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.

Source: Endocrine Society

The Seguimiento Universidad de Navarra/University of Navarra Follow-up (SUN) Cohort

Almudena Sánchez-Villegas, BPharm, PhD; Miguel Delgado-Rodríguez, MD, PhD, MPH; Alvaro Alonso, MD, PhD; Javier Schlatter, MD, PhD;Francisca Lahortiga, BA, PhD; Lluis Serra Majem, MD, PhD; Miguel Angel Martínez-González, MD, PhD, MPH

Context Adherence to the Mediterranean dietary pattern (MDP) is thought to reduce inflammatory, vascular, and metabolic processes that may be involved in the risk of clinical depression.

Objective To assess the association between adherence to the MDP and the incidence of clinical depression.

Design Prospective study that uses a validated 136-item food frequency questionnaire to assess adherence to the MDP. The MDP score positively weighted the consumption of vegetables, fruit and nuts, cereal, legumes, and fish; the monounsaturated- to saturated-fatty-acids ratio; and moderate alcohol consumption, whereas meat or meat products and whole-fat dairy were negatively weighted.

Setting A dynamic cohort of university graduates (Seguimiento Universidad de Navarra/University of Navarra Follow-up [SUN] Project).

Participants A total of 10 094 initially healthy Spanish participants from the SUN Project participated in the study. Recruitment began on December 21, 1999, and is ongoing.

Main Outcome Measure Participants were classified as having incident depression if they were free of depression and antidepressantmedication at baseline and reported a physician-made diagnosis of clinical depression and/or antidepressant medication use during follow-up.

Results After a median follow-up of 4.4 years, 480 new cases of depression were identified. The multiple adjusted hazard ratios (95% confidence intervals) of depression for the 4 upper successive categories of adherence to the MDP (taking the category of lowest adherence as reference) were 0.74 (0.57-0.98), 0.66 (0.50-0.86), 0.49 (0.36-0.67), and 0.58 (0.44-0.77) (P for trend <.001). Inverse dose-response relationships were found for fruit and nuts, the monounsaturated- to saturated-fatty-acids ratio, and legumes.

Conclusions Our results suggest a potential protective role of the MDP with regard to the prevention of depressive disorders; additional longitudinal studies and trials are needed to confirm these findings.
Author Affiliations: Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (Drs Sánchez-Villegas and Serra-Majem); Division of Preventive Medicine and Public Health, University of Jaén, Spain (Dr Delgado-Rodríguez); Department of Preventive Medicine and Public Health, Clinic of the University of Navarra, Pamplona, Spain (Drs Sánchez-Villegas, Alonso, and Martínez-González); Department of Psychiatry and Medical Psychology, University of Navarra (Drs Schlatter and Lahortiga); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (Dr Alonso).

Arch Gen Psychiatry. 2009;66(10):1090-1098.

Although most people with bulimia and binge eating disorders wait many years before seeking help, a new review shows that psychological treatment can make a large difference — and that cognitive behavioral therapy (CBT) is the most effective talk therapy for these disorders.

People with bulimia experience cycles of disordered eating behavior in which they overeat and then purge, often by self-induced vomiting or taking laxatives. Binge eating disorder includes bouts of overeating, but without purging, and researchers have linked it to obesity.

Eating disorders are most common in women, with bulimia affecting about 1 percent of women and binge eating disorder affecting 2 percent to 5 percent. Although bulimia rates appear stable, binge eating disorder increasingly is becoming common.

The review included 48 studies with 3,054 participants and strengthened earlier findings in favor of cognitive behavioral therapy. It found that 37 percent of people completely stopped binge eating when given CBT focused on binging — while 3 percent of those assigned to a waiting list control group quit.

Other therapies were less successful than CBT, helping 22 percent of participants achieve abstinence from binging by the end of treatment. One approach called interpersonal therapy did achieve comparable results — but took months longer to do so.

Lead author Phillipa Hay, M.D., is foundation chair of mental health at the University of West Sydney in Australia. “Cognitive behavioral therapy is really the treatment of choice,” she said. “It has far and away the best evidence. It hadn’t really been so definitively found in previous reviews.”

The review appears in the latest issue of The Cochrane Library, which is a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Cynthia Bulik, Ph.D., is director of the University of North Carolina Eating Disorders Program at Chapel Hill. Bulik, who had no connection with the review, said the key findings are that “bulimia nervosa is treatable; that some treatment is better than no treatment; that CBT is associated with the best outcome for bulimia nervosa.”

The original intent of CBT was to treat depression. A modified type of CBT in the studies focuses specifically on binge eating disorder symptoms. Nonetheless, participants also experienced significant improvements in mood.

“Many people have problems with depression secondary to binge eating disorders,” Hay said. “They often feel anxious and guilty because of their binging so if the eating disorder improves, the depression improves as well. We did look at the effects of CBT [for binge eating] on depression and it does help depression significantly just in itself.”

Weight, however, did not change with treatment. “None of these psychotherapies really affect people’s weight, which is good thing for people with bulimia who are normal weight but for those who are overweight or obese, they will need weight-loss therapies as well,” Hay said.

Cognitive behavioral treatment of bulimia or binge eating disorder typically involves 15 to 20 outpatient sessions with a therapist over a five-month period. CBT works by helping patients change the way they think about their behavior.

“CBT rests on the premise that unhealthy thoughts lie at both the roots of bulimia nervosa and in the maintenance of unhealthy eating behaviors,” Bulik said. “The goals of CBT are first to have the patient become his or her own detective and — via self-monitoring — start to understand their patterns of binge eating and purging and recognize and anticipate the cues (triggers) for their unhealthy behaviors.” Once these patterns and the thoughts that drive them are identified, they can be challenged and addressed.

Hay gave the example of someone who, after binging, skips lunch and breakfast the following day. That can easily produce another binge because the craving caused by intense hunger is harder to resist. The therapist would help the patient see that eating healthy meals after a binge would break the cycle, even though fasting might initially seem like a better solution.

The review also compared CBT done in conjunction with a therapist to self-help using books that teach its techniques and tactics. While guided CBT was more effective, there was not much research on self-help and Hay says the approach is “promising” and that it should receive further study. There has been more research on bulimia than binge-eating disorder—so more data would help clarify the best approaches to the latter.

Other studies have found that antidepressants can help fight bulimia and binge eating. While this review did not compare medication to psychotherapy, Hay says clinicians should try CBT first because more people stick with it. “The dropout rate is quite significantly higher with drugs,” she says.

“Some treatment is better than none,” Bulik said. “If you can’t find a therapist [who practices CBT for binge eating], don’t throw in the towel— find another kind of therapist, pick up a self-help book, do something because the outcome will be better than doing nothing at all.”Source: Health Behavior News Service

Individuals who consume a diet high in sodium or artificially sweetened drinks are more likely to experience a decline in kidney function, according to two papers being presented at the American Society of Nephrology’s annual meeting in San Diego, California.

Julie Lin MD, MPH, FASN and Gary Curhan, MD, ScD, FASN of Brigham and Women’s Hospital studied more than 3,000 women participating in the Nurses’ Health Study to identify the impact of sodium and sweetened drinks on kidney function.

“There are currently limited data on the role of diet in kidney disease,” said Dr. Lin. “While more study is needed, our research suggests that higher sodium and artificially sweetened soda intake are associated with greater rate of decline in kidney function.”

The first study, “Associations of Diet with Kidney Function Decline,” examined the influence of individual dietary nutrients on kidney function decline over 11 years in more than 3,000 women participants of the Nurses’ Health Study. The authors found that “in women with well-preserved kidney function, higher dietary sodium intake was associated with greater kidney function decline, which is consistent with experimental animal data that high sodium intake promotes progressive kidney decline.”

The second study, also conducted by Dr. Lin and Dr. Curhan, “Associations of Sweetened Beverages with Kidney Function Decline,” examined the influence of sugar-sweetened and artificially sweetened beverages on kidney function decline in the same group of Nurses’ Health Study participants. An analysis of the nationally representative NHANES III participants had previously reported an association between sugar-sweetened soda and urinary protein, but data on kidney function change was not available. This investigation reported “a significant two-fold increased odds, between two or more servings per day of artificially sweetened soda and faster kidney function decline; no relation between sugar-sweetened beverages and kidney function decline was noted” said Dr. Lin. This association persisted even after the study authors accounted for age, caloric intake, obesity, high blood pressure, diabetes, cigarette smoking, physical activity, and cardiovascular disease. The mechanisms for kidney decline in the setting of high intake of artificial sweetenters have not been previously studied and deserve further investigation.

The study participants were older Caucasian women and the authors note that the findings may not be directly applicable to men or people of other ethnicities.

The authors report no financial disclosures.

EDITOR: “Associations of Diet with Kidney Function Decline,” (SA-FC342) will be presented as part of a Free Communication Session at the American Society of Nephrology’s 42nd Annual Meeting and Scientific Exposition on Oct. 31 at 4:24 pm in Room 25 of the San Diego Convention Center in San Diego, CA. “Associations of Sweetened Beverages with Kidney Function Decline,” (SA-PO2751) will be presented as part of a Poster Session from 10:00 am – 12:00 pm in the Scientific Exposition Hall of the San Diego Convention Center also on Oct. 31. Both abstracts will be presented as part of a Press Briefing on Oct. 30 at 12:15 pm in Room 12.

ASN Renal Week 2009, the largest nephrology meeting of its kind, will provide a forum for 13,000 professionals to discuss the latest findings in renal research and engage in educational sessions related to advances in the care of patients with kidney and related disorders. Renal Week 2009 will take place October 27 – November 1 at the San Diego Convention Center in San Diego.

Founded in 1966, the American Society of Nephrology (ASN) is the world’s largest professional society devoted to the study of kidney disease. Comprised of 11,000 physicians and scientists, ASN continues to promote expert patient care, to advance medical research, and to educate the renal community. ASN also informs policymakers about issues of importance to kidney doctors and their patients. ASN funds research, and through its world-renowned meetings and first-class publications, disseminates information and educational tools that empower physicians.

Source: American Society of Nephrology (ASN)