Diabetes Care Volume 39, March 2016
333
Guillermo E. Umpierrez
PROFILES IN PROGRESS
Abbas E. Kitabchi, PhD, MD: An
Exemplary Mentor and Clinical
Researcher
Diabetes Care 2016;39:333–336 | DOI: 10.2337/dc15-0552
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.
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
Abbas E. Kitabchi at the Clinical Research Unit, UTHSC, Memphis, TN
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
andtaughtherhowtocookPersianfood.
He completed his bachelor of science
in chemistry in 1954 and then began his
Department of Medicine, Emory University School of Medicine, Atlanta, GA
Corresponding author: Guillermo E. Umpierrez, [email protected].
© 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.
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Profiles in Progress
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
care.diabetesjournals.org
improves glucose toxicity and b-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-a, interleukin [IL]-6, IL-1b, 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 insulininduced 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 accomplishmentdeach 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
Umpierrez
on the editorial board of numerous
peer-reviewed journals in the field of diabetes and metabolism and as longstanding 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 DagogoJack, 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 greatgrandson. 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
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Profiles in Progress
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.
References
1. Kitabchi AE. Ascorbic acid in steroidogenesis.
Nature 1967;215:1385–1386
2. Kitabchi AE, Nathans AH, Kitchell CL. Adrenal
gland in vitamin E deficiency. 3. Inhibition of
adrenocorticotropic hormone-induced steroidogenesis in isolated adrenal cells by ascorbic acid. J Biol Chem 1973;248:835–840
3. Kitabchi AE, Ayyagari V, Guerra SM. The efficacy of low-dose versus conventional therapy of
insulin for treatment of diabetic ketoacidosis.
Ann Intern Med 1976;84:633–638
4. Morris LR, Kitabchi AE. Efficacy of low-dose
insulin therapy for severely obtunded patients
in diabetic ketoacidosis. Diabetes Care 1980;3:
53–56
5. Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by
various routes. N Engl J Med 1977;297:238–241
6. Sacks HS, Shahshahani M, Kitabchi AE, Fisher
JN, Young RT. Similar responsiveness of diabetic
ketoacidosis to low-dose insulin by intramuscular injection and albumin-free infusion. Ann Intern Med 1979;90:36–42
7. Fisher JN, Kitabchi AE. A randomized study of
phosphate therapy in the treatment of diabetic
ketoacidosis. J Clin Endocrinol Metab 1983;57:
177–180
8. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis.
Ann Intern Med 1986;105:836–840
9. Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the
treatment of patients with diabetic ketoacidosis. Am J Med 2004;117:291–296
10. Umpierrez GE, Latif KA, Cuervo R, Karabell
A, Freire AX, Kitabchi AE. Subcutanbeous aspart
insulin: a safe and cost effective treatment of
diabetic ketoacidosis. Diabetes 2003;52 (Suppl.
1):584A
11. Umpierrez GE, Smiley D, Kitabchi AE.
Narrative review: ketosis-prone type 2 diabetes mellitus. Ann Intern Med 2006;144:
350–357
12. Kitabchi AE, Umpierrez GE, Fisher JN,
Murphy MB, Stentz FB. Thirty years of personal
experience in hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar
state. J Clin Endocrinol Metab 2008;93:1541–
1552
13. Stentz FB, Umpierrez GE, Cuervo R, Kitabchi
AE. Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises.
Diabetes 2004;53:2079–2086
14. Razavi Nematollahi L, Kitabchi AE, Stentz
FB, et al. Proinflammatory cytokines in response
to insulin-induced hypoglycemic stress in
healthy subjects [published correction appears
in Metabolism 2009;58:1046]. Metabolism
2009;58:443–448