in 2013. He has served on the editorial board of numerous peer-reviewed journals in the field of diabetes and metabolism and as long-standing member of prestigious societies, including the ADA, the Endocrine Society, the American College of Physicians, The American Society for Clinical Investigation, and the American Association of Clinical Endocrinologists.

Dr. Kitabchi retired as division chief in January 2014. He happily turned his responsibilities as chief of endocrinology and his NIH grants to Dr. Samuel Dagogo-Jack, the 2015–2016 President of Medicine & Science of the ADA. Dr. Kitabchi still continues to stay active as professor emeritus at UTHSC and goes to his office 2 days a week to follow the progress of his current ADA research grant. The results of his dietary intervention studies in patients with prediabetes were presented at the 2015 ADA 75th Scientific Sessions.

An important part of his scientific impact was through his role as a mentor, clinician, and teacher. Over the years, he has mentored hundreds of students, residents, postdoctoral and endocrine fellows, nurses, and junior faculty, many of whom have become leaders in their respective fields. He states that much of his academic success comes from the close interaction with his trainees and collaborators. He is grateful to all of his trainees for their friendship and support, in particular his long-term collaboration with Mary Beth Murphy, C.K. Buffington, Frankie Stentz, George Burghen, Guillermo E. Umpierrez, Samuel Dagogo-Jack, Ralph DeFronzo, William C. Duckworth, Joseph Fisher, Amado Freire, A.O. Gaber, Larry Morris, Ebenezer Nyenwe, Xavier Pi-Sunyer, Mark Rumbak, Harold Sacks, Solomon S. Solomon, Judy Spencer, and Aidar Gosmanov. When I asked two of his current collaborators about Abbie’s greatest achievements, both of them highlighted his friendly personality and how easy it is to approach him. Frankie Stentz, who has worked with him for 20 years, highlights his dedication and success in maintaining over 30 years of continuous NIH funding for the General Clinical Research Center at UTHSC. Aidar Gosmanov, one of his trainees, calls him the godfather of hyperglycemic crises and states that “thanks to his contributions we have effective treatment algorithms that have reduced hospital mortality and complications of patients with DKA.”

Dr. Kitabchi is not only an excellent scientist but also a magnificent family person. He has been happily married to Lynn Kitabchi for 20 years and has four marvelous daughters, Karen, a registered nurse, Kathy, a poet, Kelly, a master in nursing, and Karly, a teacher in a Montessori school; two step-daughters, Carissa, MBA, and Blake Elizabeth, who was admitted to optometry school; eight grandchildren; and one great-grandson. These days, Dr. Kitabchi spends his free time with his wife and grandchildren. He enjoys traveling with his family to visit family in Germany, a brother in Iran, Austria, and a sister in Salt Lake City, UT. He was a ping-pong champion in high school and continues to enjoy playing with his grandchildren. He is also a good cook and continues to invite his coworkers and friends to enjoy classic Persian dishes, such as lamb and chicken kebabs, rice, and hummus with herbs and nuts. His favorite dishes are chicken khoresh (stew) with lemon herbs and Persian tahdig rice. The word tahdig means “bottom of the pot,” where the crispy golden layer is formed, which is supposed to resemble the large and wide golden dessert.

When asked about his secret for success, he replies: “You have to show dedication, as hard work pays off. Of course, this represents a great challenge to family and personal commitments.” He also says to “find your own area of clinical and research interest, be focused, pose questions, and go after them. Pursue your areas of interest with dedication and in a tireless way.” When asked about future goals, he replies: “I hope to take a trip around the world in the near future and continue to present the results of dietary intervention and latest research findings. I also want to continue to mentor and support my collaborators at the University of Tennessee and around the world.”

In summary, Dr. Kitabchi is a remarkable professional who has made important contributions to our understanding of the physiology and treatment of hyperglycemic crises as well as in other areas of endocrinology and diabetes. He is a great clinician educator with superb communication and mentoring skills. He is a marvelous and dedicated family man with an easy smile and a warm heart. As one of his mentees, I am forever grateful for his friendship and mentoring and for the opportunity to learn from him the fundamentals of clinical research.

• © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.