Weight Loss in Overweight and Obese Women Reduces Urinary Incontinence

Reducing urinary incontinence can now be added to the extensive list of health benefits of weight loss, according to a clinical trial funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Office of Research on Women’s Health (ORWH), both part of the National Institutes of Health (NIH). The paper reporting the results of the trial will be published in the January 29 issue of the New England Journal of Medicine.

The Program to Reduce Incontinence by Diet and Exercise (PRIDE), conducted in Birmingham, Alabama, and Providence, Rhode Island, recruited a total of 338 obese and overweight women who leaked urine at least 10 times per week. The women were randomly assigned to either an intensive six-month weight-loss program of diet, exercise and behavior modification (226 women) or to a group that received information about diet and exercise, but no training to help them change habits (112 women).

The investigators report that women in the intensive weight-loss group lost an average 8 percent of their body weight (about 17 pounds) and reduced weekly urinary incontinence episodes by nearly one-half (47 percent). In contrast, women in the information-only group lost an average 1.6 percent of body weight (about 3 pounds) and had 28 percent fewer episodes.
'Clearly, weight loss can have a significant, positive impact on urinary incontinence, a finding that may help motivate weight loss, which has additional health benefits such as preventing type 2 diabetes,' said NIDDK Director Griffin P. Rodgers, M.D.

Urinary incontinence affects more than 13 million women in the United States and accounts for an estimated $20 billion in annual health care costs, according to the paper. Obesity is an established and modifiable risk factor for urinary incontinence, but conclusive evidence for a beneficial effect of weight loss on urinary incontinence has been lacking. The PRIDE trial provides evidence supporting weight loss as a treatment for incontinence.

An important finding of the study is the difference between the two groups in the reduction of incontinence. Among women in the weight-loss group, 41 percent achieved a clinically relevant reduction of at least 70 percent of total incontinence episodes per week, whereas 22 percent of women in the information-only group achieved the same level of reduction.

At six months, women in the weight-loss group were significantly more satisfied with the change in their incontinence than were women in the information-only group. This was assessed through self-reported perceived change in frequency of incontinence, volume of urine loss, the degree to which incontinence was a problem, and satisfaction with the change in incontinence.

'Studies have documented that behavioral interventions help people lose weight, which helps decrease the risk of developing type 2 diabetes and high blood pressure, improve control of high blood pressure and cholesterol levels, and enhance mood and quality of life,' explained Leslee L. Subak, M.D., of the University of California, San Francisco (UCSF) and lead author of the study. 'Our results suggest that a decrease in urinary incontinence is another health benefit associated with weight loss and that weight reduction can be a first-line treatment in overweight and obese women.'

Results from previous studies suggest that a weight loss of 5% to 10% has an efficacy similar to that of other nonsurgical treatments and should be considered a first line therapy for incontinence.

Weight loss in PRIDE is comparable to that observed in the Diabetes Prevention Program (DPP) and in the ongoing Action for Health in Diabetes (Look AHEAD), two NIDDK-sponsored clinical trials in people with type 2 diabetes. The PRIDE intensive weight-loss program was modeled after these two trials.

In an interview, earlier today, the investigators noted that while the results of the study indicated that incontinence diminished in both groups, they believe that some of reduced incontinence in the 'information-only group' is based on adopting some of the additional techniques included in the educational materials.

Because weight loss and weight maintenance can be highly challenging for the individual patient, clinicians are encouraged to help their patients by identifing a number of appropriate local or online resources to which they can refer patients for additional support.

For more information:

• Subak LL, Wing R, Smith West D, et al. Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women. NEJM 360 (5):481-490, January 29, 2009.

Also read:

• Program to Reduce Incontinence by Diet and Exercise (PRIDE) click here and type NCT00091988 in the search window;
• Diabetes Prevention Program DPP and the Look AHEAD trials.
• Incontinence in women

Also read PubMed abstracts:

• Richter HE, Creasman JM, Myers DL, et al. Urodynamic characterization of obese women with urinary incontinence undergoing a weight loss program: the Program to Reduce Incontinence by Diet and Exercise (PRIDE) trial. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Dec;19(12):1653-1658. Epub 2008 Aug 5.
• Subak LL, Whitcomb E, Shen H, et al. Weight loss: a novel and effective treatment for urinary incontinence. J Urol. 2005 Jul;174(1):190-5. Click here to contact the authors.
• Subak LL, Brubaker L, Chai TC, et al. High costs of urinary incontinence among women electing surgery to treat stress incontinence. Obstet Gynecol. 2008 Apr;111(4):899-907.

More Americans Report Being Obese

An estimated 25.6 percent of US adults reported being obese in 2007 compared to 23.9 percent in 2005, an increase of 1.7 percent. And this number is climbing. In three states, the prevalence of self-reported obesity among adults age 18 or older was above 30 percent. None of the 50 states or the District of Columbia has achieved the Healthy People 2010 goal to reduce obesity prevalence to 15 percent or less.

The proportion of US adults who self-report they are obese increased nearly 2 percent between 2005 and 2007. An estimated 25.6 percent of US adults reported being obese in 2007 compared to 23.9 percent in 2005, an increase of 1.7 percent. The report also finds that none of the 50 states or the District of Columbia has achieved the Healthy People 2010 goal to reduce obesity prevalence to 15 percent or less.

In three states - Alabama, Mississippi, and Tennessee - the prevalence of self-reported obesity among adults age 18 or older was above 30 percent. Colorado had the lowest obesity prevalence at 18.7 percent. Obesity is defined as a body mass index (BMI) of 30 or above. BMI is calculated using height and weight. For example, a 5-foot, 9-inch adult who weighs 203 pounds would have a BMI of 30, thus putting this person into the obese category.

The data were derived from CDC's Behavioural Risk Factor Surveillance System, a state-based telephone survey that collects information from adults aged 18 years and older. For this survey more than 350,000 adults are interviewed each year, making BRFSS the largest telephone health survey in the world. BMI was calculated based on this self-reported information.

'The epidemic of adult obesity continues to rise in the United States indicating that we need to step up our efforts at the national, state and local levels,' said Dr William Dietz, director of CDC's Division of Nutrition, Physical Activity, and Obesity. 'We need to encourage people to eat more fruits and vegetables, engage in more physical activity and reduce the consumption of high calorie foods and sugar sweetened beverages in order to maintain a healthy weight.'

The study found that obesity is more prominent in the South, where 27 percent of respondents were classified as obese. The percentage of obese adults was 25.3 in the Midwest, 23.3 percent in the Northeast, and 22.1 percent in the West.

By age, the prevalence of obesity ranged from 19.1 percent for men and women aged 19-29 years to 31.7 and 30.2 percent, respectively, for men and women aged 50-59 years.

'Obesity is a major risk factor for a number of chronic diseases such as type 2 diabetes, heart disease and stroke. These diseases can be very costly for states and the country as a whole,' said Deb Galuska, associate director for science for CDC's Division of Nutrition, Physical Activity and Obesity.

For more information on how you can combat obesity, contact your doctor or visit the information site from the CDC.

New enzyme let mice to gorge without becoming obese, new study finds.

Researchers at the University of California, Berkeley, California, have zeroed in on an enzyme that plays a key role regulating metabolism and weight in mice and say a drug that inhibits this target could do the same for people. The new enzyme plays a far more important role than expected in controlling the breakdown of fat. The findings of their study have been published in the January 11, 2009 edition of Nature Medicine. One of the remarkable findings reported by the researchers is that mice that have had this enzyme disabled remained lean despite eating a high-fat diet and losing a hormone that suppresses appetite.

'We have discovered a new enzyme within fat cells that is a key regulator of fat metabolism and body weight, making it a promising target in the search for a treatment for human obesity,' said Hei Sook Sul, UC Berkeley professor of nutritional sciences and toxicology and principal investigator of the research.

Sul's research team also includes the three co-lead authors of the paper, all from UC Berkeley's Department of Nutritional Sciences and Toxicology, Kathy Jaworski, former post-doctoral researcher, Maryam Ahmadian, graduate student, and Robin Duncan, post-doctoral fellow.

The enzyme in the spotlight, adipose-specific phospholipase A2 (AdPLA), is found in abundance only in fat tissue. AdPLA sets off a chain of events that increases levels of a signaling molecule called prostaglandin E2 (PGE2), which suppresses the breakdown of fat. Mice that have no AdPLA have lower PGE2 levels and a higher rate of fat metabolism.

'When levels of PGE2 are decreased because of the lack of AdPLA, fat breakdown proceeds unchecked, resulting in leanness even in animals that eat all day long,' said co-lead author Duncan.

In the study, mice that had the gene for AdPLA expression knocked out were compared with a control group of normal mice. As soon as the mice were weaned at about 3 weeks of age, researchers began offering the two groups of mice an all-you-can-eat buffet of tasty, high-fat foods.

Notably, the enzyme did not appear to affect appetite since the two groups ate equivalent amounts. However, as the mice aged, the disparity in weight gain became clear. By 64 weeks of age - considered the twilight years in a lab mouse's lifespan - the mice that lacked the AdPLA enzyme averaged only 39.1 grams, a weight more typical of a low-fat diet, while the control mice weighed in at a hefty 73.7 grams.

No reduction in fat cells
The researchers noted that the missing AdPLA did not change the number of fat cells, but simply kept the cells from accumulating excess fat. The researchers also studied whether loss of AdPLA could prevent genetic obesity in mice. They compared mice that lacked leptin, the hormone that signals when the body is full, with mice that lacked both AdPLA and leptin. Leptin-deficient mice are voracious eaters, typically consuming two to three times more food per day than normal mice, and they rapidly develop obesity.

Increase AdPLA
In this study, leptin-deficient mice ate an average of 5 grams of food per day, while mice that lacked both AdPLA and leptin ate 7.5 grams. Typically, normal mice will eat only 2-3 grams per day. By 17 weeks of age, the leptin-deficient mice were already hitting the scales at 75 grams. In comparison, mice that lacked both AdPLA and leptin weighed just under 35 grams.
The researchers found that levels of AdPLA increase after eating to block fat breakdown, and decrease with fasting to allow fat breakdown to proceed efficiently. They also found that levels of AdPLA are higher in obese mice.

'This means that local signals in fat tissue allow fat cells to directly regulate fuel provision for the body, which changes our fundamental understanding of how the body regulates fat breakdown,' said Ahmadian, another study co-lead author. 'We found that mice deficient in AdPLA expend more energy than normal mice, and they also burn more fat directly within fat cells.'

Before this paper, the assumption had been that the major players in controlling fat metabolism and body weight were endocrine factors, primarily hormones that are secreted by different organs and glands and travel through the bloodstream to fat tissue, the authors said.

The new findings show that a large portion of the action is occurring within the actual fat tissue, mainly through the autocrine and paracrine action of PGE2 that acts locally within a cell or small group of cells.

How research translates
The researchers caution that previous discoveries in fat metabolism and appetite regulation have not always translated well from mice to humans. Although some people have mutations in the gene that codes for AdPLA, it remains to be seen what effect these mutations have in humans, they said.

They also noted that inhibiting the expression of AdPLA in mice led to greater insulin resistance and a four-fold increase in fat content in the liver. However, tests of liver function were largely normal.

Nevertheless, AdPLA may become an attractive target in developing a treatment to combat obesity, the researchers said. If excess fat can be burned before it escapes the fat cell, it can never get into the bloodstream to negatively affect other organs, such as the heart.

'We believe that the effects in the liver are due to the extremely high rate of fat breakdown and drastic leanness in these mice, so we are looking to see if reducing rather than completely eliminating AdPLA can provide effective protection against obesity without secondary effects,' said Duncan.

For aditional information:

• Jaworski K, Ahmadian M, Duncan RE, et al. AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency. Nat Med. 2009 Jan 11. [Epub ahead of print] Full text article. Contact the authors.

Also read PubMed abstracts:

• Duncan RE, Sarkadi-Nagy E, Jaworski K, et al. Identification and Functional Characterization of Adipose-specific Phospholipase A2 (AdPLA). J Biol Chem. 2008 Sep 12;283(37):25428-36. Epub 2008 Jul 9