Archives - News & Press Releases
Belly Fat Raises Risk of Death Even When BMI is 'Healthy'
Today.com reported that "being normal weight with belly fat more deadly than obesity" according to a new study published in the Annals of Internal Medicine. Mitchell Lazar, MD, director of the Institute for Diabetes, Obesity and Metabolism, provided comment on the data that supports these findings.
Does Brisk Walking Beat the Gym for Weight Control?
CBS News reported results from a study published in the journal Risk Analysis, which found that those who regularly walked briskly for more than 30 minutes had lower body mass index and smaller waists as compared with people who engage in regular sports or exercise. Rex Ahima, MD, PhD, director of the Obesity Unit in Penn's Institute for Diabetes, Obesity, and Metabolism is quoted throughout the story.
She Occasionally Ignores Type 2 Diabetes, But it Never Ignores Her
Mitchell Lazar, MD, PhD, director of Penn’s Institute for Diabetes, Obesity, and Metabolism, spoke with the Philadelphia Inquirer about the effects of Type 2 diabetes, and how, in addition to taking medication, individuals can take control of their lifestyle to help manage this condition.
Tricks and Be Tricky - How to make kids' Halloween as healthy and fun - as you can.
Sorting through the onslaught of sweet treats to find some relative healthy options can be chanllenging. In a Philadelphia Inquirer article, Linda Sartor, nutritionist and diabetes educator at the Penn Rodebaugh Diabetes Center, says "it all comes down to buying the fun size, the single serving size".
October 7, 2015
American Diabetes Association Awards Celebration
Mark Schutta, MD, medical director of the Penn Rodebuagh Diabetes Center was honored at the American Diabetes Association awards celebration. This event was to recognize and honor the efforts of a community that works together to prevent and cure diabtetes and to improve the live of all people affected by diabetes.
Two Penn Medicine researchers were honored with the 2015 Outstanding Statistical Application Award from the American Statistical Association (ASA).
September 15, 2015
Authors of the paper include Wensheng Guo, professor of biostatistics in the department of biostatistics & epidemiology at the Perelman School of Medicine and a scholar in the CCEB, and Anne R. Cappola, MD, ScM, associate professor in the division of endocrinology, diabetes & metabolism at Penn’s Perelman School of Medicine and an associate scholar in the CCEB.
The paper, titled “Modeling Bivariate Longitudinal Hormone Profiles by Hierarchical State Space Models” and published in the Journal of American Statistical Association, was recognized for its contribution to modeling the complex feed-back and feed-forward relationship between different hormones in humans.
Islet Cell Transplantation for Type 1 Diabetes
July 23, 2015
Michael Rickels, MD, an associate professor in the division of Endocrinology, Diabetes and Metabolism, is studying a cutting-edge therapy for severe Type I diabetics: a transplant of special pancreatic cells, according to a story produced and distributed by Ivanhoe to local media outlets across the country. These islets contain cells that produce insulin, which help severely hypoglycemic patients from suffering side-effects from low blood sugar without warning.
Diabetes Drug Study Shows Promise of Personalized Medicine
July 9, 2015
Research by Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, and Raymond Soccio, MD, PhD, clinical fellow in Endocrinology, Diabetes, and Metabolism, was featured in news outlets this week, including the Philadelphia Inquirer. In the first study of its kind, they have shown how an anti-diabetic drug can have variable effects depending on small natural differences in DNA sequence between individuals. They aim to apply this knowledge to develop personalized approaches to treating diabetes and other metabolic disorders.
>> Penn Medicine News Release
>> Philadelphia Inquirer article
>> MD Magazine article
>> Diabetes.co.uk article
June 19, 2015
Mitch Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, was interviewed by Senior Voice America for the radio show Health, Wealth & Wisdom on his lab's recent paper on how a common protein maintains double duty as a key cog in body clock and metabolic control.
>> Senior Voice America (At 40:45 mark, on track for 2nd hour of show)
Metabolic Syndrome Related To Protein That Regulates Liver Genes, Circadian Rhythms
June 10, 2015
The study explains how Rev-erbα regulates the clock in most cells of the body while also regulating metabolic genes in the liver. Instead of relying on the same mechanism for both these functions, Rev-erbα performs each of these jobs in distinct ways. This research may provide a new map for scientists wanting to treat metabolic syndrome.
Is it Always Unhealthy to Be Fat?
April 21, 2015
Conventional thinking suggests that overweight and obese people could eat better and exercise more to lose weight and be healthier. But is it always unhealthy to be overweight?
An episode of WHYY's "Radio Times" discusses the topic with experts including Rexford Ahima, MD, PhD, director of the Obesity Unit in the Institute for Diabetes, Obesity and Metabolism, who says that the effect of extra weight really depends on the individual.
For Diabetics, Fatigue and Burnout Are a Constant ChallengeMarch 9, 2015
Managing diabetes can be tough, leading to fatigue or burnout when it no longer seems possible or even valuable to stick with the program, according to the Philadelphia Inquirer. Mark Schutta, MD, medical director of the Penn Rodebaugh Diabetes Center, says, "The problem with diabetes is that it never goes away," but there are ways to combat the fatigue.
Major Hypoglycemia News From Paris Diabetes ConferenceMarch 6, 2015
Recently at the Advanced Technologies & Treatments for Diabetes conference in Paris, new study findings were announced that may lead to a new, simpler approach to glucagon "rescue" treatment for severe hypoglycemia -- a needle-free, nasally-delivered glucagon, according to the Huffington Post. Michael Rickels, MD, associate professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism, led the study showing that the newly trialed glucagon shows comparable efficacy to current injected glucagon.
Long-Term Follow-Up of Benign Thyroid Nodules Shows Favorable Prognosis
March 5, 2015
In continuing coverage, Medical News Today reports that after five years of follow-up, a majority of asymptomatic, benign thyroid nodules exhibited no significant change in size, or actually decreased in size, and diagnoses of thyroid cancer were rare, according to a study published in JAMA. Anne Cappola, MD, ScM, associate professor, and Susan J. Mandel, MD, MPH, professor, both in the division of Endocrinology, Diabetes and Metabolism, co-wrote an editorial in JAMA calling the findings good news. Cancer Therapy Advisor also covered the topic.
Molecular Clocks throughout Body, Not Just Brain, Keep Tissues Humming
February 3, 2015
An article in Scientific American highlights research from two Penn labs that study circadian clocks in peripheral tissues. Garret FitzGerald, MD, FRS, director of the Institute for Translational Medicine and Therapeutics and chair of the department of Systems Pharmacology and Translational Therapeutics, and Mitch Lazar, MD, PhD, director of the Institute for Diabetes, Obesity and Metabolism, were featured.
Low Thyroid: Why Am I Cold All the Time"
January 29, 2015
In a Time "You Asked" article about why some people feel cold more often than others, Anne Cappola, MD, ScM, associate professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism, points to metabolism. In oversimplified terms, those with a high metabolism burn more calories and enjoy increased blood flow, both of which warm you.
Weight Loss Linked to Improved Sleep, Mood
January 29, 2015
A Healio.com article reports that losing 5 percent or more of initial body weight is associated with short-term improvements in sleep quality and duration, and short- and long-term improvements in mood, according to a study led by Nasreen Alfaris, MD, MPH, a fellow in the Division of Endocrinology, Diabetes and Metabolism.
Pacreatic Islet Cell Transplatation Restores Type 1 Diabetes Patients' Ability to Defend Against Life Threatening Low Blood Sugar, According to Penn Medicine Study.December 18, 2014
Type 1 diabetes (T1D) patients who have developed low blood sugar (hypoglycemia) as a complication of insulin treatments over time are able to regain normal internal recognition of the condition after receiving pancreatic islet cell transplantation, according to a new study led led by Michael R. Rickels, MD, MS, associate professor of Medicine and medical director of the Pancreatic Islet Cell Transplant Program and other researchers at the Perelman School of Medicine at the University of Pennsylvania, published online in Diabetes.>> Penn Medicine News Release
Four Penn Faculty Named to 2014 Class of AAAS Fellows
Four faculty members from the University of Pennsylvania have been named fellows of the American Association for the Advancement of Science (AAAS). Three are from the Perelman School of Medicine and one is from the School of Arts and Sciences.
Rexford S. Ahima, MD, PhD, was elected for distinguished contributions to the fields of obesity, diabetes, and metabolism, particularly using mouse models to study adipokine signaling in the brain and peripheral organs.
Penn Researchers Unwind the Mysteries of the Cellular Clock
In the current issue of the journal Cell, Mitchell Lazar, MD PhD, the Sylvan Eisman Professor of Medicine and director of the Institute for Diabetes, Obesity and Metabolism and his team report the results of a genome-wide survey of circadian genes and genetic regulatory elements called enhancers. These are key parts of the “dark matter” of the genome; rather than encoding proteins, they control the expression of genes. Led by postdoctoral researchers Bin Fang, Logan Everett and Jennifer Jager, Lazar’s team took advantage of new tools based on high-density DNA sequencing to measure the activity of enhancers throughout the day in the livers of mice.
Penn-led Team Pieces Together Signaling Pathway Leading to Obesity
As scientists probe the molecular underpinnings of why some people are prone to obesity and some to leanness, they are discovering that weight maintenance is more complicated than the old “calories in, calories out” adage.
A team of researchers led by the University of Pennsylvania School of Veterinary Medicine’s Kendra K. Bence have now drawn connections between known regulators of body mass, pointing to possible treatments for obesity and metabolic disorders.
October 13, 2014
Somatic Mutations in the ATRX Gene Reported for the First Time in Pheochromocytomas / Paragangliomas
At the 2014 Neuroendocrine Tumor Symposium Lauren Fishbein, MD, PhD, MTR presented findings from her group that investigated somatic mutations through whole exome sequencing of 21matched tumor/germline pairs from patients with either sporadic or inherited PCC/PGL. “The idea was to compare clinically benign versus clinically aggressive PCC/PGL in order to identify markers of tumorigenesis as well as malignant potential,” she said.
Diabetes Susceptibility Gene Regulates Health of Cell's Powerhouse, Penn Study Finds
A team led by researchers from the Perelman School of Medicine at the University of Pennsylvania found that a susceptibility gene for type 1 diabetes regulates self-destruction of the cell’s energy factory. They report their findings this week in Cell. First author Scott A. Soleimanpour, MD, a postdoctoral fellow in the lab of co-senior author Doris Stoffers, MD, PhD, professor of Medicine, worked out this role of Clec16a in pancreatic beta cells. Soleimanpour is now an assistant professor at the University of Michigan Medical School. Stoffers is also a member of the Institute for Diabetes, Obesity, and Metabolism at Penn.
One in Four Americans With Diabetes Don't Know They Have It
Mark Schutta, MD, medical director of the Penn Rodebaugh Diabetes Center speaks with WHYY's "The Pulse" about new diabetes numbers from the Centers for Disease Control out this week. More than 29 million people in the United States have diabetes and one in four don't even know they have it. That's up 12 percent from 2010, when 26 million Americans had the disease. Schutta was not surprised by the increased numbers, but he has hope that education and hard work will eventually turn the tide. "Prevention is key," he said.
A New Way to Burn Calories
An image from the lab of Mitch Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, showing brown fat in a PET scan of a mouse, accompanies a feature in Science about how activating immune cells in fat can convert the tissue from a type of fat that stores energy to one that burns it. This may open up potential new therapies for obesity and diabetes.
Activating Beige Fat
The ability of beige fat tissue to burn energy by producing heat has made it an appealing target for a potential obesity therapy. Beige fat is an energy-burning form of adipose tissue embedded in white fat, the energy-storing kind. In studies to find out what turns on these calorie-chewing cells, two independent teams ended up converging upon the same innate immune pathway. Their papers, published in Cell, demonstrate that beige fat activation relies upon the signaling of particular interleukins and the activation of adipose tissue macrophages. “The role of immune cells in regulating fat cell differentiation programs hasn’t been well established,” said Patrick Seale, PhD, assistant professor of Cell and Developmental Biology, in The Scientist. “It suggests they’re playing a role in the function of the fat cells themselves.”>> The Scientist article
Nearing 300 Pounds, Gina DiGregorio Knew It Was Time For A Change. Now, She's 137 Pounds Lighter.
Penn Rodebaugh Diabetes Center helps Gina DiGregorio on her weight loss journey.
Bucks Entrepreneur's Raw Foods Flying off the Shelves
The Philadelphia Inquirer looks into a Bucks County raw food company, interviewing nutritionist Linda Sartor, RD, MA, CDE, LDN, of the Penn Rodebaugh Diabetes Center, who noted that "it's encouraging a greater consumption of vegetables." But a raw-foods diet is "a difficult lifestyle to maintain 100 percent" and not "necessarily the most economical."
>> Philadelphia Inquirer article
April 11, 2014
Penn Vet Researcher Unravels The Science of Obesity
Though daily cheeseburgers and ice cream sundaes can help pave the way, the road to obesity begins in the brain, where metabolism is regulated by the activity of various hormones and signaling molecules.
With a new study, the School of Veterinary Medicine’s Kendra Bence, an associate professor of animal biology, has expanded our understanding of how obesity unfolds at the molecular level. Her team’s findings point to a potential target for therapies that may one day help people who are obese arrive at a healthier weight.
March 13, 2014
The JDRF is honoring Dr. Ali Naji for representing the scientific advances in diabetes care and research.
March 18, 2014
Penn Scientists Reprogram Gut Cells to Produce Insulin
Ben Stanger, MD, PhD, assistant professor of Medicine in the division of Gastroenterology, is quoted in a WHYY Newsworks article about a recent study from his lab describing how to make insulin-producing cells from gut cells. "Our hope would be that we can take patient-derived intestinal cells, reprogram them into cells that look and function close enough to beta cells that they could be used in the patient for treatment of diabetes," he said.
>> Penn Medicine News Release
>> WHYY Newsworks article
March 6, 2014
Destruction of insulin-producing beta cells in the pancreas is at the heart of type 1 and type 2 diabetes. “We are looking for ways to make new beta cells for these patients to one day replace daily insulin injections,” says Ben Stanger, MD, PhD, assistant professor of Medicine in the Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania.
Transplanting islet cells to restore normal blood sugar levels in patients with severe type 1 diabetes is one approach to treating the disease, and using stem cells to create beta cells is another area of investigation. However, both of these strategies have limitations: transplantable islet cells are in short supply, and stem cell-based approaches have a long way to go before they reach the clinic. “It’s a powerful idea that if you have the right combination of transcription factors you can make any cell into any other cell. It’s cellular alchemy,” comments Stanger. New research from Stanger and postdoctoral fellow Yi-Ju Chen, PhD, reported in Cell Reports this month, describes how introducing three proteins that control the regulation of DNA in the nucleus -- called transcription factors -- into an immune-deficient mouse turned a specific group of cells in the gut lining into beta-like cells, raising the prospect of using differentiated pancreatic cells as a source for new beta cells.
Could Turning Down the Thermostat Help You Lose Weight?
Dutch researchers say keeping temperatures a little chillier at home and the office might be an additional weapon in the fight against obesity, HealthDay reports. The paper is largely based on theory, said Mitchell Lazar, MD, PhD, chief of the division of endocrinology, diabetes and metabolism at the University of Pennsylvania. "But there is certainly evidence in people as well as rodents to suggest that reducing temperature makes the body burn more calories to keep up body temperature," said Lazar, who was not involved in the new study.
Is it worth turning down the thermostat if you're trying to shed some pounds? It's too soon to be certain that strategy would work, said Lazar, who also is the director of the University of Pennsylvania's Institute for Diabetes, Obesity and Metabolism. "It would do no harm," he said. "It's worth a try for someone who is having trouble losing weight by diet and exercise alone."
>> HealthDay news syndicate article
January 21, 2014
A number of credible but controversial studies in recent years have found that people with certain chronic illnesses live longer if they're carrying too many pounds than if they're of "normal" weight, the Philadelphia Inquirer reports. The outside researchers mined two past studies - one that followed 8,900 nurses for 36 years and another that tracked 2,500 health professionals for 26 years. They concluded that diabetics who are too heavy get no survival benefit. On the contrary, the heavier the diabetic, the likelier an early death.
"These are epidemiological studies," said endocrinologist Rexford Ahima, MD, PhD, professor of Medicine. "They don't prove cause and effect. We are making inferences. My argument would be: Why don't we design experiments to study the direct effect of weight management in these groups? We could see how physically fit people are, how much muscle they have, not just how much they weigh. Those studies need to be done."
>> Philadelphia Inquirer article
January 16, 2014
Klaus Kaestner, PhD, professor of Geneticsand postdoctoral fellow Dana Avrahami, PhD,from the Perelman School of Medicine, University of Pennsylvania, published a study this week in the Journal of Clinical Investigation, with colleague Benjamin Glaser, MD, from the Hadassah-Hebrew University Medical Center, Jerusalem, and colleagues. In this study, they were able to replicate human pancreatic beta cells – the cells in our body that produce the critical hormone insulin – in a mouse model in which donor cells were transplanted. The newly replicated cells retained features of mature beta cells and showed a physiological response to glucose. Kaestner is also a member of the Institute for Diabetes Obesity and Metabolism.
January 10, 2014
If you're overweight or obese, it may pay off to shed even just a few extra pounds, reports NBCNews.com. People who might be jolted into action by the new study should realize that even small changes in lifestyle can result in big differences, experts said. You don’t need to be pencil thin, said Rexford Ahima, MD, PhD, a professor of medicine and director of the obesity unit at the Institute for Diabetes, Obesity and Metabolism . “There is such a thing as healthy weight,” Ahima said. “But it’s not going back to where you were in high school. If you’re overweight or obese, you should aim to be 5 to 10 percent less than you are today. Many studies have shown that a 5 to 10 percent weight reduction can impart benefit.”
December 25, 2013
Kaestner Lab Publication in Cell Metabolism
Congratulations to Vasumathi Kameswaran and the Kaester lab for the recent publication in Cell Metabolism entitle "Epigenetic Regulation of the DLK1-MEG3 MicroRNA Cluster in Human Type 2 Diabetic Islets".
December 11, 2013
Sleep-Deprived Mice Show Connections Among Lack of Shut-eye, Diabetes, Age
Sleep, or the lack of it, seems to affect just about every aspect of human physiology. Yet, the molecular pathways through which sleep deprivation wreaks its detrimental effects on the body remain poorly understood. Although numerous studies have looked at the consequences of sleep deprivation on the brain, comparatively few have directly tested its effects on peripheral organs.
Working with Penn colleague Joe Baur, Ph.D., assistant professor of Physiology, Nirinjini Naidoo, Ph.D. started a collaboration to look at the relationship of sleep deprivation, the UPR, and metabolic response with age.
December 11, 2013
Recently, Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, has been studying the effects of deleting the gene for histone deacetylase 3 (HDAC3) from mice. HDAC3 is an enzyme that removes epigenetic marks from histone proteins and is thus a key regulator of gene expression. In a series of papers, the Lazar team reported that mice that lacked HDAC3 were more susceptible to heart disease when fed a high fat diet, and that they had altered fat storage and blood glucose metabolism.
December 11, 2013
Just as the earth rotates in a 24-hour cycle, humans and other animals have an internal rhythm. Penn researchers have been working to identify the molecules and pathways that maintain our sleep-wake clock or circadian rhythm. They’ve also made inroads into understanding how malfunctions in the clock influence — or even trigger — disease.
Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at Penn, reported recently that two nuclear receptor genes — Rev-erb alpha and Rev-erb beta — are necessary for maintaining the clock.
November 22, 2013
Targets of Anticancer Drugs Have Broader Functions than What Their Name Suggests
Drugs that inhibit the activity of enzymes called histone deacetylases (HDACs) are being widely developed for treating cancer and other diseases, with two already on the market. Researchers have shown that a major HDAC still functions in mice even when its enzyme activity is abolished, suggesting that the beneficial effects of HDAC inhibitors may not actually be through inhibiting HDAC activity, and thus warranting the reassessment of the molecular targets of this class of drugs.
The study, appearing online in Molecular Cell this week, was conducted in the laboratory of Mitchell A. Lazar, M.D., PhD, director of the Institute for Diabetes, Obesity, and Metabolism. The Lazar lab has been working on HDAC3 for over a decade, focusing on the pivotal role of this enzyme in hormone-mediated regulation of gene expression and metabolism. They previously showed that depletion of HDAC3 in mouse liver upregulates expression of many genes involved in lipid synthesis, which causes a remarkable fatty liver. In the current study, they put “enzyme-dead” HDAC3 proteins back in the mouse liver and found, surprisingly, that the fatty liver can be rescued to a large degree. HDAC inhibitors bind zinc metal in the catalytic site of HDAC proteins. However, in addition to HDACs, the human body has nearly 300 enzymes that also depend on zinc and therefore are potentially also inhibited by HDAC inhibitors, notes lead author Zheng Sun, PhD, a postdoctoral fellow in the Lazar lab.
November 6, 2013
Testosterone treatments may increase risks for heart attacks, strokes and death in older men with low hormone levels and other health problems, a big Veterans Affairs study suggests. The Associated Press reports that an editorial in JAMA said it is uncertain if the study results apply to other groups of men, including younger men using the hormone for supposed anti-aging benefits. “There is only anecdotal evidence that testosterone is safe for these men,” said editorial author Anne Cappola, MD, ScM, associate professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism, a hormone expert at University of Pennsylvania and an associate JAMA editor.
“In light of the high volume of prescriptions and aggressive marketing by testosterone manufacturers, prescribers and patients should be wary” and more research is needed, she wrote. In speaking with Reuters, Cappola said, “"For the men who are healthier, my question would be, why are you taking this? And is there any risk that's acceptable for the benefits they are getting?" Among healthy men, "We just don't know what the benefits are." Coverage appeared in hundreds of outlets in the United States and around the world.
Penn Medicine News release
Associated Press article (picked up by Washington Post, USA Today, Huffington Post, Miami Herald, NPR, Atlanta Journal Constitution)
Reuters article (picked up by Chicago Tribune, Yahoo! News)
Bloomberg News (picked up by San Francisco Chronicle, Boston Globe)
Wall Street Journal article
NBC News article
Fox News article
Los Angeles Times article
Medpage Today article
Cardiology Today article
CBS3 Philadelphia segment
Everyday Health article
November 6, 2013
Pancreas transplants for patients are not typically an option for many Type 1 diabetes patients, CNN.com reports, because they are difficult to perform, said Michael Rickels, MD, associate professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism. But an experimental procedure using the pancreas' islet cells is being tested at medical centers around the country. If it's approved by the Food and Drug Administration, it could make a difference for patients who are no longer able to successfully manage their diabetes. Rickels and his colleagues recently published a study in the journal Diabetes detailing a new protocol, which gives the extracted islets three days to "rest" before they're transferred to the living recipient. All of the patients in Rickels' study were able to come off insulin therapy for at least a year after a single transplant.
November 5, 2013
Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, commented on an article in Scienceline about a study that showed how circadian rhythm genes regulate metabolism when we’re not eating by rhythmically controlling the supply of one specific molecule. He says this research further illuminates how the circadian clock and energy metabolism affect each other, which fits in with current research on the circadian rhythm. Knowing the specific components of this complicated relationship could help develop a drug to help people with chronically disrupted circadian rhythms, he added.
October 31, 2013
The American Thyroid Association (ATA) recently presented the Van Meter Award, to Anne R. Cappola, MD, ScM, associate professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism in the Perelman School of Medicine at the University of Pennsylvania. Dr. Cappola is an internationally recognized clinical investigator whose research on the hormonal changes associated with aging is impacting how clinicians evaluate and treat thyroid dysfunction in older people.
The award was established in 1930 to recognize outstanding contributions by a young clinical scientist to research on the thyroid gland. Dr. Cappola accepted the honor during the award lecture on October 18 at the ATA’s 83rd Annual Meeting in San Juan, Puerto Rico.
October 28, 2013
For nearly 300 years, investigators have known that body temperature follows a circadian, or 24-hour, rhythm, with a peak during the day and a low at night. The benefit of this control during evolution may have been to allow conservation of energy while sleeping because keeping body temperature above the surrounding temperature requires heat production from metabolic processes inside the body. But, it is also critical to be able to adapt to changes in ambient temperature, regardless of the time of day. However, the mechanism responsible for coordinating daily body temperature rhythm and adaptability to environmental challenges is unknown.
Now, the laboratory of Mitchell A. Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, explains in Nature how body temperature rhythms are synchronized while maintaining the ability to adapt to changes in environmental temperature no matter the time of day or night. "Food is plentiful in our present day society, and for most people there is unlikely to be an advantage of saving calories at night", says Lazar. "If this same mechanism exists in people, and we can target it safely, we could have a new way to combat obesity and its associated conditions such as diabetes and heart disease.” Lazar's team, including lead author Zachary Gerhart-Hines, PhD, found that the ability of mice to withstand a cold-temperature challenge was greater at 5:00 AM, when the mice are awake, compared to 5:00 PM when they are normally sleeping.
October 28, 2013
An article from the Philadelphia Inquirer reporters on the increasing opportunity for kidney transplants between spouses. Ali Naji, MD, Surgical Director of the Kidney and Pancreas Transplant Program, says that "the love and affection between the spouses adds tremendous positive gratification." "A lot of spouses see it as not just doing something for the other person, but as doing something for the relationship," says Penn social worker Carolyn Cristofalo, MSW, LCSW. "People want to move on with their lives together." While blood relatives may often be the most compatible match, advances in immunosuppression drugs have dramatically increased success rates for transplants between unrelated persons. "It's harder to say no to a spouse who's trying to donate," says Donna Collins, RN, MSN, transplant coordinator. "If they get turned down, it can be devastating to them." The article profiles three pairs of spousal donors/recipients from Penn's transplant program.
October 7, 2013
A Florida mom received an unpleasant surprise in the mail recently. No, it wasn't an unexpected bill; it was a letter that said her 11-year-old daughter, Lily, was overweight. "I can understand the individual parent's angst," obesity expert Rexford Ahima, MD, PhD, professor of medicine, told Yahoo Shine. Ahima explains that measuring BMI is valuable for public health screenings but not as a specific diagnostic tool. "It's useful when you are comparing populations," but he says that it doesn't distinguish factors such as gender, age, and ethnicity that may affect the result. However, despite BMI's limitations, Ahima says it's the best, cheapest tool we have for identifying kids who might be at risk. "The intention to use it as a guide is OK, but in order to evaluate the information on an individual basis, then the child's physician should be involved."
New Islet Cells Boost Insulin Sensitivity
Islet cell transplantation improved insulin sensitivity in patients with long-standing type 1 diabetes, despite immunosuppressive drug regimens that have been associated with insulin resistance, researchers found.>> Read more
The Truth About Your BMI
In continuing coverage, Women's Health magazine's website reports that the best way to check if your weight is healthy may not necessarily be to calculate your body-mass index (BMI), according to a perspective recently published in the journal Science: It argues that BMI isn’t an accurate measure of metabolic health. In the perspective, two researchers from the Perelman School of Medicine write that BMI doesn’t tell the whole story. “The fact is that BMI basically reflects your weight and height,” says co-author Rexford Ahima, M.D., Ph.D., a professor of medicine and the director of the Obesity Unit in the Institute for Diabetes, Obesity, and Metabolism. A few of the many things it does not reflect: your family history, muscle mass, and where your excess fat is located.
Out of Synch
Few environmental factors are as reliable as the 24-hour day, and an evolutionary argument can be made for why the diurnal rhythms of the Earth’s rotation are so coupled with human metabolism. Human behavior, physiology, and biochemistry reflect the daily cycles of the planet, and people who fall out of sync with these cycles are more likely to suffer from diabetes, obesity, and heart disease. But according to new research, it’s not just disrupted sleep that can lead to these myriad physiological symptoms; it’s also the altered patterns of food consumption that go along with keeping such strange hours.
The work of Mitch Lazar, MD, PhD, director of the Institute for Diabetes, Metabolism, and Obesity and Georgios Paschos, PhD, research assistant professor of Pharmacology, was highlighted in a feature in The Scientist about why eating at the wrong times is tied to such negative and profound effects on our bodies.
MSystemically blocking the mechanistic target of rapamycin (mTOR) protein with an immunosuppressant drug has been shown to increase longevity in mice. Taking a new approach, researchers show in Cell Reports that cutting down the levels of mTOR through a genetic alteration also extends mouse lifespan, and delays the appearance of biomarkers of aging.
Joseph Baur, PhD, assistant professor of Physiology and a member of the Institute for Diabetes, Obesity, and Metabolism, who did not participate in the research, noted in The Scientist that this was the first study to use a genetically induced reduction of mTOR resulting in lifespan extension among both sexes of mice.
BMI Doesn't Offer TMI, According to Penn Researchers
In continuing coverage, BMI, the body mass index is a simple measure that has long been used to assess people's risks for poor health and shortened life expectancy. But WHYY and Newsworks.org report that researchers at the University of Pennsylvania caution that the measure is not as powerful and accurate as previously assumed, and doesn't offer a comprehensive picture of a person's health and disease risks.
Rex Ahima, MD, PhD, professor of Medicine and Director of the Obesity Unit in the Institute for Diabetes, Obesity and Metabolism, says this quick and simple tool works on many levels, but it's limited. "It doesn't even distinguish between men and women, also the distribution of body fat," said Ahima.
Mitchell Lazar, MD, PhD, professor of Medicine and Genetics and Director of the Institute of Diabetes, Obesity, and Metabolism spoke with Newsworks.org and argued that doctors are on the right track to associate obesity with diabetes and other health problems, but the revered BMI charts don't give doctors complete information, and the healthy weight range may differ from patient to patient. NBC10 ran the Newsworks.org article and additional coverage appeared in outlets including Huffington Post and New York Daily News.
Obesity/Mortality Paradox Demonstrates Urgen Need for More Metabolic Measures
Researchers from the Perelman School of Medicine at the University of Pennsylvania point out that the body mass index (BMI), based on the weight and height, is not an accurate measure of body fat content and does not account for critical factors that contribute to health or mortality, such as fat distribution, proportion of muscle to fat, and the sex and racial differences in body composition.
In a new perspective article in the journal Science, Rexford Ahima, MD, PhD, Professor of Medicine and Director of the Obesity Unit in the Institute for Diabetes, Obesity and Metabolism, and Mitchell Lazar, MD, PhD, Professor of Medicine and Genetics and Director of the Institute of Diabetes, Obesity, and Metabolism, discuss the challenges of studying the health and mortality risks of obesity.
For nearly 1 in 5 Americans, BMI may tell the wrong story
August 22, 2013
Obese is bad and lean is good. End of story, right? Wrong, say a pair of University of Pennsylvania physicians and obesity researchers who are calling for better ways to assess individual health prospects than the body mass index, or BMI, the Los Angeles Times reports.
Rexford Ahima, MD, PhD, Professor of Medicine and Director of the Obesity Unit in the Institute for Diabetes, Obesity and Metabolism, and Mitchell Lazar, MD, PhD, Professor of Medicine and Genetics and Director of the Institute of Diabetes, Obesity, and Metabolism, write a Perspective piece in Science saying that "there is an urgent need for accurate, practical, and affordable tools for assessing body composition, adipose hormones, myokines, cytokines and other biomarkers as predictive tools" that would let physicians separate the fat-but-fit from those in danger, and to identify the trim ones who look healthy but are actually at risk of illness and early death. “The BMI doesn’t tell you anything about how fat is distributed in the body, or about the fat-muscle ratio, and doesn't take into account racial differences or differences between male and female,” Ahima told The Telegraph (of India).More media coverage:
> Penn Medicine News release
> Los Angeles Times article
> Huffington Post via Scientific American article
> Full Scientific American article
> Telegraph (India) article
> Live Science article
> Fast Company’s CoExist article
> HealthCentral article
August 8, 2013
A Diabetes Educator's Take on Day 1 of the AADE Annual Meeting
The first day of the American Association of Diabetes Educators Annual Meeting and Exhibition offered interesting presentations on a number of important topics, ranging from patient experiences of living with diabetes to strategies for optimizing clinical practice. Linda E. Sartor, RD, MA, CDE, LDN, RYT, of Penn's Rodebaugh Diabetes Center, details what she took away from a few sessions in blog posts on Endocrine Today.
New Award Recipient
July 15, 2013
Dr. Anne Cappola receives a new K24 Midcareer Investigator Award in Patient-Oriented Research in Aging.
The scientific goal of this proposal is to investigate the physiological underpinnings and clinical ramifications of subclinical hypothyroidism in the elderly.
New Award Recipient
July 8, 2013
Dr. Joseph Baur has been awarded a University Research Foundation Award for a project entitled "Control of Adipocyte Function and Fate by mTORC2."
AMA Declares Obesity a Disease
June 19, 2013
The American Medical Association voted to declare obesity a disease, a move that effectively defines 78 million American adults and 12 million children as having a medical condition requiring treatment, the Los Angeles Times reports.
"As things stand now, primary care physicians tend to look at obesity as a behavior problem," said Rexford Ahima, MD, PhD, of the University of Pennsylvania's Institute for Diabetes, Obesity and Metabolism. "This will force primary care physicians to address it, even if we don't have a cure for it." The new designation follows a steep 30-year climb in Americans' weight — and growing public concern over the resulting tidal wave of expensive health problems.
Dr. Steger receives two awards
June 15, 2013
Dr. David Steger received a Pilot award from the McCabe Advisory Committee.
Dr. Steger also received a new five year R01 entitled "Transcriptional and Epigenomic Control of Adipose Tissue Development."
A major goal of this research is to understand the complex interplay between transcription factors and epigenomic modification that regulates gene expression programs establishing and maintaining adipocyte cells.
May 10, 2013
Not All Cytokine-producing Cells Start Out the Same Way, According to Penn Study
Interleukin 17, or IL17, is a well-studied cytokine that regulates immune function at mucosal surfaces in the body but is dysregulated in many diseases, such as multiple sclerosis, rheumatoid arthritis, and psoriasis.
Not all IL17-producing cells are the same, and the rules regarding how particular cell types are instructed to produce this important mediator differ. Research published this week in Nature Immunology, from the Perelman School of Medicine at the University of Pennsylvania by Gary Koretzky, MD, PhD, the Francis C. Wood professor of Medicine and Investigator in the Abramson Family Cancer Research Institute; Martha Jordan, PhD, research assistant professor in Pathology and Laboratory Medicine, Jiyeon Kim, an MD-PhD student in the Koretzky lab, and other members of the Perelman School community including Morris Birnbaum, MD, PhD from the Department of Medicine and scientists in the laboratory of Celeste Simon, PhD, from the Abramson Family Cancer Research Institute and the Department of Cell and Developmental Biology, sheds light on the intricacies of those instructions.
May 2, 2013
VP & Council Member of Endocrine Society: Dr. Mandel, Dr. Lazar
Dr. Susan Mandel, professor of medicine and radiology, associate chief of the Division of Endocrinology, Diabetes and Metabolism and director of the Fellowship Training Program at the University of Pennsylvania’s Perelman School of Medicine, has been elected vice president, Physician-in-Practice, of The Endocrine Society. Dr. Mandel will serve a three-year term as vice president, Physician-in-Practice (2013-2016).
In addition, Dr. Mitchell Lazar, Sylvan Eisman Professor of Medicine, Chief of the Division of Endocrinology, Diabetes and Metabolism and Director of the Institute for Diabetes, Obesity and Metabolism at the Perelman School of Medicine, was elected to serve as a council member, at-large.
They will collaborate with other newly elected Officers and Council members to lead the world’s oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology. Founded in 1916, The Endocrine Society members represent all basic, applied and clinical interests in endocrinology.
April 30, 2013
Not All Cytokine-producing Cells Start Out the Same Way, According to Penn Study
A study led by Tracy Bale of both Penn Medicine and the Vet School suggests that deep brain stimulation could one day be an effective treatment for binge-eating disorder. Read More.
April 12, 2013
No Need for Genetic Testing for Most Thyroid Cancers
In the majority of patients with papillary thyroid cancer, the most common form of thyroid cancer, there is no need for genetic testing, reports Medscape. However, there might be a role for such testing in the 7% of patients who present with an aggressive form of the disease.
This finding comes from a study published in the April 10 issue of JAMA that explores the association between the BRAF V600E mutation and mortality in patients with papillary thyroid cancer. US News and World Report, via HealthDay says that according to JAMA editorialists, Anne Cappola, MD, ScD, and Susan Mandel, MD, MPH, of the Perelman School of Medicine at the University of Pennsylvania, "Although these findings do not support widespread BRAF V600E testing, they do support the need for additional study of how BRAF testing can be used to improve the already excellent prognosis of patients with papillary thyroid cancer." While the study found an association between the gene mutation and thyroid cancer survival, it did not establish a cause-and-effect relationship.
Mutation Hikes Death Risk in Thyroid Cancer
Medpage Today reports that patients with papillary thyroid cancer (PTC) who are carriers of the BRAF V600E mutation may have worse mortality, researchers reported in the April 10 issue of JAMA. In an accompanying editorial by Penn endocrinologists Anne Cappola, MD, ScD and Susan Mandel, MD, MPH, the findings provide two important insights.
First, they suggest that this mutation "mediates features of the clinically aggressive tumors that account for the vast majority of PTC mortality," and provides a "strong biological rationale for current trials of targeted tyrosine kinase inhibitor therapy" for patients with the mutation who have advanced disease. On the other hand, the results suggest that screening for the mutation "doesn't add predictive value for PTC-related mortality beyond the information collected in the process of PTC tumor staging."
Brown Fat, White Fat, Good Fat, Bad Fat
Fat has been villainized; but all fat was not created equal. Our two main types of fat—brown and white—play different roles. Two teams of NIH-funded researchers have enriched our understanding of adipose tissue. One of those teams is led by Patrick Seale, PhD, assistant professor of Cell and Developmental Biology and a member of the Institute for Diabetes, Obesity, and Metabolism. His work was highlighted in the NIH Director's Blog, describing how the body can recruit white fat and transform it into brown.
Reprogramming Cells to Fight Diabetes
For years researchers have been searching for a way to treat diabetics by reactivating their insulin-producing beta cells, with limited success. The "reprogramming" of related alpha cells into beta cells may one day offer a novel and complementary approach for treating type 2 diabetes. Treating human and mouse cells with compounds that modify cell nuclear material called chromatin induced the expression of beta cell genes in alpha cells, according to a new study that appears online in the Journal of Clinical Investigation.
Reprogramming alpha cells to treat diabetes
In differentiated cells, a stable phenotype is maintained in part by chromatin alterations, referred to as epigenetic marks, which determine the relative transcriptional activity of cell type-specific genes. In this issue, Nuria Bramswig from the Kaestner Lab and colleagues analyzed the epigenetic state of pancreatic cells, and found that in glucagon-producing alpha cells, many genes related to the beta cell program were simultaneously marked by activating and repressing modifications.
Bramswig et al. further found that treating human or mouse islets with chromatin-modifying compounds induced the expression of beta cell genes in alpha cells. These findings suggest that treating islets with chromatin remodelers may be a method to drive transdifferentiation of alpha cells toward a beta cell phenotype, perhaps creating a new source of these cells diabetes therapy.
Penn Team Finds that Most-Used Diabetes Drug Works in Different Way than Previously Thought Findings Could Lead to Diabetes Treatments with Less Side-Effects
A team, led by senior author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Medicine, with the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, found that the diabetes drug metformin works in a different way than previously understood. Their research in mice found that metformin suppresses the liver hormone glucagon’s ability to generate an important signaling molecule, pointing to new drug targets. The findings were published online this week in Nature.
Penn Study Details Dimmer Switch for Regulating Cell's Read of DNA Code
A team led by Mitchell A. Lazar, M.D., Ph.D., director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, has been studying HDAC3 for several years. They discovered that the enzyme activity of HDAC3 requires interaction with a specific region on another protein, which they dubbed the Deacetylase Activating Domain or "DAD.” This “nuts and bolts” discovery on the epigenetic control of a person’s genome has implications for cancer and neurological treatments.
The Endocrine Society Laureate Awards Announced
With the addition of two new awards, bringing the total number of Laureate Awards to 13 and valued at $89K, the Laureate Awards represent the pinnacle of achievement in the field of endocrinology. Congratulations to Dr. Mitchell A. Lazar and Dr. Doris Stoffers, MD, PhD.
Gerald D. Aurbach Award Lecture
Mitchell A. Lazar, MD, PhD
Dr. Mitchell A. Lazar is a truly outstanding and worthy recipient of the 2013 Gerald D. Aurbach Award. Mitch has made seminal discoveries in the area of the nuclear hormone receptors and their coregulators, particularly corepressors. His pioneering studies at the intersection of transcriptional regulatory mechanisms with physiology and metabolism have had major impact on our understanding of metabolic disease.
Ernst Oppenheimer Award
Doris A. Stoffers, MD, PhD
Dr. Doris Stoffers discovered that mutations in the Pdx1 gene lead to Maturity Onset Diabetes of the Young in humans. Her influential studies of Pdx1 molecular function and regulation have had a major impact on our current understanding of the development, physiology, and pathophysiology of the insulin-producing, pancreatic beta cell.
Early Career Development Grant for $50,000
Congratulations to Lauren Fishbein, MD, PhD for receiving the Early Career Development Grant from the North American Neuroendocrine Tumor Society (NANETS). This grant was created to encourage the applicants to pursue basic/translational and/or clinical research in neuroendocrine cancers. Dr. Fishbein's project has the potential to lead to contributions to the field and a productive career as a NET scientist.
Dr. Fishbein was recognized at the award session during the NANETS symposium in San Diego, CA on Saturday, October 13, 2012.
A Peptide Controls Blood Sugar in People with Congenital Hyperinsulinism
A pilot study in adolescents and adults has found that an investigational drug shows promise as the first potential medical treatment for children with the severest type of congenital hyperinsulinism, a rare but potentially devastating disease in which gene mutations cause insulin levels to become dangerously high.
Is that Thyroid Lump Cancerous? New Test is More Accurate
Penn Medicine specialists helped validate a new gene-expression test, Afirma, that may be used to determine whether lumps on the thyroid gland are harmful, the Philadelphia Inquirer reports. "It's not perfect, but it's the best thing we've have to date," said Susan Mandel, MD, MPH, a professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism, who was part of the validation study. "This is a win-win.”
July 2, 2012
Researchers find clues to living longer, healthier lives
Clues to Living Longer, Healthier Lives Researchers seeking to unravel the mysteries of aging have yet to find the legendary fountain of youth, but they have found intriguing clues to living longer, healthier lives. About 15 years ago, researchers discovered simple gene mutations in a molecular pathway that doubled the life spans of worms, and even made them look and act young. "It was a big shock to see these results," commented Joseph Baur, PhD, assistant professor of Physiology, in a Philadelphia Inquirer article about the aging process and extending life.
"Before researchers showed a change in just one gene could change lifespan, most people thought there were thousands of different factors driving aging and you would never be able to change enough of them to make a difference. This gave us hope that we might understand aging. Baur's research on growth-regulating pathways is highlighted.
June 25, 2012
Gene Expression Test Identifies Low-Risk Thyroid Nodules
A new test can be used to identify low-risk thyroid nodules, reducing unnecessary surgeries for people with thyroid nodules that have indeterminate results after biopsy. The results of the multi-center trial, which includes researchers from the Perelman School of Medicine at the University of Pennsylvania, appear online in the New England Journal of Medicine.
"This test, currently available at Penn Medicine, can help us determine whether these nodules with indeterminate biopsy results are likely to be benign," said Susan Mandel, MD, MPH, professor of Medicine in Endocrinology, Diabetes and Metabolism in the Perelman School of Medicine at Penn."If so, patients may be able to avoid unnecessary surgeries and lifelong thyroid hormone replacement treatment."
Progress towards an 'Artificial Pancreas'
A developing technology that utilizes computer algorithms to automate insulin delivery is gaining momentum to help those with Type I diabetes that cannot produce their own insulin. An approach to create such an artificial pancreas called a “closed-loop system” was a topic of much buzz at Sunday’s American Diabetes Association conference, reports the Philadelphia Inquirer. “
Closing the loop is the holy grail for the artificial pancreas,” says Michael Rickels, MD, assistant professor of Medicine in Endocrinology with the Rodebaugh Diabetes Center at the Hospital of the University of Pennsylvania. “It will happen, the only question is when.”
>> Philadelphia Inquirer article
Dr. Klaus Kaestner receives the MERIT award
The National Diabetes and Digestive and Kidney Diseases advisery Council has recommended Dr. Klaus Kaester grant application to receive MERIT (Method to Extend Research in Time) status.
MERIT awards are designed to provide a few outstanding investigators with the opportunity for long-term stable support. Investigators may not apply for a MERIT award. Program staff and members of the Institute National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements.
Testosterone Chases Viagra in Libido Race as Doctors Fret
Prescriptions for testosterone replacement therapies have more than doubled since 2006 to 5.6 million, according to data compiled by Bloomberg. Peter Snyder, MD, professor of Endocrinology, requires his male patients take multiple blood tests in the morning to ensure their testosterone levels are below the normal range of 300 to 1,200 nanograms per deciliter.
“It’s likely the dramatic increase in use of testosterone is mostly for people whose blood test is a little bit low, but for no obvious reason other than age,” Snyder said. “It really isn’t clear that those people are going to benefit.” Snyder, who is studying the effects of testosterone in older men, said the increased popularity signals an overuse of the drugs. He said he won’t prescribe testosterone unless a patient has significantly low testosterone and symptoms, like depression, low sex drive or fatigue.
May 7, 2012
Liver Fat Gets a Wake-Up Call That Maintains Blood Sugar Levels, According to Penn Study
A Penn research team, led by Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, reports in Nature Medicine that mice in which an enzyme called histone deacetylase 3 (HDAC3) was deleted had massively fatty livers, but lower blood sugar, and were thus protected from glucose intolerance and insulin resistance, the hallmark of diabetes.
Insulin resistance occurs when the body does a poor job of lowering blood sugars. Typically, patients with obesity and type 2 diabetes have fatty livers, and the dogma in the field, says Lazar, is that the fatty livers contribute to the insulin resistance and diabetes in a vicious cycle. These findings are "a clear counterexample to this thinking," he says.
The researchers observed that the extra fat in the liver did not cause insulin resistance because it was sequestered in tiny lipid droplets inside individual liver cells, coated by a specific protein. The metabolites that would otherwise be used by the body to make glucose were re-routed to make fat, leading to reduced glucose in the bloodstream. The advantage of the lower blood sugar is tempered by the excess liver fat, which can lead to problems of its own, including liver failure.
May 1, 2012
Authored by Dr. Mitchell Lazar, the paper, "Diet-induced Lethality Due to Deletion of the Hdac3 Gene in Heart and Skeletal Muscle," has been designated as one of the best papers published by the Journal of Biological Chemistry in 2011. The journal's editors selected only 20 papers—out of the more than 4,000 that were published last year—to receive this special designation. One paper was chosen for each of their affinity groups, and this paper represents the Metabolism affinity group. Dr. Lazar is the Sylvan Eisman Professor of Medicine and director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine.
May 1, 2012
Arthur H. Rubenstein, MBBCh Former Perelman School of Medicine Dean, Receives Prestigous Medal for Medical Service
Arthur H. Rubenstein, MBBCh, was awarded the highest honor of the Association of American Physicians (AAP), the George M. Kober Medal, this week at the annual joint meeting of the AAP and the American Society for Clinical Investigation.
Since 1925, the association has bestowed the award for research in scientific medicine that rises to the highest level of achievement. Rubenstein and mentor Donald Steiner developed the first accurate way to measure insulin secretion in diabetic patients being treated with insulin derived from the pancreas of cattle or pigs. This method was key to the commercial production of human insulin for diabetics. Rubenstein and Steiner were also part of a team that discovered the first case of diabetes caused by abnormal insulin.
Circadian Rhythms: The Timekeepers Within
Circadian rhythms have a direct impact on human health, and understanding about how the internal timekeepers in the brain and other organs communicate and what happens to put them out of sync is important. The most recent discoveries involve so-called clock genes, first identified in 1994. The liver, for example, relies on its clock genes to predict when food will be consumed so its cells will be revved up to metabolize and store nutrients.
“If people eat when the liver isn’t anticipating nutrients coming into the body, it can’t regulate sugar and fat metabolism properly,” says Mitchell A. Lazar, director of the Institute for Diabetes, Obesity, and Metabolism, in Proto magazine. “That dissonance can lead to extra fat in the liver and contribute to diabetes and lipid disorders.”
April 8, 2012
Study finds gene variants behind childhood obesity risk
Scientists have discovered two gene variants that appear to play a critical role in the development of common childhood obesity, according to a large genetic study released Sunday. The discovery could eventually lead to treatments and specific lifestyle advice for heavy children.Scientists have discovered two gene variants that appear to play a critical role in the development of common childhood obesity, according to a large genetic study released Sunday. The discovery could eventually lead to treatments and specific lifestyle advice for heavy children.
This research "robustly" shows that these two gene variants predispose some children to obesity more than others, said Struan Grant, associate director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "Childhood obesity is partly in your genes. It's partly your lifestyle."
April 4, 2012
Penn Medicine Researchers Find that Molecular Pair Controls Time-Keeping a Metabolism
The 24-hour internal clock controls many aspects of human behavior and physiology, including sleep, blood pressure, and metabolism. Disruption in circadian rhythms leads to increased incidence of many diseases, including metabolic disease and cancer. Each cell of the body has its own internal timing mechanism, which is controlled by proteins that keep one another in check.
One of these proteins, called Rev-erb alpha, was thought to have a subordinate role because the clock runs fairly normally in its absence. New work, published in Genes and Development this month, from the lab of Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, found that a closely related protein called Rev-erb beta serves as a back-up for Rev-erb alpha. When both are not functioning, the cellular clock loses its time-keeping function.
Duality of Longevity Drug Explained by Perelman School of Medicine Researchers
Rapamycin-induced longevity in mice can be uncoupled from diabetes-inducing side effects
A Penn- and MIT-led team explained how rapamycin, a drug that extends mouse lifespan, also causes insulin resistance. The researchers showed in an animal model that they could separate the effects, which depend on inhibiting two protein complexes, mTORC1 and mTORC2, respectively. The study suggests that molecules that specifically inhibit mTORC1 may combat age-related diseases without the insulin-resistance side effect, which can predispose people to diabetes.
Senior author Joseph A. Baur, PhD, assistant professor of Physiology, comments: “The hope is that we're getting close to understanding how these things are happening and may be able to design a better molecule in the future. I don't think anyone who's healthy at this point would have much hope of improving their lifespan by taking rapamycin, given what we know of the side effects.”
Revising the "Textbook" on Liver Metabolism Offers New Targets for Diabetes Drugs, According to Penn Study.
A team led by researchers from the Institute for Diabetes, Obesity and Metabolism (IDOM) at the Perelman School of Medicine, University of Pennsylvania, has overturned a "textbook" view of what the body does after a meal. The study appears online this week in Nature Medicine, in advance of print publication. Normally after a meal, insulin shuts off glucose production in the liver, but insulin resistance — when the hormone becomes less effective at lowering blood sugars — can become a problem.
The Penn group showed that mice without the genes Akt1 and Akt2 in their livers were insulin resistant and defective in their response to feeding with respect to blood sugar levels. In these mice, blood sugar levels remained high after a meal. When Akt is not present, another gene, Foxo, is on all the time, and the liver "thinks" the body is fasting. In response, glucose production stays on to keep cells supplied in energy-rich molecules.
But then, says senior author Morris Birnbaum, MD, PhD, professor of medicine and IDOM Associate Director, "In further experiments, we expected that Akt and Foxo knockout mice — when we gave them a meal — to be locked into a fed state metabolically if both proteins were gone," says Birnbaum. "But, the liver responded normally after a meal, so we asked what is regulating the liver and glucose production in the absence of both the Akt and Foxo proteins?"
January 30, 2012
Brown Fat Revelations May Lead to New Weight Loss Drugs
Mitch Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, and Patrick Seale, PhD, assistant professor of Cell and Developmental Biology, are mentioned in a Popular Mechanics research round-up on brown fat. Brown fat has long been known to exist in infants and animals such as mice, but until recently, scientists thought it disappeared before human adulthood, leaving only the white fat that's associated with weight gain. Some studies confirmed that not only is brown fat common in adults, it's also important to metabolism: Younger, thinner people have more detectable brown fat. Animal studies also suggest brown fat boosts weight loss.
January 19, 2012
Gender Differences in Liver Cancer Risk Explained by Small Changes in Genome, Penn Study Finds
.Men are four times more likely to develop liver cancer compared to women, a difference attributed to the sex hormones androgen and estrogen. Although this gender difference has been known for a long time, the molecular mechanisms by which estrogens prevent -- and androgens promote -- liver cancer remain unclear.
Now, new research, published in Cell from the lab of Klaus Kaestner, PhD, professor of Genetics in the Perelman School of Medicine at the University of Pennsylvania, has found that the difference depends on which proteins the sex hormones bind next to. Specifically a group of transcriptional regulatory proteins called Foxa 1 and 2.
January 12, 2012
Hormone May Spur New Drugs to Fight Fat
Boston scientists discovered a hormone secreted by muscles in exercise that could lead to creation of new obesity, diabetes and other drugs. “It’s a new molecule and a new pathway and a new mechanism for thinking about how to get at this very, very difficult problem of treating chronic diseases that are affecting tens of millions of people,” said Mitchell A. Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism. Lazar noted that the discovery also raises questions about the role of the hormone in the body.
December 16, 2011
Walk 3 mph or Faster to Outpace the Grim Reaper, Scientists Say MSNBC.com reports that Australian researchers with a wry sense of humor say they have calculated the average walking speed of the specter of death -- and it’s about 2 miles per hour. Slow walking is probably both a marker for poor health and an alert that some things need to be changed to improve the health of a senior, said Anne Cappola, MD, ScM, associate professor of Epidemiology and Medicine in Endocrinology, Diabetes and Metabolism and a fellow of Penn's Institute on Aging.
Researchers are looking into the theory that you can get people to live longer if you can get them moving faster, Cappola said. “People are trying things like resistance training and getting people to walk more,” she added. “That can be difficult when older people are living in confined living spaces or are afraid to go outside because of where they live. People need to walk faster,” she said. “And if they’re doing it to outrun death that works just fine.”
December 15, 2011
2012 AACE Awards Recipient
Congratulations to Susan J. Mandel, MD, MPH for being selected by the American Association of Clinical Endocrinologists (AACE) to receive the H. Jack Baskin, MD Endocrine Teaching.
The award will be presented at the AACE 21st Annual Scientific & Clinical Congress in Philadelphia.
November 16, 2011
New R01 Grant for Dr. Lazar
Congratulations Dr. Lazar!
Dr. Lazar received a new R01 for his project, Biology of the orphan receptor Rev-erb alpha. $626,292 for the initial year funding.
November 16, 2011
New R01 Grant for Dr. Snyder
Congratulations Dr. Snyder!
Dr. Peter Snyder received a new R01 grant for his project, The Bone Trial of the Testosterone Trial. $739,401 for initial year funding.
Dr. Mitchell A. Lazar receives grant from the JPB Foundation for project entitled, "The Epigenetics of Diabetes".
These studies will provide a molecular understanding of how subtle changes to chromatin structure, induced by environmental factors such as intrauterine condition and diet, can cause or exacerbate diabetes. The research team hopes that the work will lead to novel hypotheses that advance the field of diabetes, and to unrecognized therapeutic targets that can be evaluated in animals and, with rapidity, in patients with diabetes.
October 24, 2011Penn Study Explains Paradox of Insulin Resistance Genetics
Obesity and insulin resistance are almost inevitably associated with increases in lipid accumulation in the liver, a serious disease that can deteriorate to hepatitis and liver failure. A real paradox in understanding insulin resistance is figuring out why insulin-resistant livers make more fat. Insulin resistance occurs when the body does a poor job of lowering blood sugars.
The signals to make lipid after a meal come from hormones - most notably insulin - and the direct effect of nutrients on the liver. In a recent issue of Cell Metabolism, Morris Birnbaum, MD, PhD, professor of Medicine at the Perelman School of Medicine, University of Pennsylvania, describes the pathway that insulin uses to change the levels of gene expression that control lipid metabolism. Birnbaum is also associate director of the Institute of Diabetes, Obesity, and Metabolism at Penn.
October 11, 2011
Endocrine Society Award: Dr. Bale
Dr. Tracy Bale is the recipient of the 2011 Richard E. Weitzman Memorial Award. Presented annually by the Endocrine Society, the award aims to bring to light the work of a young researcher in the field.
Dr. Bale holds a dual appointment at Penn; she is an associate professor of neuroscience in the department of animal biology at the School of Veterinary Medicine, as well as associate professor of neuroscience in the department of psychiatry at the Perelman School of Medicine.
Her research expertise and areas of interest include prenatal stress, neurodevelopmental disorders, depression, stress, obesity and neuroendocrinology.
October 11, 2011
Pfizer Animal Health Award for Research Excellence: Dr. Bence
Dr. Kendra Bence, assistant professor in the department of animal biology at the School of Veterinary Medicine, has been named recipient of the 2011 Pfizer Animal Health Award for Research Excellence.
Her research expertise and areas of interest include mouse models of obesity/diabetes, neuronal control of energy balance, protein phosphatases and signal transduction.
The Pfizer Animal Health Award for Research Excellence is presented annually to one member of Penn Vet’s faculty. The award intends to foster innovative research, on which the scientific advancement of the profession depends, by recognizing outstanding research effort and productivity.
October 6, 2011
Stanley N. Cohen Biomedical Research Award
Dr. Klaus H. Kaestner has been selected as the sixteenth recipient of the Stanley N. Cohen Biomedical Research Award.
Established in honor of Dr. Stanley N. Cohen, a 1960 Penn School of Medicine alumnus whose contributions launched a new era in biological research technology, this award recognizes achievement in the broad field of biomedical research.
The award recognizes Dr. Kaestner’s groundbreaking ideas and scientific discoveries in the study of pancreas and liver development, with its important implications for the understanding and treatment of diabetes and digestive diseases.
Congratulations to Dr. Kaestner on receiving this prestigious award!
September 23, 2011
AstraZeneca and the University of Pennsylvania join efforts to combat the global obesity and diabetes epidemics
Patrick Seale, Ph.D., Principal Investigator at the IDOM received funding from Astra Zeneca for a research collaboration projected entitled, Recruitment of thermogenic brown adipocytes in situ from adult adipose-derived stem cells. The funding is for a period of three years
September 12, 2011Penn Researchers Find High-Fat Diet and Lack of Enzyme Can Lead to Heart Disease in Mice
Writing in the Journal of Biological Chemistry, Mitchell Lazar, MD, PhD, the Sylvan Eisman Professor of Medicine and director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine at the University of Pennsylvania, and colleagues, describe that mice lacking a gene-expression-controlling enzyme fed a high-fat diet experience rapid thickening of the heart muscle and heart failure. This molecular link between fat intake and an enzyme tasked with regulating gene expression – at least in mice – has implications for people on so-called Western diets and combating heart disease. Modulating the enzyme's activity could be a new pharmaceutical target.
August 3, 2011
The NIDDK-funded Beta Cell Biology Consortium (BCBC) has just announced a new Transformative Collaborative Project Award to Drs. Klaus Kaestner from IDOM and Benjamin Glaser from Hadassah Medical School to investigate “Non-neoplastic replication to expand functional beta-cell mass” (NORM). This two year award will focus on the proliferation and expansion of fully differentiated, mature human beta-cells. This research has implications for type 2 as well as type 1 diabetes, as insufficient beta-cell mass is also a hallmark of advanced type 2 diabetics.
July 26, 2011
Contratulations to Carrie Burns, MD, Kolin Hoff, MD, Mitchell A. Lazar, Susan Mandel, MD, MPH, Mark Schutta, MD and Peter Snyder, MD for being named to a highly selective list of America's Top Doctors (ATD) by achieving national recognition for outstanding work.
U.S. News Media Group announced U.S. News Top Doctors, a free searchable directory available at www.usnews.com/top-doctors that lists nearly 30,000 peer-nominated physicians across the country.
U.S. News Top Doctors was created in collaboration with Castle Connolly Medical Ltd., publisher of America's Top Doctors and other consumer health guides. It draws from Castle Connolly's database of Top Doctors, all recommended for their clinical skills by other doctors and individually vetted by a physician-led research team. Consumers can search for a Top Doctor by location, hospital affiliation, and a full range of specialties and subspecialties.
"A Top Doctor in Castle Connolly's estimation, is among the top 1% in the nation in his or her specialty."
April 11, 2011
Prestigious Searle for Seale
Congratulations to Patrick Seale, PhD! Dr. Seale has been selected as a 2011 Searle Scholar recipient. The Searle Scholars Program makes grants to selected academic institutions to support the independent research of outstanding individuals who have recently begun their first appointment at the assistant professor level, and whose appointment is a tenure -track position.
March 31, 2011
Congratulations to Anne Cappola, MD, ScM!
Dr. Cappola has just been nominated to become a member of The Endocrine Society's Advocacy and Public Outreach Core Committee (APOCC). She will begin her three year term on July 1, 2011.
March 23, 2011
Far from Radiation, Potassium Iodide Pills in Demand
Those just-in-case pills health officials hand out to people living near nuclear power plants are in big demand, even in Southeast Pennsylvania--more than 6,000 miles away from the radiation leaks in Japan. Some people think of the potassium iodide as a cure-all, anti-radiation medicine, according to WHYYRadio.
But Dr. Susan Mandel, MD, MPH, director of the Penn Thyroid Center, said the salt pills have a very specific use. "It literally feeds the thyroid, so it prevents the thyroid from taking up the damaging radioactive iodine. It doesn't protect against any of the other radioactivity that's being released, and it doesn't protect any other organ," Mandel said. "It doesn't protect against plutonium, cesium, all those other things."
March 22, 2011
Circadian Clock Research and Links With Weight Gain and Digestion
The Wall Street Journal mentions research from the lab of Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity and Metabolism, in an article about circadian rhythms. The team recently found a clock-gene mechanism that reduces the production of fat in the liver at certain times of the day.
Such findings suggest manipulating these clock genes could have implications for diabetes or fatty liver disease. NIH Research Matters also featured the study, in which Lazar's team discovered a molecular link between the body's biological clock and fat production in the liver. The finding may help explain why disrupting daily cycles, such as rotating shift work, increases the risk of diseases like obesity and diabetes. Liver cells undergo epigenetic modifications that vary with the time of day.
March 10, 2011Molecules Work the Day Shift to Protect the Liver from Accumulating Fat, Says Penn Study
Abnormal sleep patterns, such as those of shift-workers, can be risk factors for obesity and diabetes. Investigators have known for decades that fat production by the liver runs on a 24-hour cycle, the circadian rhythm, and is similar to the sleep-wake cycle.
A research team led by Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania School of Medicine, has discovered molecules that act as “shift workers” to maintain the daily rhythm of fat metabolism. When those molecules do not do their jobs, the liver dramatically fills with fat. These findings are reported in this week’s issue of Science.
July 26, 2011
Penn Receives $10 Million to Create Center for Orphan Disease Research and Therapy
Former Perelman School Dean Arthur H. Rubenstein, MBBCh, has agreed to serve as Acting Director of a first-of-its-kind interdisciplinary center focused on discovering novel treatments for orphan diseases. The Center will bring together, without institutional walls, all necessary approaches to attacking and treating orphan diseases: establishing dedicated research support facilities, translating findings into therapies, fostering targeted grant awards, and educating physicians and researchers.
July 21, 2011
Penn Endocrinology Ranked #11 in the nation
More than 1,000 hospitals are listed in Diabetes & Endocrinology. All are experienced in treating difficult cases—a hospital is listed only if at least 144 inpatients in need of a high level of expertise in this specialty were treated there in 2007, 2008, and 2009 or if enough specialists recommended the hospital for such patients. The top 50 hospitals are ranked, based on score. The rest are listed alphabetically.
>> Read More
July 1, 2011
Nuclear Receptor in the Crosshairs of Diabetes
Mitch Lazar, MD, PhD, director of the Institute of Diabetes, Obesity, and Metabolism, comments in a Science-Business eXchange (SciBX) article about a new signaling pathway that could be a type 2 diabetes target. “The data suggest that DLPC functions as an insulin sensitizer, so it addresses the key defect in type 2 diabetes,” sais Lazar. “This is similar to compounds that target PPARγ, such as thiazolidinediones, but it does not seem to have the weight gain problem associated with PPARγ compounds, so that would be a plus.”
June 22, 2011
Penn Medicine Valley Forge brings expert medical care to the suburbs. Penn Medicine has a much more integrated model than other suburban medical practices, where multiple specialties deliver care in larger clinical spaces sharting staff and faciliies. All physicians use the same electronic medical record that is linked across the health system to enhance communication and streamline patient care.
June 7, 2011
PENN Trial offers hope in insulin-cell transplants
Andy Gordon, 57, of Silver Spring, Md., a Type 1 diabetic since age 12, no longer needs his insulin pump: An islet-cell transplant in an experimental procedure at the University of Pennsylvania has changed his life.
May 27, 2011
Thyroid Drug Shortage Presents Tough Choices for Cancer Patients
Forty percent of patients who need a drug used in the treatment and monitoring of thyroid cancer will not be able to get it until later this summer, according to the medication’s manufacturer.
Since thyroid cancer is typically slow-moving, most physicians are recommending that low-risk patients wait out the shortage. “It would be difficult to say that delaying therapy two or three months will change the outcome of their disease,” said Dr. Susan Mandel, a professor of medicine at the University of Pennsylvania, who notes that some doctors do not use Thyrogen to treat thyroid cancer at all. “But physicians want to get patients who have just had surgery on with their lives, and instead we are telling them they can’t be treated now.”
May 23, 2011
Uncovering Process That Determines Fate of Stem Cells May Lead to Better Treatments for Type 1 Diabetes
By looking at markers on proteins known as histones, a team of researchers led by Ken Zaret, PhD, professor of Cell and Developmental Biology and associate director of the Penn Institute for Regenerative Medicine, set out to find clues that may indicate the ultimate fate of a stem cell. This knowledge could be used to steer these cells toward developing into insulin-producing pancreatic cells, or other personalized cells for therapy and research. Endocrineweb highlighted the research on their site.
January 5, 2011
Warnings about diabetes and obesity could start popping up on soda cans, if a petition sent to the FDA this week gains any traction, according to a WHYY Radio report. The Philadelphia Department of Health, along with numerous other organizations around the country, signed the letter urging the government to require health warnings on beverages with large amounts of sugar or other caloric sweeteners.
Mark Schutta, MD, director of the Penn Rodebaugh Diabetes Center said he sees too many patients whose health problems stem from excessive soda consumption. “How's it going to hurt the overall health of the American population? The bottom line is, it's not. The only thing it can potentially hurt is the consumption of these drinks and the profit margin for soda manufacturers,” he said. “In the quantities that people are consuming these drinks, it's just not something that's good for anyone's health.”
December 20, 2010
Congratulations to Rebecca Simmons, MD!
Dr. Simmons has received a Research Award (Grant) from the American Diabetes Association. The title of the grant is "Epigenetic Regulation of ß-cell Failure."
November 22, 2010
Congratulations to Rex Ahima, MD, PhD.! Dr. Ahima is the editor of “Metabolic Basis of Obesity", which was recently published by Springer and he is also the co-editor of "Year in Obesity and Diabetes", which was recently published by Annals of the New York Academy of Sciences.
October 27, 2010
Congratulations to Susan Mandel, MD, MPH who received the 2011 Distinguished Educator Award from the Endocrine Society. This Award is presented in recognition of exceptional achievement as an educator in the discipline of endocrinology and metabolism.
October 25, 2010
Congratulations to Klaus Kaestner, Ph.D.! His recent project, "Novel Pathways for Expansion of Beta-Cell Mass" has been funded by the Juvenile Diabetes Research Foundation.
October 20, 2010
Congratulations to Kenneth Zaret, PhD, for being elected to the Board of Directors of the International Society of Differentiation (2010-2016)!
October 1, 2010
Congratulations to Patrick Seale, PhD, for being selected as a 2010 NIH Director’s New Innovator Award Recipient!
September 29, 2010
Congratulations to Diva De León Crutchlow, MD. Her recent project "Development of Exendin-(9- 39) for the Treatment of Congenital Hyperinsulinism" has been funded by the NIH Rapid Access to Interventional Development (NIH- RAID).
This project will support the preclinical development of the GLP-1 receptor antagonist Exendin-(9-39) for the treatment of congenital hyperinsulinism, a rare genetic disease resulting in persistent hypoglycemia in children. Dr. De León’s preliminary preclinical and clinical studies support the use of exendin-(9-39) as a novel and effective treatment for this condition.
Currently, there are not effective therapies for children with the most severe and common form of congenital hyperinsulinism and most of these children require a near-total pancreatectomy to ameliorate the hypoglycemia, thus the development of this peptide represents a major breakthrough in the field.
Furthermore, the outcomes of this translational research project may have implications for treatment of other forms of hyperinsulinism and other forms of hypoglycemia in which GLP-1 may play a role including post-prandial hypoglycemia after Nissen fundoplication and gastric bypass surgery.
September 28, 2010
New Diet Rules: 6 Surprising Ways to Lose Weight
Marie Claire magazine notes that low-carb diets reigned during the Atkins craze, but in the long run, people can't maintain them. According to a study in the Annals of Internal Medicine, dieters who ate carbs in moderation lost about five pounds more than carb-avoiders. Eat five servings of grains daily, especially whole ones (oatmeal, brown rice), says Marion Vetter, MD, RD, medical director at the Center for Weight and Eating Disorders and lead author of the study. "Carbs provide great energy and fiber," she says. Besides, "avoiding them isn't realistic."
September 14, 2010
Freeze! Zap! Bye-Bye, Fat
Two new devices—one that deflates fat cells, one that destroys them—have just been cleared for "body contouring" in doctors' offices by the Food and Drug Administration. Some experts worry that forcing fat out of fat cells can increase the level in the bloodstream. Another danger is that losing fat cells could will lower leptin levels, signaling to the brain to eat more. "That's one of the reasons it's so, so hard to maintain weight loss—the body is trying to defend a weight it got used to," says Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity and Metabolism in an article in the Wall Street Journal.
Congratulations to Anne R. Cappola, MD, ScM,, on being awarded the American Federation for Aging Research's Dorothy Dillon Eweson Lecturer on the Advances in Aging Research at the 2010 Endocrine Society Commitee Meeting.
Morris J. Birnbaum, MD, PhD., was appointed Associate Dean of Research Core Facilities.
Doris Stoffers, MD, PhD., is the PI on a 3.5 million dollar - 5 year NIH U01 from the Beta Cell Biology Consortium beginning August 1, 2010 and entitled "Formation of Endocrine Pancreas Progenitors".
Doris Stoffers, MD, PhD., is the recent recipient of a 3 year research grant from the Juvenile Diabetes Research Foundation.
Congratulations to Judith A. Long, MD, on her promotion to Associate Professor.
Anne R. Cappola, MD, ScM, receives Endocrine Society Award
Congratulations to Dr. Anne Cappola on receiving an Abbott Thyroid Clinical Research Mentor Award.
Congratulations to Judith A. Long, MD, on receiving an R01 grant from NIDDK, entitled “A Randomized Trial of Incentives and Peer Mentors to Improve Diabetic Outcomes.”
Dr. Judith Long will conduct a randomized controlled trial in a predominantly African American population from West Philadelphia with poorly controlled diabetes evaluating the effectiveness of: one-on-one peer mentoring, financial incentives, and one-on-one peer mentoring plus financial incentives in improving glucose control.
May 17, 2010
A Fat Cell Grows Up: Stages from Early to Mature Cell Offer Clues for Anti-Obesity Drug Development, Penn Researchers Report
Getting from point A to B may sound simple, but not so in the formation of fat cells.
In a finding with potential drug-development implications, Mitchell A. Lazar, M.D., Ph.D., director of the Institute for Diabetes, Obesity, and Metabolism at the University of Pennsylvania School of Medicine, and colleagues report in the current issue of Genes & Development the discovery of an intermediate state between early-stage fat cells and fully mature ones that is only present transiently during the fat-cell formation process. This intermediate state is induced by hormones related to cortisol, which are known to contribute to obesity and metabolic disturbances in people.
May 10, 2010
Prescription Tattoos: Coming to a Pharmacy Near You
A Discovery News article describes how scientists are developing medical tattoos that would stop hackers from messing with pacemakers and drastically reduce the number of needle sticks needed to monitor glucose levels. "The technology here is very innovative, and in principle it's very promising," said Rexford Ahima, MD, PhD, director of the IDOM Obesity Unit.
Ahima notes that human trials would still be necessary before patients are injected with nanosensor tattoos for diabetes, but that eventually the technique could be used for other diseases. "This may encourage patients, especially type 2 diabetics who often don't check their glucose levels as much as they should, to check their levels more often," and with less pain, said Ahima.
The Effect of Soda on Your Body
Do you know what an average soda does to your body? To find out, a reporter from ABC News World News with Diane Sawyer went to Penn’s Rodebaugh Diabetes Center and drank 20 ounces of cola on an empty stomach. That's about the same amount the average American drinks in a day, making it the No. 1 source of calories in our diets, or 7 percent of the average person's caloric intake. After 40 minutes, the reporter’s glucose level went from 79 to 111.
"This is the point where the glucose that you drank is really starting to get absorbed into the bloodstream, and this is where the pancreas is really starting to do its maximal work," said Mark Schutta, MD, director of the Rodebaugh Center.
"The real issue is the empty calories that are in these drinks," said Michael Rickels, MD, MS, associate director of the Type 1 Diabetes Unit. "If you consume two of those drinks every day ... you'll gain a pound every week from them. And if you just think about that over the course of a year, that's 52 extra pounds that you could put on your body. And that is really dangerous for anybody." Coverage also appeared on ABCNews.com and ABC affiliates in San Francisco, Seattle, Denver and Idaho Falls.
ABC World News with Diane Sawyer segment
ABC News online
Additional coverage on ABC affiliates (#5-8, 10)
April 6, 2010
Quality of care among obese patients
In a study published by the Journal of the American Medical Association (JAMA), Virginia W. Chang, MD, PhD, and colleagues report findings which may help understand why the risk of death associated with obesity is not as high as it used to be. The paper was covered by USAToday.com, ABC affiliates in Los Angeles, CA, and other TV outlets.
Mitchell A. Lazar, MD, PhD, will deliver the Calloway Memorial Lecture at UC Berkeley on April 21, 2010.
Arthritis Drug Shows Promise In Type 2 Diabetes Study
A low-cost drug known since the time of the Pharaohs improved diabetes symptoms in a Boston study being published today, and its success supports an entirely new way of understanding the disease. A Boston Globe article notes that the drug, called salsalate, is also being studied as a potential treatment for repeat heart attacks and to stall development of Type 2 diabetes. Glucose levels, a measure of how well the body processes sugar, improved significantly in all three of the groups that took the medication.
Mitchell A. Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, said he was pleased with the results overall, but was surprised that the drug failed to lower rates of bad cholesterol and that insulin levels did not go down, both markers of effective treatments.
Congratulations to Nan Wu, a graduate student in the Lazar Lab, on receiving a travel scholarship to attend the Nuclear Receptor Keystone Symposium in March, 2010.
Rex Ahima, MD, PhD elected to the Association of American Physicians
The Association of American Physicians is a nonprofit, professional organization founded in 1885 by seven physicians, including Dr. William Osler, for “the advancement of scientific and practical medicine.” Now the Association is composed of about 1200 active members and approximately 550 emeritus and honorary members from the United States, Canada and other countries.
Testosterone Replacement Therapy Trial Launched - Dec. 21, 2009
In continuing coverage, an article in the Wall Street Journal describes the Testosterone Trials, led by Peter Snyder, MD, professor of Medicine in Endocrinology. Unlike women and estrogen, men don't lose testosterone uniformly. "There's no question that testosterone declines with age, but at this point we don't know if the decline…is a normal phenomenon or a pathological phenomenon," says Snyder. "There are enough men in their 90s who have testosterone levels that are normal for a man of 25 to make you wonder. Additional coverage appeared online at Urology.About.com.>> Urology.About.com article
Hormone Boosts for Men Get a Test - Nov. 30, 2009
To determine if some of the debilities of elderly men are due to low testosterone, the government is funding a national study to see whether older men with low testosterone benefit from boosting it, according to a front-page story in the Philadelphia Inquirer.
Led by University of Pennsylvania endocrinologist Peter Snyder, MD, professor of Medicine, the $45 million clinical trial, which this month began recruiting 800 men older than 64, is by far the largest ever to compare the effects of the quintessential male hormone with a placebo. It will investigate whether in some men, symptoms of aging such as ebbing energy, limp libido, and muddy memory are partly due to testosterone deficiency.
It is, Snyder said, an "unprecedented opportunity" to shed light on the question: Is unusually low testosterone pathological, or just a natural part of aging? Additional coverage appeared in the Penn Almanac.
Several Penn Medicine physicians and staff members are mentioned throughout a multi-story supplement on diabetes appearing today in the Philadelphia Inquirer and Daily News.
Scott Soleimanpour, MD, a research fellow working in the Institute for Diabetes, Obesity and Metabolism, was profiled.
Doris Stoffers, MD, PhD, associate professor of Medicine, in whose lab Soleimanpour works, is also mentioned. Soleimanpour's basic research on beta cells, clinical duties at the Rodebaugh Diabetes Center, and experiences living with Type 1 diabetes are featured. "I have my little Star Trek Enterprise banner over there," he says pointing to a corkboard decorated with a small "to boldly go where no one has gone before" banner. Soleimanpour says he's fascinated by "that whole idea of exploring new frontiers, being able to think of new ideas that no one has ever thought about."
Facing Down Diabetes - Nov. 19, 2009
In an article about managing diabetes on 54 cents a day, Mark Schutta, MD, medical director of the Penn Rodebaugh Diabetes Center, notes that “there’s no doubt that some of the new drugs can be a great help to many patients.” They can offer game-changing benefits like weight loss or a lower risk for hypoglycemia, he says. If cost is an issue – as a month’s supply can cost more than $100 or $200 if paid out of pocket – a typical patient who is newly diagnosed with Type 2 diabetes could conceivably control his blood sugar and help prevent heart attacks and strokes for about half a dollar a day.
Tracking hunger hormones.
Why do we eat? Rexford Ahima, MD, PhD is trying to answer that question by studying the hormones that regulate hunger and appetite. "Our main research question is how fat cells communicate with the brain, liver and muscle," said Ahima, who directs the obesity unit of the University of Pennsylvania's Institute for Diabetes, Obesity and Metabolism. Disrupting these messages can cause overeating, obesity and diabetes.
As men age, their testosterone levels naturally drop. But for some men, the male sex hormone may sink so low that they not only lose all interest in sex, but suffer more falls, have memory problems and experience anemia. Articles in the Philadelphia Business Journal, Pittsburgh Post-Gazette and St. Paul Pioneer-Press highlight a Penn-led study which will explore whether applying testosterone gel to the abdomen, torso or upper arms can reverse those effects.
The study is being funded by the National Institutes of Health and coordinated at the University of Pennsylvania. The men will be tracked for two years to see if the group getting testosterone has significant improvement in vitality and wellbeing, said Peter Snyder, MD, principal investigator and professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism. Previous studies have linked low testosterone to thinking difficulties, low energy, falls, brittle bones, anemia and even heart problems. The evidence from these studies is "tantalizing but not convincing," Dr. Snyder said. "I think there is considerable evidence that testosterone treatment might do good in all these areas, and I think it's worthwhile spending our time finding out."
Link between diabetes and heart disease scrutinized
The link between diabetes and heart disease is well-known -- diabetics are two to four times more likely to have cardiovascular disease than nondiabetics, and two-thirds will die of an early heart attack or stroke. But the link itself is poorly understood. Fat is "packaged" differently in diabetes, researchers now realize, and can cause a low-grade inflammation in obese people that might contribute to both diabetes and heart disease.
Fatty acids from weight gain also cue the liver to make too much "bad" LDL cholesterol and too little "good" HDL cholesterol, said Daniel Rader, MD, director of preventive cardiology, in the Los Angeles Times. HDL molecules normally remove cholesterol from the fatty plaques in the arteries that can rupture and cause heart attacks or strokes. The low HDL levels in diabetes allow these risky plaques to grow, he explained. Now researchers realize that fat tissue itself can become inflamed, and this could explain how obesity induces both diabetes and heart disease.
In 2003, studies in both mice and people showed that fat tissue harbors macrophages that increase in number with obesity. "These macrophages spew out inflammatory molecules that circulate in the body and cripple the ability of insulin to work in other cells, leading to diabetes," said Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity and Metabolism, also commenting in the LA Times article.
IDOM receives Challenge Grant from the NIDDK
Congratulations to Dr. Mitch Lazar for receiving a Challenge Grant from the NIDDK for his project, " Genome-wide Epigenetic Control of Circadian Metabolism by Heme Receptor Rev-erb." The proposed experiments aim to determine the extent that Rev-erb contributes to, or even controls, circadian and metabolic processes and the crosstalk that occurs between them. Ultimately, greater insight into the regulation of circadian rhythm and metabolism by Rev-erb will contribute greatly to our understanding of how these physiological processes are interrelated, and potentially dysregulated in obesity and diabetes, which are epidemic in the United States.
"Connecting Obesity, Aging, and Diabetes"
Congratulations to Dr. Rex Ahima for making Nature Medicine News and Views. Experiments in mice suggest that obesity increases the production of free radicals in fat cells, shortens telomeres and activates the p53 tumor suppressor and the promotion of insulin resistance.
IDOM Faculty to serve on JCEM Editorial Board
Congratulations to Dr. Michael Rickels for being invited to serve on the Editorial Board of the Journal of Clinical Endocrinology and Metabolism from January 1, 2010 - December 31, 2013.
Congratulations to Dr. Rex Ahima for being elected to serve on the nominating committee of the Obesity Society for 2009 - 2011.
Inner Workings of Molecular Thermostat Point to Pathways to Fight Diabetes, Obesity, According to Penn Study
Best known as the oxygen-carrying component of hemoglobin, the protein that makes blood red, heme also plays a role in chemical detoxification and energy metabolism within the cell. Heme levels are tightly maintained, and with good reason: Too little heme prevents cell growth and division; excessive amounts of heme are toxic.
Researchers at the University of Pennsylvania School of Medicine have discovered a molecular circuit involving heme that helps maintain proper metabolism in the body, providing new insights into metabolic disorders such as obesity and diabetes. The work builds on 2007 findings from the same team, led by Mitchell Lazar, MD, PhD, Director of Penn’s Institute for Diabetes, Obesity, and Metabolism, showing that a protein called Rev-erbα coordinates the daily cycles of heme. The new research, published online in Genes & Development, makes it clear that Rev-erbα, by controlling the production of heme, also plays a key role in maintaining the body’s correct metabolism. This happens through a molecular pathway that allows the cell to monitor and adjust internal heme levels, creating more when heme levels fall, and slowing it down when levels rise.
‘Brown fat’ may be key in obesity battle
Recent discoveries are highlighting a good type of fat, called “brown fat,’’ that offers a potential new weapon to scientists looking for ways to fight obesity.
Unlike better-known white fat, brown fat converts stored energy into heat. Two groups of Boston researchers have reported finding cellular switches that can be flipped on to make brown fat cells out of ordinary skin cells and other types of cells. Still, researchers cautioned that brown fat discoveries are far from a treatment for obesity. The physiological effects of increasing brown fat will need to be carefully examined, commented Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism in the Boston Globe, but because brown fat’s normal job in the body is to burn energy, it is an exciting new avenue for research. “There is hope in terms of a new direction, but it’s still early-stage,” he says.
IDOM Scientists receive funding from Stimulus package.
Congratulations to Drs. Rexford Ahima and Nancy Cooke for receiving awards from the American Recovery and Reinvestment Act of 2009!
Dr. Rexford Ahima, Associate Professor of Medicine, has received a stimulus award to support a University of Pennsylvania undergraduate student in the summers of 2009 and 2010. The project will investigate the role of a lipid droplet protein, Tail-Interacting Protein of 47kDa (TIP47), in the pathogenesis of fatty liver and diabetes.
Dr. Nancy E. Cooke, Professor of Medicine and Genetics, has received two stimulus awards for summer students. The first, entitled “Activation of the human placental gene expression” will fund a talented University of Pennsylvania undergraduate to explore remote regulatory elements within the human growth hormone chromatin locus that are of critical importance in activating the expression of gestational hormones during the second and third trimester of pregnancy.
The second stimulus award entitled “LCR activation of the human growth hormone gene” will fund a second talented University of Pennsylvania undergraduate to explore the role of non-coding RNA transcripts in directing pituitary somatotrope differentiation and growth hormone gene expression. Both of these studies involve the creation and analysis of specially engineered transgenic mice.
"HONOR ROLL" OF BEST HOSPITALS IN AMERICA
The Hospital of the University of Pennsylvania (HUP) is ranked as one of the top 10 hospitals in the United States by U.S. News & World Report, for the second consecutive year. The publication's prestigious annual ranking of hospitals placed HUP eighth out of more than 4,800 facilities surveyed.
The Hospital of the University of Pennsylvania was the only hospital in the Philadelphia region, and one of only 21 hospitals nationwide, to receive the "Honor Roll" recognition for excellence in multiple specialties.
HUP Endocrinology is ranked tenth out of more than 1,000 hospitals!
For more information, visit U.S.News & World Report's web site.
July 27, 2009 - Researchers have linked a growing number of chronic diseases to the metabolic disorder known as insulin resistance; two general theories have emerged about its mechanism. Unambiguous evidence on the initial stages of disease is missing, making it an excruciatingly difficult task to pin down the causes at the cellular and molecular level.
“The field is in a funny stage right now,” comments Mitchell Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity and Metabolism in Science magazine, “It’s gone from having too few candidate explanations [for insulin resistance] to having too many.” Now when someone comes along with yet another possibility, Lazar says, “you go, ‘Okay, get in line, buddy.’ There are a lot of things that have to be figured out.”>> Read Science Article
Dr. Kendra Bence was awarded an RO1 grant for $1,968,750 from NIH/NIDDK for Neuronal Protein Tyrosine Phosphatases in Metabolism. The project began 7/1/2009 and will end 6/30/2014.
Dr. Wei Guo was awarded the American Heart Association Established Investigator Award.
New Role Discovered for Molecule Important in Development of Pancreas, Penn Study Finds - Implications for New Diabetes Treatments
July 9, 2009 - For years researchers have been searching for a way to treat diabetics by reactivating their insulin-producing beta cells, to no avail. Now, they may be one step closer...
“The protein, Pdx1, is a pivotal molecule in the regulation of beta-cell development and we hope this type of information could help in efforts to generate beta-cell replacements for the treatment of diabetes," says senior author Doris Stoffers, MD, PhD, Associate Professor of Medicine at the University of Pennsylvania School of Medicine. Stoffers is also a member of the Institute for Diabetes, Obesity, and Metabolism at Penn.
Fulbright Africa Scholar
July 09, 2009 - Dr. Charlene Comphor has been selected as a Fulbright Africa Scholar for the spring semester 2010.
She will be doing adolescent obesity research and fostering research productivity among faculty at the University of Botswana.
Appetite-Stimulating Hormone is First Potential Medical Treatment for Frailty in Older Women
17 Jun 2009 – Older women suffering from clinical frailty stand to benefit from the first potential medical treatment for the condition, according to a study presented last week by Penn Medicine researchers at ENDO, The Endocrine Society’s 91st Annual Meeting. Ghrelin, a hormone that stimulates appetite, was... Read more
Joseph Baur, Ph/D receives award from the American Federation for Aging Research
Congratulations to Dr. Joseph Baur for receiving an award of $75,000 from the American Federation for Aging Research (AFAR). Dr. Baur will try to understand whether cells with more mitochondria function better.
Congratulations to Anne R. Cappola, MD, ScM for her two recent awards:
- The Austrian Award for Junior faculty presented during the Department of Medicine Research Day
- The Edward Rose Teaching Award for outstanding teaching and mentorship of Endocrinology Fellows in either clinical practice or in research.
Medical Student Summer Research Program in Diabetes
This is the first year of Penn's participation in a medical student summer research training program in the field of diabetes, obesity and metabolism sponsored by the NIDDK.
Four medical students selected from a national competition will each spend two months working with an IDOM investigator in an area of their interest. Each student will develop a project and prepare results for presentation at a national research symposium being held at Vanderbilt University. - Michael R. Rickels, M.D., M.S., Director, NIDDK Medical Student Research Program.
The first two students are below:
Ben Vereen Speaks at HUP
Tony Award winning Actor Ben Vereen visited HUP to talk about his Type II Diabetes with Rodebaugh Diabetes Center patients. Coverage appeared on 6 ABC and the NBC 10! Show.
Each year, Philadelphia Magazine compiles its "Top Doctors" list of the region's best physicians. The physicians at Penn Medicine always figure prominently on this list, and 2009 was no exception.
Congratulations to the physicians listed below who were included in Philadelphia Magazine's Top Doctors 2009 - Seth Braunstein, MD, Susan Mandel MD, MPH, & Stanley Schwartz, MD.
Anne R. Cappola, MD, ScM named of the 15 doctors highlighted in Philadelphia Magazine's Next Generation of Great Philadelphia Doctors.
In a finding that helps resolve a long-standing question in developmental biology, Klaus H. Kaestner, PhD, Professor of Genetics, and colleagues report in the journal Developmental Cell this week about how the mammalian gut forms.
Susan J. Mandel, M.D., M.P.H. elected to Endocrine Society Leadership Council as Physician-in-Practice-Seat
Mitchell A. Lazar, M.D., Ph.D. has been awarded the 2009 Stanley J. Korsmeyer ASCI Award, for his outstanding contributions to our understanding of the transcriptional regulation of metabolism.
January 27, 2009
Some People May Simply Be Hard-Wired To Overeat, Brain Scans Show. Rexford Ahima, MD, PhD, Director of the Obesity Unit in the Institute of Diabetes, Obesity and Metabolism, is quoted in an MSNBC.com article on a British study... >> MSNBC Article.
December 22, 2008
Editing Errors: Penn Study Finds Reduction in Antibody Gene Rearrangement in B Cells Related to Type 1 Diabetes, Lupus. Implications for new tests and more personalized treatments for autoimmune diseases.
Three University of Pennsylvania Professors Named 2007 AAAS Fellows
Three faculty members of the University of Pennsylvania have been named Fellows of the American Association for the Advancement of Science (AAAS). This year AAAS recognized 471 members for their scientifically or socially distinguished efforts to advance science or its applications. The new Fellows will be officially inducted February 16 during the 2008 AAAS annual meeting in Boston
Researchers at the University of Pennsylvania School of Medicine have discovered a potential new target for treating type 2 diabetes, according to a new study that appeared online this week in Nature. The target is a protein, along with its molecular partner, that regulates fat metabolism.
Replacing faulty or missing cells with new insulin-making cells has been the object of diabetes research for the last decade. Past studies in tissue culture have suggested that one type of pancreas cell could be coaxed to transform into insulin-producing islet cells. Now, researchers at the University of Pennsylvania School of Medicine have demonstrated that these pancreatic acinar cells do not become insulin-producing cells in an animal model. However, they did show that injured pancreatic cells readily regenerate back into healthy acinar cells, which has implications for treating cancer and inflammation of the pancreas.
Fifty-four million Americans -- that's one in six of us -- have pre-diabetes and most don't even realize it. Mark Schutta, MD, medical director of the Penn Rodebaugh Diabetes Center, is urging at-risk patients to be proactive and ask your doctor to give you a simple blood test for pre-diabetes -- to arm yourself with information before the damage is done.
Three professors at the University of Pennsylvania School of Medicine were elected yesterday as members of the Institute of Medicine (IOM), one of the nation's highest honors in biomedicine. The new members bring Penn's total to 58, out of over 1500 worldwide. Overall, 65 new members were named this year.
Mitchell Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism, at the University of Pennsylvania School of Medicine, is the 2006 recipient of The Endocrine Society's Edwin B. Astwood Award Lecture. Lazar will present his talk, entitled, "Nuclear Receptors and Endocrinology" at the society's 88th annual meeting, this week in Boston, MA.
The media was invited to join The Sopranos TV actress, Aida Turturro, as she toured the Penn Rodebaugh Diabetes Center. After the tour, the media attended a discussion between Turturro and several Penn diabetes patients as they talk about the daily challenges of living with diabetes.