Download m etaBolism, endoCrinoloGy & diaBetes

M e ta b o l i s m , E n d o c r i n o lo g y & D i a b e te s
Peter R. Arvan, MD, PhD
Division Chief/Professor
Emeritus Faculty
Stefan S. Fajans, MD (active)
Ralph F. Knopf, MD (active)
Sumer B. Pek, MD (active)
Professor
Ariel L. Barkan, MD
Charles F. Burant, MD, PhD
William F. Chandler, MD (secondary)
Thomas J. Giordano, MD, PhD (secondary)
Roger J. Grekin, MD
Milton D. Gross, MD (secondary)
William H. Herman, MD, MPH
Ronald J. Koenig, MD, PhD
Ormond A. MacDougald, PhD (secondary)
Richard M. Mortensen, MD, PhD (secondary)
Massimo T. Pietropaolo, MD
David E. Schteingart, MD
Meng Tan, MD
Stress Hyperglycemia
Adjunct Professor
Henry G. Bone III, MD
Douglas A. Greene, MD
Marcia F. McInerney, PhD
Associate Professor
Gary D. Hammer, MD, PhD
Craig A. Jaffe, MD
Arno K. Kumagai, MD
Robert W. Lash, MD
Martin G. Myers Jr, MD, PhD
Adjunct Associate Professor
Martin J. Stevens, MD
Assistant Professor
Annette M. Chang, MD
Tae-Hwa Chun, MD, PhD
Eleni V. Dimaraki, MD
Liselle Douyon, MD
Nazanene H. Esfandiari, MD
Diane C. Fingar, PhD (secondary)
Jennifer R. Franzese, MD
Roma Y. Gianchandani, MD, MBBS
Elif A. Oral, MD
Rodica Pop-Busui, MD, PhD
Jennifer A. Wyckoff, MD
Research Assistant Professor
Ming Liu, MD, PhD
Heike Muenzberg, PhD
Ghada A. Soliman, MD, PhD
Adjunct Assistant Professor
Anthony Weinert, DPM
Instructor
Palak Choksi, MBBS
Crystal M. Holmes, DPM
Clinical Lecturer
Israel Hodish, MD, PhD
Angela R. Subauste, MD
Adjunct Clinical Lecturer
Susan L. Johnson, MD
Vivian H. Lin, MD
Research Investigator
Arun K. Das, PhD
Leena Haataja, PhD
Mayumi Inoue, MD, PhD
Stephen I. Lentz, PhD
Bin Xu, PhD
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The pancreas produces
insulin to keep glucose
levels in balance.
High blood sugar affects over half of patients undergoing
heart or blood vessel surgery, even patients who don’t
have diabetes. “Stress hyperglycemia”, as this condition is
known, results from the flood of stress hormones released
by the body during cardiac surgery, cooling of the body by
heart-lung bypass machines, post-operative medications and
parenteral nutrition. Research has clearly shown that high
blood glucose perioperatively can increase the risk of postoperative infections and other complications, so cardiac and
vascular surgery patients typically have their sugar monitored and treated closely during and after their procedures.
This knowledge is the foundation for the Hospital Intensive
Insulin Program (HIIP), established by Roma Gianchandani,
MD, MBBS (below), program director. Established in late
2004 with strong backing by the Surgery department, the
program received a Clinical Innovation Fund Award soon
after its inception. The HIIP oversees management of blood
glucose levels in patients with diabetes and postoperative
stress hyperglycemia after cardiac, thoracic and vascular
surgery­—from their time in intensive care until discharge.
“Glycemic management teams are very desirable entities, and
hospitals all over the country are struggling to set them up,”
says Dr. Gianchandani. “We’re fortunate to have had one
here for the last three years.”
Comprised of several hard-working faculty and physician
assistants who contribute to its success, the HIIP program
actively trains health care professionals who provide
frontline diabetes care. In addition to caring for patients,
the HIIP team has worked with the rest of the University
Hospital to establish glucose management programs. The
team has helped standardize several inpatient protocols
and is currently leading efforts to institute basal-bolus
insulin therapy hospital-wide.
A significant shift in hospital blood glucose management
has already occurred since the program began. “Since this
adds another dimension to patient care and workload,
health care providers have performed marvelously. When
we first started out, blood glucose levels of 200 mg/dl or
above did not raise an eyebrow, while today I’m happy to
see that a much lower number will initiate a call to us,” says
Dr. Gianchandani.
According to scientific literature, blood glucose control leads
to shortened hospital stays; the HIIP team has seen that in
its own review of the program, too. Glucose control in this
complex patient group eliminates the disadvantage that high
blood sugars confer on patient outcomes.
Hospital glucose management also provides an opportunity
for patients with diabetes undergoing major procedures to
re-evaluate and focus on their sugar control, which can lessen
the likelihood of future complications. This is being studied
by the HIIP team through a new outpatient clinic, which
completes the blood glucose management loop. A recent
study, presented at the American Diabetes Association’s
2008 Scientific Sessions, found that of 1,400 patients, nearly
half had elevated sugar levels after surgery; about 15 percent
still needed insulin and other medications to control it when
they went home. A follow-up study to look more closely at
whether patients with stress-induced hyperglycemia have any
underlying glucose abnormalities also is underway.
Dr. Gianchandani believes the HIIP will pave the way for
the hospital to acquire Joint Commission certification for
inpatient diabetes care. This will mean embedding glucose
control in the U-M Health System culture, especially in areas where the data for glycemic management are compelling, she adds.
Metabolism, Endocrinology & Diabetes
New Intensive Insulin Program Brings Blood Sugar
Control Full-Circle
Department of Internal Medicine 2008 Annual Report • 41
Systems Biology at the Heart of Michigan
Metabolomics and Obesity Center
Obesity is not only common, affecting about one-third of adult
men and women in the United States; it’s a complex metabolic
condition associated with other serious illnesses, including type
2 diabetes, heart disease, stroke and several types of cancer. The Michigan Metabolomics and Obesity Center was founded
to explore obesity and other metabolic diseases using a “systems biology” approach, that is, from multiple perspectives and
at many levels, starting with the molecular level. “Metabolomics”
is the study of how molecules resulting from the breakdown of
the foods we eat are used and stored by the body—and how
these metabolites are influenced by our genetic makeup to
cause weight gain, weight loss, disease or health.
“We’re trying to collect a large amount of data on individuals, including clinical measures such as height, weight, blood pressure,
glucose, insulin and lipid levels and exercise capacity,” explains
Charles Burant, MD, PhD (far lower right), the center’s
director and the Dr. Robert C. and Veronica Atkins Professor of
Metabolism. The data can then be combined with information
about gene expression and with metabolomic and proteomic
measurements. Measurements are taken at baseline and after
perturbation, such as after eating certain types of foods, limiting
calories or taking medications.
“Several computational methods allow us to see how the various
components of the system react, and that allows us to better
understand which metabolites and metabolic pathways are
important in how an individual reacts to the different perturbations,” Dr. Burant says. That knowledge may lead to the discovery
of targeted interventions, such as a personalized diet or medication regimen, to ward off metabolic disease.
Through the center, Dr. Burant and other researchers also are
exploring why people who have the hepatitis C virus (HCV)
with fatty liver disease have higher levels of the virus in their
blood—as well as a higher risk of developing diabetes. The
team undertook a study involving gene transcription and
metabolomic analyses and found that people with HCV have a
different type of fat in the liver than those who are overweight,
and that cure rates among HCV patients with fatty liver disease
are lower. Dr. Burant says the team has likely found one of the
main pathways involved and is now planning tests for the effects
of different diets on viral levels in patients.
The center’s work is supported by an infrastructure that allows
for coordinated and complex analyses through several laboratories: an animal phenotyping core; a human phenotyping core
and a metabolomics core. To date, much of the research at the
center has been experimental, but investigators are recruiting
for clinical studies. And plans are underway for a new investigational weight management clinic, which would put several of
the tools developed by center members to use in personalized
interventions for patients. Interventions would be based not
only on what patients like to eat, but how they eat—when they
crave certain foods, how much and when they tend to eat. The
goal is to design individual programs to allow people to lose
weight and, more importantly, to maintain the loss in order to
improve health. Funded by the U-M Endowment for the Basic Sciences and
the Office of the Dean, the center is already serving as a hub
for several dozen researchers from numerous disciplines,
departments and schools across the University. “With this type
of systems biology approach, no one can investigate these
complex interactions alone; no one lab can do everything, and
so we have a lot of collaborations already underway with different departments within the Medical School, the College of
Engineering, the School of Kinesiology and with the Center for
Computational Medicine and Biology,” says Dr. Burant.
One such multidisciplinary collaboration includes research
into the role of different types of lipids in the development of
diabetes. Dr. Burant and colleagues are discovering that animals
fed a diet with fat from lard develop diabetes within three
weeks; animals fed an identical diet, only with fat from soy, never
develop the disease. “If we can understand why and the pathways involved,” he says, “we might be able to understand the
pathways in humans and why certain individuals get diabetes
and others don’t.”
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Laboratory mice help scientists study
metabolism and obesity.
Department of Internal Medicine 2008 Annual Report • 43