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NIDDK Recent Advances & Emerging Opportunities 2013

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

The NIDDK Recent Advances & Emerging Opportunities is a compendium that highlights examples of the many research advances published by NIDDK-funded scientists and their colleagues in the most recent fiscal year, along with the technologies that made these achievements possible. This compendium also includes a section devoted to recent advances in obesity research at NIDDK.

This section provides examples of recent scientific advances from NIH-sponsored research, and is not intended to be a comprehensive list.

Diet Beverages and Body Weight (February 2014)

National Heart, Lung, and Blood Institute (NHLBI)

Overweight and obese adults who drink diet beverages consume significantly more solid-food calories—particularly from snacks—than those who drink sugary beverages. The findings highlight the challenges in using diet beverages to help control weight. Diet beverage use has skyrocketed in recent decades. It’s now a common weight control strategy. It might make sense to think that diet beverages would help you lose weight due to their lack of calories. But the body’s mechanisms for maintaining weight are subtle and complex. Studies into how diet beverages affect weight control have found conflicting results. “The results of our study suggest that overweight and obese adults looking to lose or maintain their weight—who have already made the switch from sugary to diet beverages—may need to look carefully at other components of their solid-food diet, particularly sweet snacks, to potentially identify areas for modification,” says the lead researcher on the study, Sara N. Bleich, Ph.D.

Gut Microbes and Diet Interact to Affect Obesity (September 2013)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute on Aging (NIA)

Gut microbes from lean people helped prevent mice from becoming obese–but only if the animals ate a healthy diet. This research could point the way to new treatments for obesity. The human gut harbors a complex community of microbes that affect many aspects of our health. Evidence, mostly from studies of rodents, suggests that the gut microbiota may play a role in the development of obesity. In earlier research, a team led by Jeffrey Gordon, M.D., at the Washington University School of Medicine showed that obese and lean human twins have clear differences in their gut microbial communities. Most notably, the communities from obese twins have less diverse bacterial species. In their new study, the scientists used a mouse model to further explore the role that gut microbes play in obesity and metabolism. The team took gut microbes from four sets of human twins in which one was lean and the other obese. They introduced the microbes of each twin into different groups of mice that had been raised in a previously germ-free environment. They then observed weight and metabolic changes in the mouse groups when fed the same diet. Mice populated with microbes from a lean twin stayed slim, whereas those given microbes from an obese twin quickly gained weight. The "lean" and "obese" microbes had different measurable effects on the body's metabolism. "These experiments show that eating a healthy diet encourages microbes associated with leanness to become incorporated into the gut," Gordon says. "But a diet high in saturated fat and low in fruits and vegetables thwarts the invasion of microbes associated with leanness. This is important as we look to develop next-generation probiotic cocktails composed of defined collections of naturally occurring human gut microbes as a treatment for obesity."

NIH Math Model Predicts Effects of Diet, Physical Activity on Childhood Weight (July 2013)

National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK)

Researchers at the NIH have created and confirmed the accuracy of a mathematical model that predicts how weight and body fat in children respond to adjustments in diet and physical activity. While the model may help to set realistic expectations, it has not been tested in a controlled clinical trial to determine if it is an effective tool for weight management. The model evolved from one developed at the NIH in 2011 to predict weight change in adults. The model for children considers their unique physiology, including changes in body composition as they grow. “Obese children are much more likely to become obese adults, which makes achieving or maintaining a healthy weight early in life vitally important,” said NIDDK Director Griffin P. Rodgers, M.D. “This study suggests that we may need to approach weight management and obesity prevention differently in youth than in adults.”

Gut Microbes Affect Weight After Gastric Bypass (April 2013)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of General Medical Sciences (NIGMS)

A study in mice suggests that gastric bypass surgery may result in weight loss in part by altering microbes in the gut. The finding may lead to a better understanding of how microbes influence energy balance. Gastric bypass is a type of surgery used to treat severe obesity. In a procedure known as Roux-en-Y gastric bypass (RYGB), part of the stomach and small intestine are removed. The procedure results in significant weight loss as well as improvements in associated conditions such as type 2 diabetes. Decreased calories, however, can’t fully account for all these effects. The digestive tract is home to trillions of microbes, both helpful and harmful, that outnumber the body’s cells by 10 to 1. A team of researchers wondered whether some of the benefits of RYGB surgery might come from changes in digestive tract microbes. This research shows that the beneficial effects of RYGB surgery are due in part to changes in the gut microbial community.

NIH Study Shows People with Serious Mental Illnesses Can Lose Weight (March 2013)

National Institute of Mental Health (NIMH)

People with serious mental illnesses such as schizophrenia, bipolar disorder, and major depression can lose weight and keep it off through a modified lifestyle intervention program, a NIMH-funded study reported. Over 80 percent of people with serious mental illnesses are overweight or obese, which contributes to them dying at three times the rate of the overall population. They succumb mostly to the same things the rest of the population experiences—cardiovascular disease, diabetes, and cancer. Although antipsychotic medications increase appetite and cause weight gain in these patients, they are not the only culprits. Like the general population, sedentary lifestyle and poor diet also play a part. Lifestyle modifications such as diet and exercise should work for these patients, yet they are often left out of weight loss studies. This study could usher in new forms of weight loss treatment for people with serious mental illness.

Benefits of Quitting Smoking Outpace Risk of Modest Weight Gain (March 2013)

National Heart, Lung, and Blood Institute (NHLBI)

The improvement in cardiovascular health that results from quitting smoking far outweighs the limited risks to cardiovascular health from a modest amount of weight gained after quitting, reports a National Institutes of Health-funded community study. The study found that former smokers without diabetes had about half as much risk of developing cardiovascular disease as current smokers, and this risk level did not change when post-cessation weight gain was accounted for in the analysis. This study is the first epidemiological effort to directly address the health impact of the weight gain that many people experience following smoking cessation.

NIH Scientists Identify Molecular Link Between Metabolism and Breast Cancer
(February 2013)

National Cancer Institute (NCI)

A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer, according to new findings by researchers at the National Cancer Institute (NCI) and their colleagues. Metabolic imbalance is often caused by elevated carbohydrate intake, which can lead to over-activating a molecule called C-terminal binding protein (CtBP). This over-activation, in turn, can increase the risk of breast cancer. “Our new work suggests that targeting CtBP may provide a way of treating breast cancer and possibly preventing breast cancer,” said Gardner. “Research should continue to focus on the link between obesity, CtBP and breast cancer. This will require more population-based studies and multidisciplinary teams of scientist to investigate these links.”

“Biggest Loser” Study Finds Modest Diet and Exercise Can Sustain Weight Loss
(October 2012)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Exercise and healthy eating reduce body fat and preserve muscle in adults better than diet alone, according to a study funded and conducted by NIDDK. The study examined data from 11 participants from the reality television program “The Biggest Loser.” The results suggest that participants could sustain their weight loss and avoid weight regain by adopting moderate lifestyle changes, such as 20 minutes of daily vigorous exercise and a 20-percent calorie restriction.

Weight Loss and Increased Fitness Slow Decline of Mobility in Adults (March 2012)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Weight loss and increased physical fitness nearly halved the risk of losing mobility in overweight or obese adults with type 2 diabetes, according to four-year results from the Look AHEAD (Action for Health in Diabetes) trial funded by the NIDDK. A total of 5,145 participants were randomly assigned to either an intensive lifestyle intervention group (ILI) or a diabetes support and education group (DSE). Participants receiving the intervention attended group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity. The DSE group attended three meetings each year that provided general education on diet, activity, and social support. After four years of the study, participants in the ILI group experienced a 48 percent reduction in mobility-related disability compared with the DSE group. Furthermore, 20.6 percent of ILI participants reported severe disability, compared to 26.2 percent of participants in the DSE group. Weight loss was a slightly stronger predictor of better mobility than improved fitness, but both contributed significantly to the observed reduction in risk.

NIH Research Model Predicts Weight with Varying Diet, Exercise Changes (August 2011)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Researchers at the NIDDK have created a mathematical model—and an accompanying online weight simulation tool—of what happens when people of varying weights, diets, and exercise habits try to change their weight. The findings challenge the commonly held belief that eating 3,500 fewer calories—or burning them off exercising—will always result in a pound of weight loss. Instead, the researchers’ computer simulations indicate that this assumption overestimates weight loss, because it fails to account for how metabolism changes. The computer simulations show how these metabolic changes can significantly differ among people. However, the computer simulation of metabolism is meant as a research tool, and not as a weight-loss guide for the public. The researchers hope to use the knowledge gained from developing the model and from clinical trials in people to refine the tool for everyone. “This research helps us understand why one person may lose weight faster or slower than another, even when they eat the same diet and do the same exercise,” said Kevin Hall, Ph.D., an obesity researcher and physicist at the NIDDK and the paper’s first author. “Our computer simulations can then be used to help design personalized weight management programs to address individual needs and goals.”

NIH Findings in Mice Have Potential to Curb Obesity and Type 2 Diabetes (July 2011)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Scientists at the NIDDK have uncovered a pathway in mice that allows white fat—a contributor to obesity and type 2 diabetes—to burn calories in a way that’s normally found in brown fat and muscle. White fat is used to store calories. However, too much white fat (obesity) increases the risk of type 2 diabetes and other diseases. Brown fat generates heat to maintain body temperature and, like muscle, has lots of iron-containing, calorie-burning mitochondria in its cells. Changing white fat into brown fat or muscle is a potential new approach to treating obesity and type 2 diabetes, although the research is a long way from being applicable to people. The findings were exciting and unexpected, said Sushil Rane, Ph.D., a researcher at the NIDDK and the paper’s senior author. “We weren’t looking to have white fat acquire the properties of brown fat, but that’s what we found, with the fat getting browner from increased mitochondria and displaying genes typically expressed in muscle. It was a striking difference. Efforts to reduce obesity by dieting are mostly unsuccessful in the long term, so finding ways to prevent excess fat storage is an urgent medical need.” Rane continued, “Our discovery that white fat can be reduced by partially transforming it to brown fat and muscle opens up new avenues to combat the obesity epidemic.”