News and Notices

Does obesity cause brains to shrink?

Obesity is an important cause of cardiovascular diseases, but has also recently been associated with dementia in elderly women. In men, obesity in middle age has also been shown to increase long-term risk of being hospitalized with a dementia diagnosis. In a study aiming at determining whether body type affects global brain volume, a marker of atrophy, in middle-aged men and women magnetic resonance imaging was used to assess global brain volume for 114 individuals 40–66 years of age (mean 54.2 (SD 6.6) years; 43 men and 71 women). A regression model was used to determine the effect of age, body mass index (BMI), and other cardiovascular risk factors on brain volume and cognition. Age and BMI were each associated with decreased brain volume whereas BMI did not predict cognition in this sample. Elevated diastolic blood pressure, however, was associated with poorer episodic learning performance. These findings suggest that middle-aged obese adults may already be experiencing differentially greater brain atrophy, and may also be at greater risk for future cognitive decline.

Ward MA, et al. The effect of body mass index on global brain volume in middle-aged adults: a cross-sectional study. BMC Neurol 2005; 5:23.

Beware of ‘puppy fat'

The metabolic syndrome, a concept that recently has been challenged, but nevertheless conveniently describes a set of cardiovascular risk factors that are associated with obesity-increased risk of type 2 diabetes mellitus and cardiovascular disease, begins to develop during adolescence. Early predictors of the presence of the syndrome at the ages of 18 and 19 years in black and white girls were studied by using longitudinal data on participants in a 10-year US cohort study. Cut offs from the Adult Treatment Panel III were used to document changes in the prevalence of abnormal syndrome elements and the syndrome in girls aged 9 and 10 years, when cases were rare, and those aged 18 and 19 years, when prevalence had reached 3%. Only one girl of each group had three factors or more at ages 9 and 10 (0.2%), but 20 black girls (3.5%) and 12 white girls (2.3%) had the syndrome 10 years later. Low high-density lipoprotein cholesterol was prevalent throughout the period in both black and white girls. The prevalence of other variables was low at enrolment but increased during follow-up, except for abnormal triglyceride levels in black girls, which remained low throughout follow-up. In multivariate models, early measures of waist circumference and triglyceride level were significant predictors for development of the syndrome. The strong association of childhood central adiposity with early development of the metabolic syndrome probably means that ‘puppy fat’ in humans is probably not innocuous.

Morrison JA, et al. Development of the metabolic syndrome in black and white adolescent girls: a longitudinal assessment. Pediatrics 2005; 116:1178–1182.

Physical activity may be beneficial also in cancer patients

Physical activity may not only prevent cardiovascular disease but may also be beneficial in cancer patients. A recent meta-analysis, which systematically reviewed the evidence from trials examining the effectiveness of physical exercise in improving the level of physical functioning and psychological well-being of cancer patients during and after medical treatment included 34 randomized clinical trials and controlled clinical trials and assessed them for their results and overall quality. Only few of the trials met standard quality criteria. Failure to conceal the sequencing of treatment allocation before patient recruitment, failure to blind the outcome assessor, and failure to employ an intention-to-treat analysis strategy were the most prevalent shortcomings. Positive results were observed for several outcomes, however, including physiologic measures, objective performance, self-reported functioning and symptoms, wellbeing, and overall health-related quality of life. Despite their shortcomings the trials reviewed suggested that cancer patients may benefit from physical exercise both during and after treatment.

Knols R, et al. Physical exercise in cancer patients during and after medical treatment: a systematic review of randomized and controlled clinical trials. J Clin Oncol 2005; 23:3830–3842.

Body image and weight control in young male and female students in 22 countries over the world

Young women in the United States and Western Europe are usually concerned about their weight but less is known about attitudes to weight in other regions of the world. A study collecting data from 18 512 university students from 22 countries across the world (the International Health Behaviour Survey) assessed associations between body mass index (BMI), weight perceptions, and attempts to lose weight. Perceived overweight increased systematically across sex and country-standardized BMI deciles in all countries. More women than men felt overweight at any decile. Women had low levels of perceived overweight in the lowest decile but rates rapidly increased to 50% in the fifth decile. Men, even in the highest deciles, were less aware that they were overweight and few of them were trying to lose weight. Perceived overweight profiles across BMI deciles were similar across all regions, suggesting that perceptions of overweight derive from local comparisons. The patterning for trying to lose weight was more diverse, with men and women from Asian countries showing higher levels of trying to lose weight at all deciles. There seems to be a consistent patterning of women's overestimation of weight at lower BMI deciles and men's underestimation of weight at the higher deciles.

Wardle J, et al. Body image and weight control in young adults: international comparisons in university students from 22 countries. Int J Obes (Lond) 2005; Sep 6 [Epub ahead of print].

Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis

Fast-food consumption has increased greatly in the USA during the past three decades. The effect of fast food on risk of obesity and type 2 diabetes, however, has received little attention. This study investigated the association between reported fast-food habits and changes in body-weight and insulin resistance over a 15-year period in the USA.

Participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study included 3031 young (age 18–30 years in 1985–1986) black and white adults who were followed up with repeated dietary assessment. Multiple linear regression models were used to investigate the association of frequency of fast-food restaurant visits (fast-food frequency) at baseline and follow-up with 15-year changes in bodyweight and the Homoeostasis Model Assessment (HOMA) for insulin resistance.

Fast-food frequency was lowest for white women (about 1.3 times per week) compared with the other ethnic-sex groups (about twice a week). After adjustment for lifestyle factors, baseline fast-food frequency was directly associated with changes in bodyweight in both black (P = 0.0050) and white people (P = 0.0013). Change in fast-food frequency over 15 years was directly associated with changes in bodyweight in white individuals (P < 0.001), with a weaker association recorded in black people (P = 0.1004). Changes were also directly associated with insulin resistance in both ethnic groups (P = 0.0015 in black people, P < 0.0001 in white people). By comparison with the average 15-year weight gain in participants with infrequent (less than once a week) fast-food restaurant use at baseline and follow-up (n = 203), those with frequent (more than twice a week) visits to fast-food restaurants at baseline and follow-up (n = 87) gained an extra 4.5 kg of bodyweight (P= 0.0054) and had a two-fold greater increase in insulin resistance (P = 0.0083).

In conclusion, fast-food consumption has strong positive associations with weight gain and insulin resistance, suggesting that fast food increases the risk of obesity and type 2 diabetes.

Pereira MA, et al. Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. Lancet 2005; 365:36–42.

Continuous positive airway pressure for central sleep apnea and heart failure

The Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure trial tested the hypothesis that continuous positive airway pressure (CPAP) would improve the survival rate without heart transplantation of patients who have central sleep apnea and heart failure.

After medical therapy was optimized, 258 patients who had heart failure (mean age ± SD, 63 ± 10 years; ejection fraction, 24.5 ± 7.7%) and central sleep apnea (number of episodes of apnea and hypopnea per hour of sleep, 40 ± 16) were randomly assigned to receive CPAP (128 patients) or no CPAP (130 patients) and were followed for a mean of 2 years. During follow-up, sleep studies were conducted and measurements of the ejection fraction, exercise capacity, quality of life, and neurohormones were obtained.

Three months after undergoing randomization, the CPAP group, as compared with the control group, had greater reductions in the frequency of episodes of apnea and hypopnea (− 21 ± 16 versus −2 ± 18 per h, P≤0.001) and in norepinephrine levels (− 1.03 ± 1.84 versus 0.02 ± 0.99 nmol/l, P = 0.009), and greater increases in the mean nocturnal oxygen saturation (1.6 ± 2.8 versus 0.4 ± 2.5%, P < 0.001), ejection fraction (2.2 ± 5.4 versus 0.4 ± 5.3%, P=0.02), and the distance walked in 6 min (20.0 ± 55 versus −0.8 ± 64.8 m, P=0.016). There were no differences between the control group and the CPAP group in the number of hospitalizations, quality of life, or atrial natriuretic peptide levels. An early divergence in survival rates without heart transplantation favored the control group, but after 18 months the divergence favored the CPAP group, yet the overall event rates (death and heart transplantation) did not differ (32 versus 32 events, respectively; P= 0.54).

Although CPAP attenuated central sleep apnea, improved nocturnal oxygenation, increased the ejection fraction, lowered norepinephrine levels, and increased the distance walked in 6 min; it did not affect survival. Our data do not support the use of CPAP to extend life in patients who have central sleep apnea and heart failure.

Bradley TD, et al. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005; 353:2025–2033.

Obstructive sleep apnea as a risk factor for stroke and death

Previous studies have suggested that the obstructive sleep apnea syndrome may be an important risk factor for stroke. It has not been determined, however, whether the syndrome is independently related to the risk of stroke or death from any cause after adjustment for other risk factors, including hypertension.

In this observational cohort study, consecutive patients underwent polysomnography, and subsequent events (strokes and deaths) were verified. The diagnosis of the obstructive sleep apnea syndrome was based on an apnea-hypopnea index of five or higher (five or more events per hour); patients with an apnea-hypopnea index of less than five served as the comparison group. Proportional hazards analysis was used to determine the independent effect of the obstructive sleep apnea syndrome on the composite outcome of stroke or death from any cause.

Among 1022 enrolled patients, 697 (68%) had the obstructive sleep apnea syndrome. At baseline, the mean apnea-hypopnea index in the patients with the syndrome was 35, as compared with a mean apnea-hypopnea index of 2 in the comparison group. In an unadjusted analysis, the obstructive sleep apnea syndrome was associated with stroke or death from any cause (hazard ratio, 2.24; 95% confidence interval, 1.30–3.86; P = 0.004). After adjustment for age, sex, race, smoking status, alcohol consumption status, body mass index, and the presence or absence of diabetes mellitus, hyperlipidemia, atrial fibrillation, and hypertension, the obstructive sleep apnea syndrome retained a statistically significant association with stroke or death (hazard ratio, 1.97; 95% confidence interval, 1.12–3.48; P = 0.01). In a trend analysis, increased severity of sleep apnea at baseline was associated with an increased risk of the development of the composite end point (P=0.005).

In conclusion, the obstructive sleep apnea syndrome significantly increases the risk of stroke or death from any cause, and the increase is independent of other risk factors, including hypertension.

Yaggi HK, et al. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353:2034–2041.

Randomized trial of lifestyle modification and pharmacotherapy for obesity

Weight-loss medications are recommended as an adjunct to a comprehensive program of diet, exercise, and behavior therapy but are typically prescribed with minimal or no lifestyle modification. This practice is likely to limit therapeutic benefits.

In this 1-year trial, the authors randomly assigned 224 obese adults to receive 15 mg of sibutramine per day alone, delivered by a primary care provider in eight visits of 10–15 min for each lifestyle-modification counseling alone, delivered in 30 group sessions; sibutramine plus 30 group sessions of lifestyle-modification counseling (i.e. combined therapy); or sibutramine plus brief lifestyle-modification counseling delivered by a primary care provider in eight visits of 10–15 min each. All participants were prescribed a diet of 1200–1500 kcal per day and the same exercise regime.

At 1 year, subjects who received combined therapy lost a mean (± SD) of 12.1 ± 9.8 kg, whereas those receiving sibutramine alone lost 5.0 ± 7.4 kg, those treated by lifestyle modification alone lost 6.7 ± 7.9 kg, and those receiving sibutramine plus brief therapy lost 7.5 ± 8.0 kg (P≤0.001). Those in the combined-therapy group who frequently recorded their food intake lost more weight than those who did so infrequently (18.1 ± 9.8 versus 7.7 ± 7.5 kg, P = 0.04).

Thus, the combination of medication and group lifestyle modification resulted in more weight loss than either medication or lifestyle modification alone. The results underscore the importance of prescribing weight-loss medications in combination with, rather than in lieu of lifestyle modification.

Wadden TA, et al. Randomized trial of lifestyle modification and pharmacotherapy far obesity. N Engl J Med 2005; 353:2111–2120.

Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia

Rimonabant, a selective cannabinoid-1 receptor (CB₁) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia.

Authors randomly assigned 1036 overweight or obese patients (body mass index, the weight in kilograms divided by the square of the height in meters, 27–40) with untreated dyslipidemia (triglyceride levels > 1.69–7.90 mmol/l, or a ratio of cholesterol to high-density lipoprotein (HDL) cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 or 20 mg daily for 12 months in addition to a hypocaloric diet.

The rates of completion of the study were 62.6, 60.3, and 63.9% in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P≤0.001) mean weight loss (repeated-measures method, −6.7 ± 0.5 kg, and last-observation-carried-forward analyses, −5.4 ± 0.4 kg), reduction in waist circumference (repeated-measures method, −5.8 ± 0.5 cm, and last-observation-carried-forward analyses, −4.7 ± 0.5 cm), increase in HDL cholesterol (repeated-measures method, + 10.0 ± 1.6%, and last-observation-carried-forward analyses, + 8.1 ± 1.5%), and reduction in triglycerides (repeated-measures method, −13.0 ± 3.5%, and last-observation-carried-forward analyses, −12.4 ± 3.2%). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7%, and last-observation-carried-forward analyses, 46.2%; P < 0.001) for a change that was partly independent of weight loss alone.

Thus, selective CB₁-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.

Després JP, et al. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353:2121–2134.