Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese postmenopausal women

Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet toward whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of ≥10%, and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week. Participants were predominantly non-Hispanic whites (85%) with a mean age of 58.0 ± 5.0 years, a mean BMI of 30.9 ± 4.0 kg/m(2) and an average of 47.8 ± 4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants' intervention assignment. Three hundred and ninety nine women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was -8.5% for the D group (P < 0.0001 vs. C), -2.4% for the E group (P = 0.03 vs. C), and -10.8% for the D+E group (P < 0.0001 vs. C), whereas the C group experienced a nonsignificant -0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle-change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention.     

Pretreatment weight change is associated with obesity treatment outcomes

Clinical experience suggests some individuals begin obesity treatment weighing more than they did at pretreatment assessment. Weight fluctuations between baseline screening and the first treatment session were examined among individuals enrolling in a group behavioral obesity treatment outcome study. Participants (N = 480, 94% female; 28% African American; M BMI = 35.7) were classified into those who started treatment having gained weight (≥ +1.15% above screening weight), lost weight (≤ -1.15% below screening weight) or remained weight stable. The majority of participants were weight-stable (61%) during the waiting period, but 23% lost weight (-2.36 ± 1.26 kg) and 16% gained weight (+2.11 ± 1.04 kg) between baseline screening and initiating treatment. Those who lost during the pretreatment period went on to have the greatest losses at 6-months (-8.9 ± 4.9 kg), with significantly greater weight losses than either the weight-stable (-6.1 ± 5.8 kg) or the weight-gain (-5.7 ± 5.8 kg) groups. Further, those who lost weight during the waiting period went on to attend a significantly higher proportion of treatment sessions and submitted more self-monitoring diaries than those who gained weight and those who stayed weight stable while waiting. Thus, pretreatment weight change was associated with treatment outcomes and may be relevant for research screening. Further, pretreatment weight change may be a clinical marker for likely success in behavioral weight control and as such warrants additional investigation to inform potential methods for enhancing outcomes for individuals in obesity treatment.     

Obesity negatively impacts aerobic capacity improvements both acutely and 1-year following cardiac rehabilitation

Cardiac rehabilitation (CR) produces a host of health benefits related to modifiable cardiovascular risk factors. The purpose of the present investigation was to determine the influence of body weight, assessed through BMI, on acute and long-term improvements in aerobic capacity following completion of CR. Three thousand nine hundred and ninety seven subjects with coronary artery disease (CAD) participated in a 12-week multidisciplinary CR program. Subjects underwent an exercise test to determine peak estimated metabolic equivalents (eMETs) and BMI assessment at baseline, immediately following CR completion and at 1-year follow-up. Normal weight subjects at 1-year follow-up demonstrated the greatest improvement in aerobic fitness and best retention of those gains (gain in peak METs: 0.95 ± 1.1, P < 0.001). Although the improvement was significant (P < 0.001), subjects who were initially classified as obese had the lowest aerobic capacity and poorest retention in CR fitness gains at 1-year follow-up (gain in peak eMETs: 0.69 ± 1.2). Subjects initially classified as overweight by BMI had a peak eMET improvement that was also significantly better (P < 0.05) than obese subjects at 1-year follow-up (gain in peak eMETs: 0.82 ± 1.1). Significant fitness gains, one of the primary beneficial outcomes of CR, can be obtained by all subjects irrespective of BMI classification. However, obese patients have poorer baseline fitness and are more likely to "give back" fitness gains in the long term. Obese CAD patients may therefore benefit from additional interventions to enhance the positive adaptations facilitated by CR.     

Weight loss due to a very low calorie diet differentially affects insulin sensitivity and interleukin-6 serum levels in nondiabetic obese human subjects

Inflammatory mechanisms are involved in the pathogenesis of type 2 diabetes with interleukin (IL)-6 being particularly important. While long term exercise has been shown to be associated with reduction in IL-6 serum levels in several reports, the discussion on the effect of dietary intervention on IL-6 serum levels is controversial. In the present study, we aimed to investigate the effect of weight loss due to a very low calorie diet (VLCD) on insulin sensitivity and IL-6 serum levels in nondiabetic obese human individuals. 10 patients with obesity were examined during 12 weeks of a VLCD (800 kcal/d). Body composition was measured by impedance analysis. Blood samples were taken before, during, and after the dietary intervention. Leptin, adiponectin, and IL-6 serum levels were measured by ELISA. The body weight decreased significantly from 123.9±6.2-103.5±5.6 kg with a significant reduction in body fat content (43.2±2.3-36.1±3.1%). Leptin levels exhibited a significant decrease from 56.8±5.6-27.9±5.6 ng/ml while adiponectin levels increased significantly from 7.5±0.9-10.6±1.1 μg/ml. Thereby the leptin-to-adiponectin ratio, a novel marker for insulin sensitivity, significantly improved. Mean IL-6 serum concentrations were within the normal range (3.2±0.8 pg/ml) before the study and were not significantly altered by the nutritional therapy. Despite improvement of insulin sensitivity, IL-6 serum levels did not change throughout the study period, suggesting that in nondiabetic obese human subjects IL-6 might have only a minor role in the impairment of insulin sensitivity.     

A green tea extract high in catechins reduces body fat and cardiovascular risks in humans

Objective: The body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract (GTE) high in catechins was investigated in humans with typical lifestyles. Research Methods and Procedures: Japanese women and men with visceral fat‐type obesity were recruited for the trial. After a 2‐week diet run‐in period, a 12‐week double‐blind parallel multicenter trial was performed, in which the subjects ingested green tea containing 583 mg of catechins (catechin group) or 96 mg of catechins (control group) per day. Randomization was stratified by gender and body mass index at each medical institution. The subjects were instructed to maintain their usual dietary intake and normal physical activity. Results: Data were analyzed using per‐protocol samples of 240 subjects (catechin group; n = 123, control group; n = 117). Decreases in body weight, body mass index, body fat ratio, body fat mass, waist circumference, hip circumference, visceral fat area, and subcutaneous fat area were found to be greater in the catechin group than in the control group. A greater decrease in systolic blood pressure (SBP) was found in the catechin group compared with the control group for subjects whose initial SBP was 130 mm Hg or higher. Low‐density lipoprotein (LDL) cholesterol was also decreased to a greater extent in the catechin group. No adverse effect was found. Discussion: The continuous ingestion of a GTE high in catechins led to a reduction in body fat, SBP, and LDL cholesterol, suggesting that the ingestion of such an extract contributes to a decrease in obesity and cardiovascular disease risks.     

Higher Levels of Osteoprotegerin and Immune Activation/Immunosenescence Markers Are Correlated with Concomitant Bone and Endovascular Damage in HIV-Suppressed Patients

HIV-infected patients appear to have a significantly greater risk of non-AIDS comorbidities such as osteoporosis and atherosclerosis. Subjects with osteoporosis are at a higher risk of developing cardiovascular disease than those with normal bone mass, therefore a possible relation between these two conditions can be hypothesized. In the setting of HIV infection, several factors might contribute to bone disease and endothelial dysfunction. The aim of our study was to evaluate the relationship between bone and cardiovascular disease and to investigate the role of traditional factors, T-cell phenotype and osteoprotegerin in HIV positive subjects on effective antiretroviral therapy. We included 94 HIV positive subjects on antiretroviral therapy with virological suppression and 41 healthy subjects matched for age and gender as a control group. Carotid-Intima Media Thickness (c-IMT) and bone mineral density (BMD) were performed by ultrasound and DEXA, respectively. CD4⁺/CD8⁺ T-cell activation, senescence and osteoprotegerin plasma levels were measured by flow-cytometry and ELISA, respectively. Among HIV positive patients, 56.4% had osteopenia/osteoporosis and 45.7% had pathological c-IMT (>0.9mm). Subjects with pathological c-IMT and BMD exhibited higher CD4⁺ and CD8⁺ activated, CD8⁺ senescent and osteoprotegerin than subjects with normal c-IMT and BMD. HIV positive subjects with osteopenia/osteoporosis had higher c-IMT than subjects with normal BMD, and linear regression analysis showed a negative correlation between BMD and c-IMT. Several factors are implicated in the pathogenesis of non-AIDS comorbidities in HIV positive patients. Osteoprotegerin together with inflammation and immunosenescence in HIV positive patients could affect bone and vascular system and could be considered as a possible common link between these two diseases.     

Artery Wall Assessment Helps Predict Kidney Transplant Outcome

Background

Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation.

Methods

In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality.

Results

A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P<0.0001), fasting glucose (β=0.168, P=0.045), smoking (β=0.228, P=0.003) and VCAM-1 levels (β=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (β=-0.677, P<0.0001), post-transplant diabetes (β=0.225, P=0.003) and triglycerides (β=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021).

Conclusion

A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival.     

A weekly administered sustained-release growth hormone reduces visceral fat and waist circumference in abdominal obesity

Administration of recombinant human growth hormone (rhGH) in obesity has been known to lead to a decrease in visceral adiposity and an increase in lean body mass. Most studies have used supraphysiological doses of rhGH, which were administered daily or every other day. We aimed to evaluate whether weekly administered low dose of sustained-release rhGH (SR-rhGH) could play a therapeutic role in the treatment of abdominal obesity. Prospective, single-arm, open-label, multicenter pilot study was carried out. Participants were 26 adults aged 40-65 years old with abdominal obesity (male: waist circumference >90?cm, female: waist circumference >85?cm). The subjects were given 3?mg of SR-rhGH, administered subcutaneously, weekly for 26 weeks. SR-rhGH treatment for 26 weeks increased the IGF-1 level by 56.53±76.09?μg/l (SDS 0.77±1.12) compared to the baseline (p=0.0022). After 26 weeks, SR-rhGH treatment reduced abdominal visceral adipose tissue (VAT) (140.35±75.97 to 128.43±73.85?cm2, p=0.0038). Average waist circumference decreased from 96.25±6.41 to 91.93±6.13?cm (p<0.0001) after treatment. However, body weight or lean body mass did not show any significant change. In conclusion, SR-rhGH treatment for 26 weeks reduced abdominal visceral fat and waist circumference without severe adverse events. Further studies may be considered on the role of weekly administered SR-rhGH as a treatment for abdominal obesity.     

Endurance training amplifies the pulsatile release of growth hormone: effects of training intensity.

The effects of intensity of run training on the pulsatile release of growth hormone (GH) were investigated in 21 eumenorrheic untrained women. The O2 consumption (VO2) at the lactate threshold (LT); fixed blood lactate concentrations (FBLC) of 2.0, 2.5, and 4.0 mM; peak VO2; maximal VO2; body composition; and pulsatile release of GH were measured. Subjects in both the at-lactate threshold (/LT, n = 9) and above-lactate threshold (greater than LT, n = 7) training groups increased VO2 at LT and FBLC of 2.0, 2.5, and 4.0 mM and VO2max after 1 yr of run training. However, the increase observed in the greater than LT group was greater than that in the /LT group (P less than 0.05). No change was observed for the control group (n = 5). No among- or within-group differences were observed for body weight, although trends for reductions in percent body fat (P less than 0.06) and fat weight (P less than 0.15) were observed in the greater than LT group, and both training groups significantly increased fat-free weight (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of Carotid Intima-Media Thickness in Children and Adults With and Without Obesity: A Hysteresis Model

ObjectiveTo describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups.MethodsA quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling.ResultsThe additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P < .0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as R², and the cubic function estimated parameters like a polynomial model.ConclusionThis practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood.     

PLTP activity decreases with weight loss: changes in PLTP are associated with changes in subcutaneous fat and FFA but not IAF or insulin sensitivity

Phospholipid transfer protein (PLTP) activity is elevated in obese and diabetic subjects. No prospective studies have examined the effect of weight loss on PLTP activity and assessed whether the resultant changes in activity are related to changes in body weight, insulin resistance, or both. PLTP activity was measured at baseline in 46 subjects (body mass index = 19-64 kg/m2) and after diet-induced weight loss in 19 of the obese subjects. Total body fat mass (FM) by dual-energy X-ray absorptiometry, intraabdominal fat (IAF), and abdominal subcutaneous fat (SQF) by CT scan, insulin sensitivity (SI) by frequently sampled intravenous glucose tolerance test, leptin, and lipids were determined. At baseline, PLTP activity correlated with FM (r = 0.36, P = 0.02) and SQF (r = 0.31, P = 0.045), but not with IAF (r = 0.16, P = 0.32) or SI (r = 0.10, P = 0.52). With diet-induced weight loss (16 +/- 7.3 kg), PLTP activity significantly decreased 9.1% (P = 0.002). The change in PLTP activity correlated with the change in SQF (r = 0.55, P = 0.014) (33.6% decrease), but not with IAF (r = 0.09, P = 0.73) or SI (r = 0.18, P = 0.44), and was highly correlated with the change in nonesterified fatty acid (NEFA) (r = 0.71, P < 0.001). In conclusion, elevated PLTP activity in obese subjects is likely a result of increased body fat, reflected by SQF, and is influenced by NEFAs but is not directly related to insulin resistance.     

Dietary adherence during weight loss predicts weight regain

This study examined the relationship between previous dietary adherence during a low-calorie diet weight loss intervention and subsequent weight change during a 2-year follow-up for weight maintenance. One hundred and sixteen healthy, recently weight reduced (lost ~12 kg, BMI 22-25 kg/m2) premenopausal women were studied. Dietary adherence was assessed by doubly labeled water (DLW) and body composition change. Comparisons were made between the upper and lower tertiles for previous dietary adherence and subsequent weight change at 1- and 2-year follow-up. Percent weight regained was significantly lower (30.9 ± 6.7% vs. 66.7 ± 9.4%; P < 0.05) in the upper compared to the lower adherence tertile for previous weight loss dietary adherence (49.9 ± 8.8% vs. 96.8 ± 12.8% P < 0.05) at 1- and 2-year follow-up, respectively. This difference was partly explained by increases in daily activity-related energy expenditure (AEE) (+95 ± 45 kcal/day vs. -44 ± 42 kcal/day, P < 0.05) and lower daily energy intake (2,066 ± 71 kcal/day vs. 2,289 ± 62 kcal/day, P < 0.05) in the higher tertile for previous dietary adherence, compared to the lower. These findings suggest that higher adherence (i.e., higher tertile) to the previous low-calorie diet predicts lower weight regain over 2-year follow-up for weight maintenance, which is explained by lower energy intake and higher physical activity. Finally, how well an individual adheres to a low-calorie diet intervention during weight loss may be a useful tool for identifying individuals who are particularly vulnerable to subsequent weight regain.     

Impact of chronic exercise training on the blood pressure response to orthostatic stimulation

Exercise training elicits morphological adaptations in the left ventricle (LV) and large-conduit arteries that are specific to the type of training performed (i.e., endurance vs. resistance exercise). We investigated whether the mode of chronic exercise training, and the associated cardiovascular adaptations, influence the blood pressure responses to orthostatic stimulation in 30 young healthy men (10 sedentary, 10 endurance trained, and 10 resistance trained). The endurance-trained group had a significantly larger LV end-diastolic volume normalized by body surface area (vs. sedentary and resistance-trained groups), whereas the resistance-trained group had a significantly higher LV wall thickness and aortic pulse wave velocity (PWV) compared with the endurance-trained group. In response to 60° head-up tilt (HUT), mean arterial pressure (MAP) rose in the resistance-trained group (+6.5 ± 1.6 mmHg, P < 0.05) but did not change significantly in sedentary and the endurance-trained groups. Systolic blood pressure (SBP) decreased in endurance-trained group (-8.3 ± 2.4 mmHg, P < 0.05) but did not significantly change in sedentary and resistance-trained groups. A forward stepwise multiple regression analysis revealed that LV wall thickness and aortic PWV were significantly and independently associated with the MAP response to HUT, explaining ～41% of its variability (R(2) =0.414, P < 0.001). Likewise, aortic PWV and the corresponding HUT-mediated change in stroke volume were significantly and independently associated with the SBP response to HUT, explaining ～52% of its variability (R(2) = 0.519, P < 0.0001). Furthermore, the change in stroke volume significantly correlated with LV wall thickness (r = 0.39, P < 0.01). These results indicate that chronic resistance and endurance exercise training differentially affect the BP response to HUT, and that this appears to be associated with training-induced morphological adaptations of the LV and large-conduit arteries.     

Association of the FTO gene with BMI

Variants in the FTO gene have been strongly associated with obesity in a very large sample (38,759) of diabetic and control subjects. To replicate these findings, the previously reported SNP in the FTO gene (rs9939609, T/A) was genotyped in 5,607 subjects from five different Utah studies. The studies included a random sample of the Utah population, families selected for aggregation of extreme thinness, families selected for severe obesity, a series of unrelated severe obesity subjects, and families participating in a 25-year longitudinal study of cardiovascular disease and aging. Results show a strong significant increase in the rs9939609 A allele frequency with increasing BMI (P < 0.0001). In the longitudinal study, FTO genotypes were significantly associated with BMI at a baseline exam, a 2(1/2)-year follow-up exam and a 25-year follow-up exam using an additive genetic model. The mean genotype difference in BMI ranged from 1.3 to 2.1 kg/m(2) across exams. The genotype difference in BMI means was established in youth, and at-risk subjects under age 20 at baseline had a significantly larger 25-year BMI increase (10.0 for A/A; 9.7 for A/T, and 8.5 kg/m(2) for T/T, P = 0.05). We conclude that the BMI increases associated with FTO genotypes begin in youth and are maintained throughout adulthood.     

The role of nutrition, body condition and lactation on calving success in muskoxen

Relationships between nutrition, body weight (BW), body condition score (BCS) and fertility were explored in 11 captive female muskoxen between 1988–1994. In 1987, six adult female muskoxen were allocated to high plane (HP) or low plane (LP) nutritional treatments (HP n = 3; LP n = 3), which were maintained year-round through spring 1995 (HP n = 6; LP n = 5). Treatment group size fluctuated annually. Age, lactation status, calving date and calf birth weight were recorded for each cow. Body weight was measured weekly and BCS measured bi-weekly throughout the mating season from 1 August to 31 October. Sixty-one complete observations of BW and BCS in autumn, lactation status and calving success were collected. Body weight and BCS differed significantly ( t -test) with pregnancy ( P < 0.001) and nutritional treatment ( P < 0.001). A significant logistic regression model was generated for the relationship between BW in October and pregnancy ( P < 0.001). When BCS each month was combined with BW in October, BCS in September was the most significant variable ( P < 0.001) and the only one to enter the model. Neither lactational status nor year, in combination or alone, was significant. Both BW in autumn (176 kg provides a 50% probability of a female calving the following spring) and BCS (score of six provides a 50% probability of successful calving) can be useful predictors of fertility in muskoxen. The ability of muskoxen to make significant gains in weight and body condition in autumn may represent a nutritional control point regulating reproduction in this species.     

Implantable gastric stimulator does not prevent the increase in plasma ghrelin levels that occurs with weight loss

The SHAPE (Screened Health Assessment and Pacer Evaluation) trial was a 24 month randomized multicenter placebo-controlled study to determine the efficacy of an implantable gastric stimulator (IGS) for weight loss. This report is an investigator-initiated sub-study at one site designed to assess whether IGS affects plasma levels of ghrelin and peptide YY (PYY). The device was implanted in all subjects but was activated in the Treatment group (n = 7, BMI = 41.5 ± 2.0 kg/m2) and remained inactive in the Control (n = 6, BMI = 39.5 ± 1.7 kg/m2) during the first 12 months. IGS was activated in both groups during months 12-24. Fasting venous blood was drawn at months 0, 12, and 24 and an oral glucose tolerance test (OGTT) was performed at month 12. Although there was no difference in weight loss at 6 months (Control: -6.6 ± 1.5% vs. Treatment: -6.2 ± 1.4%), at 24 months the Control group exhibited weight gain from baseline (+2.2 ± 1.5%) that was significantly different from the weight loss in the Treatment group (-1.9 ± 1.4%; P < 0.05). At 12 months, fasting ghrelin was significantly increased (P < 0.05) in the Treatment group (285 ± 35 to 336 ± 35 pg/ml; weight change, -4.9 ± 1.4%), but not in the Control (211 ± 36 to 208 ± 35 pg/ml; weight change, -3.4 ± 1.5%). No significant change was observed in postprandial suppression of plasma ghrelin or in fasting and postprandial PYY levels. In conclusion, IGS does not prevent the increase in fasting plasma ghrelin levels associated with weight loss. Further studies are needed to determine whether changes in technology can improve weight loss and maintenance, perhaps using gut hormones as biomarkers of possible efficacy.     

Weight loss and sleep-disordered breathing in childhood obesity: effects on inflammation and uric acid

Sleep-disordered breathing (SDB) is prevalent in childhood obesity. It may be an independent risk factor for the metabolic syndrome. Possible mechanisms are inflammation and oxidative stress. Adenotonsillectomy in childhood obesity is associated with a high recurrence rate and risk of postoperative weight gain. Therefore, this study assessed the effects of SDB on inflammation and oxidative stress in childhood obesity before and after weight loss. We included 132 obese subjects between 10 and 18 years consecutively. Median age was 15.4 years (10.1-18.0). Mean BMI z-score was 2.72 ± 0.42. Leukocytes and differentiation, high sensitivity C-reactive protein (hs-CRP), and uric acid (UA) were determined at baseline and subjects underwent a sleep assessment. SDB was diagnosed in 39%. Linear regression analysis showed an association between UA(log) and oxygen desaturation index(log) (ODI(log)) (r = 0.20; P = 0.03), between leukocytes(log) and respiratory disturbance index(log) (RDI(log)) (r = 0.23; P = 0.01), and between lymphocytes(log) and RDI(log) (r = 0.19; P = 0.04). Follow-up was organized after 4-6 months of treatment. Median decrease in BMI z-score was 32%. Laboratory measurements were repeated. Subjects with SDB at baseline underwent a second sleep study. Of these 49 subjects, 12 showed residual SDB. This corresponds with a treatment success rate of 71%. Unlike changes in inflammatory markers, improvements in UA were associated with improvements in RDI and ODI (respectively: r = 0.44; P = 0.007, r = 0.41; P = 0.01). In conclusion, weight loss is effective in treating obese children with SDB. At baseline, a link exists between inflammation and SDB. Oxidative stress is reflected by UA at baseline and the concentration decreases after treatment according to improvements in SDB.     

Identification of a novel duplication CFTRdup2 and functional impact of large rearrangements identified in the CFTR gene

The aim of this study was to investigate associations of two candidate gene SNPs of the endocannabinoid receptor type 1 gene (CNR1) with overweight, obesity and obesity-related traits in Chinese retired women. The study subjects were a subsample of the Taizhou Retiree Women Cohort, consisting of 2812 retired women aged 50-64 years recruited from Taizhou, Jiangsu, China. Neither rs2023239 nor rs806381 polymorphism was significantly associated with body mass index-defined overweight and obesity or waist-to-hip-ratio-defined obesity. For obesity-related traits, rs2023239 was significantly associated with glutamate pyruvate transaminase (GPT) (median, 18.00 vs 17.00 for TT and TC genotypes, respectively, P=0.043). The rs806381 also showed significant association with triglyceride (TG) (mean±SD, 1.46±0.20 vs 1.53±0.20 for GA and GG+AA genotypes, respectively, P=0.013) under the dominant genetic model. In conclusion, the rs2023239 and rs806381 polymorphisms of CNR1 were not associated with increased overweight and obesity risk. But the rs2023239 polymorphism was significantly associated with GPT, and the rs806381 polymorphism was significantly associated with TG.     

Inheritance pattern of familial hypercholesterolemia and markers of cardiovascular risk

Studies in children and adults have resulted in conflicting evidence in the quest for the answer to the hypothesis that offspring from hypercholesterolemic mothers might have an increased cardiovascular risk. Previous studies might have suffered from limitations such as cohort size and clinical sampling bias. We therefore explored this hypothesis in large cohorts of both subjects with familial hypercholesterolemia (FH) and unaffected siblings in a wide age range. In three cohorts (cohort 1: n = 1,988, aged 0–18 years; cohort 2: n = 300, 8–30 years; cohort 3: n = 369, 18–60 years), we measured lipid and lipoproteins as well as carotid intima-media thickness (c-IMT) in offspring from FH mothers versus FH fathers. For LDL cholesterol, triglycerides (TGs), and c-IMT, we performed a pooled analysis. No significant differences could be observed in c-IMT, lipid, or lipoprotein levels from offspring of FH mothers versus FH fathers. Pooled analyses showed no significant differences for either LDL cholesterol [mean difference 0.02 (−0.06,0.11) mmol/l, P = 0.60], TGs [mean difference 0.07 (0.00,0.14) mmol/l, P = 0.08], or c-IMT [mean difference −0.00 (−0.01,0.01) mm, P = 0.86]. Our data do not support the hypothesis that cardiovascular risk markers are different between offspring from FH mothers and FH fathers.     

Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects

Maintenance of reduced or elevated body weight results in respective decreases or increases in energy expended in physical activity, defined as 24-h energy expenditure excluding resting energy expenditure and the thermic effect of feeding, beyond those attributable to weight change. We examined skeletal muscle work efficiency by graded cycle ergometry and, in some subjects, rates of gastrocnemius muscle ATP flux during exercise by magnetic resonance spectroscopy (MRS), in 30 subjects (15 males, 15 females) at initial weight and 10% below initial weight and in 8 subjects (7 males, 1 female) at initial weight and 10% above initial weight to determine whether changes in skeletal muscle work efficiency at altered body weight were correlated with changes in the energy expended in physical activity. At reduced weight, muscle work efficiency was increased in both cycle ergometry [mean (SD) change = +26.5 (26.7)%, P < 0.001] and MRS [ATP flux change = -15.2 (23.2)%, P = 0.044] studies. Weight gain resulted in decreased muscle work efficiency by ergometry [mean (SD) change = -17.8 (20.5)%, P = 0.043]. Changes in muscle efficiency at altered body weight accounted for 35% of the change in daily energy expended in physical activity.