October 6, 2009 (Newswise) - Resveratrol, a molecule found in red grapes, has been shown to improve diabetes when delivered orally to rodents. Until now, however, little has been known about how these beneficial changes are mediated in the body. A new study accepted for publication in Endocrinology, a journal of The Endocrine Society, shows that the brain plays a key role in mediating resveratrol's anti-diabetic actions, potentially paving the way for future orally-delivered diabetes medications that target the brain.Resveratrol activates sirtuins, a class of proteins that are thought to underlie many of the beneficial effects of calorie restriction. Previous studies in mice have provided compelling evidence that when sirtuins are activated by resveratrol, diabetes is improved. Sirtuin activators are now being tested in humans as anti-diabetic compounds.
Sirtuins are expressed virtually everywhere throughout the body and until now, little has been known about what tissues mediate resveratrol's beneficial effects. Knowing where in the body the beneficial effects of activated sirtuins are mediated could help in the development of more effective targeted diabetes medications.
"We know that sirtuins are expressed in parts of the brain known to govern glucose metabolism, so we hypothesized that the brain could be mediating resveratrol's anti-diabetic actions," said Roberto Coppari, PhD, of the University of Texas Southwestern Medical Center and co-author of the study. "To test the hypothesis, we assessed the metabolic consequences of delivering resveratrol directly into the brain of diabetic mice. We found that resveratrol did activate sirtuins in the brain of these mice which resulted in improving their high levels of blood sugar and insulin."
"These findings may lead to new strategies in the fight against type 2 diabetes," said Coppari. "By knowing that the brain mediates resveratrol's anti-diabetic actions, industry can now focus on developing sirtuin activators that directly target the brain. When orally-delivered, these drugs will likely improve diabetes without affecting the other organs in which activation of sirtuins may not always be beneficial."
Other researchers working on the study include Giorgio Ramadori, Laurent Gautron, Teppei Fujikawa, Claudia Vianna and Joel Elmquist of the University of Texas Southwestern Medical Center in Dallas, Tex.

The article, "Central administration of resveratrol improves diet-induced diabetes," will appear in the December 2009 issue of Endocrinology.

October 6, 2009 (Newswise) - Fat and muscle mass, as potentially determined by a person's ethnic background, may contribute to diabetes risk, according to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).Obesity, a worldwide health concern, is associated with increased insulin resistance, type 2 diabetes and cardiovascular disease. The prevalence of obesity is increasing in all populations across the globe, yet past research has found that body fat distribution varies widely among different ethnic groups. Researchers in this study investigated which ethnic groups were most likely to be at increased risk for diabetes due to higher total body fat and lower muscle mass.

"We know certain ethnic backgrounds show significant differences in amounts of body fat and lean mass," said Scott Lear, PhD, of Simon Fraser University in Vancouver, Canada and lead author of the study. "What we didn't know, until now, is if these differences are related to insulin levels and insulin resistance, and therefore lead to an increased risk for diabetes. Our findings indicate they are."

In this study, researchers measured insulin levels and compared the amount of total body fat to lean mass in 828 men and women of Aboriginal, Chinese, European and South Asian origin to determine how differences in fat mass and lean mass may be related to insulin levels and insulin resistance in each group. Of the four ethnic groups studied, South Asians were found to have both higher fat mass, lower muscle mass and greater insulin levels, placing them at increased risk for insulin resistance and diabetes.

"An individual's ethnic background may determine the amount of body fat and lean mass they have, and therefore may also be associated with diabetes risk," said Lear. "In populations at increased risk for diabetes, interventions that reduce fat mass and increase muscle mass, such as caloric restriction and regular exercise should be investigated."

Other researchers working on the study include Simi Kohli of Simon Fraser University in British Columbia, Canada; Gregory Bondy of the University of British Columbia in Canada; Andre Tchernof of Laval University Medical Research Centre in Laval, Canada; and Allan Sniderman of McGill Health Science Centre in Montreal, Canada.

The article, "Ethnic variation in fat and lean body mass and the association with insulin resistance," will appear in the December 2009 issue of JCEM.

October 2, 2009 (Newswise) - When Sonia Sotomayor was named Supreme Court nominee, the type 1 diabetes community seized the news as proof that diabetes is no longer a life-limiting condition.Unfortunately, the number of children with type 1 diabetes - Ms. Sotomayor was diagnosed at age 8 - is on the upswing. In type 1 diabetes, formerly known as juvenile-onset diabetes, the pancreatic beta cells that produce insulin are destroyed by an autoimmune process. Type 1 diabetics must regiment their diets and take insulin multiple times a day to control blood sugar levels and prevent diabetic coma. Although there is much excitement in the field, to date there is no cure for type 1 diabetes.

Doctors don't know why the numbers are rising or what causes type 1 diabetes, but Dr. Soumya Adhikari, assistant professor of pediatrics at UT Southwestern Medical Center, said the warning signs are clear.

"The biggest thing to watch out for is somebody who starts having to go to the bathroom (to urinate) all the time or drinking all the time," said Dr. Adhikari, who practices at Children's Medical Center Dallas. "In the Texas heat, people typically see that and think, 'It's hot - they're probably urinating more because they are drinking more,' and nine out of 10 times that's right. But, if it seems atypical compared to what they did last summer or they're losing weight or otherwise seem ill, it's probably worth at least considering having their blood sugar tested."

Other symptoms can include abdominal pain, sudden vision changes, drowsiness, nausea, and heavy, labored breathing.

October 2, 2009 (Newswise) - In a study of adults who survived cancer as children, St. Jude Children's Research Hospital investigators found that many survivors lead sedentary lifestyles and are more likely to be less physically active than their siblings. Childhood cancer survivors are at greater risk of diabetes, obesity and heart disease than the rest of the population.Cancer treatments such as cranial radiation can damage the hypothalamus and pituitary; the result is an abnormal metabolism, which increases the risk of obesity and diabetes. Also, chemotherapy with the drug anthracycline increases the risk of heart disease; and radiation to the body can cause blood vessels to become less pliant.

"Physical activity is a key step that survivors can take to reduce the health risk of these effects," said Kiri Ness, Ph.D., of the Epidemiology and Cancer Control department at St. Jude. "Medical center programs to encourage physical activity in adult survivors could help significantly. However, one problem is that researchers have not firmly established the factors that affect cancer survivors' participation in physical activity."

To understand those factors, Ness and her colleagues drew data from the Childhood Cancer Survivor Study (CCSS), a St. Jude-led consortium of 30 centers in the United States and Canada. The study gathers extensive data from the participating centers on more than 20,000 childhood cancer survivors who received diagnoses between 1970 and 1986.

The researchers analyzed 9,301 CCSS participants' answers to questions about their physical activity; as a comparison, the scientists also analyzed the same answers given by 2,886 siblings. The investigators compared those answers with information on physical activity obtained from a massive health survey database maintained by the Centers for Disease Control and Prevention.

Because of the cohort's large size, the researchers explored the relationships between health and exercise in all the different types of cancer. Also, because the cohort is older, Ness and her colleagues were able to investigate adult behaviors and relate them back to the data on their childhood cancers.
"Thus, we could identify who has the highest risk of having an inactive lifestyle," Ness said. "Knowing this makes it possible to begin to design interventions that will address the problems that put survivors at most risk."

The researchers found that the cancer survivors showed significant deficits in physical activity compared to their siblings. Survivors were less likely than their siblings to meet physical activity guidelines and more likely to report inactive lifestyles.

"It was particularly striking that 23 percent of the survivors reported that they were completely inactive over the previous month, compared with 14 percent of their siblings," Ness said.
The researchers' analysis revealed that survivors of medulloblastoma, a type of brain tumor, and osteosarcoma, a type of bone cancer, reported the most inactive lifestyles. Also associated with inactivity were treatments with cranial irradiation or amputation as well as other factors, including gender, race, age and education level. If survivors smoked, were underweight or obese or had suffered from depression, they were also prone to inactivity.

Ness hopes the findings will spark more research on the role of fitness in cancer survivors' quality of life, as well as the design of facilities and programs to encourage good fitness in survivors.
"For instance, if we know that patients with medulloblastoma who received cranial irradiation are at a high risk for having inactive lifestyles as adults, we might design a rehabilitation program they can undergo while they are still children to encourage physical activity as they age," she said.
Ness and her colleagues plan to investigate whether programs to encourage exercise in both children and adult childhood cancer survivors can help them avoid obesity, diabetes and other health problems.

September 24, 2009 (EurekAlert) - Being too optimistic could harm weight loss efforts. Research published in BioMed Central's open access journal, BioPsychoSocial Medicine, reveals the psychological characteristics that may contribute to weight loss.Hitomi Saito from Doshisha University, Japan, worked with a team of researchers to psychologically profile 101 obese patients undergoing combined counselling, nutrition and exercise therapy at the Kansai Medical University Hospital Obesity Clinic over a period of 6 months. Patients' psychosocial characteristics before and after attending the clinic were assessed using psychological questionnaires designed to identify patients' personality types. Patients who were able to improve their self-awareness through counselling were more likely to lose weight than those who were not. Optimism and self-orientation characteristics improved for most patients after the 6-month program, although this was not related to weight loss. In fact, patients who started the program with high levels of self-orientation and optimistic characteristics were less likely to lose weight.

This result supports previous findings that some negative emotion has a positive effect on behavior modification because patients care more about their disease. However, the overall improvement in optimistic ego state is not necessarily detrimental, as this increased optimism should result in patients maintaining the healthy lifestyle achieved at the clinic.

"It is important to enhance patients' self-effectiveness and self-control in order to reduce psychological stress and to maintain the weight loss", state the authors, however they are careful to stress that; "The weight loss should be attributed not simply to the intervention of the clinical psychologists but to the total effect of the intervention of a holistic medical care team."

September 24, 2009 (EurekAlert) - Diabetes prevalence is highest in the Southern and Appalachian states and lowest in the Midwest and the Northeast of America. Researchers writing in BioMed Central's open access journal Population Health Metrics have used two public data sources to investigate the prevalence of diagnosed and undiagnosed diabetes mellitus at the State level.Goodarz Danaei, from the Harvard School of Public Health, Boston, worked with a team of researchers to combine the data from the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System. He said, "Diabetes mellitus is the sixth leading cause of death in the United States, accounting for approximately 70,000 annual deaths. To our knowledge, this is the first study to estimate what the true level of diabetes disease is in every state and how the different states perform in terms of diagnosed vs. undiagnosed diabetes".

Age-standardized diabetes prevalence was highest in Mississippi, West Virginia, Louisiana, Texas, South Carolina, Alabama and Georgia, ranging from 15.8% to 16.6% for men and 12.4% to 14.8% for women. The lowest prevalences were found in Vermont, Minnesota, Montana, and Colorado, just 7% for women in the Northeast and some Western states. These results currently provide the only estimates of total diabetes and undiagnosed diabetes in U.S. states. According to Danaei, "States like Minnesota and Alabama with the highest estimated diabetes prevalence in our analysis also have the highest levels of blood pressure and cardiovascular disease risk. This concentration of cardiovascular risks and diabetes points to the need for lifestyle and health care interventions in these states".

The researchers hope their figures will provide motivation, guidance, and benchmarks for designing, implementing, and evaluating diabetes prevention and state level control programs at the state level.

September 21, 2009 (EurekAlert) - Results of a multicenter study in Asia, demonstrating that drug-eluting stents are effective with a low rate of complications in diabetic patients, will be presented at the 21st annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation (CRF).
The study, "The Effect of Drug-Eluting Stents on Clinical and Angiographic Outcomes in Diabetic Patients: Multicenter Registry in Asia," compared the safety and efficacy of sirolimus (SES), paclitaxel (PES), zotarolimus ( ZES), biolimus A9 (BES) and everolimus-eluting (EES) stents on the outcome of percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM).

The study will be presented as a poster abstract (TCT-363) on Tuesday, September 22 between 8:00 a.m. and 10:00 a.m. in Hall D of The Moscone Center. Sunao Nakamura, MD, lead investigator for the study, will report on the results of the investigations. Dr. Nakamura is Vice President and Director of the Cardiovascular Center at New Tokyo Hospital as well as Clinical and Visiting Professor of Kumamoto University in Matsudo, Japan.

The investigation consisted of a prospective analysis of 1,373 patients with DM treated with different drug-eluting stents (508 SES, 420 PES, 204 ZES, 120 BES and 121 EES) in six high-volume Asian centers. The study endpoints were the incidence of MACE at 30 days, the restenosis rate at 9 months and target lesion revascularization (TLR) at 9 months.

The incidence of MACE with this study cohort was 0.8% in patients receiving SES, 1.2% in PES, 1.0% in ZES, 0.8% in BES and 0.0% in EES. The restenosis rate at 9 months was 7.9% for those receiving SES, 12.6% for PES, 16.2% for ZES, 5.0% for BES and 6.7% for EES. TLR at 9 months was 6.5% in patients receiving SES, 10.7% with PES, 13.7% with ZES, 5.0% with BES and 4.1% with EES.

The researchers concluded that the use of drug-eluting stents in patients with DM was safe with low acute complications. Further, patients treated with SES, BES and EES showed a lesser rate of restenosis when compared with other drug-eluting stents.

September 21, 2009 (EurekAlert) - The higher incidence of diabetes among African Americans when compared to whites may have more to do with living conditions than genetics, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health. The study, available online in advance of publication in the October 2009 edition of the Journal of General Internal Medicine, found that when African Americans and whites live in similar environments and have similar incomes, their diabetes rates are similar, which contrasts with the fact that nationally diabetes is more prevalent among African Americans than whites.Researchers from the Hopkins Center for Health Disparities Solutions and Case Western Reserve University School of Medicine compared data from the 2003 National Health Interview Survey (NHIS) with the Exploring Health Disparities in Integrated Communities Southwest Baltimore (EHDIC-SWB) Study. The Baltimore study was conducted in a racially integrated urban community without race differences in socioeconomic status.

In recent decades the United States has seen a sharp increase in diabetes prevalence, with African Americans having a considerably higher occurrence of type 2 diabetes and other related complications compared to whites.

"While we often hear media reports of genes that account for race differences in health outcomes, genes are but one of many factors that lead to the major health conditions that account for most deaths in the United States," said Thomas LaVeist, PhD, director of the Hopkins Center for Health Disparities Solutions and lead author of the study.

Some researchers have speculated that disparities in diabetes prevalence are the result of genetic differences between race groups. However, LaVeist noted that those previous studies were based on national data where African Americans and whites tend to live in separate communities with different levels of exposure to health risks. The EHDIC-SWB study accounts for racial differences in socioeconomic and environmental risk exposures to determine if the diabetes race disparity reported in national data is similar when black and white Americans live under comparable conditions.

"I don't mean to suggest that genetics play no role in race differences in health, but before we can conclude that health disparities are mainly a matter of genetics we need to first identify a gene, polymorphism or gene mutation that exists in one race group and not others. And when that gene is found we need to then demonstrate that that gene is also associated with diabetes," LaVeist said. "On the other hand, there is overwhelming evidence that behavior, medical care and the environment are huge drivers of race differences in health. It seems more likely that the answer to health disparities will be found among these factors."

Researchers in this study found that within their sample of racially integrated communities without race differences in socioeconomic and environmental factors, prevalence estimates of diabetes are similar between African Americans and whites. According to the study, "Previous research has demonstrated that when African Americans and whites access similar health care facilities their health care outcomes are more similar."

The study's authors said their findings support the need for future health disparities research and creative approaches to examining health disparities within samples that account for socioeconomic and social environmental factors.

Additional authors of "Environmental and Socio-Economic Factors as Contributors to Racial Disparities in Diabetes Prevalence" are Roland J. Thorpe, Jr., PhD; Jessica E. Galarraga, MPH; Kelly M. Bower, MSN, MPH, RN; and Tiffany L. Gary-Webb, PhD.

February 25, 2009 (EurekAlert) - Researchers at Purdue University have precisely measured the impact of a high-fat diet on the spread of cancer, finding that excessive dietary fat caused a 300 percent increase in metastasizing tumor cells in laboratory animals.The researchers used an imaging technique to document how increasing fat content causes cancer cells to undergo changes essential to metastasis. Then they used another technique to count the number of cancer cells in the bloodstream of mice fed a high-fat diet compared to animals fed a lean diet.

The findings suggest that the combined tools represent a possible new diagnostic technique to determine whether a patient's cancer is spreading, said Ji-Xin Cheng, an assistant professor in Purdue's Weldon School of Biomedical Engineering and Department of Chemistry.

"It is generally accepted that diet and obesity are accountable for 30 percent of preventable causes of cancer, but nobody really knows why," Cheng said. "These findings demonstrate that an increase in lipids leads directly to a rise in cancer metastasis."

Researchers have theorized that tumor cells need more lipids than ordinary tissues to provide energy and material for tumor growth and metastasis.

"Before this work, however, most of the evidence was anecdotal, but here we present a mechanistic study," said Thuc T. Le, a National Institutes of Health postdoctoral fellow at Purdue who is working with Cheng.

Findings were detailed in a paper published on Jan. 30 in the journal BMC Cancer. The paper was written by Le; Terry B. Huff, a graduate research assistant in Purdue's Department of Chemistry; and Cheng. The research is supported by the Purdue Cancer Center.

The researchers implanted a cancerous lung tumor under the skin in each of the mice studied, and the animals were separated into two groups: one fed a high-fat diet and the other a lean diet.

The researchers then used an imaging method called coherent anti-Stokes Raman scattering, or CARS, to document how increasing lipids from fat intake induces changes to cancer cell membranes. Those changes, including processes called membrane phase separation and membrane rounding, enhance cancer metastasis.

"If the cancer cells don't have excess lipids they stick together and form very tight junctions in tumors, but increasing lipids causes them to take on a rounded shape and separate from each other," Le said.

The change in shape is critical to the ability of cancer cells to separate and spread throughout the body via the bloodstream.

The researchers then used another technique, called intravital flow cytometry, to count the number of cancer cells in the bloodstream of the mice. The technique works by shining a laser though the skin and into blood vessels, where the dyed cancer cells are visible.

Results showed the increase in lipids had no impact on the original tumors implanted in the mice. However, the rate of metastasis rose a dramatic 300 percent in the mice fed a high-fat diet.

The researchers later also examined the animals' lungs and counted the number of cancer cells that had migrated to the lungs as a result of metastasis. Those findings supported the other results showing increased metastasis in animals fed a high-fat diet.

The researches used the imaging and cell-counting tools to document that linoleic acid, which is predominant in polyunsaturated fats, caused increasing membrane phase separation, whereas oleic acid, found in monounsaturated fats, did not. Increased membrane phase separation could improve the opportunity of circulating tumor cells to adhere to blood vessel walls and escape to organs far from the original tumor site. The new findings support earlier evidence from other research that consuming high amounts of polyunsaturated fat may increase the risk of cancer spreading.

The findings suggest that combining CARS and intravital flow cytometry represents a possible new diagnostic tool to screen patients for cancer. The tool can be used to count lipid-rich tumor cells circulating in a patient's blood by shining a laser through the skin and into blood vessels. Because lipids can be detected without the need for dyes, the technique might be developed into a convenient method to diagnose whether a patient's cancer is spreading aggressively, Cheng said.

"These findings open the possibility of an entirely new, relatively simple method for diagnosing whether cancer is metastasizing," he said.

Future work will focus on not only how obesity increases metastasis but also how it might play a direct role in initiating the development of cancers.

February 25, 2009 (EurekAlert) - A new study suggests that the metabolic response to obesity and insulin resistance, particularly as it pertains to the liver, differs among ethnic groups in the U.S. African-Americans are more resistant to the buildup of fat in the abdominal adipose tissue and liver, and to high triglyceride levels associated with insulin resistance. These findings are in the March issue of Hepatology, a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD). The article is also available online at Wiley Interscience (www.interscience.wiley.com).The abnormal accumulation of fat in the liver is related to obesity and is widely prevalent in the U.S. It is related to 20 percent of all newly diagnosed cases of chronic liver disease, which can progress and become life-threatening.

Previous studies have reported significant differences by ethnicity in the prevalence of non-alcoholic fatty liver disease (NAFLD). They have also suggested that African-Americans with NAFLD tend not to develop more serious liver disease. The reasons are unknown, but may help determine which individuals are at risk for NAFLD development and progression.

Researchers led by Jeffrey Browning of the University of Texas Southwestern Medical Center in Dallas sought to examine the issue in a large population-based study. They included 2170 African-American, Hispanic and Caucasian participants and examined metabolic factors for each, including total/regional adiposity, insulin resistance, and hypertriglyceridemia. They also measured each patient's levels of liver fat. They sought to understand how ethnic differences affect the interplay of all of these factors.

The researchers took blood samples from each patient to establish their level of insulin resistance. They then used proton magnetic resonance spectroscopy, dual energy x-ray absorptiometry and multi-slice abdominal MR imaging to determine each patient's hepatic triglyceride contant (HTGC) and fat distribution throughout the body.

They found that there was a close association between intraperitoneal fat and liver fat regardless of ethnicity. "Controlling for intraperitoneal fat content almost entirely eliminated ethnic differences in levels of HTGC and prevalence of hepatic steatosis," they report. "This was not the case with insulin resistance, total adiposity or other fat depots."

Interestingly, they found that the metabolic response to obesity and insulin resistance differed in African-Americans when compared to Hispanics and Caucasions. African-Americans appeared to be more resistant to the buildup of triglycerides in the abdominal visceral compartment and also to high triglyceride levels associated with insulin resistance.

They suggest that there is an insulin resistance phenotype. It could be a function of the organ that primarily contributes to lower insulin sensitivity. Or, it could be a function of the body's ability to expand subcutaneous fat in response to overnutrition. "Further study is needed to establish the basis for this insulin resistance paradox," they write.