Comparison of Overall Obesity and Body Fat Distribution in Predicting Risk of Mortality

Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30–102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988–1994. During a 12‐year follow‐up (102,172 person‐years), 1,188 men and 925 women died. In multivariable‐adjusted analyses, waist‐to‐thigh ratio (WTR) in both sexes (P_trend <0.01 for both) and waist‐to‐hip ratio (WHR) in women (P_trend 0.001) were positively associated with mortality in middle‐aged adults (30–64 years), while BMI and waist circumference (WC) exhibited U‐ or J‐shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5–24.9 kg/m²) and obese (BMI ≥30.0 kg/m²) adults. In older adults (65–102 years), a higher BMI in both sexes (P_trend <0.05) and WC in men (P_trend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle‐aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.     

Longitudinal association of body mass index with lung function: The CARDIA Study

Background

Lung function at the end of life depends on its peak and subsequent decline. Because obesity is epidemic in young adulthood, we quantified age-related changes in lung function relative to body mass index (BMI).

Methods

The Coronary Artery Risk Development in Young Adults (CARDIA) study in 1985–86 (year 0) recruited 5,115 black and white men and women, aged 18–30. Spirometry testing was conducted at years 0, 2, 5 and 10. We estimated 10 year change in FVC, FEV₁ and FEV₁/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years, controlling for race, sex, smoking, asthma, physical activity, and alcohol consumption.

Measurements and Main Results

Participants with baseline BMI < 21.3 kg/m² experienced 10 year increases of 71 ml in FVC and 60 ml in FEV₁ and neither measure declined through age 38. In contrast, participants with baseline BMI ≥ 26.4 kg/m² experienced 10 year decreases of 185 ml in FVC and 64 ml in FEV₁. FEV₁/FVC increased with increasing BMI. Weight gain was also associated with lung function. Those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. In contrast, FEV₁ decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study.

Conclusion

Among healthy young adults, increasing BMI in the initially thin participants was associated with increasing then stable lung function through age 38, but there were substantial lung function losses with higher and increasing fatness. These results suggest that the obesity epidemic threatens the lung health of the general population.     

Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54–96 years from the Baltimore Longitudinal Study of Aging

Cardiorespiratory fitness (VO₂ peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO₂ peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA). Individual species of ceramide were quantified by HPLC–tandem mass spectrometry. VO₂ peak was measured by a graded treadmill test. We applied multiple regression models to test the associations between ceramide species and VO₂ peak, while adjusting for age, sex, blood pressure, serum LDL, HDL, triglycerides, and other covariates. We found that higher levels of circulating C18:0, C20:0, C24:1 ceramides and C20:0 dihydroceramides were strongly associated with lower aerobic capacity (P < 0.001, P < 0.001, P = 0.018, and P < 0.001, respectively). The associations held true for both sexes (with men having a stronger association than women, P value for sex interaction <0.05) and were unchanged after adjusting for confounders and multiple comparison correction. Interestingly, no significant association was found for C16:0, C22:0, C24:0, C26:0, and C22:1 ceramide species, C24:0 dihydroceramide, or total ceramides. Our analysis reveals that specific long‐chain ceramides strongly associate with low cardiovascular fitness in older adults and may be implicated in the pathogenesis of low fitness with aging. Longitudinal studies are needed to further validate these associations and investigate the relationship between ceramides and health outcomes.     

Adiposity and age explain most of the association between physical activity and fitness in physically active men

Background

To determine if there is an association between physical activity assessed by the short version of the International Physical Activity Questionnaire (IPAQ) and cardiorespiratory and muscular fitness.

Methodology/Principal Findings

One hundred and eighty-two young males (age range: 20–55 years) completed the short form of the IPAQ to assess physical activity. Body composition (dual-energy X-Ray absorptiometry), muscular fitness (static and dynamic muscle force and power, vertical jump height, running speed [30 m sprint], anaerobic capacity [300 m running test]) and cardiorespiratory fitness (estimated VO₂max: 20 m shuttle run test) were also determined in all subjects.Activity-related energy expenditure of moderate and vigorous intensity (EEPA_moderate and EEPA_vigorous, respectively) was inversely associated with indices of adiposity (r = −0.21 to −0.37, P<0.05). Cardiorespiratory fitness (VO₂max) was positively associated with LogEEPA_moderate (r = 0.26, P<0.05) and LogEEPA_vigorous (r = 0.27). However, no association between VO₂max with LogEEPA_moderate, LogEPPA_vigorous and LogEEPA_total was observed after adjusting for the percentage of body fat. Multiple stepwise regression analysis to predict VO₂max from LogEEPA_walking, LogEEPA_moderate, LogEEPA_vigorous, LogEEPA_total, age and percentage of body fat (%fat) showed that the %fat alone explained 62% of the variance in VO₂max and that the age added another 10%, while the other variables did not add predictive value to the model [VO₂max  = 129.6−(25.1× Log %fat) − (34.0× Log age); SEE: 4.3 ml.kg⁻¹. min⁻¹; R² = 0.72 (P<0.05)]. No positive association between muscular fitness-related variables and physical activity was observed, even after adjusting for body fat or body fat and age.

Conclusions/Significance

Adiposity and age are the strongest predictors of VO₂max in healthy men. The energy expended in moderate and vigorous physical activities is inversely associated with adiposity. Muscular fitness does not appear to be associated with physical activity as assessed by the IPAQ.     

Skeletal Muscle Metabolism and Body Fat Content in Men and Women

The purpose of the present study was to verify the relationships between indicators of body Eat content and specific characteristics of skeletal muscle in a large sample of men and women. Six skinfold thicknesses (σ6S) and maximal oxygen uptake (VO₂ max) were measured in 348 Caucasian subjects (149 women and 199 men). Fiber type proportions (type I, type IIA, and type IIB) and activity levels of marker enzymes for the Krebs cycle (malate dehydrogenase, MDH) and for the fatty acid oxidation (3-hydroxya-cyl CoA dehydrogenase, HADH) pathways were determined in vastus lateralis muscle samples. No significant correlation was found between fiber type proportions and σ6S. Significant and negative correlations were, however, obtained in both genders between the σ6S and MDH enzyme activity (r = ?0.23; p<0.01), but not between the σ6S and HADH enzyme activity. When individuals with low and high amount of subcutaneous fat but paired for VO₂max were compared, vastus lateralis of fat men exhibited the same proportion of type I fiber (38.6 ± 10.3 vs 38.5 ± 13.4 %) and HADH activity level (3.43 ± 1.05 vs. 334 ± 0.81 U/g), but had about 20% less MDH enzyme activity than vastus lateralis of leaner men (158 ± 35 vs. 198 ± 43 U/g;p<0.05). No difference was found in any of these muscle phenotypes when comparisons were made between women with low and high amount of subcutaneous fat but also paired for VO₂max. Moreover, no relations were observed between skeletal muscle fiber type proportion or metabolic markers with relative subcutaneous fat distribution. In conclusion, these results indicate that the proportion of fiber type of skeletal muscle is not a determinant of body fat content or fat distribution in men and women. However, the results of the present study suggest, at least in men, that a low oxidative capacity of skeletal muscle, undetected by muscle fiber typing, is associated with an augmented body fat content.     

Fatness but Not Fitness Relative to the Fat-Free Mass Is Related to C-Reactive Protein in 18 Year-Old Adolescents

Introduction

The interaction between fatness, fitness, and C-reactive protein (CRP) in adolescents is not well characterized but may be important to prevent low grade inflammation. The purpose of this study was to assess the relationship between adiposity, different expressions of fitness, and CRP in late adolescence using direct measures of fitness and fatness.

Methods

Anthropometric measurements were taken on 245 eighteen-year-old participants (116 girls). Fasting CRP, glucose, and insulin were measured and homeostatic model assessment (HOMA) calculated. Body composition was estimated via dual energy X-ray absorptiometry. Fitness was assessed with maximal oxygen uptake (VO₂max) during a treadmill test and also expressed relative to the fat-free mass (VO₂max_FFM).

Results

Prevalence of overweight/obesity based on body mass index (BMI) was 20.7% and 25.6% among girls and boys, respectively (p = 0.407), but 42.5% and 58.1% when based on body fat percentage (%fat, p = 0.015). Higher proportion of boys (81.3%) than girls (54.5%) were highly fit (p<0.001), but the percentage of girls with high levels of CRP was greater (12.1% vs 6.2%, p = 0.028). Adiposity, indicated with BMI, waist circumference, fat mass, android fat mass (aFM), or %fat, was positively associated with CRP independent of VO₂max (r = 0.13-0.18, p<0.05) and VO₂max_FFM (r = 0.24-0.32, p<0.001). VO₂max, was negatively associated with CRP independent only of BMI and waist circumference (r = -0.21, p = 0.001), but not %fat, fat mass or aFM (r = -0.08 to -0.12, p>0.05). VO₂max_FFM was unrelated to CRP with (r = -0.07 to -0.11, p>0.05) or without (r = -0.10, p = 0.142) adjustment for adiposity. Additional adjustment for HOMA did not change any of the relationships, although the coefficients were attenuated.

Conclusions

Fatness has a greater association with CRP than fitness in late adolescence. However, VO₂max_FFM, which is truly independent of adiposity, is unrelated to CRP, indicating that the effects of fitness might be mediated via the fatness component embedded in fitness expressed relative to body mass.     

The Association of Systemic Microvascular Changes with Lung Function and Lung Density: A Cross-Sectional Study

Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45–84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV₁) (P<0.001) and FEV₁/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV₁ (P = 0.002) but not FEV₁/FVC. Myocardial blood flow (n = 126) was associated with lower FEV₁ (P = 0.02), lower FEV₁/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.     

Regular Multicomponent Exercise Increases Physical Fitness and Muscle Protein Anabolism in Frail,Obese, Older Adults

Aging is associated with a decline in strength, endurance, balance, and mobility. Obesity worsens the age‐related impairment in physical function and often leads to frailty. The American College of Sports Medicine recommends a multicomponent (strength, endurance, flexibility, and balance) exercise program to maintain physical fitness. However, the effect of such an exercise program on physical fitness in frail, obese older adults is not known. We therefore determined the effect of a 3‐month long multicomponent exercise training program, on endurance (peak aerobic capacity (VO₂ peak)), muscle strength, muscle mass, and the rate of muscle protein synthesis (basal rate and anabolic response to feeding) in nine 65‐ to 80‐year‐old, moderately frail, obese older adults. After 3 months of training, fat mass decreased (P < 0.05) whereas fat‐free mass (FFM), appendicular lean body mass, strength, and VO₂ peak increased (all P < 0.05). Regular strength and endurance exercise increased the mixed muscle protein fractional synthesis rate (FSR) but had no effect on the feeding‐induced increase in muscle protein FSR (～0.02%/h increase from basal values both before and after exercise training; effect of feeding: P = 0.02; effect of training: P = 0.047; no interaction: P = 0.84). We conclude that: (i) a multicomponent exercise training program has beneficial effects on muscle mass and physical function and should therefore be recommended to frail, obese older adults, and (ii) regular multicomponent exercise increases the basal rate of muscle protein synthesis without affecting the magnitude of the muscle protein anabolic response to feeding.     

Racial Differences in Metabolic Predictors of Obesity among Postmenopausal Women

NICKLAS, BARBARA S., DORA M. BERMAN, DAWN C. DAVIS, C. LYNNE DOBROVOLNY, AND KAREN E. DENNIS. Racial differences in metabolic predictors of obesity among postmenopausal women. Ober Res. Objective: This study determined whether there are racial differences in resting metabolic rate (RMR), fat oxidation, and maximal oxygen consumption (VO,max) in obese [body mass index (BMI = 34±2 kg/m²)], postmenopausal (58±2 years) women. Research Methods and Procedures: Twenty black and 20 white women were matched for fat mass and lean mass (LM), as determined by dual energy X-ray absorptiometry. RMR and fat oxidation were measured by indirect calorimetry in the early morning after a 12-hour fast using the ventilated hood technique. VO₂max was measured on a treadmill during a progressive exercise test to voluntary exhaustion. Results: RMR, adjusted for differences in LM, was 5% higher in white than black women (1566±27 and 1490±26 kcal/day, respectively; p<0. 05); and fat oxidation rate was 17% higher in white than black women (87±4 and 72±3 g/day, respectively; p<0. 01). VO₂max (L/minute) was 150 mL per minute (8%) higher (p<0. 05) in white than black women. VO₂max correlated with LM in black (r = 0. 44, p = 0. 05) and white (r=0. 53, p<0. 05) women, but the intercept of the regression line was higher in white than black women (p<0. 05), with no significant difference in slopes. In a multiple regression model including race, body weight, LM, and age, LM was the only independent predictor of RMR (r² = 0. 46, p<0. 0001), whereas race was the only independent predictor of fat oxidation (r² = 0. 18,p<0. 05). The best predictors of VO,max were LM (r² = 0. 22, p<0. 05) and race (cumulative r² = 0. 30, p<0. 05). Discussion: These results show there are racial differences in metabolic predictors of obesity. Determination of whether these ethnic differences lead to, or are an effect of, obesity status or other lifestyle factors requires further study.     

Relationships between Insulin Sensitivity and Measures of Body Fat in Asymptomatic Men and Women

Objective: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (S_I) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist‐to‐hip ratio (WHR). Research Methods and Procedures: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non‐Hispanic white subjects from Rochester, MN (age 19‐60 years; 123 men and 133 women) to determine the S_I index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with S_I after sex stratification and adjustment for age. Results: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in S_I among women than among men. In men, after controlling for age, all of the predictive information of S_I was provided by waist circumference (additional R² = 0.39, p < 0.001); none of the DXA measures improved the ability to predict S_I. In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of S_I was percentage head fat (additional R² = 0.03, p < 0.001). Discussion: Equivalent increases in most measures of body fat had lesser impact on S_I in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures.     

Aerobic Fitness in Children and Young Adults with Primary Ciliary Dyskinesia

Background

Although aerobic fitness is regarded as an overall prognostic measure of morbidity and mortality, its evaluation in the chronic progressive sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and inconsistently reported. Here we assessed peak oxygen uptake (VO_2peak) in a large well-characterized cohort of PCD patients, and explored whether VO_2peak was associated with parameters of pulmonary function, self-reported physical limitations, and physical activity level.

Methods

VO_2peak, spirometry, diffusing capacity, whole-body plethysmography, and nitrogen multiple breath inert gas washout (N₂ MBW) were assessed in a cross-sectional, single-occasion study of clinically stable children and young adults with PCD. We used a questionnaire including self-reported physical limitations in everyday life or in vigorous activities, and estimation of weekly hours of strenuous physical activity. VO_2peak in PCD patients was compared with that in matched, healthy control subjects and a national reference.

Results

Forty-four PCD patients aged 6–29 years exhibited reduced VO_2peak compared to healthy controls (P<0.001) and the national reference. VO_2peak was abnormal (z-score <–1.96) in 34% of PCD patients. Spirometric values, RV/TLC, and indices of N₂ MBW were significantly abnormal, but VO_2peak only correlated with FEV₁ and DL_CO/V_A. VO_2peak correlated with complaints of moderate or significant limitations in vigorous activities (P = 0.0001), exhibited by 39% of PCD patients.

Conclusion

One-third of PCD patients exhibited substantially lower aerobic fitness than healthy subjects. Aerobic fitness correlated with FEV₁, DL_CO/V_A and self-reported complaints of limitations in vigorous physical activity. These findings are most likely explained by PCD pulmonary disease and its impact on pulmonary function and physical ability. Considering fitness as an important outcome and including regular strenuous physical activity in PCD treatment would probably altogether increase pulmonary clearance, lung function, aerobic fitness, and quality of life, and prevent lifestyle-related diseases.     

Gene promoter methylation is associated with lung function in the elderly: The normative aging study

Lung function is a strong predictor of mortality. While inflammatory markers have been associated with lung function decrease, pathways are still poorly understood and epigenetic changes may participate in lung function decline mechanisms. We studied the cross-sectional association between DNA methylation in nine inflammatory genes and lung function in a cohort of 756 elderly men living in the metropolitan area of Boston. Participants donated a blood sample for DNA methylation analysis and underwent spirometry at each visit every 3 to 5 y from 1999–2006. We used separate multivariate mixed effects regression models to study the association between each lung function measurement and DNA methylation within each gene. Decreased CRAT, F3 and TLR2 methylation was significantly associated with lower lung function. One interquartile range (IQR) decrease in DNA methylation was associated with lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁), respectively by 2.94% (p < 10^?4) and 2.47% (p < 10^?3) for F3, and by 2.10% (p < 10^?2) and 2.42% (p < 10^?3) for TLR2. Decreased IFNγ and IL6 methylation was significantly associated with better lung function. One IQR decrease in DNA methylation was associated with higher FEV₁ by 1.75% (p = 0.02) and 1.67% (p = 0.05) for IFNγ and IL6, respectively. These data demonstrate that DNA methylation may be part of the biological processes underlying the lung function decline and that IFNγ and IL6 may have ambivalent roles through activation of negative feedback.     

CT Air Trapping Is Independently Associated with Lung Function Reduction over Time

Purpose

We aimed to study the association between lung function decline and quantitative computed tomography (CT) air trapping.

Materials and Methods

Current and former heavy smokers in a lung cancer screening trial underwent volumetric low-dose CT in inspiration and expiration. Spirometry was obtained at baseline and after 3 years. The expiratory to inspiratory ratio of mean lung density (E/I-ratio_MLD) was used to quantify air trapping. CT emphysema was defined as voxels in inspiratory CT below −950 Hounsfield Unit. Linear mixed modeling was used to determine the association between CT air trapping and lung function.

Results

We included 985 subjects with a mean age of 61.3 years. Independent of CT emphysema, CT air trapping was significantly associated with a reduction in forced expiratory volume in one second (FEV₁) and the ratio of FEV₁ over the forced vital capacity (FEV₁/FVC); FEV₁ declines with 33 mL per percent increase in CT air trapping, while FEV₁/FVC declines 0.58% per percent increase (both p<0.001). CT air trapping further elicits accelerated loss of FEV₁/FVC (additional 0.24% reduction per percent increase; p = 0.014).

Conclusion

In a lung cancer screening cohort, quantitatively assessed air trapping on low-dose CT is independently associated with reduced lung function and accelerated decline of FEV₁/FVC.     

A comparison of adiposity measures as predictors of all-cause mortality: the Melbourne Collaborative Cohort Study

Objective: Our goal was to examine five different measures of adiposity as predictors of all‐cause mortality. Research Methods and Procedures: Subjects were 16,969 men and 24,344 women enrolled between 1990 and 1994 in the Melbourne Collaborative Cohort Study (27 to 75 years of age). There were 2822 deaths over a median follow‐up period of 11 years. BMI, waist circumference, and waist‐to‐hip ratio were obtained from direct anthropometric measurements. Fat mass and percentage fat were estimated by bioelectric impedance analysis. Results: Comparing the top quintile with the second quintile, for men there was an increased risk of between 20% and 30% for all‐cause mortality associated with each of the anthropometric measures. For women, there was an increased risk of 30% (95% confidence interval for hazard ratio, 1.1–1.6) observed for waist circumference and 50% (1.2–1.8) for waist‐to‐hip ratio, but little or no increased risk for BMI, fat mass, and percentage fat. Waist‐to‐hip ratio was positively and monotonically associated with all‐cause mortality for both men and women. There was a linear association between waist circumference and all‐cause mortality for men, whereas a U‐shaped association was observed for women. Discussion: Measures of central adiposity were better predictors of mortality in women in the Melbourne Collaborative Cohort Study compared with measures of overall adiposity. We recommend measuring waist and hip circumferences in population studies investigating the risk of all‐cause mortality associated with obesity. The use of additional measures such as bioelectric impedance is not justified for this outcome.     

Larger Thigh and Hip Circumferences Are Associated with Better Glucose Tolerance: The Hoorn Study

Objective: A higher waist‐to‐hip ratio, which can be due to a higher waist circumference, a lower hip circumference, or both, is associated with higher glucose levels and incident diabetes. A lower hip circumference could reflect either lower fat mass or lower muscle mass. Muscle mass might be better reflected by thigh circumference. The aim of this study was to investigate the contributions of thigh and hip circumferences, independent of waist circumference, to measures of glucose metabolism. Research Methods and Procedures: For this cross‐sectional study we used baseline data from the Hoorn Study, a population‐based cohort study of glucose tolerance among 2484 men and women aged 50 to 75. Glucose tolerance was assessed by a 75‐g oral glucose tolerance test; hemoglobin A_1c and fasting insulin were also measured. Anthropometric measurements included body mass index (BMI) and waist, hip, and thigh circumferences. Results: Stratified analyses and multiple linear regression showed that after adjustment for age, BMI, and waist circumference, thigh circumference was negatively associated with markers of glucose metabolism in women, but not in men. Standardized β values in women were ?0.164 for fasting, ?0.206 for post‐load glucose, ?0.190 for hemoglobin A_1c (all p < 0.001), and ?0.065 for natural log insulin levels (p = 0.061). Hip circumference was negatively associated with markers of glucose metabolism in both sexes (standardized betas ranging from ?0.093 to ?0.296, p < 0.05) except for insulin in men. Waist circumference was positively associated with glucose metabolism. Discussion: Thigh circumference in women and hip circumference in both sexes are negatively associated with markers of glucose metabolism independently of the waist circumference, BMI, and age. Both fat and muscle tissues may contribute to these associations.     

Occupation and three-year incidence of respiratory symptoms and lung function decline: the ARIC Study

Background

Specific occupations are associated with adverse respiratory health. Inhalation exposures encountered in these jobs may place workers at risk of new-onset respiratory disease.

Methods

We analyzed data from 8,967 participants from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort study. Participants included in this analysis were free of chronic cough and phlegm, wheezing, asthma, chronic bronchitis, emphysema, and other chronic lung conditions at the baseline examination, when they were aged 45-64 years. Using data collected in the baseline and first follow-up examination, we evaluated associations between occupation and the three-year incidence of cough, phlegm, wheezing, and airway obstruction and changes in forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) measured by spirometry. All associations were adjusted for age, cigarettes per day, race, smoking status, and study center.

Results

During the approximately three-year follow-up, the percentage of participants developing chronic cough was 3%; chronic phlegm, 3%; wheezing, 3%; and airway obstruction, defined as FEV₁ < lower limit of normal (LLN) and FEV₁/FVC < LLN, 2%. The average annual declines in FEV₁ and FVC were 56 mL and 66 mL, respectively, among men and 40 mL and 52 mL, respectively, among women. Relative to a referent category of managerial and administrative support occupations, elevated risks of new-onset chronic cough and chronic phlegm were observed for mechanics and repairers (chronic cough: RR: 1.81, 95% CI: 1.02, 3.21; chronic phlegm: RR: 2.10, 95% CI: 1.23, 3.57) and cleaning and building service workers (chronic cough: RR: 1.85, 95% CI: 1.01, 3.37; chronic phlegm: RR: 2.28, 95% CI: 1.27, 4.08). Despite the elevated risk of new-onset symptoms, employment in cleaning and building services was associated with attenuated lung function decline, particularly among men, who averaged annual declines in FEV₁ and FVC of 14 mL and 23 mL, respectively, less than the declines observed in the referent population.

Conclusions

Employment in mechanic and repair jobs and cleaning and building service occupations are associated with increased incidence of respiratory symptoms. Specific occupations affect the respiratory health of adults without pre-existing respiratory health symptoms and conditions, though long-term health consequences of inhalation exposures in these jobs remain largely unexplored.     

ADRB2 Haplotype Is Associated With Glucose Tolerance and Insulin Sensitivity in Obese Postmenopausal Women

The β₂‐adrenergic receptor (ADRB2) mediates obesity, cardiorespiratory fitness, and insulin resistance. We examined the hypothesis that ADRB2 Arg16Gly‐Gln27Glu haplotype is associated with body composition, glucose tolerance, and insulin sensitivity in obese, postmenopausal women. Obese (>35% body fat), postmenopausal (age 45–75 years) women (n = 123) underwent genotyping, dual‐energy X‐ray absorptiometry, and computed tomography scans, exercise testing (VO_2max), 2‐h oral glucose tolerance tests (OGTTs), and hyperinsulinemic‐euglycemic clamps (80 mU/m²/min). Analysis of covariance (ANCOVA) tested for differences among haplotypes, with race, % body fat, and VO_2max as covariates. We found that ADRB2 haplotype was independently associated with % body fat, abdominal fat distribution, VO_2max, insulin sensitivity (M/ΔInsulin), and glucose tolerance (ANOVA, P < 0.05 for all). Women homozygous for Gly16–Gln27 haplotype had the highest % body fat (52.7 ± 1.9%), high abdominal fat, low M/ΔInsulin (0.49 ± 0.08 mg/kg/min/pmol/l/10²), and impaired glucose tolerance (IGT) during an OGTT (G₁₂₀ = 10.2 ± 0.9 mmol/l). Women homozygous for Gly16–Glu27 haplotype also had low M/ΔInsulin (0.51 ± 0.05 mg/kg/min/pmol/l/10²) and IGT (G₁₂₀ = 8.2 ± 0.7 mmol/l). Subjects with Arg16–Gln27/Gly16–Gln27 haplotype combination had the highest VO_2max (1.84 ± 0.07 l/min) and M/ΔInsulin (0.7 ± 0.04 mg/kg/min/pmol/l/10²), and normal glucose tolerance (G₁₂₀ = 6.4 ± 0.4 mmol/l), despite being obese. These data show associations of the ADRB2 Arg16Gly‐Gln27Glu haplotype with VO_2max and body composition, and an independent association with glucose metabolism, which persists after controlling for body composition and fitness. This suggests that ADRB2 haplotypes may mediate insulin action, glucose tolerance, and potentially risk for type 2 diabetes mellitus (T2DM) in obese, postmenopausal women.     

Genetic variants associated with lung function: the long life family study

Background

Reduced forced expiratory volume in 1 second (FEV₁) and the ratio of FEV₁ to forced vital capacity (FVC) are strong predictors of mortality and lung function is higher among individuals with exceptional longevity. However, genetic factors associated with lung function in individuals with exceptional longevity have not been identified.

Method

We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia. The association between SNPs and FEV₁ and FEV₁/FVC was analyzed using a linear mixed effects model adjusted for age, age², sex, height, field center, ancestry principal components and kinship structure to adjust for family relationships separately for ever smokers and never smokers. In the linkage analysis, we used the residuals of the FEV₁ and FEV₁/FVC, adjusted for age, sex, height, ancestry principal components (PCs), smoking status, pack-years, and field center.

Results

We identified nine SNPs in strong linkage disequilibrium in the CYP2U1 gene to be associated with FEV₁ and a novel SNP (rs889574) associated with FEV₁/FVC, none of which were replicated in the CHARGE/SpiroMeta consortia. Using linkage analysis, we identified a novel linkage peak in chromosome 2 at 219 cM for FEV₁/FVC (LOD: 3.29) and confirmed a previously reported linkage peak in chromosome 6 at 28 cM (LOD: 3.33) for FEV₁.

Conclusion

Future studies need to identify the rare genetic variants underlying the linkage peak in chromosome 6 for FEV₁.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0134-x) contains supplementary material, which is available to authorized users.     

Association between muscular strength and metabolic risk in Japanese women, but not in men

We examined whether cardiorespiratory fitness (maximal oxygen uptake, VO(2)max) and muscular strength (grip strength) are associated with individual and clustered metabolic risk factors independently of abdominal adiposity in Japanese men (n=110) and women (n=110) aged 20-69 years. Blood pressure, triglycerides (TG), HDL cholesterol, and fasting plasma glucose (FPG) were assessed and metabolic risk score was calculated, which is the sum of the z scores for each individual risk factor. Waist circumference was measured and the area of visceral fat was assessed by MRI. Multiple linear regression analysis revealed that VO(2)max was inversely associated with TG in men (p<0.05) and grip strength was negatively associated with FPG and metabolic risk score in women (p<0.001 and p<0.05, respectively), independently of waist circumference. Adjusting for visceral fat instead of waist circumference, similar results were obtained in women (p<0.01 and p<0.05, respectively), but the association between VO(2)max and TG in men was attenuated to nonsignificant. This cross-sectional study demonstrates that muscular strength is inversely associated with plasma glucose levels and clustered metabolic risk factors independently of abdominal adiposity in Japanese women, but not in men.     

The Association of Normal Range Glycated Hemoglobin with Restrictive Lung Pattern in the General Population

Glycated hemoglobin (HbA1c) is an important diagnostic indicator of diabetes mellitus, and some authors have argued that it is related to impaired lung function in the diabetic population. However, there was rare study for association between lung function and HbA1c in the non-diabetic population. We investigated whether HbA1c below the diagnostic threshold is related to deficits in lung function. We analyzed biochemical and spirometry data from a nation-wide, population-based, case-control study (the KNHANES IV and V). Eligible as cases were all native Koreans aged 40 years or more with no medical illness. A total of 3670 participants were divided into 4 groups according to HbA1c (%) as follows: Group I (n = 842), ≥ 4.0 and ≤ 5.3; Group II (n = 833), > 5.3 and ≤ 5.5; Group III (n = 898), > 5.5 and ≤ 5.7; and Group IV (n = 1097), > 5.7 and ≤ 6.4. Group I had the greatest forced vital capacity (FVC, 96.3 ± 0.5% pred, P < 0.0001), forced expiratory volume per second (FEV₁, 93.8 ± 0.5% pred, P < 0.0001) and FEV₁/FVC (0.792 ± 0.003, P < 0.0001) compared with the other groups. Linear regression showed that HbA1c was closely related to FVC (β = -6.972154, P < 0.0001) and FEV₁ (β = -5.591589, P < 0.0001), but not to FEV₁/FVC. Logistic regression analysis revealed a significant association between HbA1c and a restrictive spirometric pattern (FVC < 80% pred., FEV₁/FVC ≥ 0.70; OR = 3.772, 95% CI = 1.234-11.53), indicating that elevated HbA1c is closely associated with lung impairment in the non-diabetic population. In the healthy population, relatively high HbA1c level is associated with decrements of FVC and FEV₁ and may be a reliable predictor of poor lung function, especially the restrictive pattern.