A look at the latest research

researchers Find Link Between PANCREATIC PROTEIN AND T2D

Patients with type 2 diabetes (T2D) have elevated levels of human islet amyloid polypeptide (hIAPP), and researchers have linked its accumulation with the loss of insulin-producing beta cells.

In a study published online in the Journal of Clinical Investigation, Safi a Costes, PhD, of the Larry L. Hillborn Islet Research Center at UCLA, and colleagues suggest that autophagy prevents the accumulation of toxic forms of hIAPP that contribute to the destruction of beta cells. Because autophagy is known to play a critical role in clearing damaged and toxic proteins, this process does not appear to be at work in people with T2D.

“Only a few previous studies have reported that autophagy is important for beta cell function and survival,” Costes said in a university release. “Th ese studies, however, were not conducted to address the role of this pathway in the regulation of the amyloidogenic protein, which is an important contributor to type 2 diabetes.”

Th e study also reveals some similarities between type 2 diabetes and neurodegenerative diseases such as Alzheimer’s, diseases that share in common an accumulation of toxic forms of amyloid proteins, she added. “For instance, it demonstrates the importance of autophagy in clearing out these harmful proteins to prevent both type 2 diabetes and Alzheimer’s,” Costes said.

In order to investigate whether autophagy plays a role in hIAPP clearance, the researchers used pancreatic beta cells in a culture and isolated pancreatic islets from mice that express the human form of islet amyloid polypeptide as well as human islets. Th ey also developed a novel mouse model defi cient for autophagy specifi cally in beta cells with expression of the human form of islet amyloid polypeptide.

The scientists found that these mice developed diabetes. A loss of autophagy in combination with the expression of hIAPP resulted in an accumulation of hIAPP and increased beta cell death, which are characteristic of T2D in humans. “The goal of our work is to understand the cellular mechanisms responsible for beta cell destruction to enable identification and validation of novel targets for beta cell protection and allow the development of next generation treatments as well as combination therapies for type 2 diabetes,” Costes said.

More Likely to take Extended sick Leave than Healthy Peers

People who have hyperthyroidism are more likely to take sick leave for extended periods than their healthy colleagues, particularly in the first year after diagnosis, according to a new study published in the Journal of Clinical Endocrinology & Metabolism

“When we examined sick leave records, our research found patients with hyperthyroidism faced a signifi – cantly higher risk of missing work for three weeks or longer due to illness compared to healthy controls,” says one of the study’s authors, Mette Andersen, MA, Nexø of the National Research Centre for the Working Environment and the University of Copenhagen in Denmark. “People who experienced eye complications from Graves’ disease were the most likely to require extended sick leave. Th is same population also was the most likely to leave the workforce altogether and retire on a disability pension.”

Th e longitudinal register study is the largest systematic assessment of the eff ect of thyroid conditions on the workplace conducted to date, Nexø says. Researchers analyzed sick leave and disability pension claims among 862 Danes who were treated in one of two university outpatient clinics in 2007 for a thyroid condition. Th e study authors then compared claim rates in this population to a group of 7,043 controls using national and municipal records from 1994 to 2011. In Denmark, people who miss work for more than three weeks due to illness are compensated by local municipalities, so the researchers were able to track when subjects missed work for an extended period due to illness.

The analysis revealed that Graves’ disease patients with eye complications were seven times more likely than healthy peers to have an extended sick leave from work within a year of diagnosis. In subsequent years, the risk diminished but remained twice as high compared to healthy peers. This population was more than four times as likely to retire on a disability pension compared to healthy controls.

People with hyperthyroidism without eye complications also faced a heightened risk of taking an extended sick leave. Th ey were twice as likely as peers to miss weeks of work due to illness within a year of diagnosis. The study also examined records for people with hypothyroidism, or an underactive thyroid. While the risk of taking sick leave was not signifi – cantly affected, people with hypothyroidism faced longer recovery than healthy peers if they had to take sick leave in the first year after diagnosis. In subsequent years, the researchers did not find signifi cant indication that the hypothyroidism aff ected workplace absenteeism.

“The findings demonstrate the potential socioeconomic effects thyroid conditions can have but also indicate that socioeconomic effects diminish once the disorders are treated,” Nexø says. “It’s important not only for patients but for employers and society as a whole, to ensure that people who have thyroid conditions receive the medical care they need.”

Has a Link Been Found Between EDCs

While many studies have linked endocrine-distrupting chemicals (EDCs) to a variety of health concerns in both males and females of all ages, a recent study in the Journal of Clinical Endocrinology & Metabolism also seems to show a link between EDCs and reduced testosterone levels in not just men, but women and children as well. In a crosssectional study of the general U.S. population from 2011 to 2012, data from the U.S. National Health and Nutrition Examination Survey showed that multiple phthalates were associated with signifi cantly reduced testosterone in both males and females regardless of age.

“Because exposure to phthalates is so common and testosterone plays an important role in all life stages for both sexes, these fi ndings could have large public health signifi cance,” says study co-author John D. Meeker, ScD, CIH, associate professor of environmental health sciences and associate dean for research at the School of Public Health at the University of Michigan in Ann Arbor. “Future eff orts should focus on better defi ning and possibly intervening to reduce the impacts of these relationships.”

Since various animal and cellular studies have shown that some phthalates block the eff ects of testosterone, Meeker and study co-author Kelly K. Ferguson, PhD, set out to prove if the same was true in humans. “Phthalates have been found to be anti-androgenic in animal and in vitro studies through a number of possible specifi c mechanisms,” he explains. “We still don’t know how this may be happening in males or females at diff erent life stages in humans, and it is possible that the diff erent specifi c phthalate chemicals may be acting through diff ering or multiple mechanisms simultaneously.”

Phthalates are commonly found in plastics and personal care products, items that most people use on a regular basis. “Due to the increasing evidence in human studies that phthalates and other EDCs may impact male reproductive health or other systems, there is a point at which some level of precaution should kick in and efforts made to reduce the population’s exposure to these chemicals,” Meeker says, adding that since the study was conducted on the population level, how these findings might impact individuals is difficult to interpret. “Things are also complicated by the fact that most products that contain phthalates aren’t labeled as such,” he says, “making it very difficult for clinicians to be able to make sound recommendations for patients to avoid or reduce exposure.”

— Mark A. Newman

BRAIN BENEFITS from Weight Loss Following Bariatric surgery

Weight loss surgery can curb alterations in brain activity associated with obesity and improve cognitive function involved in planning, strategizing, and organizing, according to a new study published in Journal of Clinical Endocrinology & Metabolism.

The longitudinal study led by Cintia Cercato, MD, PhD, of the University of São Paolo in São Paolo, Brazil, examined the eff ect of RYBG surgery on the brain function of 17 obese women. Researchers used positron emission tomography (PET) scans and neuropsychological tests to assess brain function and activity in the participants prior to surgery and six months after the procedure. Th e same tests also were run once on a control group of 16 lean women.

“When we studied obese women prior to bariatric surgery, we found some areas of their brains metabolized sugars at a higher rate than normal weight women,” Cercato says. “In particular, obesity led to altered activity in a part of the brain linked to the development of Alzheimer’s disease — the posterior cingulate gyrus. Since bariatric surgery reversed this activity, we suspect the procedure may contribute to a reduced risk of Alzheimer’s disease and other forms of dementia.”

Prior to surgery, the obese women had higher rates of metabolism in certain areas of the brain, including the posterior cingulate gyrus. Following surgery, there was no evidence of this exacerbated brain activity. Th eir brain metabolism rates were comparable to the activity seen in normal weight women.

After surgery, the obese women also performed better on a test measuring executive function — the brain’s ability to connect past experience and present action — than they did before the procedure. Five other neuropsychological tests measuring various aspects of memory and cognitive function showed no change following the surgery.

“Our findings suggest the brain is another organ that benefits from weight loss induced by surgery,” Cercato says. “The increased brain activity the obese women exhibited before undergoing surgery did not result in improved cognitive performance, which suggests obesity may force the brain to work harder to achieve the same level of cognition.”

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