Obesity Indexes and Total Mortality among Elderly Subjects at High Cardiovascular Risk: The PREDIMED Study

Background

Different indexes of regional adiposity have been proposed for identifying persons at higher risk of death. Studies specifically assessing these indexes in large cohorts are scarce. It would also be interesting to know whether a dietary intervention may counterbalance the adverse effects of adiposity on mortality.

Methods

We assessed the association of four different anthropometric indexes (waist-to-height ratio (WHtR), waist circumference (WC), body mass index (BMI) and height) with all-cause mortality in 7447 participants at high cardiovascular risk from the PREDIMED trial. Forty three percent of them were men (55 to 80 years) and 57% were women (60 to 80 years). All of them were initially free of cardiovascular disease. The recruitment took place in 11 recruiting centers between 2003 and 2009.

Results

After adjusting for age, sex, smoking, diabetes, hypertension, intervention group, family history of coronary heart disease, and leisure-time physical activity, WC and WHtR were found to be directly associated with a higher mortality after 4.8 years median follow-up. The multivariable-adjusted HRs for mortality of WHtR (cut-off points: 0.60, 0.65, 0.70) were 1.02 (0.78–1.34), 1.30 (0.97–1.75) and 1.55 (1.06–2.26). When we used WC (cut-off points: 100, 105 and 110 cm), the multivariable adjusted Hazard Ratios (HRs) for mortality were 1.18 (0.88–1.59), 1.02 (0.74–1.41) and 1.57 (1.19–2.08). In all analyses, BMI exhibited weaker associations with mortality than WC or WHtR. The direct association between WHtR and overall mortality was consistent within each of the three intervention arms of the trial.

Conclusions

Our study adds further support to a stronger association of abdominal obesity than BMI with total mortality among elderly subjects at high risk of cardiovascular disease. We did not find evidence to support that the PREDIMED intervention was able to counterbalance the harmful effects of increased adiposity on total mortality.

Trial Registration

Controlled-Trials.com ISRCTN35739639     

Lifestyles and Risk Factors Associated with Adherence to the Mediterranean Diet: A Baseline Assessment of the PREDIMED Trial

Background

The traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern.

Aim

To evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects.

Methods

We included 7305 participants (men aged 55–80 y, women 60–80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to estimate odds ratios (OR) and 95% confidence intervals for lower adherence to the MedDiet (<9 points out of 14) and ascertain factors independently associated with it.

Results

Former smoking (OR = 0.87; 95% CI, 0.78–0.98), physical activity (OR for the 3^rd vs. the 1^sttertile: 0.69; 0.62–0.78), and higher educational level (OR for university vs. less than primary school: 0.54; 0.38–0.77) were associated with higher MedDiet adherence. Conversely, having a larger waist-to-height ratio (OR for 0.1 units, 1.35; 1.22–1.49), being diabetic (OR = 1.13; 1.03–1.24), being single (OR = 1.27; 1.01–1.61) or divorced or separated (OR = 1.44; 1.09–1.89), and current smoking (OR = 1.28; 1.11–1.47) were associated with lower adherence.

Conclusions

Participants with little education, a larger waist-to-height ratio, or diabetes and those who were less physically active, single, divorced or separated, or smokers were less likely to adhere to the MedDiet, an ideal model for food choices. Stronger efforts of health promotion are needed in these groups to foster adoption of the MedDiet.     

Shift Work and Obesity among Canadian Women: A Cross-Sectional Study Using a Novel Exposure Assessment Tool

Background/Objectives

It has been suggested that the association between shift work and chronic disease is mediated by an increase in obesity. However, investigations of the relationship between shift work and obesity reveal mixed findings. Using a recently developed exposure assessment tool, this study examined the association between shift work and obesity among Canadian women from two studies: a cohort of university alumni, and a population-based study.

Methods

Self-administered questionnaire data were used from healthy, currently employed females in a population-based study, the Ontario Women’s Diet and Health case-control study (n = 1611 controls), and from a subset of a of university alumni from the Canadian Study of Diet, Lifestyle, and Health (n = 1097) cohort study. Overweight was defined as BMI≥25 to <30, and obesity as BMI≥30. Reported occupation was converted to occupational codes and linked to a probability of shift work value derived from Survey of Labour and Income Dynamics data. Regular evenings, nights, or rotating work comprised shift work. Polytomous logistic regression estimated the association between probability of shift work, categorized as near nil, low, medium, and high probability of shift work, on overweight and obesity, controlling for detected confounders.

Results

In the population-based sample, high probability of shift work was associated with obesity (reference = near nil probability of shift work, OR: 1.88, 95% CI: 1.01–3.51, p = 0.047). In the alumni cohort, no significant association was detected between shift work and overweight or obesity.

Conclusions

As these analyses found a positive association between high probability of shift work exposure and obesity in a population-based sample, but not in an alumni cohort, it is suggested that the relationship between shift work and obesity is complex, and may be particularly susceptible to occupational and education-related factors within a given population.     

Cross-Sectional Assessment of Nut Consumption and Obesity,Metabolic Syndrome and Other Cardiometabolic Risk Factors: The PREDIMED Study

Introduction

Prospective studies have consistently suggested that nut consumption is inversely related to fatal and non-fatal coronary heart disease. Limited data are available on the epidemiological associations between nut intake and cardiometabolic risk factors.

Objective

To evaluate associations between frequency of nut consumption and prevalence of cardiometabolic risk factors [obesity, metabolic syndrome (MetS), type-2 diabetes, hypertension, and dyslipidemia] in a Mediterranean population at high cardiovascular risk.

Materials and Methods

Cross-sectional study of 7,210 men and women (mean age, 67 y) recruited into the PREDIMED study. MetS was defined by the harmonized ATPIII and IDF criteria. Diabetes and hypertension were assessed by clinical diagnosis and dyslipidemia (high triglycerides, low HDL-cholesterol, and hypercholesterolemia) by lipid analyses. Nut consumption was assessed using a validated food frequency questionnaire and categorized as <1, 1–3, and >3 servings/wk. Control of confounding was done with multivariate logistic regression.

Results

Compared to participants consuming <1 serving/wk of nuts, those consuming >3 servings/wk had lower adjusted odds ratios (OR) for obesity (0.61, 95% confidence interval 0.54 to 0.68; P-trend <0.001), MetS (0.74, 0.65 to 0.85; P-trend<0.001), and diabetes (0.87, 0.78 to 0.99; P-trend = 0.043). Higher nut consumption was also associated with lower risk of the abdominal obesity MetS criterion (OR 0.68, 0.60 to 0.79; P-trend<0.001). No significant associations were observed for the MetS components high blood pressure, dyslipidemia, or elevated fasting glucose.

Conclusions

Nut consumption was inversely associated with the prevalence of general obesity, central obesity, MetS, and diabetes in subjects at high cardiovascular risk.     

The Addition of Dexfenfluramine to Fluoxetine in the Treatment of Obesity: A Randomized Clinical Trial

Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n=13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n=20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean ± SEM 6.2 ± 2.8 kg and Group II 13.4 ± 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m². However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.     

Mediterranean Style Diet and 12-Year Incidence of Cardiovascular Diseases: The EPIC-NL Cohort Study

Background

A recent meta-analysis showed that a Mediterranean style diet may protect against cardiovascular diseases (CVD). Studies on disease-specific associations are limited. We evaluated the Mediterranean Diet Score (MDS) in relation to incidence of total and specific CVDs.

Methods

The EPIC-NL Study is a cohort of 40,011 men and women aged 20–70 years, examined between 1993 and 1997, with 10–15 years of follow-up. Diet was assessed with a validated food frequency questionnaire and the MDS was based on the daily intakes of vegetables, fruits, legumes and nuts, grains, fish, fatty acids, meat, dairy, and alcohol. Cardiovascular morbidity and mortality were ascertained through linkage with national registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) adjusted for age, sex, cohort, smoking, physical activity, total energy intake, and educational level.

Results

In 34,708 participants free of CVD at baseline, 4881 CVD events occurred, and 487 persons died from CVD. A two unit increment in MDS (range 0–9) was inversely associated with fatal CVD (HR: 0.78; 95%CI: 0.69–0.88), total CVD (HR: 0.95 (0.91–0.98)), myocardial infarction (HR: 0.86 (0.79–0.93)), stroke (HR: 0.88 (0.78–1.00)), and pulmonary embolism (HR: 0.74 (0.59–0.92)). The MDS was not related to incident angina pectoris, transient ischemic attack and peripheral arterial disease.

Conclusion

Better adherence to a Mediterranean style diet was more strongly associated with fatal CVD than with total CVD. Disease specific associations were strongest for incident myocardial infarction, stroke and pulmonary embolism.     

The Effect of Dehydroepiandrosterone Combined with a Low-Fat Diet in Spontaneously Obese Dogs: A Clinical Trial

Dehydroepiandrosterone (DHEA) has been shown to have antiobesity activity in rodents and spontaneously obese dogs. This study evaluated the effect of DHEA or placebo combined with a low-fat/high-fiber diet in spontaneously obese dogs in a clinical trial. Spontaneously obese, euthyroid dogs, referred to the University of Wisconsin School of Veterinary Medicine for treatment of their obesity, were evaluated for percent overweight, rate of weight loss, serum cholesterol, plasma lipoprotein and serum biochemistry profiles, complete blood count, and endocrine profiles (T4, T3, Cortisol, insulin, and DHEA-sulfate). DHEA-treated dogs had a significantly increased rate of actual and percent excess weight loss compared with placebo-treated dogs. Serum cholesterol decreased in both treatment groups; however, DHEA-treated dogs had a significantly greater reduction than placebo-treated dogs. DHEA-treated dogs had a significant 32% reduction in total plasma cholesterol, which was due to a 27% reduction in the lipoprotein fraction containing the high-density lipoprotein (HDL) and a 50% reduction in the lipoprotein fraction containing the low-density lipoprotein (LDL). Placebo-treated dogs did not have a significant reduction in total plasma cholesterol or in the fraction containing LDL; however, they did have a significant 11% reduction in the fraction containing HDL. Significant decreases in serum T4 and T3 observed in dogs receiving DHEA were not noted in dogs receiving placebo. DHEA in combination with caloric restriction results in a faster rate of weight loss than does caloric restriction alone. In addition, DHEA has hypocholesterolemic activity, particularly affecting the lipoprotein fraction containing the LDL cholesterol.     

Sertraline and Relapse Prevention Training Following Treatment by Very-Low-Calorie Diet: A Controlled Clinical Trial

WADDEN, THOMAS A, SUSAN J BARTLETT, GARY D FOSTER, ROBERT A GREENSTEIN, BARBARA J WINGATE, ALBERT J STUNKARD AND KATHLEEN A LETIZIA. Sertraline and relapse prevention training following treatment by very-low-calorie diet: a controlled clinical trial. Obes Res. This study examined the combination of sertraline, a selective serotonin reuptake inhibitor, and relapse prevention training in the maintenance of weight loss following treatment by a very-low-calorie diet. A total of 53 women who had lost a mean (± SD) of 22.9 ± 7.1 kg from a pretreatment weight of 103.1 ± 17.8 kg were randomly assigned to a 54-week weight maintenance program that was combined with either: 1) 200 mg/d of sertraline; or 2) placebo. During the first 6 weeks, sertraline subjects lost significantly more weight and reported significantly greater reductions in hunger and preoccupation with food than did subjects on placebo. After this time, however, women in both conditions regained weight steadily. The 13 sertraline subjects who completed the 54-week study regained 17.7 ± 10.6 kg of their original 26.3 ± 7.6 kg loss, equal to a regain of 70.9 ± 41.7%. The 17 placebo completers regained 11.8 ± 9.0 kg of their 23.4 ± 7.8 kg loss, equal to a 46.5 ± 34.6% regain. End-of-treatment differences between groups in weight change were not statistically significant. Nor were there significant differences between the two conditions at any time in changes in fat-free mass, resting metabolic rate or dysphoria, all of which tended to increase with weight regain. The results are discussed in relation to findings from other long-term studies that combined diet and medication.     

Plasma HMGB-1 Levels in Subjects with Obesity and Type 2 Diabetes: A Cross-Sectional Study in China

Object

To detect the levels of plasma High-Mobility Group Box-1(HMGB1) in Chinese subject with obesity and type 2 diabetes mellitus (T2DM), and to investigate the correlations between plasma HMGB1 concentration and parameters of body fat, insulin resistance (IR) metabolism and inflammation.

Methods

This study recruited 79 normal glucose tolerance (NGT) subjects and 76 newly diagnosed T2DM patients. NGT and T2DM groups were divided into normal weight (NW) and obese (OB)subgroups respectively. Anthropometric parameters such as height, weight, waist circumference, hip circumference and blood pressure were measured. Plasma concentrations of HMGB1, IL-6, fasting plasma glucose (FPG), 2 hours post challenge plasma glucose (2hPG), serum lipid, glycated hemoglobin (HbA_1C) and fasting insulin (FINS) were examined. The homeostasis model assessment (HOMA) was performed to assess IR status.

Results

Plasma HMGB1 levels were higher in T2DM group than that in NGT group. The concentrations of serum HMGB1 were also higher in subjects with OB than those in subjects with NW both in NGT and T2DM groups. Plasma levels of HMGB1 were positively correlated with waist hip ratio (WHR), blood pressure, FPG, FINS, HOMA-IR, TG, IL-6 and negatively correlated with HOMA-βand high-density lipoprotein-cholesterol (HDL-c) independent of age, gender and BMI. Plasma levels of HMGB1 were significantly correlated with diabetes in fully adjusted models.

Conclusion

Plasma HMGB1 levels were increased in Chinese subjects with pure T2DM, which might be caused by IR. Serum HMGB1 participated in the pathological process of obesity and T2DM via its proinflammatory effect.     

Multiple Dimensions of Socioeconomic Position and Obesity among Employees: The Helsinki Health Study

Objective: To examine socioeconomic differences in obesity using several different socioeconomic indicators, ranging from childhood socioeconomic environment and adult socioeconomic status to material resources and economic satisfaction. Research Methods and Procedures: The data derived from the Helsinki Health Study baseline surveys in 2000 and 2001. Respondents to postal surveys were middle‐aged employees of the City of Helsinki (4, 975 women and 1, 252 men, response rate 68%). Associations between eight socioeconomic indicators and obesity (BMI ≥ 30 kg/m²), calculated from self‐reported data, were examined by fitting a series of logistic regression models. Results: In women, all socioeconomic indicators except household income and economic satisfaction were associated with obesity. Parental education and childhood economic difficulties, i.e., socioeconomic conditions in childhood, remained associated with obesity after adjusting for all indicators of current socioeconomic position. Indicators of adult socioeconomic status, own education and occupational class, were no longer associated with obesity when childhood socioeconomic conditions were adjusted for. Home ownership and economic difficulties were associated with obesity after full adjustments. In men, the findings paralleled those among women, but few associations reached statistical significance. Discussion: Obesity was associated with several dimensions of socioeconomic position. Childhood socioeconomic disadvantage was associated with obesity independently of the various indicators of current socioeconomic position. Associations between obesity and both educational level and occupational class disappeared after adjustment for other indicators of socioeconomic position. This suggests that the variation observed in the prevalence of obesity by these key socioeconomic indicators may reflect differences in the related material resources.     

Work,Diabetes and Obesity: A Seven Year Follow-Up Study among Danish Health Care Workers

Objectives

The rise in prevalence of diabetes is alarming and research ascribes most of the increase to lifestyle. However, little knowledge exists about the influence of occupational factors on the risk for developing diabetes. This study estimates the importance of work and lifestyle as risk factors for developing diabetes mellitus among healthcare workers and explores the association of work factors and obesity, which is a risk factor for diabetes.

Methods

Questionnaire-based prospective cohort study among 7,305 health care workers followed for seven years in the Danish National Diabetes Register. We used bivariate comparisons to give an unadjusted estimate of associations, followed by adjusted survival analysis and logistic regression models to estimate the influences of potential risk factors related to job, health and lifestyle on diabetes and obesity.

Results

During seven years of follow up, 3.5% of participants developed diabetes, associated with obesity (HR  =  6.53; 95% CI 4.68–9.10), overweight (HR  =  2.89; CI 2.11–3.96) age 50–69 y (HR  =  2.27; 95% CI 1.57–3.43) and high quality of leadership (HR  =  1.60; CI 1.19–2.16). Obesity at baseline was most common among the youngest employees, and was mainly associated with developing diabetes (OR  =  3.84; CI 2.85–5.17), impaired physical capacity and physical inactivity. In the occupational setting, obesity was associated with shift work, severe musculoskeletal pain, low influence, but also by good management, fewer role conflicts and a positive work-life balance. Looking only at non-smokers, removed the influence of age and pain. However, non-smokers also had higher depression scores and more role conflicts.

Conclusions

Confirming obesity as the strongest risk factor for developing diabetes, the present study identified few occupational risk factors. However, obesity, the key risk factor for diabetes, had a more variable relation with work than did diabetes.     

The Thermic Effect of Food and Obesity: A Critical Review

DE JONGE, LILIAN, GEORGE BRAY. The thermic effect of food and obesity: A critical review. This review has examined the factors that influence the thermic effect of food (TEF) by evaluating 49 studies that have compared subjects who are obese with those who are lean. Meal size, meal composition, the nature of the previous diet, insulin resistance, physical activity, and ageing influence TEF. In the studies of individuals who are obese or lean, of those who used intravenous glucose infusions, all but one found an impaired thermic response. A total of 29 out of 49 studies of individuals of normal weight or with obesity were identified where there was no difference in age between the groups, and where the subjects who were “overweight” were clearly obese. Of these 29, 22 reported a statistically significant reduction in TEF, 3 studies were not designed to look primarily at the effect of obesity on TEF, and the other 4 may not have had sufficiently palatable meals. From this review, we conclude that the reduction of TEF in obesity is related to the degree of insulin resistance, which may be influenced by a low level of sympathetic activity.     

Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized,Double-Blind,Parallel-Group Trial

Background/Objectives

The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads.

Subjects/Methods

The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water.

Results

Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects.

Conclusions

It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01875575","term_id":"NCT01875575"}}NCT01875575     

The Validation and Clinical Implementation of BRCAplus: A Comprehensive High-Risk Breast Cancer Diagnostic Assay

Breast cancer is the most commonly diagnosed cancer in women, with 10% of disease attributed to hereditary factors. Although BRCA1 and BRCA2 account for a high percentage of hereditary cases, there are more than 25 susceptibility genes that differentially impact the risk for breast cancer. Traditionally, germline testing for breast cancer was performed by Sanger dideoxy terminator sequencing in a reflexive manner, beginning with BRCA1 and BRCA2. The introduction of next-generation sequencing (NGS) has enabled the simultaneous testing of all genes implicated in breast cancer resulting in diagnostic labs offering large, comprehensive gene panels. However, some physicians prefer to only test for those genes in which established surveillance and treatment protocol exists. The NGS based BRCAplus test utilizes a custom tiled PCR based target enrichment design and bioinformatics pipeline coupled with array comparative genomic hybridization (aCGH) to identify mutations in the six high-risk genes: BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11. Validation of the assay with 250 previously characterized samples resulted in 100% detection of 3,025 known variants and analytical specificity of 99.99%. Analysis of the clinical performance of the first 3,000 BRCAplus samples referred for testing revealed an average coverage greater than 9,000X per target base pair resulting in excellent specificity and the sensitivity to detect low level mosaicism and allele-drop out. The unique design of the assay enabled the detection of pathogenic mutations missed by previous testing. With the abundance of NGS diagnostic tests being released, it is essential that clinicians understand the advantages and limitations of different test designs.     

The Impact of Short-Term Video Games on Performance among Children with Developmental Delays: A Randomized Controlled Trial

This prospective, randomized controlled study investigated the effects of short-term interactive video game playing among children with developmental delays participating in traditional rehabilitation treatment at a rehabilitation clinic. One hundred and one boys and 46 girls with a mean age of 5.8 years (range: 3 to 12 years) were enrolled in this study. All patients were confirmed to suffer from developmental delays, and were participating in traditional rehabilitation treatment. Children participated in two periods of 4 weeks each, group A being offered intervention of eight 30-minute sessions of interactive video games in the first period, and group B in the second, in addition to the traditional rehabilitation treatment. The physical, psychosocial, and total health of the children was periodically assessed using the parent-reported Pediatric Quality of Life Inventory-Generic Core Scales (PedsQL); and the children’s upper extremity and physical function, transfer and basic mobility, sports and physical functioning, and global functioning were assessed using the Pediatric Outcomes Data Collection Instrument. Parental impact was evaluated using the PedsQL-Family Impact Module for family function, PedsQL-Health Satisfaction questionnaire for parents’ satisfaction with their children’s care and World Health Organization-Quality of Life-Brief Version for quality of life. Compared with the baseline, significant improvements of physical function were observed in both groups (5.6 ± 19.5, p = 0.013; 4.7 ± 13.8, p = 0.009) during the intervention periods. No significant improvement of psychosocial health, functional performance, or family impact was observed in children with developmental delays. Short-term interactive video game play in conjunction with traditional rehabilitation treatment improved the physical health of children with developmental delays.Trial Registration: ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02184715","term_id":"NCT02184715"}}NCT02184715