Forgotten but not gone: the rediscovery of fatty heart, the most common unrecognized disease in America.

Until 60 years ago, fatty heart was an accepted clinical entity. Since then, its very existence has been questioned, despite the fact that 2 of 3 Americans are now obese or overweight and obesity has been shown to be correlated with cardiac functional abnormalities. In 2000, a syndrome of "lipotoxic cardiomyopathy" resembling earlier pathologic descriptions of fatty human hearts was described in rodents, and fatty infiltration of cardiomyocytes was subsequently reported in patients with congestive failure. Now, magnetic resonance spectroscopy has been adapted to permit routine noninvasive screening for fatty heart. The use of this technique in human volunteers indicates that cardiomyocyte fat correlates well with body mass index and is elevated in uncomplicated obesity. It is more severe when glucose tolerance becomes abnormal or diabetes is present. It is associated with impaired diastolic filling, even in seemingly asymptomatic obese volunteers. Because fatty heart can be readily prevented by lifestyle modification and pharmacologic interventions that reduce caloric intake and increase fatty acid oxidation, it seems important to recognize its existence so as to intervene as early as possible.

Burden and prognostic importance of subclinical cardiovascular disease in overweight and obese individuals.

BACKGROUND: The burden and prognostic importance of subclinical cardiovascular disease (CVD) in obesity has not been investigated systematically. METHODS AND RESULTS: We examined prevalence of subclinical disease in 1938 Framingham Study participants (mean age, 57 years; 59% women) by use of 5 tests (electrocardiography, echocardiography, carotid ultrasound, ankle-brachial pressure, and urinary albumin excretion) and stratified by body mass index (BMI) (normal, < 25; overweight, 25 to < 30.0; obese, > or = 30 kg/m2) and waist circumference (WC) (increased, > or = 88 cm for women or > or = 102 cm for men). We investigated risk of overt CVD associated with adiposity according to presence versus absence of subclinical disease on any of the 5 tests. Prevalence of subclinical disease was higher in overweight (40.0%; adjusted odds ratio, 1.68) and obese individuals (49.7%; odds ratio, 2.82) compared with individuals with normal BMI (29.3%) and in individuals with increased WC (44.9%; odds ratio, 1.67) compared with normal WC (31.9%). On follow-up (mean 7.2 years), 139 participants had developed overt CVD. Presence of subclinical disease was associated with > 2-fold risk of overt CVD in all BMI and WC strata, with no evidence of an interaction between BMI and subclinical disease. CVD risk was attenuated in participants with obesity or increased WC but without subclinical disease (adjusted hazard ratio for obesity, 1.57; 95% confidence interval, 0.74 to 3.33; adjusted hazard ratio for increased WC, 1.22; 95% confidence interval, 0.69 to 2.15), compared with individuals with normal BMI or WC and no subclinical disease, respectively. CONCLUSIONS: In our community-based sample, overweight and obesity were associated with high prevalence of subclinical disease, which partly contributed to the increased risk of overt CVD in these strata.

Short-term manipulation of plasma free fatty acids does not change skeletal muscle concentrations of ceramide and glucosylceramide in lean and overweight subjects.

CONTEXT: Increased plasma free fatty acid (FFA) concentrations may be in part responsible for the increased levels of ceramide in skeletal muscle of obese subjects. OBJECTIVE: We studied the effect of lowering and increasing plasma FFA levels on muscle ceramide and glucosylceramide concentrations in lean and obese subjects. DESIGN: Plasma FFAs were either increased or decreased for 6 h by infusing a lipid emulsion or using Acipimox, respectively. Muscle biopsies were performed before and after the intervention for measurements of ceramide and glucosylceramide. STUDY SUBJECTS: Eight lean [body mass index 21.9 (range, 19.6-24.6) kg/m2] and six overweight/obese [body mass index 34.4 (27.8-42.5) kg/m2] subjects without type 2 diabetes mellitus participated in the study. MAIN OUTCOME MEASURE: Differences in muscle ceramide and glucosylceramide upon manipulation of plasma FFAs were measured. RESULTS: There were no differences in muscle ceramide and glucosylceramide between lean and obese subjects, respectively. Increasing or decreasing plasma FFAs for 6 h had no effect on ceramide [high FFAs: 24 (19-25) vs. 24 (22-27) pmol/mg muscle, P=0.46; and 22 (20-28) vs. 24 (18-26) pmol/mg muscle, P=0.89 in lean and obese, respectively; low FFAs: 26 (24-35) vs. 23 (18-27) pmol/mg muscle, P=0.17 and 24 (15-44) vs. 24 (19-42) pmol/mg muscle, P=0.6 in lean and obese, respectively] and glucosylceramide [high FFAs: 2.0 (1.7-4.3) vs. 3.4 (2.1-4.6) pmol/mg muscle, P=0.17; and 3.0 (1.3-6.7) vs. 2.6 (1.2-3.9) pmol/mg muscle, P=0.89 in lean and obese, respectively; low FFAs: 2.2 (1.0-4.4) vs. 1.7 (1.4-3.0) pmol/mg muscle, P=0.92; and 6.6 (1.0-25.0) vs. 4.3 (1.3-7.6) pmol/mg muscle, P=0.7 in lean and obese, respectively] concentrations in skeletal muscle. CONCLUSION: Short-term manipulation of plasma FFAs has no effect on ceramide and glucosylceramide concentrations in skeletal muscle from lean and obese subjects.

Markers of mitochondrial biogenesis and metabolism are lower in overweight and obese insulin-resistant subjects.

BACKGROUND: Impaired mitochondrial function in skeletal muscle is implicated in the development of insulin resistance. However, potential differences in fatness and fitness may influence previous results. METHODS: Subjects (n=18) were divided into insulin-sensitive (IS) and insulin-resistant (IR) groups by median glucose infusion rate during a hyperinsulinemic euglycemic clamp. Weight, VO2max (maximal aerobic capacity), and percentage body fat were measured before and after 6 continuous weeks of aerobic exercise training at 55-70% VO2max (40 min/session, 4 d/wk). RESULTS: Age, percentage fat, and VO2max were not different between IS and IR groups at baseline. Expression of the nuclear encoded PGC1alpha and mitochondrial encoded gene COX1 were significantly lower in the IR group (P<0.05). Citrate synthase activity and protein levels of subunits from complexes I and III of the respiratory chain were also lower in the IR group (P<0.05). Insulin sensitivity and aerobic fitness were increased after exercise training in both groups (P<0.001), and the expression of mitochondrial encoded genes CYTB and COX1 was also increased (P<0.01). However, there was no change in PGC1alpha expression, mitochondrial enzyme activity, or protein levels of complexes of the respiratory chain in response to exercise in either group. CONCLUSION: This study confirms that IR men have reduced markers of mitochondrial metabolism, independent of fatness and fitness. Moderate exercise training did not alter these markers despite improving fitness and whole body insulin sensitivity. This study suggests that additional mechanisms may be involved in improving insulin resistance after exercise training in obese men.

Raised serum, adipocyte, and adipose tissue retinol-binding protein 4 in overweight women with polycystic ovary syndrome: effects of gonadal and adrenal steroids.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Recent studies have shown that serum retinol-binding protein 4 (RBP4) levels increase with obesity. Currently, no data exist on the relative expression of RBP4 in either serum or adipose tissue of PCOS women. OBJECTIVES: mRNA expression of RBP4 from sc and omental (om) adipose tissue and sc adipocytes in overweight PCOS women were compared with matched controls; RBP4 protein in adipose tissue and serum RBP4 levels were also assessed. Additionally, we studied the effects of testosterone, 17beta-estradiol, androstenedione, and dehydroepiandrosterone sulfate on RBP4 expression in adipose tissue explants. DESIGN: Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of RBP4. Biochemical measurements were also performed. RESULTS: Compared with controls, there was significant up-regulation of RBP4 mRNA in sc (P < 0.05) and om (P < 0.01) adipose tissue as well as isolated sc adipocytes (P < 0.01) of PCOS women. In addition to elevated serum RBP4 levels in PCOS women (P < 0.05), RBP4 protein levels were significantly greater in sc and om adipose tissue of PCOS women (P < 0.05 and P < 0.05, respectively). Furthermore, in human sc and om adipose tissue explants, 17beta-estradiol significantly increased RBP4 mRNA expression, protein levels, and secretion into the culture media (P < 0.05). CONCLUSIONS: The precise reason for elevated levels of RBP4 in overweight PCOS women is unknown, but it appears that 17beta-estradiol may play a role in their regulation in adipose tissue.

Overweight and obesity affect treatment response in major depression.

BACKGROUND: Epidemiologic and clinical studies suggest comorbidity between major depressive disorder (MDD) and obesity. To elucidate the impact of weight on the course of depression beyond comorbidity, we investigated psychopathology, attention, neuroendocrinology, weight change, and treatment response in MDD patients, depending on their weight. METHODS: Four hundred eight inpatients with MDD participated in the Munich Antidepressant Response Signature Study, designed to discover biomarkers and genotypes that are predictive for clinical outcome. Psychopathology and anthropometric parameters were monitored weekly in 230 patients. In subsamples, combined dexamethasone-corticotropin-releasing hormone and attention tests were conducted at admission and discharge. One thousand twenty-nine diagnosed matched controls served for morphometric comparisons. RESULTS: Patients with MDD had a significantly higher body mass index (BMI) compared with healthy controls. Patients with high BMI (> or =25) showed a significantly slower clinical response, less improvement in neuroendocrinology and attention, and less weight gain than did patients with normal BMI (18.5 < or = BMI < 25) during antidepressant treatment. CONCLUSIONS: Our findings suggest that overweight and obesity characterize a subgroup of MDD patients with unfavorable treatment outcome.

Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.

BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y), overweight (body mass index, 27.8 +/- 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005) and 21% +/- 4% in the CREX group (p < 0.004), with no change in the control group (2% +/- 2%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003) and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR. CONCLUSIONS: The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults.

High prepregnant body mass index is associated with early termination of full and any breastfeeding in Danish women.

BACKGROUND: An association between high prepregnant body mass index (BMI) and early termination of breastfeeding has been observed, but this finding may have depended on the sociocultural context. OBJECTIVE: The objective was to determine whether this association was stronger with increasing maternal obesity, was modified by gestational weight gain, and still existed when there was greater social support for breastfeeding. DESIGN: Study participants (37 459 women) were drawn from the Danish National Birth Cohort. The association of prepregnant BMI and gestational weight gain with the termination of full or any breastfeeding by 1, 16, or 20 wk postpartum was assessed with logistic regression analyses, and the risk of early termination of full and any breastfeeding during the first 18 mo postpartum was assessed with Poisson regression analyses. RESULTS: The risk of early termination of any (with similar results for full) breastfeeding rose progressively with increasing prepregnant BMI values (in kg/m(2)), from 1.12 (95% CI: 1.09, 1.16) for overweight (BMI = 25.0-29.9) women to 1.39 (95% CI: 1.19, 1.63) for obese class III women (BMI >or= 40) compared with normal-BMI women. Gestational weight gain did not add to or modify the association between prepregnant BMI and breastfeeding. CONCLUSIONS: These findings extend the observation to a broader range of BMIs that the greater the prepregnant BMI, the earlier the termination of breastfeeding. Together with the fact that this association was evident in a more supportive social context for breastfeeding, these findings suggest a biological basis for the association.

Metabolic and behavioral predictors of weight gain in Hispanic children: the Viva la Familia Study.

BACKGROUND: Despite the high prevalence of overweight among Hispanic children in the United States, definitive predictors of weight gain have not been identified in this population. OBJECTIVE: The study objective was to test sociodemographic, metabolic, and behavioral predictors of 1-y weight gains in a large cohort of Hispanic children studied longitudinally. DESIGN: Subjects (n = 879) were siblings from 319 Hispanic families enrolled in the Viva la Familia Study. Families were required to have at least one overweight child aged 4-19 y. One-year changes in weight and body composition by dual-energy X-ray absorptiometry were measured. Data were from parental interviews, birth certificates, multiple-pass 24-h dietary recalls, 3-d accelerometry, 24-h respiration calorimetry, measurements of eating in the absence of hunger, and measurement of fasting blood biochemistry indexes by radioimmunoassay. Generalized estimating equations and principal component analysis were applied. RESULTS: Weight gain increased with age (P = 0.001), peaking at approximately 10 y of age in girls and approximately 11 y of age in boys. Mean (+/-SD) weight gain was significantly higher in overweight (7.5 +/- 3.7 kg/y) than in nonoverweight (4.4 +/- 2.4 kg/y) children and in boys than in girls. When adjusted for age, age squared, sex, and Tanner stage, the final model indicated a child's body mass index (BMI; kg/m2) status, maternal BMI, energy expenditure (total energy expenditure, basal metabolic rate, and sleeping metabolic rate), and fasting blood biochemistry indexes (total triiodothyronine, insulin, leptin, and ghrelin) as independent, positive predictors of weight gain (P = 0.01-0.001). CONCLUSION: Knowledge of the metabolic and behavioral predictors of weight gain in Hispanic children will inform prevention and treatment efforts to address this serious public health problem in the United States.

Infant feeding method and obesity: body mass index and dual-energy X-ray absorptiometry measurements at 9-10 y of age from the Avon Longitudinal Study of Parents and Children (ALSPAC).

BACKGROUND: Previous studies reported inconsistent associations between breastfeeding and body mass index (BMI; in kg/m2). Associations with body fatness are unknown. OBJECTIVE: We investigated the association of breastfeeding with fatness measured by dual-energy X-ray absorptiometry. DESIGN: The prospective cohort study involved 4325 singletons with measurements at 9-10 y of age to assess the main outcomes of BMI and total and trunk fat masses. RESULTS: Prevalence of any breastfeeding was 82%. In crude analyses, breastfeeding was inversely associated with total fat mass [% change per category increase (4 categories)] in breastfeeding duration (-4.4%; 95% CI: -3.1%, -5.6%) and trunk fat mass (-0.5%; 95% CI: -1.1%, 0.1%); the odds of adiposity were measured by total [odds ratio (OR): 0.81; 95% CI: 0.75, 0.88] and trunk (OR: 0.78; 95% CI: 0.71, 0.84) fat masses in the top decile. In adjusted models, the inverse association of breastfeeding with mean total fat mass was attenuated by 59% (% change per category increase in breastfeeding duration: -1.8%; 95% CI: -0.5%, -3.1%), but associations with trunk fat mass (% change per category increase in breastfeeding duration: -0.6%; 95% CI: 0.0%, -1.3%) and the ORs for total (0.76; 95% CI: 0.69, 0.84) and trunk (0.74; 95% CI: 0.67, 0.81) fat masses in the top decile were little altered. Children breastfed >or=6 mo had the lowest odds of total fat mass in the top decile (OR: 0.45; 95% CI: 0.33, 0.62). In multivariate models, there was little evidence that breastfeeding was associated with mean or threshold values of BMI. CONCLUSIONS: The protective association of breastfeeding with mean total fat mass was attenuated somewhat after adjustment for confounders, which indicated that confounding may explain this association. Breastfeeding may protect against obesity if maintained for >or=6 mo.

Body mass index does not predict prostate-specific antigen or percent free prostate-specific antigen in men undergoing prostate cancer screening.

OBJECTIVES: Body mass index (BMI) may alter serum prostate specific antigen (PSA) and percent free PSA (%fPSA) and may mask the risk of prostate cancer. We investigated the relationship between BMI and PSA or %fPSA. MATERIALS AND METHODS: Height, weight, PSA and %fPSA were assessed in 616 consecutive screened men without prostate cancer. Continuously coded and categorised BMI was studied. Statistical analyses consisted of ANOVA, linear regression, bivariate and partial correlations. RESULTS: Median age was 57 years. Median PSA was 1.0 and median %fPSA was 26. Median BMI was 25.8 kg/m(2). Neither continuously coded nor categorised BMI correlated with either PSA or %fPSA in unadjusted or age-adjusted analyses (all p values > or = 0.3). CONCLUSIONS: Body mass index does not affect PSA or %fPSA in men without known prostate cancer, who undergo prostate cancer screening. Therefore, PSA or %fPSA-based screening or early detection efforts do not require an adjustment for BMI.

Predictors of weight change in overweight patients with myocardial infarction.

BACKGROUND: Weight loss is recommended among overweight survivors of myocardial infarction (MI). This study describes patterns of weight change among overweight patients with MI and identifies factors associated with weight change. METHODS: A prospective cohort of 1253 overweight or heavier (body mass index [BMI] > or = 25 kg/m2) post-MI patients were enrolled in the 19-center PREMIER study and followed up for 1 year to determine changes in weight. Patients were categorized at 1 month as overweight (BMI = 25-29.9 kg/m2), obese (BMI = 30-39.9 kg/m2), or morbidly obese (BMI > or = 40 kg/m2). Unadjusted percent weight change was assessed at 1 year, and multivariable linear regression was used to identify independent correlates of change. RESULTS: Mean weight change was -0.2% and varied by the severity of baseline obesity (+0.4% for overweight patients, -0.5% for obese patients, and -3.7% for morbidly obese patients [P < .001]). Multivariable analyses revealed the following to be significantly associated with weight change: depression 1 month post-MI (+2.7%, P = .001), lack of health insurance (+2%, P = .01), smoking cessation 1 month post-MI (+2.7% vs current smokers, P < .001), morbid obesity (+4.7% vs overweight patients, P < .0001), and increasing age (-0.8% per decade, P = .001). An interaction between smoking cessation and weight class was detected in that overweight patients who quit had a mean increase of 5.3% (95% CI 3.1%-7.4%), whereas no significant change was observed among obese and morbidly obese patients who quit. CONCLUSIONS: Although post-MI patients had negligible weight loss over 1 year, several sociodemographic, clinical, and lifestyle characteristics were associated with weight change. New, targeted interventions will likely be needed to improve weight management after an MI.

Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring.

Maternal malnutrition during lactation reduces prolactin (PRL) and milk production, alters milk composition, and programs the body weight of the offspring. Our study aimed to evaluate the long-term effects of maternal hypoprolactinemia at the end of lactation on food ingestion, body weight, amount of retroperitoneal white adipose tissue (RPWAT), leptinemia, and anorectic leptin effect in the adult offspring. Lactating rats were treated with bromocriptine (BRO), a PRL inhibitor, 1 mg twice a day, or saline (C - control) for the last 3 days of lactation. The body weight and food intake were monitored, and after sacrifice at 180 days, the RPWAT was weighted. In a second experiment, the anorectic leptin effect was tested on 180-day-old animals. Adult offspring whose mothers were BRO-treated showed higher body weight (10%), higher amount of RPWAT (2 x 3 times), higher total body fat (+39%), and hyperleptinemia (2 x 9 times) when compared with C, although food intake did not alter. After injection of leptin, the food ingestion at 2, 4 and 6 h was unaffected in BRO animals, confirming a resistance to the anorectic effect of leptin. Since the maternal PRL inhibition during lactation programs, a higher body weight with no alteration of food ingestion, we suggest a hypometabolic state. The leptin anorectic resistance can be due to the hyperleptinemia. We suggest that PRL changes during lactation can regulate body weight during adulthood.

Sleep-disordered breathing and the metabolic syndrome in overweight and obese children and adolescents.

OBJECTIVE: To assess whether sleep-disordered breathing (SDB) is a risk factor of the metabolic syndrome (MS) in children and adolescents who are overweight and to examine whether the severity of SDB was independently associated with glucose intolerance, insulin resistance, and/or dyslipidemia. STUDY DESIGN: Consecutive subjects who were overweight or obese underwent polysomnography, fasting blood sample, and oral glucose tolerance test (for calculation of area under the curve [AUC]). SDB was defined as a respiratory disturbance index > or = 2. MS was present when > or = 3 of these factors were present: waist circumference > or = 90th percentile; fasting glucose level > or = 110 mg/dL; triglyceride level > or = 110 mg/dL; high-density lipoprotein cholesterol level < or = 40 mg/dL; blood pressure > or = 90th percentile. RESULTS: A total of 104 subjects were included in the study (44% boys; 58% prepubertal; mean age, 11.1 +/- 2.6 years; 69% obese). Mean SaO2 (odds ratio, 0.54) and SaO2nadir (odds ratio, 0.89) were independent, significant predictors of the presence of MS. Multiple regression showed significant associations between SaO2nadir and high-density lipoprotein cholesterol level, mean SaO2 and both AUC glucose and triglyceride levels, and between the percentage of total sleep time with SaO2 > or = 95% and cholesterol level, while controlling for adiposity and sex, puberty, or both. CONCLUSION: This study supports the hypothesis of an interaction between SDB and metabolic abnormalities, independent of estimates of body fat distribution, in children and adolescents who are overweight and obese.

Adiposity in adolescents: change in actual BMI works better than change in BMI z score for longitudinal studies.

PURPOSE: Longitudinal epidemiologic studies often relate adiposity changes to suspected causal factors. In growing adolescents, this becomes complicated. Many investigators use within-child change in body mass index (BMI) z scores (Delta z) from sex- and age-specific BMI charts developed by the Centers for Disease Control and Prevention (CDC). These charts, derived from cross-sectional data, may not represent BMI growth patterns of real children. Furthermore, because cross-sectional BMIs are not Gaussian, these z scores are from month-specific transformed distributions, with possible unintended consequences when used longitudinally. Alternatively, we can directly analyze BMI change (Delta BMI). We compare these two widely used measures of change in adiposity. METHODS AND RESULTS: With real adolescent data, we show that annual Delta BMIs have nonlinear peaks that are inconsistent with the CDC curves. We also show that a specified Delta z represents a broad range of adiposity changes for children measured at the same two ages. To see how this affects power, we performed simulation studies confirming that analyzing Delta BMIs in models with hypothesized factors is more powerful than analyzing Delta zs. CONCLUSIONS: In longitudinal studies of adolescent adiposity, investigators should be encouraged to analyze Delta BMI rather than Delta z because analyses using BMI are more powerful and findings presented in BMI units are more interpretable.

Sleep-disordered breathing and uric acid in overweight and obese children and adolescents.

OBJECTIVE: The aim of this study was to determine whether the severity of sleep-disordered breathing (SDB) was associated with increased levels of uric acid (UA), both in serum and in urine, as a marker of tissue hypoxia, in a sample of overweight and obese subjects, irrespective of indexes of adiposity. METHODS: Consecutive subjects underwent polysomnography, fasting blood sampling, and 24-h urine collection. Outcome parameters were serum UA, UA excretion ([24-h urinary UA x serum creatinine]/urine creatinine) and urinary UA/creatinine ratio. RESULTS: A total of 93 subjects were included (44% boys; mean [+/- SD] age = 11.1 +/- 2.5; 73% obese). A fasting measurement of serum UA levels was available for 62 patients. The respiratory disturbance index was a significant covariate (beta = 0.09 +/- 0.03; p = 0.01) in the regression model for serum UA, controlling for sex (beta = 0.32 +/- 0.29; p = 0.3), puberty (beta = 0.87 +/- 0.34; p = 0.01), and waist circumference (beta = 0.04 +/- 0.01; p = 0.005). The percentage of total sleep time with arterial oxygen saturation < or = 89% (beta = 0.94 +/- 0.45; p = 0.04) was also significantly associated with serum UA level, controlling for sex (beta = 0.22 +/- 0.30; p = 0.5), puberty (beta = 0.83 +/- 0.35; p = 0.02), and waist circumference (beta = 0.04 +/- 0.02; p = 0.02). None of the SDB variables correlated with UA excretion or with urinary UA/creatinine ratio. CONCLUSION: This study in overweight children and adolescents demonstrated a relationship between the severity of sleep apnea and increased levels of serum UA, independent of abdominal adiposity. In view of the known associations between UA and cardiovascular risk, this finding may contribute to the mechanisms linking SDB with cardiovascular morbidity.

Being overweight influences the development of hepatic dysfunction in Japanese patients with non-small-cell lung cancer undergoing cytotoxic chemotherapy.

PURPOSE: The aim of this study was to identify risk factors for hepatic dysfunction during cytotoxic chemotherapy in Japanese patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with NSCLC who received cytotoxic chemotherapy at Okayama University Hospital between January 2003 and March 2006. "Overweight" was defined as a body mass index (BMI) of 25 or more, according to the World Health Organization (WHO) criteria. We investigated the incidence and pattern of hepatic dysfunction during chemotherapy and evaluated the possible associations between hepatic dysfunction and several clinical factors, including BMI. RESULTS: Of the 155 Japanese patients enrolled in this study, 19 (12%) were overweight. Grade 2 or worse hepatic dysfunction was observed in 5 of the 19 overweight patients (26%) but in only 13 of the 136 non-overweight patients (10%). A multivariate analysis demonstrated that a higher BMI significantly increased the risk of grade 2 or worse hepatic dysfunction after the initiation of cytotoxic chemotherapy (odds ratio=4.04, 95% confidence intervals: 1.13-14.5, p=0.032). CONCLUSION: Our data suggest that being overweight can influence the development of hepatic dysfunction in Japanese patients receiving cytotoxic chemotherapy for the treatment of NSCLC, although further investigation is required.

Effect of oral glucose loading on endothelial function in normal-weight and overweight children.

The aim of the present study was to investigate the impact of acute hyperglycaemia on endothelial function in both normal-weight and overweight children. A total of 16 overweight [BMI (body mass index) > or =85th percentile] and 15 normal-weight (BMI <85th percentile) children were evaluated for FMD (flow-mediated dilation) at baseline and 30, 60 and 120 min after glucose ingestion. At 15 min following the measurement of the final FMD, 0.3 mg of sublingual nitroglycerine was administered and the brachial artery was imaged in order to assess endothelium-independent dilation. By design, the overweight children were significantly heavier (63.2+/-4.6 compared with 41.3+/-2.5 kg; P=0.0003) and had a greater percentage body fat (43.9+/-1.8 compared with 23.8+/-2.05%; P<0.0001) than the normal-weight children. The area under the curve in response to glucose administration was significantly (P<0.0001) greater in the overweight group for both glucose and insulin. The FMD area under the curve was not significantly different at baseline or between time points after glucose ingestion, nor was there a difference in response between the two groups. Endothelium-independent dilation in the normal-weight group was significantly greater compared with the overweight group (26.7+/-1.6 compared with 20.2+/-2.0% respectively; P=0.019). In conclusion, these results suggest that acute elevation of glucose and insulin in overweight and normal-weight children are not associated with impairment in endothelial function.

Examination of cognitive function during six months of calorie restriction: results of a randomized controlled trial.

BACKGROUND: Calorie restriction increases longevity in many organisms, and calorie restriction or its mimetic might increase longevity in humans. It is unclear if calorie restriction/dieting contributes to cognitive impairment. During this randomized controlled trial, the effect of 6 months of calorie restriction on cognitive functioning was tested. METHODS: Participants (n = 48) were randomized to one of four groups: (1) control (weight maintenance), (2) calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR + EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by weight maintenance). Cognitive tests (verbal memory, visual memory, attention/concentration) were conducted at baseline and months 3 and 6. Mixed linear models tested if cognitive function changed significantly from baseline to months 3 and 6, and if this change differed by group. Correlation analysis was used to determine if average daily energy deficit (quantified from change in body energy stores) was associated with change in cognitive test performance for the three dieting groups combined. RESULTS: No consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits emerged during the trial. Daily energy deficit was not significantly associated with change in cognitive test performance. CONCLUSIONS: This randomized controlled trial suggests that calorie restriction/dieting was not associated with a consistent pattern of cognitive impairment. These conclusions must be interpreted in the context of study limitations, namely small sample size and limited statistical power. Previous reports of cognitive impairment might reflect sampling biases or information processing biases.

Lower birth weight associated with current overweight status is related with the metabolic syndrome in obese Japanese children.

The purpose of this study was to clarify the relationship between lower birth weight and current overweight status and to examine the involvement of these factors in the development of the metabolic syndrome (MS) in obese Japanese children. We examined 97 obese boys (mean age 11.3 years; mean percentage overweight [POW] 52.4%) and 29 obese girls (mean age 11.1 years; mean POW 58.3%). The anthropometric measurements, blood pressure, fasting serum insulin and blood glucose, liver enzymes, lipids and lipoproteins were measured. Birth weight and gestational weeks were also recorded. The subjects were divided into either an MS group or a Non-MS group using criteria proposed for Japanese children. We compared the weight parameters (birth weight, current weight and current weight-to-birth weight ratio [WBWR]) between the two groups and analyzed the relationships between the weight parameters and metabolic derangements. There were no significant differences in age or anthropometric measurements between the two groups. However, birth weight in the MS group was lower than that in the Non-MS group, while WBWR of the MS group was higher than that in the Non-MS group. Blood pressure and serum insulin correlated positively with WBWR. These findings suggested that lower birth weight with current overweight status was associated with the MS in obese Japanese children. We were unable to clarify whether subjects with lower birth weight who achieved proper weight gains had the same risk as subjects with appropriate birth weight. However, they should be assisted to grow adequately to prevent future metabolic derangements.