Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

Background

Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls.

Research Design and Methods

Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method).

Results

Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons).

Conclusion

Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036     

Effect of Modest Caloric Restriction on Oxidative Stress in Women,a Randomized Trial

Objectives

It is not established to what extent caloric intake must be reduced to lower oxidative stress in humans. The aim of this study was to determine the effect of short-term, moderate caloric restriction on markers of oxidative stress and inflammation in overweight and obese premenopausal women.

Materials/Methods

Randomized trial comparison of 25% caloric restriction (CR) or control diet in 40 overweight or obese women (body mass index 32±5.8 kg/m²) observed for 28 days and followed for the next 90 days. Weight, anthropometry, validated markers of oxidative stress (F₂-isoprostane) and inflammation (C-reactive protein), adipokines, hormones, lipids, interleukins, and blood pressure were assessed at baseline, during the intervention, and at follow-up.

Results

Baseline median F₂-isoprostane concentration (57.0, IQR = 40.5–79.5) in the CR group was 1.75-fold above average range for normal weight women (32.5 pg/ml). After starting of the caloric restriction diet, F₂-isoprostane levels fell rapidly in the CR group, reaching statistical difference from the control group by day 5 (median 33.5, IQR = 26.0–48.0, P<0.001) and remained suppressed while continuing on the caloric restriction diet. Three months after resuming a habitual diet, concentrations of F₂-isoprostane returned to baseline elevated levels in ∼80% of the women.

Conclusions

Oxidative stress can be rapidly reduced and sustained through a modest reduction in caloric intake suggesting potential health benefits in overweight and obese women.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00808275","term_id":"NCT00808275"}}NCT00808275     

The Vitamin D Status in Inflammatory Bowel Disease

Context

There is no consensus on the vitamin D status of children and adolescents with inflammatory bowel disease (IBD).

Aim

To determine the vitamin D status of patients with IBD by comparing their serum 25(OH)D concentration to that of healthy controls.

Hypothesis

Serum 25(OH)D concentration will be lower in patients with IBD compared to controls.

Subjects and Methods

A case-controlled retrospective study of subjects with IBD (n = 58) of 2–20 years (male n = 31, age 16.38±2.21 years; female n = 27, age16.56±2.08 years) and healthy controls (n = 116; male n = 49, age 13.90±4.59 years; female n = 67, age 15.04±4.12years). Study subject inclusion criteria: diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). Vitamin D deficiency was defined as 25(OH)D of (<20 ng/mL) (<50 nmol/L), overweight as BMI of ≥85^th but <95^th percentile, and obesity as BMI ≥95^th percentile. Data were expressed as mean ± SD.

Results

Patients with CD, UC, and their controls had mean serum 25(OH)D concentrations of 61.69±24.43 nmol/L, 53.26±25.51, and 65.32±27.97 respectively (ANOVA, p = 0.196). The overweight/obese controls had significantly lower 25(OH)D concentration compared to the normal-weight controls (p = 0.031); whereas 25(OH)D concentration was similar between the normal-weight and overweight/obese IBD patients (p = 0.883). There was no difference in 25(OH)D between patients with UC and CD, or between subjects with active IBD and controls. However, IBD subjects with elevated ESR had significantly lower 25(OH)D than IBD subjects with normal ESR (p = 0.025), as well as controls (65.3±28.0 nmol/L vs. 49.5±25.23, p = 0.045).

Conclusion

There is no difference in mean serum 25(OH)D concentration between children and adolescents with IBD and controls. However, IBD subjects with elevated ESR have significantly lower 25(OH)D than controls. Therefore, IBD subjects with elevated ESR should be monitored for vitamin D deficiency.     

The Outcomes of a 12-Week Internet Intervention Aimed at Improving Fitness and Health-Related Quality of Life in Overweight Adolescents: The Young & Active Controlled Trial

Background

Overweight and obesity among adolescents may have consequences, with potentially lasting effects on health and health-related quality of life (HRQoL). Excess weight is also associated with decreases in physical activity and cardiorespiratory fitness. The aim of the current study was to investigate the short-term effects of a 12-week Internet intervention in a primary care setting intended to increase cardiorespiratory fitness and HRQoL among overweight and obese adolescents.

Methods

In this controlled trial, participants (13–15 years) were non-randomly allocated to an intervention- or a control group. The intervention group received 12-weeks access to an online program providing tailored physical activity counseling based on principles from Self-determination Theory and Motivational Interviewing. The control group received standard follow-up by the school nurses. The primary outcome measure of cardiorespiratory fitness was determined using a shuttle run test. The secondary outcomes: HRQoL, leisure time exercise, body image and self-determined motivation for physical activity and exercise, were assessed by self-report measures. Age- and gender-adjusted body mass index (BMI) was calculated based on measurements of height and weight. To compare pre-to post intervention differences within groups, a paired samples t-test was used while crude differences between groups were analyzed with an independent samples t-test.

Results

Of the 120 participants, 108 completed the study, 75 in the intervention group and 33 in the control group. Exposure to the intervention had a small effect on cardiorespiratory fitness (0.14; 95% CI [0.01;0.28]; P = 0.04), and a moderate effect on HRQoL (5.22; 95% CI [0.90; 9.53]; P = 0.02). Moreover, the control group increased significantly in BMI, yielding a moderate preventive effect on BMI (−0.39; 95% CI [−0.74;−0.03]; P = 0.03) for the intervention group.

Conclusion

The results suggest that the Internet intervention with tailored physical activity counseling can have beneficial short-term effect on cardiorespiratory fitness, HRQoL and BMI among adolescents with overweight and obesity.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01700309","term_id":"NCT01700309"}}NCT01700309     

Dietary Patterns Differently Associate with Inflammation and Gut Microbiota in Overweight and Obese Subjects

Background

Associations between dietary patterns, metabolic and inflammatory markers and gut microbiota are yet to be elucidated.

Objectives

We aimed to characterize dietary patterns in overweight and obese subjects and evaluate the different dietary patterns in relation to metabolic and inflammatory variables as well as gut microbiota.

Design

Dietary patterns, plasma and adipose tissue markers, and gut microbiota were evaluated in a group of 45 overweight and obese subjects (6 men and 39 women). A group of 14 lean subjects were also evaluated as a reference group.

Results

Three clusters of dietary patterns were identified in overweight/obese subjects. Cluster 1 had the least healthy eating behavior (highest consumption of potatoes, confectionary and sugary drinks, and the lowest consumption of fruits that was associated also with low consumption of yogurt, and water). This dietary pattern was associated with the highest LDL cholesterol, plasma soluble CD14 (p = 0.01) a marker of systemic inflammation but the lowest accumulation of CD163+ macrophages with anti-inflammatory profile in adipose tissue (p = 0.05). Cluster 3 had the healthiest eating behavior (lower consumption of confectionary and sugary drinks, and highest consumption of fruits but also yogurts and soups). Subjects in this Cluster had the lowest inflammatory markers (sCD14) and the highest anti-inflammatory adipose tissue CD163+ macrophages. Dietary intakes, insulin sensitivity and some inflammatory markers (plasma IL6) in Cluster 3 were close to those of lean subjects. Cluster 2 was in-between clusters 1 and 3 in terms of healthfulness. The 7 gut microbiota groups measured by qPCR were similar across the clusters. However, the healthiest dietary cluster had the highest microbial gene richness, as evaluated by quantitative metagenomics.

Conclusion

A healthier dietary pattern was associated with lower inflammatory markers as well as greater gut microbiota richness in overweight and obese subjects.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01314690","term_id":"NCT01314690"}}NCT01314690     

Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef Vaccine Induced Immune Responses

Background

Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses.

Methods

Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors.

Results

Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4–27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500).

Conclusions

Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity).     

Interventions to Reduce and Prevent Obesity in Pre-Conceptual and Pregnant Women: A Systematic Review and Meta-Analysis

Background

The increasing prevalence of obesity in pregnant women is associated with adverse maternal and neonatal outcomes, and increased costs to healthcare, the economy and broader society.

Objectives

To assess the efficacy of behavioural interventions for managing gestational weight gain (GWG) in the pre-conceptual and pregnancy period in overweight, obese and morbidly obese women.

Search Methods

A search was performed for published studies in the English language, from date? 2000–31 December 2012 in five electronic databases; PubMed, Scopus, Cochrane Library, CINAHL and PsycINFO.

Selection criteria

Studies were included if they compared the efficacy or effectiveness of a particular behavioural intervention in pregnant or pre-conceptual women with standard maternity care. Studies that included women with co-morbid conditions such as diabetes mellitus and polycystic ovarian syndrome were excluded to help isolate the effect of the intervention.

Results

Fifteen studies involving 3,426 participants were included. One study (n = 692) focused on the pre-conceptual period and the remaining 14 (n = 2,734) in the pregnancy period. Pooled mean difference for GWG indicated a lower GWG in the intervention groups when compared to standard maternity care groups (n = 1771, mean difference (MD) −1.66 kg, 95% CI −3.12 to −0.21 kg). With respect to the types of participants, considerable heterogeneity between studies was shown in the obese subgroup [Tau² = 15.61; Chi² = 40.80, df = 3 (P<0.00001); I² = 93%].

Conclusions

Behavioural interventions in pregnancy may be effective in reducing GWG in obese women without comorbid conditions, but not overweight or morbidly obese women. Behavioural interventions had no effect on postpartum weight loss or retention, gestation week of delivery and infant birth weight in overweight, obese and morbidly obese women.     

Women’s Satisfaction with Body Image before Pregnancy and Body Mass Index 4 Years after Delivery in the Mothers of Generation XXI

Background

Body image satisfaction (BIS) influences body weight regulation and may contribute to long-term healthier lifestyle after pregnancy. Thus, we aimed to assess the association between BIS before pregnancy and body mass index (BMI) 4 years after the index pregnancy.

Methods

As part of the follow-up of a birth cohort, 3612 women with prepregnancy BMI >18.5 kg/m² were reevaluated 4 years after the birth of a child. BIS was defined as the difference between perceived and ideal body size before pregnancy, assessed by Stunkard Silhouettes after birth. The associations of BIS with BMI change (continuous) and BMI classes at 4 years, based on measured weight and height, were estimated using linear and multinomial regression, respectively.

Results

Among women with normal prepregnancy BMI, those who felt too small, regarding their ideal, had a 0.25 kg/m² smaller increase in BMI within 4 years and a lower likelihood of becoming overweight or obese [multivariate-adjusted odds ratio (OR) = 0.63; 95% confidence interval (95%CI): 0.44–0.91 and OR = 0.21; 95%CI: 0.05–0.91, respectively) than those satisfied with body image. Feeling too large was associated with a 0.41 kg/m² larger increase in BMI and a higher risk of becoming overweight or obese (OR = 2.12; 95%CI:1.73–2.59 and OR = 3.42; 95%CI:2.02–5.79, respectively). A similar, non-significant, trend was observed for overweight women. Obese women who felt too large had a non-significant decrease in BMI.

Conclusions

BIS plays a role in maternal body weight after delivery. Realistic body size goals may promote the motivation to lose weight and contribute to higher success in attaining them.     

Video game playing is independently associated with blood pressure and lipids in overweight and obese adolescents

Objective

To examine the association between duration and type of screen time (TV, video games, computer time) and blood pressure (BP) and lipids in overweight and obese adolescents.

Design

This is a cross-sectional study of 282 overweight or obese adolescents aged 14–18 years (86 males, 196 females) assessed at baseline prior to beginning a lifestyle intervention study for weight control. Sedentary behaviours, defined as hours per day spent watching TV, playing video games, recreational computer use and total screen time were measured by self-report. We examined the associations between sedentary behaviours and BP and lipids using multiple linear regression.

Results

Seated video gaming was the only sedentary behaviour associated with elevated BP and lipids before and after adjustment for age, sex, pubertal stage, parental education, body mass index (BMI), caloric intake, percent intake in dietary fat, physical activity (PA) duration, and PA intensity. Specifically, video gaming remained positively associated with systolic BP (adjusted r = 0.13, β = 1.1, p<0.05) and total cholesterol/HDL ratio (adjusted r = 0.12, β = 0.14, p<0.05).

Conclusions

Playing video games was the only form of sedentary behaviour that was independently associated with increased BP and lipids. Our findings provide support for reducing time spent playing seated video games as a possible means to promote health and prevent the incidence of cardiovascular disease (CVD) risk factors in this high risk group of overweight and obese adolescents. Future research is needed to first replicate these findings and subsequently aim to elucidate the mechanisms linking seated video gaming and elevated BP and lipids in this high risk population.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00195858","term_id":"NCT00195858"}}NCT00195858     

Body mass index and mortality in chronic obstructive pulmonary disease: a meta-analysis

Background

The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades. However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up.

Methods

We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies. Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD. In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association.

Results

22 studies comprising 21,150 participants were included in this analysis. Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR  = 1.34, 95% CI  = 1.01–1.78), whereas overweight (RR  = 0.47, 95% CI  = 0.33–0.68) and obese (RR  = 0.59, 95% CI  = 0.38–0.91) patients were associated with lower mortality. We further performed a baseline risk-adjusted analysis and obtained statistically similar results.

Conclusion

Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality. However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies.     

Levels of Cholesterol in Small LDL Particles Predict Atherosclerosis Progression and Incident CHD in the HDL-Atherosclerosis Treatment Study (HATS)

Objective

Test whether angiographically-documented changes in percent stenosis and clinical endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) in the HDL-Atherosclerosis Treatment Study (HATS) were attributable to specific LDL-subclasses.

Methods

Gradient gel electrophoresis of on-study LDL-subclass cholesterol concentrations were measured in 32 placebo, 33 simvastatin-niacin, 38 antioxidant, and 39 simvastatin-niacin & antioxidant treated participants. The prespecified primary end point was the mean change per patient from the initial arteriogram to the final arteriogram in the percent stenosis caused by the most severe lesion in each of the nine proximal coronary segments.

Results

The change in the percent stenosis of the most severe proximal lesions increased in association with higher concentrations of the small LDL subfractions LDL-IIIb (24.2–24.6 nm) and LDL-IVa (23.3–24.1 nm) before (both P = 0.002) and after (P = 0.01 and P = 0.03 respectively) adjustment for treatment group and on-study HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations. The associations appeared specific to lesions with <30% baseline stenosis. When adjusted for age, sex, baseline BMI and cigarette use, the odds for primary clinical endpoints (death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia) were significantly greater in subjects with higher on-study LDL-IIIb levels both before (P = 0.01) and after (P = 0.03) adjustment for treatment group and the standard lipid values.

Conclusions

Plasma LDL-IIIb cholesterol concentrations were related to changes in coronary artery stenosis and cardiovascular events in patients with coronary artery disease and low HDL-cholesterol.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00000553","term_id":"NCT00000553"}}NCT00000553     

The Association between Hematological Parameters and Insulin Resistance Is Modified by Body Mass Index – Results from the North-East Italy MoMa Population Study

Objective

Increments in red blood cell count (RBC), hemoglobin (Hb) and hematocrit (Ht) levels are reportedly associated with higher insulin resistance (IR). Obesity may cause IR, but underlying factors remain incompletely defined, and interactions between obesity, hematological parameters and IR are incompletely understood. We therefore determined whether: 1) BMI and obesity per se are independently associated with higher RBC, hemoglobin and hematocrit; 2) hematological parameters independently predict insulin resistance in obese individuals.

Design and Methods

We investigated the associations between BMI, hematological parameters and insulin resistance as reflected by homeostasis model assessment (HOMA) in a general population cohort from the North-East Italy MoMa epidemiological study (M/F = 865/971, age = 49±1).

Results

In all subjects, age-, sex- and smoking-adjusted hematological parameters were positively associated with BMI in linear regression (P<0.05), but not after adjustment for HOMA or waist circumference (WC) and potential metabolic confounders. No associations were found between hematological parameters and BMI in lean, overweight or obese subgroups. Associations between hematological parameters and HOMA were conversely independent of BMI in all subjects and in lean and overweight subgroups (P<0.01), but not in obese subjects alone.

Conclusions

In a North-East Italy general population cohort, obesity per se is not independently associated with altered RBC, Hb and Ht, and the association between BMI and hematological parameters is mediated by their associations with abdominal fat and insulin resistance markers. High hematological parameters could contribute to identify insulin resistance in non-obese individual, but they do not appear to be reliable insulin resistance biomarkers in obese subjects.     

Gestational weight gain and body mass index in children: results from three german cohort studies

Introduction

Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring’s body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear.

Methods

We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring’s mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5–6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status.

Results

In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m² of ‘real’ BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers.

Discussion

Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers.     

Obesity or Overweight Is Associated with Worse Pathological Response to Neoadjuvant Chemotherapy among Chinese Women with Breast Cancer

Background

To evaluate the relationship between body mass index (BMI) and response to neoadjuvant chemotherapy (NCT) for breast cancer among Chinese women.

Patients and Methods

A total of 307 eligible patients were assigned to receive four cycles of paclitaxel and carboplatin before standard surgery for breast cancer from 2007 to 2011 at Shanghai Cancer Hospital. The patients were categorized as obese, overweight, normal weight, or underweight based on BMI according to World Health Organization (WHO) criteria. Pathological complete response (pCR) was defined as no invasive cancer in the breast or axillary tissue. A logistic regression and the Chi-squared test were used for detecting the predictors of pCR and determining the relationship between BMI category and pCR rate in the subgroup analysis with respect to other variables.

Results

Categorical BMI, estrogen receptor (ER), and progesterone receptor (PR) status were independent predictors of pCR according to the multivariate analysis. Patients with BMI≥25 were less likely to achieve a pCR to NCT compared with patients with BMI<25 (Odds ratio: 0.454, p = 0.033, multivariate analysis). In the subgroup analysis, the predictive value of BMI for pCR to NCT was significantly shown in post-menopausal patients (p = 0.004) and hormonal receptor status-negative patients (p = 0.038). The incidence of treatment-induced toxicity was similar among the different BMI categories.

Conclusion

Higher BMI was associated with worse pCR to NCT. Further approaches to investigating the mechanism of this influence of BMI on treatment response and a more appropriate schedule for calculating NCT dose for high-BMI-patients should be considered.     

Impact of Obesity on the Clinical Profile of a Population-Based Sample with Chronic Obstructive Pulmonary Disease

Aims

To characterize the distribution of BMI in a population-based sample of COPD patients and to evaluate the impact of obesity on their health status, exercise tolerance, systemic inflammation and comorbidity.

Methods

A population-based sample of 3,797 subjects aged 40–80 years from the EPI-SCAN study was selected. Subjects were categorized according their body mass index (BMI) as underweight (<18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²) or obese (BMI≥30.0 kg/m²). Subjects were evaluated with post-bronchodilator spirometry and 6-minute walk tests. Smoking habits, respiratory symptoms, generic and specific quality of life, daily physical activities, comorbidities and systemic inflammatory biomarkers were recorded.

Results

The prevalence of obesity or being overweight was higher in the 382 COPD patients than in the subjects without airflow limitation (29.4%, 95%CI 24.8–33.9% vs. 24.3, 95%CI 22.9–25.8; and 44.7%, 95%CI 39.7–49.6% vs. 43.0%, 95%CI 41.3–44.6, respectively; p = 0.020). In the COPD subgroup, obese subjects presented more dyspnea and less chronic cough, chronic bronchitis or chronic phlegm than normal-weight patients, as well as a worse health status. Moreover, reduced exercise tolerance and higher plasmatic C-reactive protein levels were found in the obese patients, who also presented a greater prevalence of cardiovascular disease (adjusted odds ratio 4.796, 95%CI 1.806–12.736, p = 0.002).

Conclusions

In a population-based sample, obesity is more prevalent in COPD patients than in subjects without airflow limitation. Furthermore, obesity affects the clinical manifestations, quality of life and exercise tolerance of COPD patients, and it may contribute to a phenotype characterized by increased systemic inflammation and greater frequency of cardiovascular comorbidity.     

Impact of Metformin on Endothelial Ischemia-Reperfusion Injury in Humans In Vivo: A Prospective Randomized Open,Blinded-Endpoint Study

Introduction

Large prospective studies in patients with type 2 diabetes mellitus have demonstrated that metformin treatment improves cardiovascular prognosis, independent of glycemic control. Administration of metformin potently limits infarct size in murine models of myocardial infarction. This study examined, for the first time in humans, whether metformin limits ischemia-reperfusion (IR) injury in vivo using a well-validated forearm model of endothelial IR-injury.

Methods

Twenty-eight healthy volunteers (age 41±6 years, 10 male/16 female) were randomized between pretreatment with metformin (500 mg three times a day for 3 days) or no treatment in a Prospective Randomized Open Blinded Endpoint study. Brachial artery flow mediated dilation (FMD) was measured before and after 20 minutes of forearm ischemia and 20 minutes of reperfusion. FMD analysis was performed offline by investigators blinded for the treatment arm.

Results

Baseline FMD did not differ between metformin pretreatment and no pretreatment (6.9±3.6% and 6.1±3.5%, respectively, p = 0.27, n = 26). FMD was significantly lower after forearm IR in both treatment arms (4.4±3.3% and 4.3±2.8%, respectively, P<0.001 in both conditions). A linear mixed model analysis revealed that metformin treatment did not prevent the decrease in FMD by IR.

Conclusion

A 3 day treatment with metformin in healthy, middle-aged subjects does not protect against endothelial IR-injury, measured with brachial artery FMD after forearm ischemia. Further studies are needed to clarify what mechanism underlies the cardiovascular benefit of metformin treatment.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01610401","term_id":"NCT01610401"}}NCT01610401     

Prevalence of Overweight and Obesity and Weight Loss Practice among Beijing Adults, 2011

Objective

This study aims to determine the up-to-date prevalence of overweight and obesity, the distributions of body weight perception and weight loss practice in Beijing adults.

Methods

A cross-sectional study was conducted in 2011. A total of 2563 men and 4088 women aged 18–79 years from the general population were included. Data were obtained from questionnaire and physical examination.

Results

The prevalence of overweight (BMI 24–27.9 kg/m²) and obesity (BMI≥28 kg/m²) was 42.1% and 20.3% in men and 35.6% and 17.1% in women, respectively. Age was inversely associated with overweight in both sexes, and obesity in women. Education level was negatively associated with overweight and obesity in women but not in men. Only 49.1% men and 58.3% women had a correct perception of their body weight. Underestimation of body weight was more common than overestimation, especially in men, the older people, and those with low education level. The percentage of taking action to lose weight was inversely associated with men and old age, and positively associated with higher education level, higher BMI, and self-perception as “fat” (OR = 3.78 in men, OR = 2.91 in women). Only 26.1% of overweight/obese individuals took action to lose weight. The top two weight loss practices were to reduce the amount of food intake and exercise.

Conclusion

Overweight and obesity were highly prevalent with high incorrect body weight perceptions in the general adult population in Beijing. Weight loss practice was poor in overweight and obese individuals. Actions at multiple levels are needed to slow or control this overweight and obesity epidemic.     

Increased Rate of Arterial Stiffening with Obesity in Adolescents: A Five-Year Follow-Up Study

Background

We prospectively and longitudinally determined the effects of childhood obesity on arterial stiffening and vascular wall changes. Changes in arterial stiffness measured as pulse wave velocity (PWV) and vascular morphology of the radial (RA) and dorsal pedal arteries (DPA) were examined in obese adolescents compared to lean subjects in a 5-year follow-up study.

Methodology/Principal Findings

A total of 28 obese subjects and 14 lean controls participated in both baseline (14 years old) and follow-up studies. PWV was measured by tonometer (SphygmoCor®) and recorded at RA and carotid artery, respectively. Intima thickness (IT), intima-media thickness (IMT) and RA and DPA diameters were measured using high-resolution ultrasound (Vevo 770™). Over the course of 5 years, PWV increased by 25% in the obese subjects as compared to 3% in the controls (p = 0.01). Diastolic blood pressure (DBP) increased by 23% in the obese subjects as opposed to 6% in controls (p = 0.009). BMI increased similarly in both groups, as did the IT and IMT. The change in PWV was strongly associated to the baseline BMI z -score (r = 0.51, p<0.001), as was the change in DBP (r = 0.50, p = 0.001).

Conclusions/Significance

During the transition from early to late adolescence, there was a general increase in arterial stiffness, which was aggravated by childhood obesity. The increase in arterial stiffness and DBP after 5 years was closely correlated to the baseline BMI z -score, indicating that childhood obesity has an adverse impact on vascular adaptation.