Sex- and time-specific associations of obesity with glycaemic traits: A two-step multivariate Mendelian randomization study.

AIM: To assess the sex- and time-specific causal effects of obesity-related anthropometric traits on glycaemic traits. MATERIALS AND METHODS: We used univariate and multivariate Mendelian randomization to assess the causal associations of anthropometric traits (gestational variables, birth weight, childhood body mass index [BMI], BMI, waist-to-hip ratio [WHR], BMI-adjusted WHR [WHRadj BMI]) with fasting glucose and insulin in Europeans from the Early Growth Genetics Consortium (n ≤ 298 142), the UK Biobank, the Genetic Investigation of Anthropometric Traits Consortium (n ≤ 697 734; females: n ≤ 434 794; males: n ≤ 374 754) and the Meta-Analyses of Glucose and Insulin-related traits Consortium (n ≤ 151 188; females: n ≤ 73 089; males: n ≤ 67 506), adjusting for maternal genetic effects, smoking, alcohol consumption, and age at menarche. RESULTS: We observed a null association for gestational variables, a negative association for birth weight, and positive associations for childhood BMI and adult traits (BMI, WHR, and WHRadj BMI). In female participants, increased birth weight causally decreased fasting insulin (betaIVW , -0.07, 95% confidence interval [CI] -0.11 to -0.03; p = 1.92 × 10-3 ), but not glucose levels, which was annulled by adjusting for age at menarche. In male participants, increased birth weight causally decreased fasting glucose (betainverse-variance-weighted (IVW) , -0.07, 95% CI -0.11 to -0.03; p = 3.22 × 10-4 ), but not insulin levels. In time-specific analyses, independent effects of birth weight were absent in female participants, and were more pronounced in male participants. Independent effects of childhood BMI were attenuated in both sexes; independent effects of adult traits differed by sex. CONCLUSIONS: Our findings provide evidence for causal and independent effects of sex- and time-specific anthropometric traits on glycaemic variables, and highlight the importance of considering multiple obesity exposures at different time points in the life course.

Lifestyle factors, genetic susceptibility to obesity and their interactions on coronary artery disease risk: A cohort study in the UK Biobank.

OBJECTIVE: We aimed to evaluate potential modifying effects of genetic susceptibility to obesity on the association of lifestyle factors with coronary artery disease (CAD) risk. METHODS: A total of 328,606 participants (54% women) were included using data from the UK Biobank. We evaluated the risk of developing CAD associated with obesity-related polygenic scores (PGSs) and healthy lifestyle scores (HLSs). HLSs were constructed using six lifestyle factors. Obesity PGSs were created using genetic variants identified by genome-wide association studies, including 941 variants for body mass index (BMI) and 457 for waist-to-hip ratio (WHR). Both HLSs and PGSs were categorized into three groups. RESULTS: During a 9-year median follow-up, 14,541 participants developed CAD. An unhealthy lifestyle was significantly associated with an increased CAD risk (hazard ratio [HR] = 2.24, 95% confidence interval [CI] = 2.09-2.40). High BMI and WHR PGSs were each significantly associated with an increased CAD risk (HRBMI = 1.23, 1.17-1.29; HRWHR = 1.15, 1.09-1.21). Lifestyle factors explained 41% (95% CI = 38%-45%) of CAD, while genetic variants for BMI explained only 10% (7%-14%). Risks of CAD were increased with poorer HLS independent of obesity-related PGSs. Individuals with the most unhealthy lifestyle and highest BMI PGS had the highest risk of CAD risk (HR = 2.59, 95% CI = 2.26-2.97), compared with participants with the healthiest lifestyle and lowest BMI PGS. CONCLUSIONS: While the observational nature of the study precludes the establishment of causality, our study provides supports for a causal association between obesity and CAD risk and the importance of lifestyle modification in the prevention of CAD.

Relationships between obesity and prevalence of gout in patients with type 2 diabetes mellitus: a cross-sectional population-based study.

BACKGROUND: The purpose of this study was to investigate the relationships between generalized, abdominal, and visceral fat obesity and the prevalence of gout in patients with type 2 diabetes mellitus (T2DM). METHODS: Data were obtained from the electronic medical databases of the National Metabolic Management Center (MMC) of Yuhuan Second People's Hospital and Taizhou Central Hospital (Taizhou University Hospital) between September 2017 and June 2023. Four obesity indicators were analyzed: waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and visceral fat area (VFA). The relationships between these parameters and gout prevalence were analyzed using multivariate logistic regression and restricted cubic spline (RCS) analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of the four parameters for gout. RESULTS: This cross-sectional study enrolled 10,535 participants (600 cases and 9,935 controls). Obesity was more common in patients with gout, and the obesity indicators were markedly higher in this group. After adjustment for confounders, obesity, as defined by BMI, WC, WHR, and VFA, was found to be associated with greater gout prevalence, with odds ratios (OR) of 1.775, 1.691, 1.858, and 1.578, respectively (P < 0.001). The gout odds ratios increased markedly in relation to the obesity indicator quartiles (P-value for trend < 0.001), and the obesity indicators were positively correlated with gout prevalence, as shown using RCS. The area under the ROC curve values for BMI, WC, WHR, and VFA were 0.629, 0.651, 0.634, and 0.633, respectively. CONCLUSION: Obesity-whether general, abdominal, or visceral fat obesity-was positively linked with elevated gout risk. But uncovering the causality behind the relationship requires further prospective study. Obesity indicators (BMI, WC, WHR, and VFA) may have potential value for diagnosing gout in clinical practice.

Adiposity indices and their higher predictive value for new-onset hypertension in metabolically healthy young women: findings from a population-based prospective cohort study.

BACKGROUND AND AIMS: The present study aimed to investigate the predictive ability of selected adiposity indices, such as body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and waist-to-height ratio (WHtR), for new-onset hypertension in metabolically healthy Taiwanese adults. The study also sought to establish sex-specific cutoff points for these indices and to analyze the risk of new-onset hypertension, taking into account sex and age. METHODS: This prospective cohort study utilized the Taiwan Biobank database to examine metabolically healthy participants aged between 20 and 65 at baseline. Four adiposity indices, namely BMI, WHR, WC, and WHtR, were calculated and used to predict new-onset hypertension over 4 years. Receiver operating characteristics (ROCs) and areas under the curve (AUCs) were used to evaluate the effectiveness of the parameters in predicting new-onset hypertension over 4 years. Sex-specific cutoff points were identified and used to assess the risk of new-onset hypertension. RESULTS: This study analyzed 13,375 participants over 4.28 years. The incidence of new-onset hypertension was 17.65%. The new-onset rate of hypertension was 34.39% in men and 65.61% in women. Adiposity indices effectively predict new-onset hypertension, with WHtR having the highest predictive value (i.e., AUC) for both sexes. The classification of participants into low and high categories for each adiposity index was based on sex-specific cutoff points, and the risk of new-onset hypertension was assessed according to sex and age. This study found that high adiposity indices predicted a significantly higher risk of new-onset hypertension in metabolically healthy adults. The risk was equal for both sexes. Young women had a higher risk of new-onset hypertension than middle-aged women when they were further categorized. All risk ratios of the indices in young women were over two-fold and significant. CONCLUSION: According to the sex-specific cutoff point, high adiposity indices had a higher predictive value for new-onset hypertension in metabolically healthy Taiwanese young women.

Excessive generalized and visceral adiposity is associated with a higher prevalence of diabetic retinopathy in Caucasian patients with type 2 diabetes.

BACKGROUND AND AIMS: Type 2 Diabetes Mellitus (T2D) has heterogeneous clinical phenotypes related to different risk of developing diabetes complications. We investigated the correlation between generalized and abdominal adiposity and the prevalence of both micro- and macrovascular complications in Caucasian patients with T2D. METHODS AND RESULTS: We evaluated 769 individuals with T2D consecutively referred to our diabetes center. Body mass index (BMI), waist circumference (WC), waist to hip (W/H) ratio, glycated hemoglobin (HbA1c), systolic and diastolic blood pressure, lipid profile, smoking habit, diabetes therapy, and micro- and macrovascular complications were recorded. Patients were divided into three groups based on BMI and WC: non-obese with normal WC (nWC, n = 220), non-obese with excess of abdominal fat (AF, n = 260) and obese (Ob, n = 289). We found that nWC, compared with AF and Ob individuals, were predominantly males (p<0.01), had lower HbA1c (p<0.01), diastolic blood pressure (p<0.01), triglycerides (p<0.01), and showed a significantly lower prevalence of diabetic retinopathy (DR) (p = 0.01). The rate of proliferative DR was significantly higher in Ob (13.2 %) compared to the other groups (p = 0.03). Multivariate analyses showed a significantly decreased prevalence of DR in nWC compared to both AF (OR 0.58, 95 CI 0.34-0.96; p = 0.03) and Ob (OR 0.57, 95 CI 0.33-0.98; p = 0.04) individuals. Conversely, DR was associated, mainly in women, to higher WC and W/H ratio. The prevalence of the other diabetes-related complications was similar among the studied groups. CONCLUSIONS: In our population, nWC subjects showed a lower prevalence of DR. An increased generalized and abdominal adiposity was associated to a higher prevalence of DR, especially among females.

Association of waist-to-hip ratio adjusted for body mass index with cognitive impairment in middle-aged and elderly patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. METHODS: A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. RESULTS: WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261-1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032-4.371, P for trend < 0.001). CONCLUSIONS: Our study illustrated that higher WHRadjBMI is likely to be associated with an increased risk of CI among patients with T2DM. These findings support the detrimental effects of excess visceral fat accumulation on cognitive function in middle-aged and elderly T2DM patients.

Novel anthropometric indices for predicting type 2 diabetes mellitus.

BACKGROUND: This study aimed to compare anthropometric indices to predict type 2 diabetes mellitus (T2DM) among first-degree relatives of diabetic patients in the Iranian community. METHODS: In this study, information on 3483 first-degree relatives (FDRs) of diabetic patients was extracted from the database of the Endocrinology and Metabolism Research Center of Isfahan University of Medical Sciences. Overall, 2082 FDRs were included in the analyses. A logistic regression model was used to evaluate the association between anthropometric indices and the odds of having diabetes. Furthermore, a receiver operating characteristic (ROC) curve was applied to estimate the optimal cutoff point based on the sensitivity and specificity of each index. In addition, the indices were compared based on the area under the curve (AUC). RESULTS: The overall prevalence of diabetes was 15.3%. The optimal cutoff points for anthropometric measures among men were 25.09 for body mass index (BMI) (AUC = 0.573), 0.52 for waist-to-height ratio (WHtR) (AUC = 0.648), 0.91 for waist-to-hip ratio (WHR) (AUC = 0.654), 0.08 for a body shape index (ABSI) (AUC = 0.599), 3.92 for body roundness index (BRI) (AUC = 0.648), 27.27 for body adiposity index (BAI) (AUC = 0.590), and 8 for visceral adiposity index (VAI) (AUC = 0.596). The optimal cutoff points for anthropometric indices were 28.75 for BMI (AUC = 0.610), 0.55 for the WHtR (AUC = 0.685), 0.80 for the WHR (AUC = 0.687), 0.07 for the ABSI (AUC = 0.669), 4.34 for the BRI (AUC = 0.685), 39.95 for the BAI (AUC = 0.583), and 6.15 for the VAI (AUC = 0.658). The WHR, WHTR, and BRI were revealed to have fair AUC values and were relatively greater than the other indices for both men and women. Furthermore, in women, the ABSI and VAI also had fair AUCs. However, BMI and the BAI had the lowest AUC values among the indices in both sexes. CONCLUSION: The WHtR, BRI, VAI, and WHR outperformed other anthropometric indices in predicting T2DM in first-degree relatives (FDRs) of diabetic patients. However, further investigations in different populations may need to be implemented to justify their widespread adoption in clinical practice.

Prediction of high visceral adipose tissue for sex-specific community residents in Taiwan.

Visceral adipose tissue accumulation is strongly linked with numerous chronic diseases; however, the accessibility for visceral adipose tissue measurement is limited. This study employed a cross-sectional design to determine the optimal strongest predictor of high visceral adipose tissue in each sex and identified the optimal cutoff value thereof. Purposive sampling was used to recruit 94 men and 326 women aged ≥40 years in southern Taiwan. Receiver operating characteristic curve analysis was used to explore the optimal predictor of high visceral adipose tissue (defined as ≥135 cm2 for men and ≥100 cm2 for women) in each sex. The waist-to-hip ratio was the strongest predictor for men, with a cutoff value of 0.96 yielding the maximum sensitivity (94.29%) and specificity (93.22%). By contrast, body mass index was the strongest predictor for women, with a cutoff value of 25.45 kg/m2 yielding the maximum sensitivity (87.18%) and specificity (87.55%). The results may serve as a reference for health policy-makers in screening for high visceral adipose tissue to identify individuals at high risk of developing chronic diseases for health promotion.

Beyond the assembly line: An assessment of diabetes risks among Indian male industrial workers.

Background: Diabetes mellitus is a chronic non-communicable disease that imposes a significant burden on affected individuals and the community. Considerable attention has been given to industrial accidents and ergonomics, however, lifestyle-related diseases among industrial workers have often been neglected. Therefore, the present study was conducted with the aim to assess the prevalence of obesity/overweight and ascertain the risk of diabetes mellitus among male employees of an industrial unit in South Mumbai. Methods: The cross-sectional study was conducted among male employees of an industrial unit in South Mumbai. Family history, exercise patterns, anthropometric measurements and physical vital parameters were recorded. Body composition was assessed using bioelectrical impedance analysis (BIA). The Indian Diabetes Risk Score (IDRS) was employed to evaluate the risk of diabetes mellitus. Results: In total, 3791 industrial workers participated in the study and 44.5% of participants were above 40 years. Mean height, weight, body mass index (BMI), Waist Circumference (WC) and waist to hip ratio (WHR) were 1.67 m, 71.33 kg, 25.99, 90.81 cm and 0.91 respectively. 56.1% individuals had WC more than 90 cm and 79.1% had WHR more than 0.90. 1846 (53%) and 927 (26.6%) participants had moderate and high diabetes risk respectively. The relationship between age, weight, BMI, WC, WHR, body fat mass and fat percentage, and IDRS was statistically significant. Conclusion: A substantial proportion of industrial workers were identified as overweight and at high risk of diabetes mellitus. Consequently, it becomes imperative to offer health education and implement interventions to encourage regular exercise, adopt an active lifestyle, and promote healthy dietary habits among industrial workers.

General versus central adiposity as risk factors for cardiovascular-related outcomes in a high-risk population with type 2 diabetes: a post hoc analysis of the REWIND trial.

BACKGROUND: In clinical practice, anthropometric measures other than BMI are rarely assessed yet may be more predictive of cardiovascular (CV) risk. We analyzed the placebo group of the REWIND CV Outcomes Trial to compare several anthropometric measures as baseline risk factors for cardiovascular disease (CVD)-related outcomes in participants with type 2 diabetes (T2D). METHODS: Data from the REWIND trial placebo group (N = 4952) were analyzed. All participants had T2D, age ≥ 50 years, had either a previous CV event or CV risk factors, and a BMI of ≥ 23 kg/m2. Cox proportional hazard models were used to investigate if BMI, waist-to-hip ratio (WHR), and waist circumference (WC) were significant risk factors for major adverse CV events (MACE)-3, CVD-related mortality, all-cause mortality, and heart failure (HF) requiring hospitalization. Models were adjusted for age, sex, and additional baseline factors selected by LASSO method. Results are presented for one standard deviation increase of the respective anthropometric factor. RESULTS: Participants in the placebo group experienced 663 MACE-3 events, 346 CVD-related deaths, 592 all-cause deaths, and 226 events of HF requiring hospitalization during the median follow-up of 5.4 years. WHR and WC, but not BMI, were identified as independent risk factors of MACE-3 (hazard ratio [HR] for WHR: 1.11 [95% CI 1.03 to 1.21]; p = 0.009; HR for WC: 1.12 [95% CI 1.02 to 1.22]; p = 0.012). WC adjusted for hip circumference (HC) showed the strongest association with MACE-3 compared to WHR, WC, or BMI unadjusted for each other (HR: 1.26 [95% CI 1.09 to 1.46]; p = 0.002). Results for CVD-related mortality and all-cause mortality were similar. WC and BMI were risk factors for HF requiring hospitalization, but not WHR or WC adjusted for HC (HR for WC: 1.34 [95% CI 1.16 to 1.54]; p < 0.001; HR for BMI: 1.33 [95% CI 1.17 to 1.50]; p < 0.001). No significant interaction with sex was observed. CONCLUSIONS: In this post hoc analysis of the REWIND placebo group, WHR, WC and/or WC adjusted for HC were risk factors for MACE-3, CVD-related mortality, and all-cause mortality; while BMI was only a risk factor for HF requiring hospitalization. These findings indicate the need for anthropometric measures that consider body fat distribution when assessing CV risk.

Associations among Body Mass Index, Waist-to-Hip Ratio, and Cognitive Impairment Tend to Follow an Opposite Trend and Are Sex Specific: A Population-Based Cross-Sectional Study in a Rural Area of Xi'an, China.

INTRODUCTION: The relationship between obesity and cognitive impairment (CI) is highly heterogeneous in previous studies, which may be due to insufficient consideration of anthropometric indicators and sex. This study compared the cross-sectional relationships among body mass index (BMI), waist-to-hip ratio (WHR), and CI among people aged ≥40 years, and sex-specific relationships were also considered. METHODS: This was a population-based cross-sectional study with a cluster sampling design. CI was defined as a Mini-Mental State Examination score lower than the cutoff value. Multivariate logistic regression was used. BMI and WHR were fitted as both restricted cubic splines and categorical data. Stratified analysis and interaction analysis were performed to explore the sex-specific relationship. RESULTS: A total of 1,792 subjects (40.5% male) were analyzed, and 230 were confirmed to have CI. The relationships among BMI, WHR, and CI were significant (poverall = 0.023, pnonlinear = 0.097; poverall = 0.017, pnonlinear = 0.078, respectively) but exhibited an opposite trend in the total population in the analyses with BMI and WHR as restricted cubic splines. Further categorical analyses showed that subjects with a BMI <23 kg/m2 tended to have a higher risk of CI than those with BMI ≥23 kg/m2 (16.2% vs. 11.8%, p = 0.017; OR = 1.366 [0.969-1.926], p = 0.075), and subjects with a WHR >0.92 had a significantly higher risk of CI than those with a WHR ≤0.92 (11.7% vs. 16.2%, p = 0.011; OR = 1.619 [1.161-2.258], p = 0.005). In addition, the relationship between a low BMI and CI was more significant in males (p = 0.034), while the relationship between a high WHR and CI was more significant in females (p = 0.002). Further studies are needed to confirm the sex differences because of the marginal significance result in the interaction analysis (p = 0.051 for interaction term BMI × sex; p = 0.056 for interaction term WHR × sex). CONCLUSION: The relationships among BMI, WHR, and CI exhibit an opposite trend. A low BMI or high WHR was positively associated with CI, which was more prominent in males for a low BMI and females for a high WHR.

Changes in body mass index, weight, and waist-to-hip ratio over five years in HIV-positive individuals in the HIV Heart Aging Study compared to the general population.

PURPOSE: Overweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population. METHODS: HIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain. RESULTS: The matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (- 6 kg, 95% CI - 7.46 to - 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results. CONCLUSIONS: PLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline.

Abdominal obesity and digestive system cancer: a systematic review and meta-analysis of prospective studies.

BACKGROUND: The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess  study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg's and Egger's tests. RESULTS: A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method. CONCLUSIONS: There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference.

Phenotypic and Genetic Links between Body Fat Measurements and Primary Open-Angle Glaucoma.

The phenotypic and genetic links between body fat phenotypes and primary open-angle glaucoma (POAG) are unclear. We conducted a meta-analysis of relevant longitudinal epidemiological studies to evaluate the phenotypic link. To identify genetic links, we performed genetic correlation analysis and pleiotropy analysis of genome-wide association study summary statistics datasets of POAG, intraocular pressure (IOP), vertical cup-to-disc ratio, obesity, body mass index (BMI), and waist-to-hip ratio. In the meta-analysis, we first established that obese and underweight populations have a significantly higher risk of POAG using longitudinal data. We also discovered positive genetic correlations between POAG and BMI and obesity phenotypes. Finally, we identified over 20 genomic loci jointly associated with POAG/IOP and BMI. Among them, the genes loci CADM2, RP3-335N17.2, RP11-793K1.1, RPS17P5, and CASC20 showed the lowest false discovery rate. These findings support the connection between body fat phenotypes and POAG. The newly identified genomic loci and genes render further functional investigation.

Causal relationships between obesity and pancreatobiliary diseases: a two-sample Mendelian randomization study.

Previous observational studies have investigated the relationship between obesity and the biliary tract and pancreas. The causality, however, is still to be confirmed. This study was designed to explore the causality between obesity which included body mass index(BMI), circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR), and pancreatobiliary diseases with a Two-Sample Mendelian Randomization(MR) analysis. single-nucleotide polymorphisms used in our study were derived from genome-wide association studies (GWAS). The inverse variance weighted was the dominated method to evaluate the causality. The heterogeneity was validated by Cochran's Q test. The pleiotropy was validated by MR-Egger regression and MR-PRESSO. The stability and reliability of the results were illustrated by the 'leave-one-out'sensitivity analysis. The MR results explored positive causal effects of BMI (OR: 1.021; 95% CI: from 1.016 to 1.027; P = 4.25 × 10-15) and WC (OR: 1.021; 95% CI: from 1.015 to 1.028; P = 1.65 × 10-10) on pancreatobiliary diseases. However, no causality existed between HC, WHR and pancreatobiliary diseases. This study reminded that general obesity and abdominal obesity required weight loss to prevent pancreatic biliary disease.

Prevalence of hypertension and associated risk factors in urban slums: A community based cross sectional study in India.

Hypertension is a global public health issue. Being a silent killer, very rarely symptoms are seen in the early stages till a severe medical crisis (heart attack, stroke, or chronic kidney disease) occurs. A community-based cross-sectional study was conducted to estimate the prevalence of hypertension in urban slums and to evaluate the association of hypertension with various modifiable and nonmodifiable risk factors. Data were collected by house-to-house visits in the slums. Pro forma created in the Magpi app was used to collect demographic characteristics and record anthropometric findings. SPSS version 25 was used for statistical analysis. Of the 534 participants, 71.91% were female. The prevalence of hypertension was found to be 15.36%. The risk of hypertension increased with age >50 years, female gender, and habits such as tobacco and alcohol. Awareness programs to reduce modifiable risk factors such as smoking and alcohol, promoting healthy lifestyles, as well as early diagnosis and treatment, will benefit the community.

Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study.

BACKGROUND: Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study. METHODS: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case-control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders. RESULTS: Measured BMI (≥ 30 vs. 18.5-24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57-93.53) vs. 50.89 (43.47-59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47-36.07) vs. 13.26 (10.37-16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women. CONCLUSIONS: We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

Racial differences in anthropometric measures as risk factors for triple-negative breast cancer.

PURPOSE: The incidence of triple-negative breast cancer (TNBC) is higher in Black women compared to White women which is not explained by racial differences in body mass index (BMI). As BMI has limitations as an anthropometric measure, we used different anthropometric measures to examine associations with TNBC by race. METHOD: Of 161,808 postmenopausal participants in Women's Health Initiative, eligible were a subsample of 121,744 White and Black postmenopausal women enrolled from 1993 to 1998, 50-79 years of age with anthropometric measures who were followed for breast cancer incidence until March 2019. At entry, BMI, waist circumference (WC), and waist-hip ratio (WHR) were measured using standardized methods. Breast cancers were verified by central medical record review. Associations between anthropometric measures and triple-negative breast cancer risk were examined using Cox proportional hazards regression models. RESULTS: After 17.6 years (median) follow-up, there were 87 Black women and 529 White women with incident triple-negative breast cancer. Overall, there were no significant associations between anthropometric measures and risk of triple-negative breast cancer. However, compared to White women with normal BMI, White women with obesity (BMI ≥ 30) (HR 0.76, 95% CI 0.60, 0.96) were significantly associated with a lower risk of triple-negative breast cancer. And larger waist circumference (HR per centimeter 0.99, 95% CI 0.99, 1.00) was significantly associated with a lower risk of triple-negative breast cancer among White women. CONCLUSION: Overall, among postmenopausal women, anthropometric measures were not associated with risk of TNBC. The association among White women with larger waist circumference and women with obesity with a lower risk of triple-negative breast cancer needs further confirmation.

DNA methylation and waist-to-hip ratio: an epigenome-wide association study in Chinese monozygotic twins.

PURPOSE: Epigenetic signatures such as DNA methylation may be associated with specific obesity traits. We performed an epigenome-wide association study (EWAS) by combining with the waist-to-hip ratio (WHR)-discordant monozygotic (MZ) twin design in an attempt to identify genetically independent DNA methylation marks associated with abdominal obesity in Northern Han Chinese and to determine the causation underlying. METHODS: A total of 60 WHR discordant MZ twin pairs were selected from the Qingdao Twin Registry, China. Generalized estimated equation (GEE) model was used to regress the methylation level of CpG sites on WHR. The Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was used to assess the temporal relationship between methylation and WHR. Gene expression analysis was conducted to validate the results of differentially methylated analyses. RESULTS: EWAS identified 92 CpG sites with the level of P < 10 - 4 which were annotated to 32 genes, especially CADPS2, TUSC5, ZCCHC14, CORO7, COL23A1, CACNA1C, CYP26B1, and BCAT1. ICE FALCON showed significant causality between DNA methylation of several genes and WHR (P < 0.05). In region-based analysis, 14 differentially methylated regions (DMRs) located at 15 genes (slk-corrected P < 0.05) were detected. The gene expression analysis identified the significant correlation between expression levels of 5 differentially methylated genes and WHR (P < 0.05). CONCLUSIONS: Our study identifies the associations between specific epigenetic variations and WHR in Northern Han Chinese. These DNA methylation signatures may have value as diagnostic biomarkers and provide novel insights into the molecular mechanisms of pathogenesis.