The objective of this work was to assess the association of tirzepatide with changes in insulin sensitivity and beta-cell function in Japanese patients with type 2 diabetes (T2D).

This was a prespecified analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled phase 3 study in Japanese participants with T2D. Participants were randomly assigned to receive tirzepatide 5, 10, 15 mg, or dulaglutide 0.75 mg once weekly for 52 weeks. Changes from baseline in homeostatic model assessment (HOMA2) parameters were assessed by a mixed model for repeated measures. Post hoc subgroup analyses were conducted based on high and low baseline C-peptide categories (cutoff: median 1.86 µg/l).

This analysis included 636 participants (tirzepatide 5 mg: n = 159; 10 mg: n = 158; 15 mg: n = 160; dulaglutide 0.75 mg: n = 159). Fasting insulin and C-peptide levels were significantly reduced from baseline at week 52 at all three tirzepatide doses compared with dulaglutide 0.75 mg (estimated treatment differences [ETDs] for tirzepatide 5, 10, and 15 mg, respectively: insulin, - 22.6%, - 29.8%, and - 31.0%; C-peptide, - 14.2%, - 21.5%, and - 20.7%; p < 0.001 all comparisons). Insulin sensitivity and beta-cell function indices significantly increased in all tirzepatide groups compared with the dulaglutide 0.75-mg group (ETDs for tirzepatide 5, 10, and 15 mg, respectively: HOMA2-%S [insulin], 31.8%, 43.2%, and 49.9%; HOMA2-%S [C-peptide], 24.8%, 33.9%, and 38.2%; HOMA2-%B [insulin], 27.3%, 34.9%, and 40.6%; HOMA2-%B [C-peptide], 31.6%, 40.1%, and 46.7%; p < 0.001 all comparisons). Regardless of baseline C-peptide level, the tirzepatide groups showed significant improvement in glycated hemoglobin at week 52 compared with the dulaglutide group (C-peptide < 1.86 µg/l: - 2.31% to - 2.75% vs. - 1.45%; ≥ 1.86 µg/l: - 2.43% to - 2.89% vs. - 1.12%; p < 0.001).

In these prespecified and post hoc analyses, tirzepatide was associated with improved insulin sensitivity and insulin secretion in Japanese participants with T2D, which may result in reduced fasting insulin levels.

GOV: NCT03861052.

Obesity is a global health challenge and adipose tissue exhibits distinct depot-specific characteristics impacting differentially on the risk of metabolic comorbidities.

Here, we integrate chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) data from intra-individually paired human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) samples to unveil depot-specific regulatory mechanisms.

We identified twice as many depot-specific differentially accessible regions (DARs) in OVAT compared to SAT. SAT-specific regions showed enrichment for adipose tissue enhancers involving genes controlling extracellular matrix organization and metabolic processes. In contrast, OVAT-specific regions showed enrichment in promoters linked to genes associated with cardiomyopathies. Moreover, OVAT-specific regions were enriched for bivalent transcription start site and repressive chromatin states, suggesting a "lingering" regulatory state. Motif analysis identified CTCF and BACH1 as most significantly enriched motifs in SAT and OVAT-specific DARs, respectively. Distinct gene sets correlated with important clinical variables of obesity, fat distribution measures, as well as insulin, glucose, and lipid metabolism.

We provide an integrated analysis of chromatin accessibility and transcriptional profiles in paired human SAT and OVAT samples, offering new insights into the regulatory landscape of adipose tissue and highlighting depot-specific mechanisms in obesity pathogenesis.

SS received EU-Scientia postdoctoral Fellowship and project funding from the European Union's Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie Grant, (agreement No. 801133). LlCP and TR were supported by Helse Sør-Øst grants to Y.B (ID 2017079, ID 278908). MB received funding from grants from the DFG (German Research Foundation)-Projekt number 209933838-SFB 1052 (project B1) and by Deutsches Zentrum für Diabetesforschung (DZD, Grant: 82DZD00601).

Recently, weight-adjusted-waist index (WWI), a new index for evaluating obesity, has been developed. This study aimed to examine the association between WWI and T2DM in Chinese urban adults.

A total of 5,0978 eligible participants drawn from the prospective REACTION study (Cancer Risk Assessment in Chinese People with Diabetes) were included in this study. Participants were divided into 3 groups based on baseline WWI levels. Pearson correlation analysis and binary logistic regression analysis were conducted to explore the association of WWI with T2DM risk factors and with T2DM risk.

The prevalence of obesity, central obesity and T2DM was 14.2%, 46.8% and 11.0% respectively, with a median age of 57 years. Logistic analysis showed that the WWI was significantly associated with the risk of T2DM. Compared to the lowest tertile of WWI (T1) serving as the reference group, the second tertile (T2) and the third tertile (T3) were associated with a 0.218-fold [1.218 (1.152, 1.288), P <0.001] and 0.286-fold [1.286 (1.212, 1.364), P <0.001] increase in the odds of developing T2DM respectively. After adjusting for all factors with the exception of the stratified variable, this association held true in age, sex, BMI, hypertension, and hyperlipidemia subgroup and was especially pronounced in those aged <60 years, BMI ≥24 kg/m2, and males, with interactions between WWI and age, sex, and BMI (P for interaction <0.05).

WWI was positively associated with T2DM in Chinese urban adults, especially in young and middle-aged males with BMI ≥24 kg/m2.

We assess the efficacy of artificial intelligence (AI)-based, fully automated, volumetric body composition metrics in predicting the risk of diabetes.

This was a cross-sectional and 10-year retrospective longitudinal study. The cross-sectional analysis included health check-up data of 15,330 subjects with abdominal computed tomography (CT) images between January 1, 2011, and September 30, 2012. Of these, 10,570 subjects with available follow-up data were included in the longitudinal analyses. The volume of each body segment included in the abdominal CT images was measured using AI-based image analysis software.

Visceral fat (VF) proportion and VF/subcutaneous fat (SF) ratio increased with age, and both strongly predicted the presence and risk of developing diabetes. Optimal cut-offs for VF proportion were 24% for men and 16% for women, while VF/SF ratio values were 1.2 for men and 0.5 for women. The subjects with higher VF/SF ratio and VF proportion were associated with a greater risk of having diabetes (adjusted OR 2.0 [95% CI 1.7-2.4] in men; 2.9 [2.2-3.9] in women). In subjects with normal glucose tolerance, higher VF proportion and VF/SF ratio were associated with higher risk of developing prediabetes or diabetes (adjusted HR 1.3 [95% CI 1.1-1.4] in men; 1.4 [1.2-1.7] in women). These trends were consistently observed across each specified cut-off value.

AI-based volumetric analysis of abdominal CT images can be useful in obtaining body composition data and predicting the risk of diabetes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of liver disease ranging from hepatic fat accumulation to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma in the absence of excessive alcohol consumption. MASLD is characterized by substantial inter-individual variability in terms of severity and rate of progression, with a prevalence that is generally higher in men than in women. Steroids metabolism is characterized by sexual dimorphism and may have an impact on liver disease progression; indeed, several therapeutic strategies targeting hormone receptors are under phase 2/3 development. Despite the fact that the importance of sexual dimorphism in the setting of MASLD is well recognized, the underlying molecular mechanisms that can potentially drive the disease toward progression are not clear. The aim of this review is to delve into the crosstalk between sexual dimorphism and steroid hormone perturbation under nutritional and pharmacological intervention.

Type 2 diabetes mellitus (T2DM) demonstrates a higher risk of fractures compared to the healthy population. Therefore, the aim of our study is to assess the risk of osteoporosis in T2DM patients.

A cross-sectional observational study was conducted in T2DM patients. The serum levels of bone resorption markers- carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-1) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were compared in the T2DM group (n = 43) and the control group (n = 43) and its association with duration of T2DM, HbA1c level, body mass index (BMI), oral hypoglycaemic agents (OHA), and level of functioning was evaluated.

CTX-1 and TRACP-5b were significantly lower in the T2DM group compared to the control group (p < 0.05). There was no significant correlation between the bone resorption markers and the duration of T2DM and HbA1c levels. However, a significant positive correlation was found between the level of functioning and TRACP-5b level, but no such correlation was observed in T2DM patients. The linear regression model revealed that none of the OHA affected the levels of CTX-1 and TRACP-5b.

The bone resorption markers are not influenced by the duration of T2DM and HbA1c level. However, they were significantly associated with BMI and the level of functionality. However, further research is needed to strengthen the evidence of the association between T2DM and osteoporosis.

This study offers promising insights into the anti-obesity potential of Pleurotus ferulae, an edible mushroom valued in Asian cuisine for its nutritional benefits. A hot water extract of P. ferulae (PWE) administered to high-fat diet-induced obese mice over an 8-week period significantly reduced their body weight gain and fat accumulation. PWE not only improved the body weight metrics but also positively influenced the serum lipid profile of obese mice by lowering their total cholesterol and low-density lipoprotein cholesterol levels. In vitro studies using 3T3-L1 adipocytes showed that PWE inhibited adipocyte differentiation and lipid accumulation by downregulating key adipogenic transcription factors, particularly PPARγ and C/EBPα, as well as related lipogenic genes involved in fat synthesis and storage, such as Fabp4, Fasn, and Scd1. Chemical analysis revealed that PWE is rich in polysaccharides, which have been associated with various health benefits, including anti-obesity, anti-diabetic, and anti-cancer properties. These findings suggest that the bioactive compounds in PWE may serve as functional food components that could potentially be applied for the prevention and management of obesity and other metabolic disorders.

While the TyG index has been studied in relation to stroke risk, there is a lack of research integrating fat distribution indicators like Body Roundness Index (BRI) and Fat Mass Index (FMI). Additionally, comparative studies across multiple regions are scarce. This study investigates the association between obesity-related parameters and stroke incidence, examining the mediation effects of multimorbidity, using data from rural areas in China and the United Kingdom.

This cohort study included 60,685 participants (6,980 from China and 53,705 from UK). The obesity-related parameters were calculated using established formulas. The TyG index was determined as ln [TG (mg/dL) × GLU (mg/dL) / 2]. Additionally, composite indices were created by multiplying the TyG index by BMI, WC, FMI, and RBI to assess obesity-related risks. Cox regression analyses were employed on the relationship between Triglyceride Glucose index related parameters and stroke risk. Multiple mediation analysis was applied to assess the contributions of multimorbidity to obesity indicators in stroke occurrence.

After excluding those who developed stroke within two years of enrollment, the Chinese cohort (6,638 subjects, median follow-up 4.33 years) had 237 ischemic and 21 hemorrhagic strokes. The UK cohort (53,631 subjects, median follow-up 13.85 years) had 742 ischemic and 316 hemorrhagic strokes. Chinese residents had lower BMI but higher visceral obesity (BRI), higher prevalence of multimorbidity, and higher stroke incidence compared to UK residents. Cox analyses demonstrated significant associations between BMI/TyG indices and ischemic stroke in both Chinese and UK populations, which diminished after adjusting for multimorbidity. In the Chinese rural cohort, only TyG-BRI (HR:1.13, 95%CI:0.99-1.30) approached statistical significance after full adjustment for mediators. In contrast, in the UK cohort, significant associations persisted for most TyG Index indicators when full adjustment for mediators, including BMI (HR: 1.17, 95% CI: 1.09-1.26), TyG-BMI (HR: 1.16, 95% CI: 1.07-1.26), TyG-WC (HR: 1.13, 95% CI: 1.03-1.25), TyG-FMI (HR: 1.17, 95% CI: 1.07-1.28), and TyG-RBI (HR: 1.15, 95% CI: 1.06-1.24). TyG-BRI also showed the best predictive performance for ischemic stroke in Chinese rural residents (AUC > 0.7) and exhibited an almost linear relationship with ischemic stroke occurrence. Additionally, TyG-BRI presented a U-shaped relationship with the risk of hemorrhagic stroke incidence in the UK (p overall = 0.041, p non-linear = 0.017). Multimorbidity mediated the relationship between TyG indices, and ischemic stroke incidence in both cohorts. The mediation percentage for multimorbidity was higher than the sum of individual chronic diseases, with a higher mediation percentage in the Chinese cohort (up to 51%) compared to the UK cohort (up to 27.2%).

Chinese rural residents exhibit higher levels of visceral obesity compared to residents in UK, leading to greater stroke susceptibility mediated by multimorbidity. These findings underscore the importance of comprehensive management of multimorbidity for stroke prevention. The TyG-BRI may serve as a promising predictor of ischemic stroke incidence among rural community residents.

The gut microbiota has been implicated in adult obesity, but the causality is still unclear. It has been hypothesized that an obesity-prone gut microbiota can be established in infancy, but only few studies have examined the early-life gut microbiota in relation to obesity in childhood, and no consistent associations have been reported. Here, we examine the association between the early-life gut microbiota and body mass index (BMI) development and body composition throughout childhood.

Gut microbiota from stool were collected from 700 children in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort at ages of 1 week, 1month, 1 year, 4 years, and 6 years and analyzed by 16S rRNA gene sequencing. Outcomes included BMI World Health Organization (WHO) Z scores (zBMI), overweight (zBMI > 1.04) and obesity (zBMI > 1.64) (0-10 years), and adiposity rebound and body composition from dual-energy X-ray absorptiometry at 6 years.

The early-life gut microbiota diversity, overall composition, and individual taxon abundances in unsupervised and supervised models were not consistently associated with either current or later BMI Z scores, overweight, obesity, adiposity rebound, or body composition in childhood.

In a deeply characterized longitudinal birth cohort, we did not observe any consistent associations between the early-life gut microbiota and BMI or risk of obesity in later childhood. While this does not conclusively rule out a relationship, it suggests that if such associations exist, they may be more complex and potentially influenced by factors emerging later in life, including lifestyle changes.

COPSAC is funded by private and public research funds (all listed on www.copsac.com).

Visceral fat accumulation and obesity-induced chronic inflammation have been proposed as early markers for multiple disease states, especially in women. Nevertheless, the potential impact of fat distribution on α1-acid glycoprotein(AGP), a marker of inflammation, remains unclear. This research was conducted to investigate the relationships among obesity, fat distribution, and AGP levels.

A cross-sectional observational study was performed using blood samples from adult females recruited through the National Health and Nutrition Examination Survey from 2015 to 2018. Serum levels of AGP were measured using the Tina-quant α-1-Acid Glycoprotein Gen.2 assay. Based on the fat distribution data obtained from dual-energy X-ray absorptiometry assessments, body mass index (BMI), total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral percent fat (VPF), subcutaneous percent fat (SPF), visceral fat/subcutaneous fat ratio (VSR) were used as dependent variables. To investigate the link between fat distribution and AGP, multivariate linear regression analysis was utilized. Furthermore, a sensitivity analysis was also performed.

The present study included 2,295 participants. After adjusting for covariates, BMI, TPF, APF, GPF, VPF, and SPF were found to be positively correlated with AGP levels (BMI: β = 23.65 95%CI:20.90-26.40; TPF: β = 25.91 95%CI:23.02-28.80; APF: β = 25.21 95%CI:22.49-27.93; GPF: β = 19.65 95%CI:16.96-22.34; VPF: β = 12.49 95%CI:9.08-15.90; SPF: β = 5.69, 95%CI:2.89-8.49; AGR: β = 21.14 95%CI:18.16-24.12; VSR: β = 9.35 95%CI:6.11-12.59, all P < 0.0001). All the above indicators exhibited a positive dose-response relationship with AGP. In terms of fat distribution, both AGR and VSR showed positive associations with AGP (P for trend < 0.0001). In particular, when compared to individuals in tertile 1 of AGR, participants in tertiles 2 and 3 had 13.42 mg/dL (95% CI 10.66-16.18) and 21.14 mg/dL (95% CI 18.16-24.12) higher AGP levels, respectively. Participants in the highest tertile of VSR were more likely to exhibit a 9.35 mg/dL increase in AGP compared to those in the lowest tertile (95% CI 6.11-12.59).

Overall, this study revealed a positive dose-dependent relationship between fat proportion/distribution and AGP levels in women. These findings suggest that physicians can associate abnormal serum AGP and obesity with allow timely interventions.

Interactions between tissues and cell types, mediated by cytokines or direct cell-cell exchanges, regulate growth. To determine whether mature adipocytes influence the in vitro growth of trout mononucleated muscle cells, we developed an indirect coculture system, and showed that adipocytes (5 × 106 cells/well) derived from perivisceral adipose tissue increased the proliferation (BrdU-positive cells) of the mononucleated muscle cells (26% vs. 39%; p < 0.001) while inhibiting myogenic differentiation (myosin+) (25% vs. 15%; p < 0.001). Similar effects were obtained with subcutaneous adipose tissue-derived adipocytes, although requiring more adipocytes (3 × 107 cells/well vs. 5 × 106 cells/well). Conditioned media recapitulated these effects, stimulating proliferation (31% vs. 39%; p < 0.001) and inhibiting myogenic differentiation (32 vs. 23%; p < 0.001). Adipocytes began to reduce differentiation after 24 h, whereas proliferation stimulation was observed after 48 h. While adipocytes did not change pax7+ and myoD1/2+ percentages, they reduced myogenin+ cells showing inhibition from early differentiation stage. Finally, adipocytes increased BrdU+ cells in the Pdgfrα+ population but not in the myoD+ one. Collectively, our results demonstrate that trout adipocytes promote fibro-adipocyte precursor proliferation while inhibiting myogenic cells differentiation in vitro, suggesting the key role of adipose tissue in regulating fish muscle growth.

This study aimed to explore the associations between triglyceride glucose (TyG) index-related obesity indices and periodontitis within the American population.

This cross-sectional investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) for 2009-2014. The association between the TyG-waist-to-height ratio (TyG-WHtR), TyG-weight-adjusted-waist index (TyG-WWI), TyG-waist circumference (TyG-WC), or TyG-body mass index (TyG-BMI) and periodontitis was investigated utilizing multivariable logistic regression model, subgroup, and dose-response curve analyses.

This study enrolled 4,808 adult participants. Except for TyG-BMI, which did not exhibit a relationship with periodontitis, TyG-WHtR, [odds ratio (OR) (95% confidence interval (CI))] = 2.83 [1.58-5.10], P = 0.002], TyG-WWI [OR (95% CI) = 7.50 (3.06-18.34), P < 0.001], and TyG-WC [OR (95% CI) = 2.12 (1.23-3.64), P = 0.011] were all associated with periodontitis. Participants in the highest quartile displayed an elevated risk of periodontitis relative to their counterparts in the lowest quartile, as evidenced for TyG-WWI [OR (95% CI) = 1.72 (1.26-2.33), P = 0.001] and TyG-WC [OR (95% CI) = 1.50 (1.13-1.99), P = 0.009] in the full adjustment model. Subgroup analyses suggested more pronounced positive associations between these indices and periodontitis in participants who were < 60 years old, had a BMI ≥ 25, and did not have diabetes. The dose-response curve indicated linear responses in these associations.

This investigation identified a significant and stable association between TyG-WHtR, TyG-WWI, or TyG-WC and periodontitis, which implies a robust correlation between high insulin resistance and susceptibility to periodontitis in the American population.

Central adiposity, which is visceral and subcutaneous adiposity in the abdominal region, is a known risk factor for developing chronic cardiometabolic diseases. Central adiposity can be measured relatively inexpensively using ultrasound. Ultrasound has been shown to be precise and reliable, with measurement accuracy comparable to computed tomography and magnetic resonance. Despite the advantages conferred by ultrasound, widespread adoption has been hindered by lack of reliable standard operating procedures. To consolidate the literature and bring clarity to the use of ultrasound-derived measures of central adiposity, this review outlines (i) the [patho]physiological importance of central adiposity to cardiometabolic disease risk; (ii) an overview of the history and main technical aspects of ultrasound methodology; (iii) key measurement considerations, including transducer selection, subject preparation, image acquisition, image analysis, and operator training; and (iv) guidelines for standardized ultrasound protocols for measuring central adiposity.

Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden.

This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon.

CAMEUS was measured in 154 patients [56.5% females, mean age 56.5 ± 18.0 years, body mass index (BMI) 29.8 ± 8.0 kg/m2] and was estimated at 14.7 ± 6.5 mm. CAMEUS better correlated with the presence of non-alcoholic fatty liver disease (NAFLD) (R2 = 0.248, P < 0.001) than BMI (R2 = 0.153, P < 0.001), and significantly correlated with metabolic parameters and diseases. After six months of intragastric balloon placement, the prospective cohort experienced 11.7% total body weight loss, 1.3 points improvement in hemoglobin A1c (P = 0.001), and a 29.4% average decrease in CAMEUS (-6.4 ± 5.2 mm, P < 0.001). CAMEUS correlated with improvements in weight (R2 = 0.368), aspartate aminotransferase to platelet ratio index (R2 = 0.138), and NAFLD activity score (R2 = 0.156) (all P < 0.05).

CAMEUS is a novel measure that is significantly correlated with critical metabolic indices and can be easily captured during routine EUS to risk-stratify susceptible patients. This station could allow for EUS access to sampling and therapeutics of this metabolic region.

Obesity represents a significant global public health concern. The excessive accumulation of abdominal adipose tissue is often implicated in the development of metabolic complications associated with obesity. Our study aimed to investigate the impact of particular deposits of abdominal adipose tissue on the occurrence of carbohydrate and lipid metabolism complications. We established cut-off points for visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and the VAT/SAT ratio at which selected metabolic complications of obesity-related diseases (disorders of carbohydrate and/or lipid metabolism) occur. We conducted an observational study involving 91 subjects with first- and second-degree obesity, accounting for gender differences. Anthropometric measurements were taken, body composition analysis (BIA) was conducted, and biochemical determinations were made. Our findings suggest that commonly used parameters for assessing early metabolic risk, such as BMI or waist circumference, may overlook the significant factor of body fat distribution, as well as gender differences. Both visceral and subcutaneous adipose tissue were found to be important in estimating metabolic risk. We identified the cut-off points in women in terms of their elevated fasting glucose levels and the presence of insulin resistance (HOMA-IR: homeostasis model assessment of insulin resistance) based on SAT, VAT, and the VAT/SAT ratio. In men, cut-off points were determined for the presence of insulin resistance (HOMA-IR) based on VAT and the VAT/SAT ratio. However, the results regarding lipid disorders were inconclusive, necessitating further investigation of a larger population.

To investigate the effects of simultaneous cortisol cosecretion (CCS) on body composition in computed tomography (CT)-imaging and metabolic parameters in patients with primary aldosteronism (PA) with the objective of facilitating early detection.

Retrospective cohort study.

Forty-seven patients with PA and CCS confirmed by 1-mg dexamethasone suppression test (DST) with a cutoff of ≥1.8 µg/dL were compared with PA patients with excluded CCS (non-CCS, n = 47) matched by age and sex.

Segmentation of the fat compartments and muscle area at the third lumbar region was performed on non-contrast-enhanced CT images with dedicated segmentation software. Additionally, liver, spleen, pancreas and muscle attenuation were compared between the two groups.

Mean cortisol after DST was 1.2 µg/dL (33.1 nmol/L) in the non-CCS group and 3.2 µg/dL (88.3 nmol/L) in the CCS group with mild autonomous cortisol excess (MACE). No difference in total, visceral and subcutaneous fat volumes was observed between the CCS and non-CCS group (p = .7, .6 and .8, respectively). However, a multivariable regression analysis revealed a significant correlation between total serum cholesterol and results of serum cortisol after 1-mg DST (p = .026). Classification of the patients based on visible lesion on CT and PA-lateralization via adrenal venous sampling also did not show any significant differences in body composition.

MACE in PA patients does not translate into body composition changes on CT-imaging. Therefore, early detection of concurrent CCS in PA is currently only attainable through biochemical tests. Further investigation of the long-term clinical adverse effects of MACE in PA is necessary.

Rare variants in DYRK1B have been described in some patients with central obesity, type 2 diabetes, and early-onset coronary disease. Owing to the limited number of conducted studies, the broader impact of DYRK1B variants on a larger scale has yet to be investigated.

DYRK1B was sequenced in 9,353 participants from a case-control study for obesity and type 2 diabetes. Each DYRK1B variant was functionally assessed in vitro. Variant pathogenicity was determined using criteria from the American College of Medical Genetics and Genomics (ACMG). The effect of pathogenic or likely pathogenic (P/LP) variants on metabolic traits was assessed using adjusted mixed-effects score tests.

Sixty-five rare, heterozygous DYRK1B variants were identified and were not associated with obesity or type 2 diabetes. Following functional analyses, 20 P/LP variants were pinpointed, including 6 variants that exhibited a fully inhibitory effect (P/LP-null) on DYRK1B activity. P/LP and P/LP-null DYRK1B variants were associated with increased BMI and obesity risk; however, the impact was notably more pronounced for the P/LP-null variants (effect of 8.0 ± 3.2 and odds ratio of 7.9 [95% CI 1.2-155]). Furthermore, P/LP-null variants were associated with higher fasting glucose and type 2 diabetes risk (effect of 2.9 ± 1.0 and odds ratio of 4.8 [95% CI 0.85-37]), while P/LP variants had no effect on glucose homeostasis.

P/LP, total loss-of-function DYRK1B variants cause monogenic obesity associated with type 2 diabetes. This study underscores the significance of conducting functional assessments in order to accurately ascertain the tangible effects of P/LP DYRK1B variants.

The metabolic syndrome (MetS) refers to the co-occurrence of risk factors, including hyperglycaemia, increased body weight, hypertension and dyslipidemia, which eventually lead to diabetes and cardiovascular disease, a common health problem worldwide. Recently, there has been an increasing interest in the use of plant-based products for the management of MetS, because of their less detrimental and more beneficial effects. Moringa oleifera (Moringaceae), commonly known as drumstick, is cultivated worldwide for its nutritional and medicinal properties. This review focuses on the in vivo and human studies concerning the potential of M. oleifera in the alleviation of MetS and its comorbidities. The search for relevant articles was carried out in PubMed and Google Scholar databases. Randomised controlled and clinical trials from the PubMed database were included in this review. The results suggested that the administration of M. oleifera, in vivo, shows clear signs of improvement in MetS indices. Despite fewer human studies, the existing data documented convincing results that uphold the potential of M. oleifera against MetS. Therefore, future research discussing the probable mechanism of action is much needed which could further assure the usage of M. oleifera in the treatment regimen of MetS.

Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one of the initial lines of management strategies for obesity, but they are not very efficient management strategies. Many people also use surgical intervention to maintain a healthy weight, now considered to be the most common and effective obesity management. Chemically synthesized medicines fill the gap between lifestyle interventions and minimally invasive surgical management of obesity. The most common issue associated with monotherapy without side effects is its moderate effectiveness and higher dose requirement. Combination therapy is already used for many serious and complicated disease treatments and management and has shown efficacy as well. Generally, we use two or more medicines with different mechanisms of action for a better effect. The commonly used combination therapy for obesity management includes low-dose phentermine and prolonged and slow-releasing mechanism topiramate; naltrexone, and bupropion. Phentermine with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonists with gastric hormone or Na-glucose cotransporter-2 are two more viable combo therapy. This combination strategy aims to achieve success in bariatric surgery and the scientific community is working in this direction.

Obesity is a complex and heterogeneous condition that leads to various metabolic complications, including type 2 diabetes. Unfortunately, for some, treatment options to date for obesity are insufficient, with many people not reaching sustained weight loss or having improvements in metabolic health. In this Review, we discuss advances in the genetics of obesity from the past decade-with emphasis on developments from the past 5 years-with a focus on metabolic consequences, and their potential implications for precision management of the disease. We also provide an overview of the potential role of genetics in guiding weight loss strategies. Finally, we propose a vision for the future of precision obesity management that includes developing an obesity-centred multidisease management algorithm that targets both obesity and its comorbidities. However, further collaborative efforts and research are necessary to fully realise its potential and improve metabolic health outcomes.

We aimed to investigate whether serum cortisol associate with diabetic microvascular compliments in patients with type 2 diabetes mellitus (T2DM).

The subjects were recruited from hospitalized patients with T2DM from 2019 to 2021. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to cortisol quartiles were obtained by multiple logistic regression analysis.

(1) Cortisol level was positively correlated with the severity of microalbuminuria. The OR (95% CI) of microalbuminuria and macroalbuminuria in the last quartile were 3.396 (2.030, 5.682) and 8.407 (3.726, 18.971) compared with the first quartile (p < 0.001). (2) Cortisol level was positively correlated with the severity of diabetic retinopathy (DR). The OR (95% CI) of non-proliferative diabetic retinopathy group (NPDR) and proliferative diabetic retinopathy group (PDR) in the last quartile were 2.007 (1.401, 2.875) and 7.122 (2.525, 20.090) compared with the first quartile. (3) Elevated cortisol level was associated with diabetic peripheral neuropathy. The OR (95% CI) of diabetic peripheral neuropathy (DPN) in the last quartile was 1.956 (1.371, 2.792) and that in the third quartile was 1.854 (1.319, 2.608).

High serum cortisol levels were significantly associated with diabetic microvascular compliments in inpatients. Its causality remains to be further studied.

ChiCTR2100051749.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance and closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter-gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutionary model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are affected by today's contemporary environment through epigenetic events that predispose women to lipotoxicity, with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today's obesogenic environment.

Insulin, a small protein with 51 amino acids synthesized by pancreatic β-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.

Obesity, accumulation of adipose tissue, is a global disease that can lead to cardiovascular and metabolic complications. The aim of this study was to investigate the relationship between obesity indicators and metabolic risk factors in type 2 diabetes mellitus (T2DM) patients.

A total of 337 T2DM subjects were included in our study. The metabolic risk factors including diabetes duration, fast plasma glucose (FPG), height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), estimated average glucose (eAG), glycated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (Scr), free fatty acid (FFA), uric acid (UA), cystatin c (cysc), albumin (Alb), urinary albumin creatinine ratio (UACR) were recorded. The obesity indicators included body surface area (BSA), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), para-perirenal fat thickness (PRFT), total abdominal fat (TAF), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT). The association between obesity indicators and metabolic risk factors was investigated by univariate and multivariate analysis.

HDL-c was independently associated with WHR and PRFT (β = -0.126 vs. -0.214, both p < 0.05). TG and Scr were both independently associated with PRFT (β = 0.173 vs. 0.218, both p < 0.01, respectively). UA was independently associated with BSA (β = 0.172, p < 0.01) and PRFT (β = 0.151, p < 0.01). cysc, Alb and UACR were independently associated with WC (β = 0.274 vs. 0.204 vs. 0.182, all p < 0.01).

In T2DM patients, obesity indicators were significantly associated with metabolic risk factors.

Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, and weight loss through caloric restriction and enhanced physical activity is the recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review and meta-analysis, we evaluated the anthropometric, biochemical, and hepatic impacts of IF in patients with NAFLD.

MEDLINE, EMBASE, Cochrane Central, and conference abstracts were searched for IF interventions in adults with NAFLD until April 2, 2023. Meta-analysis with a random effects model was used to compare pre-intervention and post-intervention changes in anthropometric, biochemical, and hepatic end points in the IF intervention group with the control group. Publication bias was assessed using Egger's test.

Fourteen studies were included in the systematic review and ten in the meta-analysis (n = 840 participants, 44.64% male). Studies varied in modalities for NAFLD diagnosis, duration of IF (4-52 weeks), and type of IF (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, and waist to hip ratio all significantly improved following fasting intervention (p< 0.05). Adults with NAFLD showed an improvement in serum alanine transaminase, aspartate aminotransferase, hepatic steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), and hepatic stiffness (measured by vibration-controlled transient elastography) after fasting intervention (p < 0.05).

There is limited, but moderate- to high-quality evidence to suggest that IF can improve hepatic end points and promote weight loss in adults with NAFLD. Larger randomized controlled studies with extended duration are needed to further validate our findings.

Obesity is a global health problem that affects the quality of life. It is a multidimensional chronic risk factor for major medical conditions, such as cardiovascular diseases, diabetes, and cancer. This clinical trial evaluated the efficacy of Lactobacillus sakei OK67 (DW2010), a lactic acid bacterium, in reducing body and visceral fat in overweight individuals (body mass index ≥25 kg/m² and <30 kg/m²), aged 20-60 years. A total of 100 subjects placed in a lifestyle modification program were randomly assigned to receive either DW2010 (2.0 g/day, 1.0 × 10¹⁰ CFU) or a placebo for 12 weeks. The efficacy of DW2010 was evaluated by measuring body fat mass using dual-energy X-ray absorptiometry and visceral fat area using computed tomography. After 12 weeks, the change in body fat in the DW2010 group was not markedly different from that in the placebo group. However, visceral fat area decreased more in the DW2010 group than in the placebo group (p = 0.035). During the clinical trial, no major adverse events were reported. Moreover, no statistical differences were observed in the biochemical parameters of the DW2010 and placebo groups. Overall, we concluded that the intake of DW2010 for 12 weeks is safe and potentially reduces visceral fat in lifestyle-modified overweight subjects.

To identify periods of heightened susceptibility to the association of secondhand tobacco smoke (SHS) exposure with cardiometabolic (CM) risk at age 12 years.

We used data from 212 adolescents from the HOME Study, a prospective pregnancy and birth cohort in Cincinnati, OH. Using multiple informant models, we estimated associations of maternal serum cotinine (mean of concentrations at 16 and 26 weeks of pregnancy) and children's serum cotinine concentrations (mean of concentrations at ages 1, 2, 3, and 4 years) with a CM risk summary score constructed of five risk components measured at age 12 years. We determined if these associations differed for pre- and postnatal exposure periods, and adolescent's sex.

We found some evidence that the cotinine-outcome associations differed by exposure period and sex. Postnatal, but not prenatal, cotinine was associated with higher CM risk scores and individual CM risk component values (interaction p-values = 0.04 to 0.35). Each 10-fold increase in postnatal cotinine was associated with 0.57 (95% CI: 0.32, 1.45), 0.09 (95% CI: 0.13, 0.31), 0.14 (-0.08, 0.35), 0.07 (95% CI: 0.34, 0.48), and 0.11 (95% CI: 0.04, 0.27) higher CM risk, HOMA-IR, TG to HDL-C ratio, leptin to adiponectin ratio, and visceral fat area. Postnatal cotinine was associated with higher visceral fat area among females but not males (sex × period × cotinine interaction p-value = 0.01).

Serum cotinine concentrations during the postnatal period had greater influence on adolescent's CM risk compared to the prenatal period, and these associations may be sex-specific. This study reinforces the need for ongoing public health interventions to minimize children's exposure to SHS.

This prospective observational study aimed to assess the association between maternal abdominal subcutaneous and visceral fat thickness measured with ultrasound scan during the first trimester and the risk of developing gestational diabetes mellitus (GDM).

We recruited 43 non-diabetic women with singleton pregnancy between 11 and 14 week of gestation and evaluated ultrasonographic measurements of subcutaneous fat thickness (SFT) and preperitoneal fat (PF) above the umbilicus. During the 2^nd trimester, GDM screening was performed by 75 g two-hour oral glucose tolerance test (OGTT) and diagnosis was made when one or more plasma glucose values meets or exceeds the values indicated by International Association of the Diabetes and Pregnancy Study Groups (IADPSG).

Among the 43 woman, 8 developed GDM (18.6%). Of these 37,5% (N.=3) had been diagnosed with GDM during a previous pregnancy, with a statistically significant correlation (P=0.035). Mean SFT for all patients was significantly higher in the GDM group compared to non-GDM group (27.30±8.78 mm vs. 18.56±9.99 mm; P=0.049). Mean PF for all women showed a statistically significant correlation with GDM (13.27±9.07 mm for non GDM group vs. 23.52±10.24 mm for GDM group; P=0.038).

Abdominal adiposity, both subcutaneous and visceral, seem to be a suitable predictor of GDM in early pregnancy and it can be easily assessed during a first trimester routine ultrasound, although further studies are needed to evaluate their role in the screening protocols.

The development of adipose tissue during adolescence may provide valuable insights into obesity-associated diseases. We propose an automated convolutional neural network (CNN) approach using Dixon-based magnetic resonance imaging (MRI) to quantity abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in children and adolescents.

474 abdominal Dixon MRI scans of 136 young healthy volunteers (aged 8-18) were included in this study. For each scan, an axial fat-only Dixon image located at the L2-L3 disc space and another image at the L4-L5 disc space were selected for quantification. For each image, an outer and an inner region around the abdomen wall, as well as SAT and VAT pixel masks, were generated by expert readers as reference standards. A standard U-Net CNN architecture was then used to train two models: one for region segmentation and one for fat pixel classification. The performance was evaluated using the dice similarity coefficient (DSC) with fivefold cross-validation, and by Pearson correlation and the Student's t-test against the reference standards.

For the DSC results, means and standard deviations of the outer region, inner region, SAT, and VAT comparisons were 0.974 ± 0.026, 0.997 ± 0.003, 0.981 ± 0.025, and 0.932 ± 0.047, respectively. Pearson coefficients were 1.000 for both outer and inner regions, and 1.000 and 0.982 for SAT and VAT comparisons, respectively (all p = NS).

These results show that our method not only provides excellent agreement with the reference SAT and VAT measurements, but also accurate abdominal wall region segmentation. The proposed combined region- and pixel-based CNN approach provides automated abdominal wall segmentation as well as SAT and VAT quantification with Dixon MRI and enables objective longitudinal assessment of adipose tissues in children during adolescence.

Clinical heterogeneity exists in overall obesity and abdominal obesity in terms of insulin secretion and sensitivity. Further, the impact of visceral fat (VF) on the first- and second-phase insulin secretion (FPIS and SPIS) is controversial. We aim to investigate insulin secretion and sensitivity in Chinese patients with T2DM according to different BMI and VF levels.

This study enrolled 300 participants. A dual bioelectrical impedance analyzer was used to assess the visceral and subcutaneous fat area (VFA and SFA). VF levels were categorized as normal or high, with the cutoff value of 100 cm². FPIS and SPIS were evaluated by arginine stimulation test and standardized steamed bread meal tolerance test, respectively. β-cell function (HOMA2-β), insulin resistance (HOMA2-IR), and Gutt's insulin sensitivity index (Gutt-ISI) were also calculated. Spearman's correlation analysis and multivariate linear regression analysis were adopted for statistical analysis.

Participants were categorized into four groups: normal weight-normal VF, normal weight-high VF, overweight/obese-normal VF and overweight/obese-high VF. Multivariate linear regression showed that both VFA and SFA were correlated with FPIS, HOMA2-IR and Gutt-ISI after controlling for gender and diabetes duration. After further adjustment for BMI and VFA, some associations of SFA with insulin secretion and sensitivity disappeared. After adjustment for gender, diabetes duration, BMI and SFA, VFA was positively correlated with FPIS, SPIS and HOMA2-IR. Subjects with overweight/obese-high VF were more likely to have higher FPIS, HOMA2-IR and lower Gutt-ISI (all p < 0.05).

VF affects both FPIS and SPIS, and worsens insulin sensitivity independent of BMI and subcutaneous fat in Chinese patients with T2DM.

http://www.chictr.org.cn, identifier ChiCTR2200062884.

The incretin hormone glucagon-like peptide-1 (GLP-1) slows gastric emptying, increases satiety and enhances insulin secretion. GLP-1 receptor agonists, such as liraglutide, are used therapeutically in humans to improve glycaemic control and delay the onset of type 2 diabetes mellitus (T2DM). In UCD-T2DM rats, a model of polygenic obesity and insulin resistance, we have previously reported that daily liraglutide administration delayed diabetes onset by >4 months. Growth hormone (GH) may exert anti-diabetic effects, including increasing β-cell mass and insulin secretion, while disrupting GH signalling in mice reduces both the size and number of pancreatic islets. We therefore hypothesized that GH supplementation would augment liraglutide's anti-diabetic effects.

Male UCD-T2DM rats were treated daily with GH (0.3 mg/kg) and/or liraglutide (0.2 mg/kg) from 2 months of age. Control (vehicle) and food-restricted (with food intake matched to liraglutide-treated rats) groups were also studied. The effects of treatment on diabetes onset and weight gain were assessed, as well as measures of glucose tolerance, lipids and islet morphology.

Liraglutide treatment significantly reduced food intake and body weight and improved glucose tolerance and insulin sensitivity, relative to controls. After 4.5 months, none of the liraglutide-treated rats had developed T2DM (overall p = .019). Liraglutide-treated rats also displayed lower fasting triglyceride (TG) concentrations and lower hepatic TG content, compared to control rats. Islet morphology was improved in liraglutide-treated rats, with significantly increased pancreatic insulin content (p < .05 vs. controls). Although GH treatment tended to increase body weight (and gastrocnemius muscle weight), there were no obvious effects on diabetes onset or other diabetes-related outcomes.

GH supplementation did not augment the anti-diabetic effects of liraglutide.

Abdominal subcutaneous fat tissue (ASFT) is an independent predictor of mortality. This prospective observational study aimed to establish a rapid, safe, and convenient estimation equation for abdominal subcutaneous fat area (SFA) using bioimpedance analysis (BIA) combined with sagittal abdominal diameter (SAD). A total of 520 adult subjects were recruited and were randomly divided into 2/3 (n = 346) and 1/3 (n = 174) to form a modeling group (MG) and a validation group (VG), respectively. Each subject's abdomen was scanned using computed tomography to obtain target variables (SFA_CT). Predictor variables for all subjects included bioimpedance index (h²/Z), anthropometric parameters height (h), weight (W), waist circumference (WC), hip circumference (HC), and SAD, along with age and sex (male =1, female = 0). SFA estimation equation SFA_BIA+SAD was established for the MG using stepwise multiple regression analysis. Cross-validation was performed using VG to evaluate the performance of the SFA_BIA+SAD estimation equation. Stepwise multiple regression analysis was applied from the MG, including SFA_BIA+SAD = 49.89 + 1.09 SAD-29.90 Sex + 4.71 W-3.63 h²/Z-1.50 h (r = 0.92, SEE = 28.10 cm², n = 346, p < 0.001). Mean differences in SFA_BIA+SAD relative to SFA_CT were -1.21 ± 21.53, 2.85 ± 27.16, and -0.98 ± 36.6 cm² at different levels of obesity (eutrophic, overweight, obese), respectively. This study did not have a large number of samples in different fields, so it did not have completely external validity. Application of BIA combined with SAD in anthropometric parameters achieves fast, accurate and convenient SAF measurement. Results of this study provide a simple, reliable, and practical measurement that can be widely used in epidemiological studies and in measuring individual SFA.

This review offers an overview of the relationship between diabetes, obstructive sleep apnea (OSA), obesity, and heart disease. It then addresses evidence that the traditional understanding of this relationship is incomplete or misleading. In the process, there is a brief discussion of the evolutionary rationale for the development and retention of OSA in light of blood sugar dysregulation, as an adaptive mechanism in response to environmental stressors, followed by a brief overview of the general concepts of epigenetics. Finally, this paper presents the results of a literature search on the epigenetic marks and changes in gene expression found in OSA and diabetes. (While some of these marks will also correlate with obesity and heart disease, that is beyond the scope of this project). We conclude with an exploration of alternative explanations for the etiology of these interlinking diseases.

As a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.

It remains controversial whether body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), or triglyceride glucose (TyG) index has a stronger association with diabetes. The aims of the study were to compare the magnitude of associations of four indicators with diabetes risk.

Data collected from annual health examination dataset in the Xinzheng during 2011 and 2019. A total of 41,242 participants aged ≥ 45 years were included in this study. Cox proportional hazard regression models were used to examine associations between the four indicators and diabetes risk.

After 205,770 person-years of follow up, diabetes developed in 2,472 subjects. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of diabetes (highest vs reference group) were 1.92 (1.71-2.16) for BMI, 1.99 (1.78-2.23) for WC, 1.65 (1.47-1.86) for WHtR, and 1.66 (1.47-1.87) for TyG, respectively. In addition, the risk of diabetes increased with baseline BMI (HR: 1.30; 95% CI: 1.25, 1.35) and TyG (HR: 1.25; 95% CI: 1.20, 1.30), but the lowest HR was 0.78 (95% CI 0.65-0.92) when WC was approximately 72 cm, and 0.85 (95% CI 0.72-0.99) when WHtR was approximately 0.47 in women. In joint analyses, the highest risk was observed in participants with a high BMI combined with a high WC (HR: 2.26; 95% CI: 1.98, 2.58).

In middle-aged and elderly Chinese population, BMI and WC were more strongly associated with diabetes than WHtR or TyG, especially the combined effect of BMI and WC.

The escalating prevalence of individuals becoming overweight and obese is a rapidly rising global health problem, placing an enormous burden on health and economic systems worldwide. Whilst obesity has well described lifestyle drivers, there is also a significant and poorly understood component that is regulated by genetics. Furthermore, there is clear evidence for sexual dimorphism in obesity, where overall risk, degree, subtype and potential complications arising from obesity all differ between males and females. The molecular mechanisms that dictate these sex differences remain mostly uncharacterised. Many studies have demonstrated that this dimorphism is unable to be solely explained by changes in hormones and their nuclear receptors alone, and instead manifests from coordinated and highly regulated gene networks, both during development and throughout life. As we acquire more knowledge in this area from approaches such as large-scale genomic association studies, the more we appreciate the true complexity and heterogeneity of obesity. Nevertheless, over the past two decades, researchers have made enormous progress in this field, and some consistent and robust mechanisms continue to be established. In this review, we will discuss some of the proposed mechanisms underlying sexual dimorphism in obesity, and discuss some of the key regulators that influence this phenomenon.