[GRG] NewAbs: Abnormal Pancreatic Growth Secondary to Diabetes Drug

To Members and Friends of the Los Angeles Gerontology
Research Group:Abnormal
pancreatic growth… — Steve Coles

“Research Suggests Popular Diabetes
Drugs Can Cause Abnormal Pancreatic Growth in
Humans”

by Enrique Rivero March 26, 2013;  (UCLA) — Individuals who had
taken a type of drug commonly used to treat Type-2

diabetes showed abnormalities in the pancreas, including cell
proliferation, that may be associated with an increased risk of
neuroendocrine tumors, according to a new study by researchers from UCLA
and the University of Florida. Their findings were

published on-line March 22nd in the journal Diabetes.
 The
researchers, from the Larry L. Hillblom Islet Research Center at UCLA and
the Diabetes Center at the University of Florida, found that cell mass
was increased approximately 40 percent in the pancreases of deceased
organ donors who had Type-2 Diabetes and who had been treated with
incretin therapy. This widely used type of treatment takes advantage of
the action of a gut hormone known as Glucagon-Like Peptide-1 (GLP-1) to
lower

blood sugar in the body.
 Although
there have been conflicting reports on the effects of the incretin class
of drugs on the pancreas in animal studies, this is the first study to
note such changes in the human pancreas. The research was made possible
by a unique research consortium called
nPOD (Network
for Pancreatic Organ Donors with Diabetes), led by Dr. Mark Atkinson, a
Professor of Pathology and Pediatrics at the University of Florida. The
network, which is funded by the Juvenile

Diabetes Research Foundation, obtains pancreases from deceased organ
donors, with permission of their next of kin, to better understand
diabetes by investigating tissues of those with the disease.
 
“There is an increasing appreciation that animal studies do not
always predict findings in humans,” said Dr. Peter Butler, director
of UCLA’s Hillblom Islet Research Center and chief of the endocrinology,
diabetes and

hypertension unit. “The nPOD program is therefore a very
precious resource.”
 The
researchers examined the pancreases of 20 deceased organ donors with
Type-2 diabetes. Eight had been treated for at least a year with incretin
therapy, while the other 12 had received therapies that didn’t include
incretin-based drugs. The researchers also evaluated 14 pancreases from a
control group of non-diabetic individuals of similar age.
 The
pancreases of the individuals who had been on incretin therapy were
larger than those of patients on other

types of diabetes therapies, and this larger size was associated with
increased cellular proliferation. Incretin-treated individuals showed an
increase in pancreas dysplasia, an abnormal form of cell proliferation
that is a risk factor for pancreatic cancer, as well as an expansion of
alpha cells, endocrine cells that make the hormone glucagon.
 This
latter finding is likely a consequence of GLP-1–based therapies’
suppression of the release of glucagon by alpha cells, since decreasing
the availability or action of the hormone glucagon has been shown in a
variety of prior studies to induce a proliferation of pancreatic alpha
cells. This alpha-cell expansion has been associated with the development
of pancreatic neuroendocrine tumors. Three of the eight incretin-treated
individuals had microadenomas and one has a

neuroendocrine tumor composed of alpha cells.
 Of the
eight donors who were on incretin therapy, seven had been taking
sitagliptin, sold in pill form as Januvia and marketed by
Merck, and one had been on exenatide, sold as Byetta by
Bristol-Myers Squibb. These and similar drugs are currently under
investigation by the U.S. Food and Drug Administration for their possible
links to pancreatitis and

pancreatic cancer.
 
“These findings lend additional weight to concerns regarding the
effects of long term GLP-1–related therapy, with respect to both
unintended proliferative actions on the exocrine pancreas and now also a
possible increased risk of neuroendocrine tumors,” the researchers
write. “In addition to the surveillance previously recommended for
the potential association of GLP-1– based therapy and pancreatic cancer
risk, the current data imply that surveillance for a possible increased
risk of pancreatic neuroendocrine tumors is warranted.”
 Such
surveillance approaches might include MRI imaging of the pancreas and
screening for neuroendocrine tumors, Butler said.
 “The
present studies are only from a small number of individuals, and while
the findings do raise concerns, it will be important that other
approaches are now used in a larger group of living individuals to
further investigate these findings,” he said.
 A recent
study led by Dr. Sonal Singh of Johns Hopkins University School of
Medicine and Public Health and published in JAMA Internal Medicine
suggested a doubling in the risk of hospitalization for acute
pancreatitis with the GLP-1–based therapies and also recommended further
research.
 
“Since most risk factors for acute pancreatitis are also linked to
an increased risk of pancreatic cancer, these findings of changes in the
human pancreas are very concerning,” said Singh, an Assistant
*Professor of Medicine and International Health. “Now that
GLP-1–based therapies have been shown to increase the risk of pancreatic
inflammation and abnormal cell proliferation, further studies are needed
to urgently clarify whether these linkages lead to pancreatic cancer with
long-term use.”
 Study
co-authors, in addition to Butler and Atkinson, are Alexandra E. Butler,
Tatyana Gurlo and David W. Dawson, all of UCLA, and Martha
Campbell-Thompson of the University of Florida.
__________________________
Grants from National Institute of Diabetes and Digestive and Kidney
Diseases (DK059579, DK061539 and DK077967), the Hillblom Foundation, and
the Peter and Valerie Kompaniez Foundation funded this study. The
Juvenile Diabetes Research Foundation funds the nPOD
program.
L. Stephen Coles, M.D., Ph.D., Co-Founder
Los Angeles Gerontology Research GroupURL:
http://www.grg.org
E-mail: scoles@grg.orgE-mail:
scoles@ucla.edu

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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