A body shape index (ABSI) but not body mass index (BMI) is associated with prostate cancer-specific mortality: Evidence from the US NHANES database.

BACKGROUND: Prostate cancer (PCa) is a common malignancy in males and obesity may play a role in its development and progression. Associations between visceral obesity measured by a body shape index (ABSI) and PCa mortality have not been thoroughly investigated. This study assessed the associations between ABSI, body mass index (BMI), and long-term PCa-specific mortality using a nationally representative US database. METHODS: This population-based longitudinal study collected data of males aged ≥40 years diagnosed with PCa and who underwent surgery and/or radiation from the National Health and Nutrition Examination Survey database 2001-2010. All included participants were followed through the end of 2019 using the National Center for Health Statistics Linked Mortality File. Associations between PCa-specific mortality, BMI, and ABSI were determined using Cox proportional hazards regression and receiver operating characteristic (ROC) curve analysis. RESULTS: Data of 294 men (representing 1,393,857 US nationals) were analyzed. After adjusting for confounders, no significant associations were found between BMI (adjusted hazard ratio [aHR] = 1.06, 95% confidence interval [CI]: 0.97-1.16, p = 0.222), continuous ABSI (aHR = 1.29, 95% CI: 0.83-2.02, p = 0.253), or ABSI in category (Q4 vs. Q1-Q3: aHR = 1.52, 95% CI: 0.72-3.24, p = 0.265), and greater risk of PCa-specific mortality. However, among participants who had been diagnosed within 4 years, the highest ABSI quartile but not in BMI was significantly associated with greater risk for PCa-specific mortality (Q4 vs. Q1-Q3: aHR = 5.34, 95% CI: 2.26-12.62, p = 0.001). In ROC analysis for this subgroup, the area under the curve of ABSI alone for predicting PCa-specific mortality was 0.638 (95% CI: 0.448-0.828), reaching 0.729 (95% CI: 0.490-0.968 when combined with other covariates. CONCLUSIONS: In US males with PCa diagnosed within 4 years, high ABSI but not BMI is independently associated with increased PCa-specific mortality.

Visceral Adipose Tissue Reduction Measured by Deep Neural Network Architecture Improved Reflux Esophagitis Endoscopic Grade.

INTRODUCTION: Visceral obesity is a risk factor for reflux esophagitis (RE). We investigated the risk of RE according to visceral adipose tissue (VAT) measured by deep neural network architecture using computed tomography (CT) and evaluated the longitudinal association between abdominal adipose tissue changes and the disease course of RE. METHODS: Individuals receiving health checkups who underwent esophagogastroduodenoscopy (EGD) and abdominal CT at Seoul National University Healthcare System Gangnam Center between 2015 and 2016 were included. Visceral and subcutaneous adipose tissue areas and volumes were measured using a deep neural network architecture and CT. The association between the abdominal adipose tissue area and volume and the risk of RE was evaluated. Participants who underwent follow-up EGD and abdominal CT were selected; the effects of changes in abdominal adipose tissue area and volume on RE endoscopic grade were investigated using Cox proportional hazards regression. RESULTS: We enrolled 6,570 patients who underwent EGD and abdominal CT on the same day. RE was associated with male sex, hypertension, diabetes, excessive alcohol intake, current smoking status, and levels of physical activity. The VAT area and volume increased the risk of RE dose-dependently. A decreasing VAT volume was significantly associated with improvement in RE endoscopic grade (hazard ratio: 3.22, 95% confidence interval: 1.82-5.71). Changes in subcutaneous adipose tissue volume and the disease course of RE were not significantly correlated. DISCUSSION: Visceral obesity is strongly associated with RE. VAT volume reduction was prospectively associated with improvement in RE endoscopic grade dose-dependently. Visceral obesity is a potential target for RE treatment.

Discrepancies between general and central obesity in arterial stiffness: observational studies and Mendelian randomization study.

BACKGROUND: Obesity has been linked to arterial stiffness, while no consensus was reached on the association. We aimed to clarify the association of general and central obesity with arterial stiffness by combining observational studies and Mendelian randomization (MR) study. METHODS: Two cross-sectional studies were performed in UK Biobank and Fuqing Cohort, respectively. Two-sample MR study was conducted using summary data of GWASs from GIANT consortium and UK Biobank. General obesity and central obesity were measured using body mass index (BMI) and waist circumference (WC), respectively. Arterial stiffness was measured by arterial stiffness index (ASI) in UK Biobank or branchial-ankle pulse wave velocity (baPWV) in Fuqing Cohort. RESULTS: Two observational studies found a consistent positive association of BMI and WC with arterial stiffness when adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and LDL cholesterol. However, when additionally adjusting for metabolic traits (i.e., systolic blood pressure, diastolic blood pressure, blood glucose, triglycerides, high-density lipoprotein cholesterol, and WC or BMI), the association with BMI changed to be inverse. As compared to the lowest quintile group, the adjusted ORs across groups of second to fifth quintile were 0.93, 0.90, 0.83, and 0.72 in UK Biobank and 0.88, 0.65, 0.63, and 0.50 in Fuqing Cohort. In contrast, the positive relationship with WC remained stable with the adjusted ORs of 1.23, 1.46, 1.60, and 1.56 in UK Biobank and 1.35, 1.44, 1.77, and 1.64 in Fuqing Cohort. MR analyses provided supportive evidence of the negative association with BMI (OR = 0.97, 95%CI = 0.94-1.00) and the positive association with WC (OR = 1.14, 95%CI = 1.08-1.20). CONCLUSIONS: Observational and genetic analyses provide concordant results that central obesity is independently related to arterial stiffness, while the role of general obesity depends on metabolic status.

How do lifestyle factors modify the association between genetic predisposition and obesity-related phenotypes? A 4-way decomposition analysis using UK Biobank.

BACKGROUND: Obesity and central obesity are multifactorial conditions with genetic and non-genetic (lifestyle and environmental) contributions. There is incomplete understanding of whether lifestyle modifies the translation from respective genetic risks into phenotypic obesity and central obesity, and to what extent genetic predisposition to obesity and central obesity is mediated via lifestyle factors. METHODS: This is a cross-sectional study of 201,466 (out of approximately 502,000) European participants from UK Biobank and tested for interactions and mediation role of lifestyle factors (diet quality; physical activity levels; total energy intake; sleep duration, and smoking and alcohol intake) between genetic risk for obesity and central obesity. BMI-PRS and WHR-PRS are exposures and obesity and central obesity are outcomes. RESULTS: Overall, 42.8% of the association between genetic predisposition to obesity and phenotypic obesity was explained by lifestyle: 0.9% by mediation and 41.9% by effect modification. A significant difference between men and women was found in central obesity; the figures were 42.1% (association explained by lifestyle), 1.4% (by mediation), and 40.7% (by modification) in women and 69.6% (association explained by lifestyle), 3.0% (by mediation), and 66.6% (by modification) in men. CONCLUSIONS: A substantial proportion of the association between genetic predisposition to obesity/central obesity and phenotypic obesity/central obesity was explained by lifestyles. Future studies with repeated measures of obesity and lifestyle would be needed to clarify causation.

Change in abdominal obesity after colon cancer surgery - effects of left-sided and right-sided colonic resection.

BACKGROUND: Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots. MATERIAL AND METHODS: Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately. RESULTS: A total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2-9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2-6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2-7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4-9%, p < 0.001) increase in SAT and a 4% (95% CI: 1-7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2-10%, p < 0.01) after 3 years. CONCLUSION: After 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT.

Gender differences in midlife to later-life cumulative burden and variability of obesity measures and risk of all-cause and cause-specific mortality.

BACKGROUND/OBJECTIVES: Previous studies have reported the gender-specific association between general and central obesity measures, using snapshot assessments, and mortality events. This study seeks to further explore this link by examining how the longitudinal cumulative burden and variability of obesity measures from midlife to later-life impact mortality events in the Atherosclerosis Risk in Communities (ARIC) study population, specifically in relation to gender differences. SUBJECTS/METHODS: Using data from the ARIC study, a total of 7615 (4360 women) participants free of cardiovascular disease, cancer, and early mortality events were included in the data analysis. Longitudinal cumulative burden (estimated by the area under the curve (AUC) using a quadratic mixed-effects method) and variability (calculated according to average successive variability (ASV)) were considered as exposures, separately and all together. Cox proportional hazard regression models were used to estimate multivariable-adjusted standardized hazard ratios. RESULTS: The mean age was 62.4 and the median follow-up was 16.9 years. In men, AUCs of waist-related obesity measures, and also ASVs of all obesity measures were associated with increased all-cause mortality risk. In women, waist circumference and waist-to-height ratio AUCs were associated with increased all-cause mortality risk. Regarding cardiovascular mortality, all adiposity measures ASVs in both genders and waist-related obesity measures AUCs in men were associated with increased risk. Significant gender differences were found for the associations between cumulative and variability of waist-to-hip ratio for all-cause mortality and all adiposity measures ASVs for cardiovascular mortality risk with higher impact among men. CONCLUSIONS: Cumulative burden and variability in general and central obesity measures were associated with higher all-cause and cardiovascular mortalities among men. In women, general obesity measures variability, as well as cumulative and variability of central adiposity measure, increased all-cause mortality risk.

An epigenome-wide association study of waist circumference in Chinese monozygotic twins.

OBJECTIVES: Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. METHODS: A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. RESULTS: We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. CONCLUSIONS: Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

Combined associations of visceral adipose tissue and adherence to a Mediterranean lifestyle with T2D and diabetic microvascular complications among individuals with prediabetes.

BACKGROUND: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. METHODS: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. RESULTS: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC. CONCLUSION: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D.

Glutamate and obesity - what is the link?

PURPOSE OF REVIEW: Many studies using metabolomics have tried to unravel the metabolic signature of obesity and understand the pathophysiology of this complex and heterogeneous disease. Circulating levels of the amino acid glutamate have been consistently associated with obesity and more specifically with measurements of abdominal fat accumulation. The purpose of this narrative review is to highlight recent studies documenting this association. RECENT FINDINGS: Circulating glutamate concentrations have been positively correlated with measurements of central fat accumulation such as waist circumference and visceral adipose tissue area. Moreover, elevated glutamate levels have been linked to a higher prevalence of type 2 diabetes, cardiovascular diseases and nonalcoholic fatty liver disease. The association with adiposity is detected in early life, and genetic predisposition does not appear as a major driver. Glutamate levels reflect in vivo synthesis rather than dietary intake. However, interventions generating metabolic improvements such as incretin receptor agonist treatment or dietary improvements may reduce plasma levels of this amino acid. SUMMARY: Recent findings confirm the consistent association between circulating glutamate and abdominal obesity and its cardiometabolic complications. The pathophysiological pathways underlying this phenomenon are still unclear. Furthermore, studies are needed to establish the usefulness of this analyte as a biomarker of abdominal obesity.

Exercise-induced changes in left ventricular strain are affected by interleukin-6 activity: An exploratory analysis of a randomised-controlled trial in humans with abdominal obesity.

Whilst the exercise-induced myokine interleukin-6 (IL-6) plays a beneficial role in cardiac structural adaptations, its influence on exercise-induced functional cardiac outcomes remains unknown. We hypothesised that IL-6 activity is required for exercise-induced improvements in left ventricular global longitudinal strain (LV GLS). In an exploratory study 52 individuals with abdominal obesity were randomised to 12 weeks' high-intensity exercise or no exercise in combination with IL-6 receptor inhibition (IL-6i) or placebo. LV strain and volume measurements were assessed by cardiac magnetic resonance. Exercise improved LV GLS by -5.4% [95% CI: -9.1% to -1.6%] (P = 0.007). Comparing the change from baseline in LV GLS in the exercise + placebo group (-4.8% [95% CI: -7.4% to -2.2%]; P < 0.0004) to the exercise + IL-6i group (-1.1% [95% CI: -3.8% to 1.6%]; P = 0.42), the exercise + placebo group changed -3.7% [95% CI: -7.4% to -0.02%] (P = 0.049) more than the exercise + IL6i group. However, the interaction effect between exercise and IL-6i was insignificant (4.5% [95% CI: -0.8% to 9.9%]; P = 0.09). Similarly, the exercise + placebo group improved LV global circumferential strain by -3.1% [95% CI: -6.0% to -0.1%] (P = 0.04) more compared to the exercise + IL-6i group, yet we found an insignificant interaction between exercise and IL-6i (4.2% [95% CI: -1.8% to 10.3%]; P = 0.16). There was no effect of IL-6i on exercise-induced changes to volume rates. This study underscores the importance of IL-6 in improving LV GLS in individuals with abdominal obesity suggesting a role for IL-6 in cardiac functional exercise adaptations.

Risk factors for incident cardiovascular events and their population attributable fractions in rural India: The Rishi Valley Prospective Cohort Study.

OBJECTIVE: We prospectively determined incident cardiovascular events and their association with risk factors in rural India. METHODS: We followed up with 7935 adults from the Rishi Valley Prospective Cohort Study to identify incident cardiovascular events. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) with 95% confidence intervals (95% CI) for associations between potential risk factors and cardiovascular events. Population attributable fractions (PAFs) for risk factors were estimated using R ('averisk' package). RESULTS: Of the 4809 participants without prior cardiovascular disease, 57.7% were women and baseline mean age was 45.3 years. At follow-up (median of 4.9 years, 23,180 person-years [PYs]), 202 participants developed cardiovascular events, equating to an incidence of 8.7 cardiovascular events/1000 PYs. Incidence was greater in those with hypertension (hazard ratio [HR] [95% CI] 1.73 [1.21-2.49], adjusted PAF 18%), diabetes (1.96 [1.15-3.36], 4%) or central obesity (1.77 [1.23, 2.54], 9%) which together accounted for 31% of the PAF. Non-traditional risk factors such as night sleeping hours and number of children accounted for 16% of the PAF. CONCLUSIONS: Both traditional and non-traditional cardiovascular risk factors are important contributors to incident cardiovascular events in rural India. Interventions targeted to these factors could assist in reducing the incidence of cardiovascular events.

Waist Circumference as a Tool for Identifying Visceral Fat in Women with Non-Metastatic Breast Cancer.

Abdominal adiposity is associated with tumor development and poor clinical outcomes in breast cancer (BC) and can be identified by the measurement of waist circumference (WC) and visceral adipose tissue (VAT). This study aimed to evaluate the association between waist circumference (WC) and imaging measurement of central adiposity according to age group in women with BC. Abdominal adiposity was assessed by WC and VAT, obtained by dual-energy X-ray absorptiometry (DXA). Body mass index (BMI) was assessed. The presence of inflammation was investigated by measuring C-Reactive Protein (CRP) levels. Multivariate linear regression models were applied to verify the association between WC and VAT. The significance level adopted for all tests was 5%. This study included 112 women with a mean age of 55.5 ± 11.4 years. After adjusted models, WC remained associated with VAT and for every centimeter increase in WC, there was an increase of 3.12 cm2 (CI: 2.40 - 3.85; p < 0.001) in VAT. WC was associated with VAT in women with breast cancer, proving to be a simple, fast, and noninvasive approach that can be used as a proxy to identify visceral fat.

Geographic and ethnicity variation in the prevalence of middle-aged and elderly adult obesity in China in 2020.

AIM: The objective of this study is to evaluate the mean body mass index (BMI), general obesity and abdominal obesity in adults aged ≥40 years residing in China in 2020, and to analyse variations in these factors across different geographic areas and subpopulations. METHODS: We utilized data from the National Stroke High-Risk Population Screening programme to calculate and compare the mean BMI and prevalence of obesity across various demographics, including sex, age, urban-rural locality, geographical region (province) and ethnicity status. RESULTS: In our study, we found that the standardized mean BMI level was 24.65 kg/m2 [95% confidence interval (CI): 24.50-22.84] in men and 24.31 kg/m2 (95% CI: 24.15-24.45) in women. Using the criteria from China, we found that the standardized prevalence of general obesity and abdominal obesity was 13.13% (95% CI: 13.05-13.21%) and 33.03% (95 CI: 32.92-33.14%), respectively. Our study also identified significant effects of age, sex, urban-rural locality, province and ethnicity status on the prevalence of obesity. Overall, our study estimated that in 2020, approximately 91.1 million adults aged ≥40 years in China were obese (46.5 million men and 44.6 million women), while 229.2 million adults (110.4 million men and 118.8 million women) were diagnosed with abdominal obesity. CONCLUSION: Our research has revealed compelling new evidence about the obesity epidemic among Chinese adults aged ≥40 years, particularly at the provincial and ethnic levels. As a result, more targeted and effective prevention strategies should be developed to alleviate the burden of obesity.

Visceral fat mass dynamics in a 2-year randomized STrength versus ENdurance training trial in people with obesity.

AIM: To compare the effectiveness of strength versus endurance training on reducing visceral fat in individuals with obesity. MATERIALS AND METHODS: For the STrength versus ENdurance (STEN) 24-month randomized clinical trial, we assigned 239 participants with abdominal obesity to either strength or endurance training (two to three times a week, 60 min/training session) in addition to standard nutritional counselling to promote a healthy diet. Changes in abdominal visceral adipose tissue (VAT) area quantified by magnetic resonance imaging after 12 months were defined as a primary endpoint. RESULTS: Participants (aged 44 years, 74% women, body mass index: 37 kg/m2, mean VAT volume: 4050 cm3) had an approximately 50% retention rate and a 30% good training programme adherence at 12 months. There was no difference between strength and endurance training in VAT volume dynamics after 12 and 24 months (p = .13). Only in the good adherence group did we find a trend for reduced VAT volume in both training regimens. Independently of the exercise programme, there was a continuous trend for moderate loss of abdominal subcutaneous AT volume, body fat mass, body mass index and improved parameters of insulin sensitivity. Although parameters of physical fitness improved upon both exercise interventions, the dynamics of resting energy expenditure, glucose and lipid metabolism parameters were not different between the intervention groups and did not significantly improve during the 2-year trial (p > .05). CONCLUSIONS: Despite heterogeneous individual training responses, strength and endurance training neither affected VAT volume nor key secondary endpoints differently.

Associations between Chinese visceral adiposity index and risks of all-cause and cause-specific mortality: A population-based cohort study.

AIM: To determine the associations between the Chinese visceral adiposity index (CVAI) and the risks of all-cause and cause-specific mortality. MATERIALS AND METHODS: A total of 3 916 214 Chinese adults were enrolled in a nationwide population cohort covering all 31 provinces of mainland China. The CVAI was calculated based on age, body mass index, waist circumference, and triglyceride and high-density lipoprotein cholesterol concentrations. We used a Cox proportional hazards regression model to determine the hazard ratios and 95% confidence intervals (CIs) for risk of mortality associated with different CVAI levels. RESULTS: The median follow-up duration was 3.8 years. A total of 86 158 deaths (34 867 cardiovascular disease [CVD] deaths, 29 884 cancer deaths, and 21 407 deaths due to other causes) were identified. In general, after adjusting for potential confounding factors, a U-shaped relationship between CVAI and all-cause mortality was observed by restricted cubic spline (RCS). Compared with participants in CVAI quartile 1, those in CVAI quartile 4 had a 23.0% (95% CI 20.0%-25.0%) lower risk of cancer death, but a 23.0% (95% CI 19.0-27.0) higher risk of CVD death. In subgroup analysis, a J-shaped and inverted U-shaped relationship for all-cause mortality and cancer mortality was observed in the group aged < 60 years. CONCLUSIONS: The CVAI, an accessible indicator reflecting visceral obesity among Chinese adults, has predictive value for all-cause, CVD, and cancer mortality risks. Moreover, the CVAI carries significance in the field of health economics and secondary prevention. In the future, it could be used for early screening purposes.

Investigating the causal association of generalized and abdominal obesity with microvascular complications in patients with type 2 diabetes: A community-based prospective study.

AIM: The paradoxical protective association between overweight/obesity and diabetic microvascular complications (DMC), a phenomenon well-known as the obesity paradox, has been considered a non-causal association based on methodological influences. We aimed to investigate the association of generalized and abdominal obesity, as measured by body mass index (BMI) and waist circumference (WC), respectively, with DMC in patients with type 2 diabetes (T2D), using a causal inference approach. MATERIALS AND METHODS: We enrolled 1436 patients with clinically diagnosed T2D but not DMC at baseline in a community-based prospective cohort in China between 2017 and 2019 and followed them annually until 2022 with new-onset DMC recorded. Marginal structural Cox models with inverse probability weighting were constructed to determine the causal association. Subgroup analyses were performed to identify potential effect modifiers. RESULTS: We observed 360 incident DMC cases, including 109 cases of diabetic nephropathy (DN) and 277 cases of diabetic retinopathy (DR) during four follow-up visits. Multivariable-adjusted hazard ratios (95% confidence intervals) for overall DMC, DN and DR were 1.037 (1.005-1.071), 1.117 (1.062-1.175) and 1.018 (0.980-1.059) for 1 kg/m2 increase in BMI, and 1.005 (0.994-1.017), 1.034 (1.018-1.051) and 1.000 (0.987-1.014) for 1 cm increase in WC, respectively. Similar patterns were observed across the BMI and WC categories, while the positive association appeared to be more pronounced in women. CONCLUSIONS: Generalized but not abdominal obesity was associated with an increased risk for the overall DMC, whereas both obesities were causally related to DN, albeit not DR, in T2D. Routine weight management should not be neglected in diabetes care, particularly in women.

Adiposity indicators exhibit depot- and sex-specific associations with multimorbidity onset: A cohort study of the UK Biobank.

AIM: This study investigated the depot- and sex-specific associations of adiposity indicators with incident multimorbidity and comorbidity pairs. MATERIALS AND METHODS: We selected 382 678 adults without multimorbidity (≥2 chronic diseases) at baseline from the UK Biobank. General obesity, abdominal obesity and body fat percentage indices were measured. RESULTS: Cox proportional hazard regression analyses of general obesity indices revealed that for every one-unit increase in body mass index, the risk of incident multimorbidity increased by 5.2% (95% confidence interval 5.0%-5.4%). A dose-response relationship was observed between general obesity degrees and incident multimorbidity. The analysis of abdominal obesity indices showed that for every 0.1 increment in waist-to-height ratio and waist-to-hip ratio, the risk of incident multimorbidity increased by 42.0% (37.9%-46.2%) and 27.9% (25.7%-30.0%), respectively. Central obesity, as defined by waist circumference, contributed to a 23.2% increased risk of incident multimorbidity. Hip circumference and hip-to-height ratio had protective effects on multimorbidity onset. Consistent findings were observed for males and females. Body fat percentage elevated 3% (0.2%-5.9%) and 5.3% (1.1%-9.7%) risks of incident multimorbidity in all adults and females, respectively. Arm fat percentages elevated 5.3% (0.8%-9.9%) and 19.4% (11.0%-28.5%) risks of incident multimorbidity in all adults and males, respectively. The general obesity indices, waist circumference, waist-to-height ratio, waist-to-hip ratio and central obesity increased the onset of comorbidity pairs, whereas hip circumference and hip-to-height ratio decreased the onset of comorbidity pairs. These adiposity indicators mainly affect diabetes mellitus-related comorbidity onset in males and hypertensive-related comorbidity onset in females. CONCLUSIONS: Adiposity indicators are predictors of multimorbidity and comorbidity pairs and represent a promising approach for intervention.

The relationship between glycated haemoglobin and blood glucose-lowering treatment trajectories in type 2 diabetes: The Fremantle Diabetes Study Phase II.

AIMS: To examine the relationships between glycaemia and treatment complexity over 6 years in well-characterized community-based people with type 2 diabetes. MATERIALS AND METHODS: Fremantle Diabetes Study Phase II participants who had type 2 diabetes with glycated haemoglobin (HbA1c) and blood glucose-lowering therapy (BGLT) data over 6 years were included. Group-based multi-trajectory modelling identified combined HbA1c/BGLT trajectory subgroups for diabetes durations of ≤1.0 year (Group 1; n = 160), >1.0 to 10.0 years (Group 2; n = 382;) and >10.0 years (Group 3; n = 357). Multinomial regression was used to identify baseline associates of subgroup membership. RESULTS: The optimum numbers of trajectory subgroups were three in Group 1 (low, medium, high) and four in Groups 2 and 3 (low, low/high medium, high). Each low trajectory subgroup maintained a mean HbA1c concentration of <53 mmol/mol (<7.0%) on lifestyle measures, or monotherapy (Group 3). All five medium subgroups had stable HbA1c trajectories at <58 mmol/mol (<7.5%) but required increasing oral BGLT, or insulin (Group 3, high medium). The Group 1 high subgroup showed a falling then increasing HbA1c with steady progression to insulin. The high subgroups in Groups 2 and 3 showed stable HbA1c profiles at means of approximately 64 mmol/mol (8.0%) and 86 mmol/L (10.0%), respectively, on insulin. Non-Anglo Celt ethnicity, central obesity and hypertriglyceridaemia were strongly associated with Group 1 high subgroup membership. Younger age at diagnosis and central obesity were independent associates of the most adverse HbA1c trajectories in Groups 2 and 3. CONCLUSIONS: These data demonstrate diabetes duration-dependent heterogeneity in glycaemic and treatment profiles and related clinical and laboratory variables, which have implications for management.

Low-grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators.

AIMS: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. MATERIALS AND METHODS: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. RESULTS: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%-25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%-7%) and high triglyceride levels (2%-6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%-2%). CONCLUSIONS: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%-40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.

Using CT-Based Pelvimetry and Visceral Obesity Measurements to Predict Total Mesorectal Excision Quality for Patients Undergoing Rectal Cancer Surgery.

BACKGROUND: A complete total mesorectal excision is the criterion standard in curative rectal cancer surgery. Ensuring quality is challenging in a narrow pelvis, and obesity amplifies technical difficulties. Pelvimetry is the measurement of pelvic dimensions, but its role in gauging preoperatively the difficulty of proctectomy is largely unexplored. OBJECTIVE: To determine pelvic structural factors associated with incomplete total mesorectal excision after curative proctectomy and build a predictive model for total mesorectal excision quality. DESIGN: Retrospective cohort study. SETTING: A quaternary referral center database of patients diagnosed with rectal adenocarcinoma (2009-2017). PATIENTS: Curative-intent proctectomy for rectal adenocarcinoma. INTERVENTIONS: All radiological measurements were obtained from preoperative CT images using validated imaging processing software tools. Completeness of total mesorectal excision was obtained from histology reports. MAIN OUTCOME MEASURES: Ability of radiological pelvimetry and obesity measurements to predict total mesorectal excision quality. RESULTS: Of the 410 cases meeting inclusion criteria, 362 underwent a complete total mesorectal excision (88%). Multivariable regression identified a deeper sacral curve (per 100 mm 2 [OR: 1.14; 95% CI, 1.06-1.23; p < 0.001]) and a greater transverse distance of the pelvic outlet (per 10 mm [OR:1.41, 95% CI, 1.08-1.84; p = 0.012]) to be independently associated with incomplete total mesorectal excision. An increased area of the pelvic inlet (per 10 cm 2 [OR: 0.85; 95% CI, 0.75-0.97; p = 0.02) was associated with a higher rate of complete mesorectal excision. No difference in visceral obesity ratio and visceral obesity (ratio >0.4 vs <0.4) between BMI (<30 vs ≥30) and sex was identified. A model was built to predict mesorectal quality using the following variables: depth of sacral curve, area of pelvic inlet, and transverse distance of the pelvic outlet. LIMITATIONS: Retrospective analysis is not controlled for the choice of surgical approach. CONCLUSIONS: Pelvimetry predicts total mesorectal excision quality in rectal cancer surgery and can alert surgeons preoperatively to cases of unusual difficulty. This predictive model may contribute to treatment strategy and aid in the comparison of outcomes between traditional and novel techniques of total mesorectal excision. See Video Abstract . USO DE MEDICIONES DE PELVIMETRA Y OBESIDAD VISCERAL BASADAS EN TC PARA PREDECIR LA CALIDAD DE TME EN PACIENTES SOMETIDOS A CIRUGA DE CNCER DE RECTO: ANTECEDENTES:Una escisión mesorrectal total y completa es el estándar de oro en la cirugía curativa del cáncer de recto. Garantizar la calidad es un desafío en una pelvis estrecha y la obesidad amplifica las dificultades técnicas. La pelvimetría es la medición de las dimensiones pélvicas, pero su papel para medir la dificultad preoperatoria de la proctectomía está en gran medida inexplorado.OBJETIVO:Determinar los factores estructurales pélvicos asociados con la escisión mesorrectal total incompleta después de una proctectomía curativa y construir un modelo predictivo para la calidad de la escisión mesorrectal total.DISEÑO:Estudio de cohorte retrospectivo.ÁMBITO:Base de datos de un centro de referencia cuaternario de pacientes diagnosticados con adenocarcinoma de recto (2009-2017).PACIENTES:Proctectomía con intención curativa para adenocarcinoma de recto.INTERVENCIONES:Todas las mediciones radiológicas se obtuvieron a partir de imágenes de TC preoperatorias utilizando herramientas de software de procesamiento de imágenes validadas. La integridad de la escisión mesorrectal total se obtuvo a partir de informes histológicos.PRINCIPALES MEDIDAS DE VALORACIÓN:Capacidad de la pelvimetría radiológica y las mediciones de obesidad para predecir la calidad total de la escisión mesorrectal.RESULTADOS:De los 410 casos que cumplieron los criterios de inclusión, 362 tuvieron una escisión mesorrectal total completa (88%). Una regresión multivariable identificó una curva sacra más profunda (por 100 mm2); OR:1,14,[IC95%:1,06-1,23,p<0,001], y mayor distancia transversal de salida pélvica (por 10mm); OR:1,41, [IC 95%:1,08-1,84,p=0,012] como asociación independiente con escisión mesorrectal total incompleta. Un área aumentada de entrada pélvica (por 10 cm2); OR:0,85, [IC95%:0,75-0,97,p=0,02] se asoció con una mayor tasa de escisión mesorrectal completa. No se identificaron diferencias en la proporción de obesidad visceral y la obesidad visceral (proporción>0,4 vs.<0,4) entre el índice de masa corporal (<30 vs.>=30) o el sexo. Se construyó un modelo para predecir la calidad mesorrectal utilizando variables: profundidad de la curva sacra, área de la entrada pélvica y distancia transversal de la salida pélvica.LIMITACIONES:Análisis retrospectivo no controlado por la elección del abordaje quirúrgico.CONCLUSIONES:La pelvimetría predice la calidad de la escisión mesorrectal total en la cirugía del cáncer de recto y puede alertar a los cirujanos preoperatoriamente sobre casos de dificultad inusual. Este modelo predictivo puede contribuir a la estrategia de tratamiento y ayudar en la comparación de resultados entre técnicas tradicionales y novedosas de escisión mesorrectal total. (Traducción- Dr. Ingrid Melo).