SD Increase In Body Mass Index Research Articles

Body Mass Index and the Risk of Rheumatic Disease: Linear and Nonlinear Mendelian Randomization Analyses.

Although the association between obesity and risk of rheumatic disease is well established, the precise causal relation has not been conclusively proven. Here, we estimate the causal effect of body mass index (BMI) on the risk of developing 5 different rheumatic diseases. Linear and nonlinear mendelian randomization (MR) were used to estimate the effect of BMI on risk of rheumatic disease, and sex-specific effects were identified. Analyses were performed in 361,952 participants from the UK Biobank cohort for 5 rheumatic diseases: rheumatoid arthritis (n=8,381 cases), osteoarthritis (n=87,430), psoriatic arthropathy (n=933), gout (n=13,638), and inflammatory spondylitis (n=4,328). Using linear MR, we found that 1 SD increase in BMI increases the incidence rate for rheumatoid arthritis (incidence rate ratio [IRR] 1.52 [95% confidence interval (95% CI) 1.36-1.69]), osteoarthritis (IRR 1.49 [95% CI 1.43-1.55]), psoriatic arthropathy (IRR 1.80 [95% CI 1.31-2.48]), gout (IRR 1.73 [95% CI 1.56-1.92]), and inflammatory spondylitis (IRR 1.34 [95% CI 1.14-1.57]) in all individuals. BMI was found to be a stronger risk factor in women compared to men for psoriatic arthropathy (P for sex interaction=3.3 × 10-4 ) and gout (P for sex interaction=4.3 × 10-3 ), and the effect on osteoarthritis was stronger in premenopausal compared to postmenopausal women (P = 1.8 × 10-3 ). Nonlinear effects of BMI were identified for osteoarthritis and gout in men, and for gout in women. The nonlinearity for gout was also more extreme in men compared to women (P = 0.03). Higher BMI causes an increased risk for rheumatic disease, an effect that is more pronounced in women for both gout and psoriatic arthropathy. The novel sex- and BMI-specific causal effects identified here provide further insight into rheumatic disease etiology and mark an important step toward personalized medicine.

Surrogate Adiposity Markers and Mortality

Body mass index (BMI) is an easily obtained adiposity surrogate. However, there is variability in body composition and adipose tissue distribution between individuals with the same BMI, and there is controversy regarding the BMI associated with the lowest mortality risk. To evaluate which of BMI, fat mass index (FMI), and waist-to-hip (WHR) has the strongest and most consistent association with mortality. This cohort study used incident deaths from the UK Biobank (UKB; 2006-2022), which includes data from 22 clinical assessment centers across the United Kingdom. UKB British participants of British White ancestry (N = 387 672) were partitioned into a discovery cohort (n = 337 078) and validation cohort (n = 50 594), with the latter consisting of 25 297 deaths and 25 297 controls. The discovery cohort was used to derive genetically determined adiposity measures while the validation cohort was used for analyses. Exposure-outcome associations were analyzed through observational and mendelian randomization (MR) analyses. BMI, FMI, and WHR. All-cause and cause-specific (cancer, cardiovascular disease [CVD], respiratory disease, or other causes) mortality. There were 387 672 and 50 594 participants in our observational (mean [SD] age, 56.9 [8.0] years; 177 340 [45.9%] male, 210 332 [54.2%], female), and MR (mean [SD] age, 61.6 [6.2] years; 30 031 [59.3%] male, 20 563 [40.6%], female) analyses, respectively. Associations between measured BMI and FMI with all-cause mortality were J-shaped, whereas the association of WHR with all-cause mortality was linear using the hazard ratio (HR) scale (HR per SD increase of WHR, 1.41 [95% CI, 1.38-1.43]). Genetically determined WHR had a stronger association with all-cause mortality than BMI (odds ratio [OR] per SD increase of WHR, 1.51 [95% CI, 1.32-1.72]; OR per SD increase of BMI, 1.29 [95% CI, 1.20-1.38]; P for heterogeneity = .02). This association was stronger in male than female participants (OR, 1.89 [95% CI, 1.54-2.32]; P for heterogeneity = .01). Unlike BMI or FMI, the genetically determined WHR-all-cause mortality association was consistent irrespective of observed BMI. In this cohort study, WHR had the strongest and most consistent association with mortality irrespective of BMI. Clinical recommendations should consider focusing on adiposity distribution compared with mass.

Association of Body Mass Index With Clinical Features and Outcomes in Adults With Fontan Palliation.

Background With improving survival of patients with single ventricle physiology who underwent Fontan palliation, there is also an increase in the prevalence of overweight and obesity in these patients. This tertiary care single-center study aims to determine the association of body mass index (BMI) with the clinical characteristics and outcomes in adults with Fontan. Methods and Results Adult patients (aged ≥18 years) with Fontan who were managed at a single tertiary care center between January 1, 2000, and July 1, 2019, and had BMI data available were identified via retrospective review of medical records. Univariate and multivariable (after adjusting for age, sex, functional class, and type of Fontan) linear and logistic regression, as appropriate, were utilized to evaluate associations between BMI and diagnostic testing and clinical outcomes. A total of 163 adult patients with Fontan were included (mean age, 29.9±9.08 years), with a mean BMI of 24.2±5.21 kg/m2 (37.4% of patients had BMI ≥25 kg/m2). Echocardiography data were available for 95.7% of patients, exercise testing for 39.3% of patients, and catheterization for 53.7% of patients. Each SD increase in BMI was significantly associated with decreased peak oxygen consumption (P=0.010) on univariate analysis and with increased Fontan pressure (P=0.035) and pulmonary capillary wedge pressure (P=0.037) on multivariable analysis. In addition, BMI ≥25 kg/m2 was independently associated with heart failure hospitalization (adjusted odds ratio [AOR], 10.2; 95% CI, 2.79-37.1 [P<0.001]) and thromboembolic complications (AOR, 2.79; 95% CI, 1.11-6.97 [P=0.029]). Conclusions Elevated BMI is associated with poor hemodynamics and worse clinical outcomes in adult patients with Fontan. Whether elevated BMI is the cause or consequence of poor clinical outcomes needs to be further established.

Associations of relative fat mass, a new index of adiposity, with type-2 diabetes in the general population

BackgroundRelative fat mass (RFM) is a novel sex-specific anthropometric equation (based on height and waist measurements) to estimate whole-body fat percentage. ObjectiveTo examine associations of RFM with incident type-2 diabetes (T2D), and to benchmark its performance against body-mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). MethodsThis prospective longitudinal study included data from three Dutch community-based cohorts free of baseline diabetes. First, we examined data from the PREVEND cohort (median age and follow-up duration: 48.0 and 12.5 years, respectively) using Cox regression models. Validation was performed in the Lifelines (median age and follow-up duration: 45.5 and 3.8 years, respectively) and Rotterdam (median age and follow-up duration: 68.0 and 13.9 years, respectively) cohorts. ResultsAmong 7961 PREVEND participants, 522 (6.6%) developed T2D. In a multivariable model, all adiposity indices were significantly associated with incident T2D (Pall<0.001). While 1 SD increase in BMI, WC and WHR were associated with 68%, 77% and 61% increased risk of developing T2D [Hazard ratio (HR)BMI: 1.68 (95%CI: 1.57-1.80), HRWC: 1.77 (95% CI: 1.63-1.92) and HRWHR: 1.61 (95%CI: 1.48-1.75)], an equivalent increase in RFM was associated with 119% increased risk [HR: 2.19 (95%CI: 1.96-2.44)]. RFM was associated with incident T2D across all age groups, with the largest effect size in the youngest (<40 years) age category [HR: 2.90 (95%CI: 2.15-3.92)]. Results were broadly similar in Lifelines (n = 93,870) and Rotterdam (n = 5279) cohorts. ConclusionsRFM is strongly associated with new-onset T2D and displays the potential to be used in the general practice setting to estimate the risk of future diabetes.

Genetic liability to obesity and peptic ulcer disease: a Mendelian randomization study

BackgroundEpidemiological evidence relating obesity to peptic ulcer disease (PUD) has been mixed. Here we sought to determine the causality in the association of obesity with PUD risk using the Mendelian randomization (MR) approach.MethodsThis study was based on summary-level data for body mass index (BMI), waist-to-hip ratio (WHR), and PUD derived from large genome-wide association studies (GWASs). Single nucleotide polymorphisms significantly associated with BMI and WHR (P < 5 × 10–8) were leveraged as instrumental variables. Causal estimates were pooled using several meta-analysis methods. In addition, multivariable MR was employed to account for covariation between BMI and WHR, as well as to explore potential mediators.ResultsGenetically predicted higher BMI has a causal effect on PUD, with an OR of 1.34 per SD increase in BMI (~ 4.8 kg/m2) (P = 9.72 × 10–16). Likewise, there was a 35% higher risk of PUD (P = 2.35 × 10–10) for each SD increase in WHR (0.09 ratio). Complementary analyses returned consistent results. Multivariable MR demonstrated that adjustment for WHR largely attenuated the BMI-PUD association. However, the causal association of WHR with PUD risk survived adjustment for BMI. Both the associations remained robust upon adjustment for several traditional risk factors. Replication analyses using different instrumental variants further strengthened the causal inference. Besides, we found no evidence for the causal association in the reverse analyses from PUD to BMI/WHR.ConclusionsThis MR study revealed that obesity (notably abdominal obesity) is causally associated with higher PUD risk. Programs aimed at weight loss may represent therapeutic opportunities for PUD.

Body Mass Index and Risk of Diabetic Nephropathy: A Mendelian Randomization Study.

The associations of obesity and diabetic nephropathy (DN) in type 2 diabetes are inconsistent in observational studies, and causality remains unclear. To explore the causal effect of body mass index (BMI) on DN, estimated glomerular filtration rate (eGFR), and proteinuria in type 2 diabetes by a 2-sample Mendelian randomization (MR) analysis. A total of 56 genetic variants were selected as instrumental variables for BMI in 158 284 participants from BioBank Japan, and their effects on DN risk, eGFR, and proteinuria were estimated in 3972 individuals with type 2 diabetes. Then, sex-stratified MR analysis was performed between BMI and DN. We selected generalized summary MR analysis as the primary method and 6 other robust methods to test MR assumptions. One SD increase in BMI was causally associated with higher DN risk [odds ratio (OR) 3.76, 95% CI 1.88-7.53, P < 0.001] and lower eGFR level (OR 0.71, 95% CI 0.59-0.86, P < 0.001). However, BMI was not causally associated with proteinuria (P = 0.22). Sex-stratified analyses indicated the causal effect of BMI on DN was stronger in women (OR 14.81, 95% CI 2.67-82.05, P = 0.002) than in men (OR 3.48, 95% CI 1.18-10.27, P = 0.02). Sensitivity analyses did not show evidence for violation of the MR assumptions. Genetic evidence showed that higher BMI levels were causally associated with increased risk of DN and decreased eGFR levels. Moreover, the increase in BMI level had a greater impact on DN risk in women.

Association of anthropometric indices of obesity with hypertension among public employees in northern Ethiopia: findings from a cross-sectional survey

ObjectivesThe burden of hypertension is increasing in low-income countries, including Ethiopia. Obesity is widely known to be associated with hypertension, but different anthropometric indices of obesity might differ in association...

Do the associations of body mass index and waist circumference with back pain change as people age? 32 years of follow-up in a British birth cohort

ObjectivesTo investigate whether cross-sectional and longitudinal associations of body mass index (BMI) and waist circumference (WC) with back pain change with age and extend into later life.DesignBritish birth cohort study.SettingEngland,...

Body size, body composition and endometrial cancer risk among postmenopausal women in UK Biobank.

Previous studies on the association of adiposity with endometrial cancer risk have mostly used body mass index (BMI) as the main exposure of interest. Whether more precise measures of body fat, such as body fat percentage and fat mass estimated by bioimpedance analyses, are better indicators of risk than BMI is unknown. The role of central adiposity and fat-free mass in endometrial cancer development remains unclear. We used Cox regression models to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the associations of various measures of body size/composition with the risk of endometrial cancer among 135 110 postmenopausal women enrolled in UK Biobank. During a mean follow up of 6.8 years, 706 endometrial cancers were diagnosed, with a mean age at diagnosis of 65.5 years. The HRs (95% CIs) for endometrial cancer per 1 SD increase in BMI, body fat percentage and fat mass were broadly comparable, being 1.71 (1.61-1.82), 1.92 (1.75-2.11) and 1.73 (1.63-1.85), respectively. There was an indication of positive association between central adiposity, as reflected by waist circumference (HRper 1-SD increase = 1.08, 95% CI: 1.00-1.17) and waist to hip ratio (HRper 1-SD increase = 1.13, 95% CI: 1.01-1.26), and endometrial cancer risk after accounting for BMI. Fat-free mass was not an independent predictor of risk in this cohort. These findings suggest that body fat percentage and fat mass are not better indicators of endometrial cancer risk than BMI. Further studies are needed to establish whether central adiposity contributes to risk beyond overall adiposity.

Sex and area differences in the association between adiposity and lipid profile in Malawi

BackgroundEvidence from high-income countries shows that higher adiposity results in an adverse lipid profile, but it is unclear whether this association is similar in Sub-Saharan African (SSA) populations. This study...

Birthweight, lifetime body-mass Index, and physical function in mid-adulthood: evidence from a nationwide birth cohort study

BackgroundPhysical functioning (PF) from mid-adulthood is important for maintaining independence and is linked to better health outcomes. Studies have linked obesity to poor PF; however, they have typically been cross-sectional, limited to two timepoints, or relied on retrospectively recalled height and weight. We aimed to establish associations between physical functioning at age 50 years and birthweight and body-mass index (BMI) across the life-course; BMI gains at specific life stages; and duration of obesity. MethodsThe 1958 birth cohort includes all individuals born in 1 week, in March, 1958, across Britain. BMI was calculated (4173 males, 4501 females) using height and weight measured at school (ages 7, 11, 16 years) or in participants' homes (33, 45) or were self-reported (23, 50). Primary outcome (required to be included in this study) was PF at 50 years, assessed via postal questionnaire with the validated PF subscale of the Short Form 36 Health Survey; the lowest sex-specific tenth percentile were defined as having poor PF. Missing data were imputed via multiple imputation. Associations were examined with logistic regression, and adjusted for social class, education, and health behaviours. Ethics approval and informed consent was obtained from participants at various ages. For the 50 year survey, ethics approval was provided by the London Multi-centre Research Ethics Committee (ref 08/H0718/29). FindingsBirthweight was not associated with PF. BMI at all ages from 11 years was associated with poor PF (eg, in males, adjusted odds ratio [OR] for poor PF per SD increase in BMI was 1·13 (95% CI 1·02–1.25, p=0·018) at 11 years and 1·34 (1·22–1·47, p<0·0001) at 50 years. BMI gains from adolescence were related to poor PF (eg, for females, adjusted OR per SD increase in BMI was 1·28 [1·13–1·46, p<0·0001] at 16–23 years and 1·36 [1·11–1·65, p<0·0001] at 45–50 years. Longer duration of obesity was associated with poor PF. For example, in males adjusted OR was 2·32 (1·26–4·29, p=0·007) for childhood obesity onset and 1·50 (1·16–1·96, p=0·002) for mid-adulthood obesity onset (vs never obese, ptrend<0·001). InterpretationStudy strengths include the large nationally representative cohort followed from birth and prospective measures of BMI and PF, though PF was self-reported. BMI and BMI gains from adolescence were associated with mid-adult PF. A particularly novel finding relates to duration of obesity, with earlier obesity onset associated with increased risk of poor PF, highlighting the importance of maintaining a healthy BMI from early life to mitigate the risk of poor PF in mid-adulthood. FundingDepartment of Health Policy Research Programme through the Public Health Research Consortium.

Body mass index, waist circumference, body fat mass, and risk of developing hypertension in normal-weight children and adolescents

Background and aimsWe prospectively examined the association between three adiposity indices, including body mass index (BMI), waist circumference (WC), and percentage of body fat (PBF), and risk of hypertension in normal-weight Chinese children. Methods and resultsThe current study included 1526 (713 boys and 813 girls) normal-weight Chinese children (age 6–14 years old), who were free of hypertension at baseline (2014). Heights, body weight, WC, and PBF (estimated by bioelectrical impedance analysis) were measured at the baseline. Blood pressure was repeatedly measured in 2014, 2015 and 2016. Hypertension was defined as either high systolic blood pressure and/or high diastolic blood pressure, according to age- and sex-specific 95th percentile for Chinese children. We used Cox proportional hazards model to calculate the association between exposures and hypertension. We identified 88 incident hypertension cases during two years of follow up. High BMI was associated with high risk of developing hypertension after adjusting for potential confounders. The adjusted hazard ratio for hypertension was 2.88 (95% CI: 1.24, 6.69) comparing two extreme BMI quartiles. Each SD increase of BMI (≈1.85 kg/m2) was associated with a 32% higher likelihood to developing hypertension (Hazard ratio = 1.32; 95% CI: 1.003, 1.73). In contrast, we did not find significant associations between WC or PBF and higher hypertension risk (p-trend >0.2 for both). ConclusionHigh BMI, but not WC and PBF, was associated with high risk of hypertension in normal-weight Chinese children.

Emerging Risk Factors for Stroke: What Have We Learned From Mendelian Randomization Studies?

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Paradoxical Relationship Between Body Mass Index and Thyroid Hormone Levels: A Study Using Mendelian Randomization.

Free T3 (FT3) has been positively associated with body mass index (BMI) in cross-sectional studies in healthy individuals. This is difficult to reconcile with clinical findings in pathological thyroid dysfunction. We aimed to investigate whether childhood adiposity influences FT3 levels. Mendelian randomization using genetic variants robustly associated with BMI. Avon Longitudinal Study of Parents and Children, a population-based birth cohort. A total of 3014 children who had thyroid function measured at age 7, who also underwent dual x-ray absorptiometry scans at ages 9.9 and 15.5 years and have genetic data available. FT3. Observationally at age 7 years, BMI was positively associated with FT3: β-standardized (β-[std]) = 0.12 (95% confidence interval [CI]: 0.08, 0.16), P = 4.02 × 10(-10); whereas FT4 was negatively associated with BMI: β-(std) = -0.08 (95% CI: -0.12, -0.04), P = 3.00 × 10(-5). These differences persisted after adjustment for age, sex, and early life environment. Genetic analysis indicated 1 allele change in BMI allelic score was associated with a 0.04 (95% CI: 0.03, 0.04) SD increase in BMI (P = 6.41 × 10(-17)). At age 7, a genetically determined increase in BMI of 1.89 kg/m(2) was associated with a 0.22 pmol/L (95% CI: 0.07, 0.36) increase in FT3 (P = .004) but no substantial change in FT4 0.01 mmol/L, (95% CI: -0.37, 0.40), P = .96. Our analysis shows that children with a genetically higher BMI had higher FT3 but not FT4 levels, indicating that higher BMI/fat mass has a causal role in increasing FT3 levels. This may explain the paradoxical associations observed in observational analyses. Given rising childhood obesity levels, this relationship merits closer scrutiny.

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.

Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22,193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

Body Mass Index From Age 15 Years Onwards and Muscle Mass, Strength, and Quality in Early Old Age: Findings From the MRC National Survey of Health and Development

Background.As more people live more of their lives obese, it is unclear what impact this will have on muscle mass, strength, and quality. We aimed to examine the associations of body mass index (BMI) from age 15 years onwards with low muscle mass, strength, and quality in early old age.Methods.A total of 1,511 men and women from a British birth cohort study with BMI measured at 15, 20, 26, 36, 43, 53, and 60–64 years and dual-energy x-ray absorptiometry scans at 60–64 years were included. Four binary outcomes identified those in the bottom sex-specific 20% of (a) appendicular lean mass (ALM) index (kilogram per square meter), (b) ALM residuals (derived from sex-specific models in which ALM (kilogram) = β0 + β1 height [meter] + β2 fat mass [kilogram]), (c) grip strength (kilogram), (d) muscle quality (grip strength [kilogram]/arm lean mass [kilogram]). Associations of BMI with each outcome were tested.Results.Higher BMI from age 15 years was associated with lower odds of low ALM but higher odds of low muscle quality (per 1 SD increase in BMI at 36 years, odds ratio of low ALM residuals = 0.50 [95% CI: 0.43, 0.59], and muscle quality = 1.50 [1.29, 1.75]). Greater gains in BMI were associated with lower odds of low ALM index but higher odds of low muscle quality. BMI was not associated with grip strength.Conclusions.Given increases in the global prevalence of obesity, cross-cohort comparisons of sarcopenia need to consider our findings that greater gains in BMI are associated with higher muscle mass but not with grip strength and therefore with lower muscle quality.

Association of General and Central Obesity and Atopic and Nonatopic Asthma in US Adults

Objective. To examine the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with the prevalence of asthma by atopic status and sex using nationally representative data in the US. Methods. The National Health and Nutrition Examination Survey 2005–2006 data were analyzed using areas under the receiver operating characteristic (ROC) curves (AUCs) and multivariate logistic regression models. Results. Women had higher AUCs (0.59–0.64) than men (0.50–0.58) across anthropometric indices and asthma outcomes. After controlling for sociodemographic characteristics and smoking status, only WHtR was positively associated with atopic asthma in both sexes (odds ratio per 1 SD [95% confidence interval]: men, 1.018 [1.004, 1.032], p = .01; women, 1.018 [1.006, 1.030], p = .003), and the associations persisted after further adjustment of BMI. Only in women was nonatopic asthma significantly associated with every 1 SD increase of BMI (odds ratio [95% confidence interval]: 1.018 [1.006, 1.030], p = .003), WC (1.018 [1.006, 1.030], p = .004), and WHtR (1.016 [1.004, 1.028], p = .008). Conclusions. Using US national data, this study adds to the emerging evidence suggesting two possible distinct phenotypes: (1) obese men and women with atopic asthma and (2) obese women with nonatopic asthma. The mechanistic and therapeutic implications of these findings warrant further investigation.

No association between gain in body mass index across the life course and midlife cognitive function and cognitive reserve—The 1946 British birth cohort study

BackgroundThe association between lifelong body mass index (BMI) and cognitive function has not been comprehensively studied.MethodsIn more than 2000 men and women born in 1946, we tested associations between BMI gain at 15, 20, 26, 36, 43, and 53 years with respect to the previous measure (gain at age 15 years with respect to BMI at age 11 years), and semantic fluency (animal naming) and cognitive reserve (the National Adult Reading Test) at age 53 years, and verbal memory (word list recall) and speed/concentration (letter cancellation) at ages 43 and 53 years. Measures of BMI gain were adjusted in stages for childhood intelligence, education, socioeconomic position (SEP), lifestyle, and vascular risk factors.ResultsIndependent of childhood intelligence, BMI gain between ages 26 and 36 years was associated with lower memory scores (β per SD increase in BMI in men = −0.11; 95% confidence interval [CI]: −0.19, −0.02), verbal fluency (β in women = −0.11; 95% CI: −0.20, −0.02), and lower National Adult Reading Test score (β in women = −0.08; 95% CI: −0.15, −0.01), but not with speed/concentration (β in men = 0.02; 95% CI: −0.11, 0.07). Associations were largely explained by educational attainment and SEP (P ≥ .10). However, BMI gain at 53 years in men was independently associated with better memory (β = 0.12; 95% CI: 0.03, 0.22), and both underweight (β = −1.54; 95% CI: −2.52, −0.57) and obese (β = −0.30; 95% CI: −2.52, −0.57) women at 53 years had significantly lower memory scores.ConclusionThe adverse effect of higher BMI gain on midlife cognitive function and cognitive reserve is independent of childhood intelligence but not of education and SEP. The independent association between greater BMI gain in midlife and better cognitive function deserves further investigation.

The relation between adiposity throughout the life course and variation in IGFs and IGFBPs: evidence from the ProtecT (Prostate testing for cancer and Treatment) study

Adiposity is positively associated with advanced, metastatic, and fatal prostate cancer. Obesity-related variations in insulin-like growth factors (IGF-I and -II) and their binding proteins (IGFBPs) could underlie these associations. We investigated associations of adiposity throughout the life course (determined retrospectively) with serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in a population-based study of 1,106 healthy men. IGF-I and IGF-II showed inverted U-shaped associations with adult body mass index (BMI) (p quadratic model = 0.04 and 0.06, respectively), although differences between quartiles with the highest and lowest IGF-I levels were small (no more than 5 ng/ml). IGFBP-2 was strongly inversely related to adult BMI (-22% change per SD increase in BMI; 95% confidence interval (CI) -24% to -19%) and waist circumference (-18% change per SD increase in waist circumference; 95% CI -20% to -15%) (p < 0.001). IGFBP-3 was positively related to BMI (63.5 ng/ml increase per SD increase in BMI; 95% CI -2.69 to 129.8, p = 0.06). IGFBP-2 and IGFBP-3 were strongly related to body shape change from childhood to adulthood, with men who gained the most weight having the lowest IGFBP-2 (9% lower per category body shape change; 95% CI -11% to -7%, p < 0.001) and the highest IGFBP-3 (50 ng/ml increase per category; 95% CI 8 to 92, p = 0.02). We provide evidence that adiposity and change in body shape through the life course are related to the IGF system, with the largest effect of adiposity being to lower IGFBP-2, a possible marker of insulin resistance. The results suggest that circulating IGF-I levels may not be important mediators of the association of adiposity with aggressive prostate cancer, but the role of IGFBP-2 deserves further investigation.

Waist-to-Hip Ratio, Body Mass Index, and Subsequent Kidney Disease and Death

Chronic kidney disease (CKD) and obesity are important public health concerns. We examined the association between anthropomorphic measures and incident CKD and mortality. Cohort study. Individual patient data pooled from the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Waist-to-hip ratio (WHR), body mass index (BMI). Incident CKD defined as serum creatinine level increase greater than 0.4 mg/dL with baseline creatinine level of 1.4 mg/dL or less in men and 1.2 mg/dL or less in women and final creatinine level greater than these levels, and, in separate analyses, estimated glomerular filtration rate (eGFR) decrease of 15 mL/min/1.73 m(2) or greater with baseline eGFR of 60 mL/min/1.73 m(2) or greater and final eGFR less than 60 mL/min/1.73 m(2). Multivariable logistic regression to determine the association between WHR, BMI, and outcomes. Cox models to evaluate a secondary composite outcome of all-cause mortality and incident CKD. Of 13,324 individuals, mean WHR was 0.96 in men and 0.89 in women and mean BMI was 27.2 kg/m(2) in both men and women. During 9.3 years, 300 patients (2.3%) in creatinine-based models and 710 patients (5.5%) in eGFR-based models developed CKD. In creatinine-based models, each SD increase in WHR was associated with increased risk of incident CKD (odds ratio, 1.22; 95% confidence interval [CI], 1.05 to 1.43) and the composite outcome (hazard ratio, 1.12; 95% CI, 1.06 to 1.18), whereas each SD increase in BMI was not associated with CKD (odds ratio, 1.05; 95% CI, 0.93 to 1.20) and appeared protective for the composite outcome (hazard ratio, 0.94; 95% CI, 0.90 to 0.99). Results of eGFR-based models were similar. Single measures of creatinine, no albuminuria data. WHR, but not BMI, is associated with incident CKD and mortality. Assessment of CKD risk should use WHR rather than BMI as an anthropomorphic measure of obesity.