We discovered two adult sisters in Colombia, lineally consanguineous, with severe obesity and undetectable serum leptin levels despite markedly elevated body fat. Their clinical profile included childhood-onset extreme weight gain, intense hunger, hyperphagia, hypogonadotropic hypogonadism, and family history of obesity. Direct sequencing of the LEP gene revealed a novel homozygous missense mutation in exon 3 (c.350G>T [p.C117F]). The presence of this mutation, undetectable leptin, and severe obesity confirmed a diagnosis of monogenic leptin deficiency. Here we describe the clinical outcomes of a 12-month treatment with recombinant human leptin (metreleptin). Metabolic and endocrine assessments were conducted before and after therapy. Metreleptin therapy significantly reduced BMI: from 59 to 38 kg/m2 (OBX1, age 27) and 60 to 48 kg/m2 (OBX2, age 24). Total body fat mass decreased, serum lipids normalized, and insulin sensitivity improved. Hypogonadotropic hypogonadism reversed, and menstruation resumed. Thus, metreleptin reversed the major metabolic and endocrine abnormalities associated with leptin deficiency in these sisters. Limitations include the small sample size, absence of a control group, and lack of anti-metreleptin antibody measurements. Nevertheless, our findings support that leptin replacement with metreleptin is currently the only effective hormonal treatment for this monogenic form of human obesity.

Obesity, insulin resistance (IR), and diabetes are common in heart failure with preserved ejection fraction (HFpEF) and are associated with worsening heart failure, but their independent contributions remain unknown.

In this study, we sought to determine the contribution of diabetes vs obesity to left heart abnormalities in HFpEF METHODS: Indices of adiposity (body mass index [BMI], bioimpedance fat mass, waist circumference) and IR (homeostasis-model assessment [HOMA]) were measured among PVDOMICS study participants with HFpEF. Rest and exercise pulmonary capillary wedge pressure (PCWP) responses were compared, stratified by obesity (BMI ≥30 kg/m2), IR status (HOMA-IR ≥2.6), and diabetes diagnosis. Findings were also tested in an independent HFpEF cohort.

Of 276 patients with HFpEF, 246 (89%) had increased waist/height ratio, and 166 (60%) had BMI ≥30 kg/m2, with 114 (69%) of the latter having IR and 75 (45%) having diabetes. Of 110 (40%) with HFpEF and BMI <30 kg/m2, 44 (40%) had IR and 27 (25%) had diabetes (both P < 0.0001 vs obesity phenotype). The presence of IR was not associated with worse left heart remodeling or PCWP. In contrast, obesity (regardless of IR status) was associated with greater biventricular enlargement, worse exercise performance, poorer quality of life, and higher rest and exercise PCWP (P < 0.01 for all). Obesity was associated with higher rest and dynamic PCWP responses (+4.4 mm Hg; 95% CI: +2.5 to +6.4 mm Hg; P < 0.0001), even after adjustment for HOMA-IR (+4.7 mm Hg; 95% CI: +2.7 to +6.7 mm Hg; P < 0.0001). Greater fat mass, BMI, and waist circumference were associated with higher PCWP at rest and exercise (P < 0.0009 for all), but HOMA-IR was not (+0.01 mm Hg; 95% CI: -0.13 to +0.16 mm Hg; P = 0.84). Findings were similar evaluating diabetes in place of IR, and were replicated in the independent HFpEF cohort (n = 254), where BMI remained independently associated with higher rest and exercise PCWP (+0.19 mm Hg [95% CI: +0.11 to +0.27 mm Hg] per kg/m2; P < 0.0001), but diabetes was not.

Excess adiposity is present in most patients with HFpEF, even among those not considered obese according to BMI, calling for further study of cardiometabolic therapies among patients with HFpEF and excess adiposity with BMI <30 kg/m2. Although excess body fat is associated with IR and diabetes, cardiac remodeling, hemodynamics, and functional impairment are independently correlated with body fat, but not IR. These findings suggest that diabetes is primarily a marker of greater adiposity in HFpEF, with less direct impact on heart failure severity. (Pulmonary Vascular Disease Phenomics Program [PVDOMICS]; NCT02980887).

Background Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in reproductive-aged women, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. It is often associated with insulin resistance, increasing risks for metabolic disorders such as diabetes and cardiovascular disease. Elevated interleukin-6 (IL-6) levels indicate chronic inflammation, a key component in PCOS pathogenesis, though its precise role and diagnostic potential remain unclear. Objective This study aims to evaluate the relationship between IL-6 concentrations and the severity of insulin resistance in patients with PCOS and to assess the potential of IL-6 as a diagnostic biomarker for insulin resistance within these patients. Methodology This cross-sectional study was carried out from February 2024 to January 2025 at the Departments of Medicine and Gynecology, Mardan Medical Complex Teaching Hospital, Khyber Pakhtunkhwa, Pakistan. Patients were divided into insulin-resistant and non-insulin-resistant groups based on clinical assessments. Pearson correlation and linear regression analyses were employed to investigate the relationship between IL-6 levels and study variables, adjusting for significant correlations and potential confounders. The relationship between insulin resistance and IL-6 levels was examined through linear regression. The study also evaluated IL-6's predictive ability for insulin resistance using receiver operating characteristic (ROC) curve analysis, calculating the area under the curve (AUC), with a significance threshold set at p<0.05. Results This study includes 112 patients with PCOS, and significant differences were identified between insulin-resistant (39.29%, 44 patients) and non-insulin-resistant patients (60.71%, 68 patients). IL-6 levels were notably higher in insulin-resistant patients (287.00±84.33 pg/mL) compared to non-resistant patients (159.16±52.36 pg/mL). PCOS patients revealed a complex relationship better described by a simple linear regression model (R²=0.56). Additionally, ROC curve analysis demonstrated the classifier's high diagnostic accuracy (AUC=0.91) Conclusion IL-6 levels in PCOS patients were significantly influenced by a combination of physiological, metabolic, and symptomatic factors. BMI, polycystic ovaries, and specific metabolic markers emerged as key predictors, underscoring the multifaceted role of IL-6 in the pathophysiology of PCOS.

Background and Aims: Chronic kidney disease (CKD) is a recognized extra-hepatic disease of nonalcoholic fatty liver disease (NAFLD). With the redefinition of NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD), the importance of cardiovascular metabolic factors in MASLD has been highlighted. However, whether MASLD remains independently associated with the prevalence of CKD is yet to be determined. Method: We analyzed data from 6567 non-pregnant adults from the National Health and Nutrition Examination Survey 2017-2020. MASLD was identified using liver ultrasound transient elastography and five cardiovascular risk factors. Multivariate logistic regression, subgroup analysis, and restricted cubic splines were employed to explore the associations and interactions within the data. Results: The prevalence of CKD across MASLD subgroups with different combinations of cardiometabolic risk factors varied. Univariate regression analysis indicated a significant association between MASLD and CKD (OR: 1.68, p < 0.001). This association was not significant after adjusting for diabetes (OR: 0.94, p = 0.74) or insulin resistance (OR: 1.00, p = 0.98) and was not significant in the fully adjusted model (OR: 0.87, p = 0.64). Subgroup analysis confirmed insulin resistance as a modifier in the MASLD-CKD relationship (p for interaction = 0.02). Multivariate analysis revealed that liver stiffness measurements (LSMs) were independently associated with CKD. LSM values showed an S-shaped correlation with CKD, with risk increasing above the 8.612 kPa threshold. Conclusions: This study suggests that the direct relationship between MASLD and CKD diminished when accounting for insulin resistance. Nevertheless, liver fibrosis emerges as an independent CKD risk factor, emphasizing the critical need for targeted CKD screening among MASLD patients, particularly those with insulin resistance or advanced fibrosis.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severely progressive disease that leads to right heart failure and death. Previous studies have shown that diabetes and insulin resistance (IR) are closely related to pulmonary hypertension, but the role of IR in patients with CTEPH remains unexplored. In this study, we investigated the relationship between four insulin resistance indices and disease severity, hemodynamic parameters, and adverse outcomes in patients with CTEPH.

We conducted a multicenter, retrospective cohort study involving 516 patients diagnosed with CTEPH between January 2013 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass (TyG-BMI) index were used to quantify IR levels in patients with CTEPH. The primary endpoint events were clinical worsening. Multivariable Cox regression, restricted cubic splines, and receiver operating characteristic analyses were used to evaluate the predictive value of surrogates for IR.

Compared with in low to intermediate-low risk patients, the METS-IR (36.2 ± 6.7 vs. 37.7 ± 8.7, p = 0.038) and TyG-BMI index (204.0 ± 36.2 vs. 212.6 ± 46.5, p = 0.022) were significantly increased in high to intermediate-high risk patients. METS-IR correlated with markers of disease severity, such as World Health Organization functional class, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide levels. During a mean of 2.5 years' follow-up, 110 participants experienced all-cause death or worsening condition. METS-IR independently predicted clinical worsening (hazard ratio: 1.27; 95% confidence interval 1.06-1.53 per 1.0-standard deviation increment, p = 0.009) after fully adjusting for covariates. Adding METS-IR to the COMPERA 2.0 risk score significantly improved its predictive ability, reclassification and discrimination ability.

METS-IR is an independent predictor of clinical worsening in patients with CTEPH. It offers a convenient marker for assessing disease severity and long-term outcomes in clinical risk assessment.

Introduction Insulin resistance (IR) plays a key role in the development of metabolic syndrome (MetS), type 2 diabetes, and cardiovascular disease. The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is widely used to estimate IR, but there is no consensus on the optimal cutoff values for identifying individuals at risk. This study aims to compare two methodologies, percentile distributions and receiver operating characteristic (ROC) curve analysis, for determining optimal HOMA-IR cutoff values in a population from Mexico City. Methods This cross-sectional study included 765 adults recruited from a hospital outpatient clinic in Mexico City. Participants were divided into two groups: a reference group of individuals with healthy weight and fasting plasma glucose and a MetS group of overweight or obese individuals classified based on the presence or absence of MetS. HOMA-IR values were analyzed using the 75th percentile in the reference group and ROC curve analysis in the MetS group. Optimal cutoffs were determined using the Youden index. Results We include a total of 765 patients, 218 subjects in the reference group and 547 for the ROC curve analysis. HOMA-IR percentiles 75th and 90th were 2.72 and 3.71, respectively. ROC curve analysis yielded higher cutoff values for MetS diagnosis than the percentile-based method. The percentile-based approach allowed for earlier identification of individuals at risk, including those without clinical manifestations of MetS. Conclusions This study highlights the variability in HOMA-IR cutoff values across methodologies and emphasizes the importance of population-specific reference values. A percentile-based approach proves effective for early detection of IR, facilitating preventive interventions during the preclinical stage. These findings support using percentile-based cutoffs as a practical tool for improving risk assessment and guiding clinical decision-making.

Ectopic olfactory receptors are expressed in nonolfactory tissues and perform diverse roles including regulation of glucose homeostasis. We explored the effect of citronellal treatment on olfactory receptor 4M1 subtype (OR4M1) signaling in insulin resistance and Type II diabetes in rats. We aimed to validate the anti-diabetic effect of citronellal through Asprosin/OR4M1 modulation. Exploring new antidiabetics and pharmacological targets is important to improve quality of life and limit complications. The model was established in Sprague-Dawley rats by a high-fat diet for 4 weeks followed by a single low-dose streptozotocin (STZ) (35 mg/kg/ip). One week after STZ injection, oral citronellal (100 mg/kg) was administered for 4 weeks. Citronellal lowered serum glucose and triglycerides and ameliorated OGTT and HOMA-IR results. Docking results revealed that citronellal blocked the Asprosin binding site at OR4M1. The hepatic expression of OR4M1 and Asprosin was reduced. Citronellal lowered cAMP levels causing attenuated levels of protein kinase A and downstream gluconeogenic enzymes: glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. Citronellal also inhibited the expression of hepatic TLR-4 and inhibited JNK phosphorylation. Citronellal attenuated hepatic levels of NF-κB, p-NF-κB, and downstream proteins MCP-1 and TNF-α. These results suggest that citronellal alleviates insulin resistance by mitigating Asprosin/OR4M1 and Asprosin/TLR4/JNK signaling.

To examine factors underlying why most, but not all, adults with obesity exhibit impaired insulin-mediated glucose uptake, we compared: (1) adipose tissue fatty acid (FA) release, (2) skeletal muscle lipid droplet (LD) characteristics, and (3) insulin signalling events, in skeletal muscle of adults with obesity with relatively high versus low insulin-mediated glucose uptake.

Seventeen adults with obesity (BMI: 36 ± 3 kg/m2) completed a 2 h hyperinsulinemic-euglycemic clamp with stable isotope tracer infusions to measure glucose rate of disappearance (glucose Rd) and FA rate of appearance (FA Ra). Skeletal muscle biopsies were collected at baseline and 30 min into the insulin infusion. Participants were stratified into HIGH (n = 7) and LOW (n = 10) insulin sensitivity cohorts by their glucose Rd during the hyperinsulinemic clamp (LOW< 400; HIGH >550 nmol/kgFFM/min/[μU/mL]).

Insulin-mediated suppression of FA Ra was lower in LOW compared with HIGH (p < 0.01). In skeletal muscle, total intramyocellular lipid content did not differ between cohorts. However, the size of LDs in the subsarcolemmal region (SS) of type II muscle fibres was larger in LOW compared with HIGH (p = 0.01). Additionally, insulin receptor-β (IRβ) interactions with regulatory proteins CD36 and Fyn were lower in LOW versus HIGH (p < 0.01), which aligned with attenuated insulin-mediated Tyr phosphorylation of IRβ and downstream insulin-signalling proteins in LOW.

Collectively, reduced ability for insulin to suppress FA mobilization, with accompanying modifications in intramyocellular LD size and distribution, and diminished IRβ interaction with key regulatory proteins may be key contributors to impaired insulin-mediated glucose uptake commonly found in adults with obesity.

The effects of social isolation (SI) during middle age remain unclear, so we tested the hypothesis that SI would lead to an increase in impulsive choice (IC), anxiety-like behavior, and metabolic dysfunction in middle-aged rats. Male and female rats were housed individually or in groups of four with same-sex housing mates at 11 months of age. Two months later, IC behavior was assessed using a delay-discounting task and anxiety-like behavior through a novelty-suppressed feeding (NSF) task. Lastly, glucose tolerance and insulin sensitivity following exposure to a high-fat diet were assessed using an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). The results showed that socially isolated rats displayed more IC behavior than did group-housed rats of both sexes. However, no significant effect of housing was evident in the NSF task, OGTT, or ITT. Male rats had a higher plasma insulin concentration and insulin resistance index compared to females. Our findings demonstrate that SI in middle age is sufficient to increase IC behavior and highlight inherent sex-specific differences in metabolic profiles. These findings underscore the importance of investigating mechanisms that underlie the effects of social isolation during different stages of life.

Recent evidence in 9-year-old children with overweight/obesity followed up for 7 years until late adolescence concluded that increased physical activity (PA) decreased the risk of high fasting glucose, low insulin sensitivity, and secretion. However, whether this effect persists until young adulthood is unknown.

This observational study examined the effects of cumulative sedentary time (ST), light PA (LPA), and moderate to vigorous (MVPA) on glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) in 11-year-old children followed up for 13 years until young adulthood.

Altogether 792 children from the Avon Longitudinal Study of Parents and Children, UK, who had data on at least 2 measures of accelerometer-based movement behaviour during 11-, 15-, and 24-year follow-up clinic visits with complete fasting glucose, insulin, and HOMA-IR measures at ages 15, 17, and 24 years were included. ST, LPA, and MVPA were measured with an accelerometer.

Cumulative ST from ages 11-24 years was associated with increased odds (odds ratio 1.20, 95% CI 1.00-1.44, P = .047) and cumulative LPA was associated with the decreased odds of hyperinsulinemia (0.80, 0.66-0.96, P = .017) among participants with overweight/obesity. Cumulative MVPA was inversely associated with insulin but after accounting for the mediating role of fat mass, MVPA effect on lowering insulin decreased by 58% resulting in statistical nonsignificance. In the temporal path analyses, among participants with overweight/obesity, higher glucose at age 15 years was associated with lower LPA and MVPA at 24 years. Higher LPA at 15 years was associated with lower insulin and HOMA-IR at 24 years and vice versa.

Promoting LPA while decreasing body fat mass and ST may be considered crucial intervention targets to attenuate the risk of hyperinsulinemia and insulin resistance from childhood through young adulthood.

Excessive iron accumulation in metabolic organs such as the adipose tissue, liver, and skeletal muscle is associated with increased diabetes risk. Tissue-resident macrophages serve multiple roles, including managing inflammatory tone and regulating parenchymal iron homeostasis, thus protecting against metabolic dysfunction upon iron overload. The scavenger receptor CD163 is uniquely present on tissue-resident macrophages and plays a significant role in iron homeostasis by clearing extracellular hemoglobin-haptoglobin complexes, thereby limiting oxidative damage caused by free hemoglobin in metabolic tissues. We show that the absence of CD163 exacerbates glucose intolerance and insulin resistance in male mice with obesity. Additionally, loss of CD163 reduced the expression of iron regulatory genes (Tfr1, Cisd1, Slc40a1) in adipose tissue macrophages and anti-inflammatory (M2-like) bone marrow-derived macrophages (BMDMs). Furthermore, CD163 deficiency mediated a proinflammatory shift and limited hemoglobin scavenging specifically in M2-like BMDMs. To this end, iron buffering was diminished in inguinal white adipose tissue (iWAT) macrophages in vivo, which culminated in iron spillover into adipocytes and CD45+ CD11B- nonmyeloid immune cells in iWAT. These findings show that CD163 on tissue-resident macrophages is critical for their anti-inflammatory and hemoglobin scavenging roles, and its absence results in impaired systemic insulin action in an obese setting.

The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1 mg/L) than subjects with overweight (87.0 ± 12.8 mg/L) and obesity (83.1 ± 6.6 mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r =  - 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.

Insulin resistance (IR) is considered a major driver of the pathophysiology of polycystic ovary syndrome (PCOS), mediating the progression of hyperandrogenism and metabolic and reproductive dysfunction in patients with PCOS. Early detection of the risk of concurrent IR is essential for women with PCOS. To address this need, this study developed a predictive nomogram for assessing the risk of IR in women with PCOS, aiming to provide a tool for risk stratification and assist in clinical decision-making.

Patients with untreated PCOS-IR diagnosed in a single-center retrospective cohort study from January 2023 to December 2023 were included for nomogram construction and validation. The area under the ROC curve (AUC), calibration curve, Hosmer-Lemeshow (H-L) goodness-of-fit test, and decision curve analysis (DCA) were used to evaluate the nomogram's discrimination, calibration, and clinical decision performance. A risk stratification model based on the nomogram was then developed.

A total of 571 patients were included in the study; 400 patients enrolled before September 2023 were divided into the training and validation sets, and 171 patients enrolled later were used as the external validation set. The variables identified by logistic regression and the random forest algorithm-body mass index (BMI, OR 1.43), triglycerides (TG, OR 1.22), alanine aminotransferase (ALT, OR 1.03), and fasting plasma glucose (FPG, OR 5.19)-were used to build the nomogram. In the training, internal validation, and external validation sets, the AUCs were 0.911 (95% CI 0.878-0.911), 0.842 (95% CI 0.771-0.842), and 0.901 (95% CI 0.856-0.901), respectively. The nomogram showed good agreement between predicted and observed outcomes, and patients were categorized into low-, medium-, and high-risk groups based on their scores.

Independent predictors of untreated PCOS-IR risk were incorporated into a nomogram that effectively classifies patients into risk groups, providing a practical tool for guiding clinical management and early intervention.

Studies have linked per- and polyfluoroalkyl substances (PFAS) to chronic metabolic diseases. However, the relationship between PFAS exposure and insulin resistance (IR), a key pathophysiological basis of these metabolic diseases, in nondiabetic individuals have yet to be determined.

This study analyzed data from 3909 participants (aged ≥20) from the NHANES 2003-2018 to investigate the associations between serum levels of seven PFAS and and IR indicators, including including HOMA-IR, HOMA-β, fasting insulin, QUICKI, and TyG index. Linear and logistic regression models were used, along with a restricted cubic spline to assess dose-response. Weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models were used to assess the association between mixed PFAS exposure and IR.

Linear regression revealed that elevated exposure to PFOS [β (95 % CI): 0.04 (0.02, 0.06)], PFOA [0.04 (0.01, 0.06)], and Me_PFOSA_AcOH [0.04 (0.02, 0.06)] was associated with a higher TyG index in adults. Notably, Me_PFOSA_AcOH was negatively associated with IR when assessed by HOMA-IR >2.6 [OR (95 % CI): 0.88 (0.79, 0.98)], although this was not supported by linear regression findings. When IR was defined by a TyG index >8.6, exposure to the highest quartiles of PFOS, PFOA, and Me_PFOSA_AcOH was associated with an increased risk of IR by 63 %, 42 %, and 85 %, respectively [1.63 (1.21, 2.20); 1.42 (1.06, 1.92); 1.85 (1.37, 2.50)]. PFOS, PFOA, and Me_PFOSA_AcOH demonstrated a nonlinear dose-response relationship with IR risk. The WQS and qgcomp models revealed significant positive correlations with the TyG index.

Mixed PFAS exposure in US nondiabetic adults was positively associated with IR, as indicated by the TyG index, particularly for PFOS, PFOA, and Me_PFOSA_AcOH. Further research is needed to establish causality, and reinforcing environmental risk mitigation strategies to reduce PFAS exposure is recommended.

To explore the separate and joint association of estimated glucose disposal rate (eGDR) and high-sensitivity C-reactive protein (hsCRP) with cardiometabolic multimorbidity (CMM).

A total of 6900 participants aged 45 years or older with available data on eGDR and hsCRP and without cardiometabolic diseases at baseline from the China Health and Retirement Longitudinal Study were included. CMM was defined as the coexistence of two or more cardiometabolic diseases, including heart diseases, stroke, and diabetes.

During a median follow-up of 9.0 years, 464 (6.7 %) participants developed CMM. Low eGDR and high hsCRP separately and jointly increased the risk of CMM. The adjusted hazard ratio (HR) was 1.67 (95 % confidence interval [CI] 1.33-2.09) for low eGDR versus high eGDR, 1.43 (95 % CI 1.12-1.82) for high hsCRP versus low hsCRP) and 2.40 (95 % CI 1.77-3.27) for low eGDR plus high hsCRP versus high eGDR plus low hsCRP. The C-statistic, discriminatory power and risk reclassification significantly improved with the addition of combined eGDR and hsCRP for CMM (P < 0.001).

Low eGDR and high hsCRP were individually and jointly associated with increased risk of incident CMM. The findings highlighted the importance of joint evaluation of eGDR and hsCRP for primary prevention of CMM.

The systemic immunity-inflammation index (SII) is a newly developed biomarker that provides an integrated measure of inflammation in the body. We aim to evaluate the relationship between SII and body fat distribution.

Adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were included. The SII was computed using lymphocyte (LC), neutrophil (NC), and platelet (PC) counts as its components. Body fat distribution was assessed by (total, android, gynoid) percentage fat, total abdominal fat area, subcutaneous adipose tissue area, visceral adipose tissue area, and the ratio of visceral to subcutaneous adipose tissue area (V/S ratio). Multivariable weighted linear regression and subgroup analysis were use to examine the relationships between fat distribution and SII. Restricted cubic splines (RCS) and threshold effect analysis were used to examine analyze nonlinear associations.

After exclusions, a total of 11,192 adults with a weighted mean age of 38.46 ± 0.26 years were studied. In multivariable weighted linear regression, each level increase in log2SII was associated with increased of 0.23 SDs total percentage fat (95% CI = 0.03, 0.43) and 0.26 SDs android percentage fat (95% CI = 0.06, 0.47). Besides, the subgroup analysis showed that the positive association between SII and android percentage fat was mainly among obese individuals (BMI > 30 kg/m2) and non-obese individuals without DM or hypertension. Meanwhile, the relationship between SII and the V/S ratio was found to be significant in the female subgroup, the obese subgroup, individuals with non-alcoholic fatty liver disease (NAFLD), and those without diabetes mellitus. Finally, SII exhibited an inverted U-shaped relationship with total percentage fat, android percent fat and total abdominal fat. Accordingly, threshold effect analysis indicated a positive association between lower SII levels and total percentage fat, android percentage fat and total abdominal fat area.

In the nationwide study, it was observed that the SII exhibited a significant correlation with higher levels of body fat, specifically android fat. This association was particularly noticeable within specific subgroups of the population.

Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce.

This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance.

A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors.

PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.

Insulin resistance (IR) is closely linked to cardiometabolic diseases. Preventing and improving IR in nondiabetic populations is critically important. We aimed to investigate the relationship between Life's Essential 8 (LE8), the latest tool from the American Heart Association quantifying cardiovascular health, and IR among nondiabetic populations in the United States.

This cross-sectional study used data on 11 246 nondiabetic adults aged ≥20 years from the 2005 to 2018 the National Health and Nutrition Examination Survey. The LE8 score was classified into 2 subscale scores: health factor score and health behavior score. IR was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Weighted logistic and linear regression models analyzed associations among the LE8 score, health behavior score, health factor score, and IR. Restricted cubic spline models assessed dose-response relationships. Adjusted subgroup analyses and inverse probability of treatment weighting method also evaluated the LE8-IR relationship. Of the 11 246 participants, 4860 (43.2%) had IR. The mean LE8 score was 70.07 (95% CI, 69.57-70.58). In fully adjusted models, higher LE8 scores were associated with lower IR odds (odds ratio per 10-unit increase, 0.57 [95% CI, 0.54-0.61]). Nonlinear LE8-IR dose-response was observed. Similar patterns were seen for health behavior and health factor subscores, with stronger IR correlations for health factors. The inverse LE8-IR association was significantly more pronounced among White participants and those with higher education, higher income, and without hypertension, cardiovascular disease, or chronic kidney disease. Significant negative LE8-IR associations persisted after inverse probability of treatment weighting.

LE8 and subscale scores are negatively associated with IR in a nonlinear relationship. Promoting optimal cardiovascular health adherence may improve IR in nondiabetic populations.

To evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven cardiovascular disease and some classic cardio-metabolic risk factors.

The study included 461 obese patients with an average age of 53.2 ± 10.7 years, divided into three groups - group 1 without carbohydrate disturbances (n = 182), group 2 with prediabetes (n = 193) and group 3 with newly diagnosed diabetes mellitus (n = 86).

The patients with new-onset diabetes had significantly higher mean CIMT values compared to those with prediabetes or without carbohydrate disturbances and a higher frequency of abnormal IMT values. CIMT correlated significantly with age, systolic BP, diastolic BP and fasting blood glucose and showed a high predictive value for the presence of diabetic neuropathy and sudomotor dysfunction. Patients with abnormal CIMT values had a higher incidence of arterial hypertension, dyslipidemia, metabolic syndrome, peripheral neuropathy, and sudomotor dysfunction. Patients who developed type 2 diabetes during follow-up had a significantly higher initial mean CIMT, which showed the highest predictive value for the risk of new-onset diabetes, with CIMT≥0.7 mm having 53 % sensitivity and 83 % specificity for the risk of progression to diabetes mellitus.

Patients with new-onset diabetes mellitus had significantly greater intima media thickness of the common carotid artery and a greater frequency of abnormal CIMT values compared to those with normoglycemia and prediabetes. CIMT has a high predictive value for the presence of diabetic neuropathy, sudomotor dysfunction and the risk of new onset diabetes.

We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM).

Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study.

Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9-11.1) vs. 9.8 (7.1-12.4) mIU/ml) and TT (13.2 (10.4-16.5) vs. 16.7 (12.8-21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values < 0.05). After adjusting for potential confounding factors, FSH and LH were negative, while progesterone was positively associated with the risk of MAFLD in men, and the adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 0.919 (0.856-0.986), 0.888 (0.802-0.983), and 8.069 (2.019-32.258) (all p-values < 0.05), respectively. In women, there was no statistically significant association between sex- or thyroid-related hormones and the risk of MAFLD.

FSH and LH levels were negative, whereas progesterone was positively associated with the risk of MAFLD in men with T2DM. Screening for MAFLD and monitoring sex-related hormones are important for T2DM patients, especially in men.

Excessive iron accumulation in metabolic organs such as the adipose tissue, liver, and skeletal muscle is associated with increased diabetes risk. Tissue-resident macrophages serve multiple roles including managing inflammatory tone and regulating parachymal iron homeostasis; thus protecting against metabolic dysfunction upon iron overload. The scavenger receptor CD163 is uniquely present on tissue-resident macrophages, and plays a significant role in iron homeostasis by clearing extracellular hemoglobin-haptoglobin complexes, thereby limiting oxidative damage caused by free hemoglobin in metabolic tissues. We show that the absence of CD163 exacerbates glucose intolerance and insulin resistance in male mice with obesity. Additionally, loss of CD163 reduced the expression of iron regulatory genes (Tfr1, Cisd1, Slc40a1) in adipose tissue macrophages and anti-inflammatory (M2-like) bone marrow-derived macrophages (BMDMs). Further, CD163 deficiency mediated a pro-inflammatory shift and limited hemoglobin scavenging specifically in M2-like BMDMs. To this end, iron buffering was diminished in inguinal white adipose tissue (iWAT) macrophages in vivo, which culminated in iron spillover into adipocytes and CD45+CD11B- non-myeloid immune cells in iWAT. These findings show that CD163 on tissue-resident macrophages is critical for their anti-inflammatory and hemoglobin scavenging roles, and its absence results in impaired systemic insulin action in an obese setting.

Insulin resistance (IR) elevates cardiovascular disease (CVD) and mortality risks. Insulin resistance (IR) increases the risk of CVDs and mortality. Recently, the American Heart Association introduced the Life's Essential 8 (LE8) framework to assess cardiovascular health (CVH). However, its impact on mortality in IR populations is unknown.

Analyzing 2005-2018 National Health and Nutrition Examination Survey data, we studied 5301 IR adults (≥20 years). LE8 scores were calculated and participants were categorized into low, moderate, and high CVH groups. Systemic immune-inflammation index (SII) and heart age/vascular age (HVA) were measured as potential mediators. Cox models estimated all-cause and CVD mortality hazard ratios (HRs), stratified by LE8 score and sex, and adjusted for covariates. Mediation analyses assessed SII and HVA's indirect effects. This study is an observational cohort study.

Over a 7.5-year median follow-up, 625 deaths occurred, including 159 CVD-related. Compared to low CVH, moderate and high CVH groups showed reduced all-cause (HR = 0.72, 95% CI 0.58-0.89; HR = 0.38, 95% CI 0.22-0.67) and CVD mortality (HR = 0.42, 95% CI 0.26-0.69; HR = 0.15, 95% CI 0.04-0.57). A 10-point LE8 increase correlated with 15% and 31% reductions in all-cause and CVD mortality, respectively. SII and HVA mediated up to 38% and 12% of these effects. The LE8's protective effect was more pronounced in men.

LE8 effectively evaluates CVH and lowers mortality risk in IR adults, partially mediated by SII and HVA. The findings inform clinical practice and public health strategies for CVD prevention in IR populations.

The worldwide prevalence of obesity highlights the potential contribution of endocrine-disrupting chemicals (EDCs). However, common epidemiological measures such as body mass index and waist circumference may misrepresent the intricate obesity risks these chemicals pose across genders. This study delves deeper into abdominal fat by differentiating between subcutaneous and visceral regions by analyzing data from National Health and Nutrition Examination Surveys (NHANES). We particularly investigated the gender-specific associations between organophosphorus flame-retardant metabolites (mOPFRs), phthalates (mPAEs) and accumulated fat indexes from 2536 people. Aiding by Bayesian Kernel Machine Regression (BKMR), we found while co-exposure to mOPFRs and mPAEs was linked to general and abdominal obesity across the entire and gender-specific populations, a gender-specific fat distribution emerged. For women, urinary BDCPP and MBzP were linked to an increased subcutaneous fat index (SFI) [BDCPP OR: 1.12 (95% CI: 1.03-1.21), MBzP OR: 1.09 (95% CI: 1.01-1.18)], but not to visceral fat index (VFI). These metabolites had a combined linkage with SFI, with BDCPP (weighting 22.0%) and DPHP (weighting 31.0%) being the most influential in Quantile g-computation model (qgcomp) model. In men, BCEP exposure exclusively associated with the elevated VFI [OR: 1.14 (95% CI: 1.03-1.26)], a trend further highlighted in mixture models with BCEP as the predominant association. Intriguingly, only males displayed a marked correlation between these metabolites and insulin resistance in subpopulation. An attempted mediation analysis revealed that elevated C-reactive protein mediated 12.1% of the association between urinary BCEP and insulin resistance, suggesting a potential role of inflammation. In conclusion, the gender-specific fat distribution and insulin resistance that associated with mOPFRs represented the potential risk of these chemicals to man.

Malaria in pregnancy can have adverse outcomes if untreated. Both malaria and pregnancy are associated with insulin resistance and diabetes. Although malaria is treated prophylactically with gestational diabetes mellitus (GDM) screened for in pregnancy as part a routine antenatal care, their impacts have not been examined in terms of other forms of dysglycaemia. This cross-sectional study examined insulin resistance and its relationship with dysglycaemia and malaria among pregnant women in the Cape Coast Teaching Hospital (CCTH).

Using a structured questionnaire, demographic and clinical information were obtained from 252 pregnant women aged 18-42 years. Weight and height were measured for computation of body mass index (BMI). Measurement of insulin, lipid profile and glucose were taken under fasting conditions followed by oral glucose tolerant test. Insulin resistance and beta-cell function were assessed by the homeostatic model as malaria was diagnosed by microscopy.

The respective prevalence of GDM, gestational glucose intolerance (GGI) and insulin resistance were 0.8% (2/252), 19.44% (49/252) and 56.75% (143/252). No malaria parasite or dyslipidaemia was detected in any of the participants. Apart from BMI that increased across trimesters, no other measured parameter differed among the participants. Junior High School (JHS) education compared with no formal education increased the odds (AOR: 2.53; CI: 1.12-5.71; P = 0.03) but 2nd trimester of pregnancy compared to the 1st decreased the odds (AOR: 0.32; CI: 0.12-0.81; P = 0.02) of having insulin resistance in the entire sample. In a sub-group analysis across trimesters, pregnant women with JHS education in their 3rd trimester had increased odds (AOR: 4.41; CI: 1.25-15.62; P = 0.02) of having insulin resistance.

Prevalence of GDM and GGI were 0.8% and 19.44% respectively. The odds of insulin resistance increased in pregnant women with JHS education in the 3rd trimester. Appropriate measures are needed to assuage the diabetogenic risk posed by GGI in our setting.

Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD.

We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship.

A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively.

Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels.

Insulin resistance (IR) and adipose tissue amplify the metabolic and reproductive outcomes in women with polycystic ovary syndrome (PCOS). It has been widely discussed that body composition influences metabolic health. Still, limited studies were focused on the role of the fat-free mass index (FFMI) in assessing IR in PCOS women.

We aimed to explore the associations between FFMI/fat mass index (FMI) and IR in women with PCOS and assess the role of FFMI in predicting IR in women with PCOS.

In the current cross-sectional study, women with PCOS aged between 18 and 40 years were enrolled from October 2018 to July 2022. Baseline demographic information was obtained using standardized self-administered questionnaires. Anthropometric, biochemical, and hormonal information was measured and recorded by investigators. Pearson's correlation and multivariable logistical regression were used to analyze the associations of FFMI/FMI and IR. In addition, receiver operating characteristic (ROC) curves were implied to measure the predictive role of FFMI/FMI for IR in women with PCOS.

A total of 371 women with PCOS, reproductive age (27.58 ± 4.89) were enrolled. PCOS women with IR have higher levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), homeostatic model assessment of insulin resistance (HOMA-IR), FMI, and FFMI than that without IR. FMI (r = 0.492, p < 0.001) and FFMI (r = 0.527, p < 0.001) were positively associated with IR. After adjusting for potential confounders, FMI and FFMI were significantly associated with IR in PCOS women, and the OR was 1.385 (95%CI: 1.212-1.583) and 2.306 (95%CI: 1.675-3.174), respectively. Additionally, the FFMI (0.847, 95%CI: 0.784-0.888) has a larger area of ROC (AUC) than the FMI (0.836, 95%CI: 0.799-0.896), while there is no difference in predicting IR (95%CI: -0.18-0.41, p = 0.456).

These results indicated that FFMI and FMI could significantly increase the risk of IR, both of which could be feasible predictors of IR in PCOS women.

We prospectively evaluated the association of the insulin resistance of third-trimester Nigerian pregnant women with their newborn infants' insulin resistance and birth size. Pregnancy-associated insulin resistance (IR), often assessed with homeostatic model assessment of IR (HOMA-IR), is associated, especially among women with gestational diabetes (GDM), with abnormal neonatal birth size and body composition, predisposing the baby to metabolic disorders like diabetes and obesity. The associations of maternal IR with neonatal IR, birth size and body composition are less studied in nondiabetic pregnant women, especially in sub-Saharan settings like Nigeria.

We originally recruited 401 third trimester, nondiabetic pregnant women to a prospective cohort study, followed up until birth. Blood samples of mothers and babies were obtained, respectively, at recruitment and within 24 hours postbirth for fasting serum glucose (FSG) and insulin (FSI) assays, and HOMA-IR was calculated as [(FSI × FSG)/22.5)].

Complete data for 150 mother-baby dyads was analysed: the mothers, with a mean (standard deviation [SD]) age of 31.6 (4.5) years, had live births at a mean (SD) gestational age of 39.2 weeks. The proportions of infants with wasting, stunting, impaired fetal growth (either wasting or stunted), small-for-gestation-age, large-for-gestational-age, low birthweight, and macrosomia were 4.2% (95% confidence interval, 1.1-10.3), 19.7% (12.9-28.0), 23.1% (15.8-31.8), 10.1% (5.3-17.0), 12.6% (7.2-19.9), 0.8% (0.02-4.5), and 5.0% (1.8-10.5), respectively. Maternal HOMA-IR was not associated with neonatal HOMA-IR (p=0.837), birth weight (p=0.416) or body composition measured with weight-length ratio (p=0.524), but birth weight was independently predicted by maternal weight (p=0.006), body mass index (p=0.001), and parity (p=0.012).

In this nondiabetic/non-GDM cohort, maternal HOMA-IR was not associated with neonatal IR, body size or body composition. Larger studies are required to confirm these findings, with addi-tional inclusion of mothers with hyperglycaemia for comparison.

Berries are a rich source of antioxidant polyphenols and other nutrients that are associated with good health. Allostatic load (AL) is an aggregate measure of chronic stress-induced physiological dysregulations across cardiovascular, metabolic, autonomic, and immune systems; the extent of these dysregulations, collectively or in each system, can be characterized by a composite score or a domain score assessed by integrated biomarkers. It was hypothesized that the anti-inflammatory and other effects of berries lower AL. The association was determined between berry consumption and AL composite and domain scores in the 2003-2010 National Health and Nutrition Examination Survey (NHANES).

Berry intake was measured using two 24 h dietary recalls collected from US adults in the 2003-2010 NHANES (n = 7684). The association with AL and its specific domains was examined using population weight-adjusted multivariable linear regression.

The mean AL composite scores for consumers of any berries (11.9), strawberries (11.6), and blueberries (11.6), respectively, were significantly lower than nonconsumers (12.3), after fully adjusting for sociodemographic, lifestyle, and dietary confounders. A significant dose-response relationship was determined between greater consumption of total berries, strawberries, and blueberries and lower mean AL composite scores (p-trend < 0.05, for all). Consistently, mean cardiovascular and metabolic domain scores remained significantly lower in the consumers of total berries (mean cardiovascular domain score: 4.73 versus 4.97 for nonconsumers; mean metabolic domain score: 2.97 versus 3.1), strawberries (4.73 versus 4.95; 2.99 versus 3.1), and blueberries (4.6 versus 4.95; 2.92 versus 3.11). Berry consumers also had significantly lower mean AL immune scores (1.52 versus 1.56) and lower mean AL autonomic scores (2.49 versus 2.57) than nonconsumers (initial sample: n = 15,620).

The current study indicates that consumption of berries lowers the AL composite scores and potentially reduces stress-related disease risks in the US adult population.

Insulin resistance (IR) is associated with cardiometabolic multimorbidity (CMM). We aimed to explore the predictive value of six surrogate IR indexes-Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), triglyceride-glucose (TyG), atherogenic index of plasma (AIP), TyG-body mass index (TyGBMI), and TyG-waist circumference (TyGwaist)-to establish the CMM incidence in Chinese middle-aged and older populations.

To estimate the odds ratio (OR) with a 95% confidence interval (95% CI) for incident CMM using six surrogates, we analysed data from the China Health and Retirement Longitudinal Study using multivariate logistic regression models. The nonlinear dose-response correlation was evaluated using restricted cubic spline analysis; predictive performance was assessed using receiver operator characteristic curves.

Among 6451 eligible participants, 268 (4.2%) developed CMM during the 4-year follow-up period. The ORs (95% CI) for incident CMM increased with increasing CVAI quartiles (Q) [Q2: 1.71, 1.03-2.90; Q3: 2.72, 1.70-4.52; Q4: 5.16, 3.29-8.45; all p < 0.05] after full adjustment, with Q1 as the reference. Other indexes yielded similar results. These associations remained significant in individuals with a normal body mass index. Notably, CVAI, AIP, and TyG exhibited a linear dose-response relationship with CMM (Pnonlinear ≥0.05), whereas LAP, TyGBMI, and TyGwaist displayed significant nonlinear correlations (Pnonlinear <0.05). The area under the curve for the CVAI (0.691) was significantly superior to that of other indexes (all p < 0.05).

The six IR surrogates were independently associated with CMM incidence. CVAI may be the most appropriate indicator for predicting CMM in middle-aged and older Chinese populations.

Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS.

In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. The clinical effectiveness and adverse effects were evaluated, followed by plasma proteomic analysis and verification of critical biomarkers by ELISA.

Eighty(80%) patients completed the study. Both interventions improved menstrual cycle, polycystic ovaries, LH(luteinizing hormone) and HbA1c(hemoglobin A1c) levels after the 12-week treatment. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI (Body Mass Index), and waist circumference, FBG(fasting blood glucose), AUCI(area under curve of insulin),TC (Total Cholesterol), IL-6(Interleukin-6) and improving insulin sensitivity, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in improving hyperandrogenemia, including T(total testosterone), LH, LH/FSH(Luteinizing hormone/follicle-stimulating hormone), SHBG(sex hormone-binding globulin) and FAI (free androgen index). By contract, GLP-1RA+Met group only improved LH. Plasma proteomic analysis revealed that the interventions altered proteins involved in reactive oxygen species detoxification (PRDX6, GSTO1, GSTP1, GSTM2), platelet degranulation (FN1), and the immune response (SERPINB9).

Both CPA/EE+Met and GLP-1RA + Met treatment improved reproductive functions in overweight PCOS women. GLP-1RA + Met was more effective than CPA/EE + Met in reducing body weight, BMI, and waist, and improving metabolism, and ovulation in overweight women with PCOS, with acceptable short-term side effects. CPA/EE + Met was more effective in reducing hyperandrogenemia. The novel plasma biomarkers PRDX6, FN1, and SERPINB9, might be indicators and targets for PCOS treatment. TRIAL REGISTRATION CLINICALTIALS.

NCT03151005. Registered 12 May, 2017, https://clinicaltrials.gov/ct2/show/NCT03151005 .

Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short-term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk-predicting model using a nomogram.

In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model.

Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability.

The prediction model developed in this study holds predictive value for short-term DR following BMS in patients with obesity and T2DM.

Previous studies have shown that the serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is related to metabolic syndrome. However, no existing study has examined the relationship between UHR and insulin resistance (IR). Therefore, this study aims to explore the association between the UHR and IR in patients with type 2 diabetes mellitus (T2DM).

Patients with type 2 diabetes mellitus (1,532 males and 1,013 females) were enrolled. Insulin resistance was measured by homeostatic model assessment of insulin resistance (HOMA-IR) and was defined as HOMI-IR ≥ 2.69. Pearson correlation, multiple logistic regression, ROC analysis, and subgroup analysis were used to evaluate the association between UHR and IR.

UHR was associated with HOMA-IR in patients with type 2 diabetes mellitus (pearson's correlation coefficient = 0.274 in males and 0.337 in females, P < 0.001). Multiple logistic regression analysis showed that UHR was significantly correlated with insulin resistance (OR = 1.06, 95%CI = 1.03-1.08 in males and OR = 1.11, 95%CI = 1.08-1.15 in females). The area under the ROC curve (AUC) of UHR (AUC = 0.665 for males and 0.717 for females, all P < 0.01) was the largest compared with that of UA and HDL-C in insulin resistance. Subgroup analysis showed that there was a more significantly positive correlation among subjects with BMI ≥ 24 kg/m2 , age < 60 years old, HbA1c < 7%, non-hypertension, or in female subjects.

Elevated UHR is significantly correlated with insulin resistance, which can be used as an indicator of insulin resistance in patients with type 2 diabetes mellitus.

The aim of this study was to determine the effect on the anthropometric and biochemical parameters for women with insulin resistance when lyophilized dried cornelian cherry (Cornus mas L., CM) was added to medical nutrition therapy (MNT). The study was conducted with 84 women aged 18-45, who had been diagnosed with insulin resistance. Participants were randomized into four groups: MNT + 20 g lyophilized dried CM group (DCm, n = 22), MNT group (D, n = 21), only 20 g lyophilized dried CM group (Cm, n = 21), and the control group (C, n = 20). All participants were followed for 12 weeks. While pre- and post-intervention biochemical parameters were recorded from patient files, anthropometric measurements and food consumption records were taken every 15 days. Pre-intervention groups were homogeneously distributed. Post-intervention, among the groups, all anthropometric measurements were similar between the DCm and D, while the percentage of decrease in insulin resistance-related parameters was approximately two times greater in DCm than in D (p < .05). When the Cm and C were compared, it was found that all post-intervention anthropometric measurements were similar, but the percentage of decrease in fasting blood glucose, fasting insulin, and HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) values were greater in C (p < .05). In this study, it was concluded that CM consumption resulted with a decrease in insulin resistance-related biochemical parameters independent of body weight change. Nevertheless, MNT has positive effects on women with insulin resistance, and adding lyophilized dried CM to MNT improves insulin resistance-related parameters and may be beneficial for preventing the development of diabetes.

To evaluate the efficacy of preoperative glutamine infusion in reducing insulin requirements in patients with uncontrolled type 2 diabetes, defined as glycated hemoglobin (HbA1c) >7%, undergoing urgent coronary artery bypass graft (CABG) surgery.

A randomized controlled trial.

At Ain Shams University Hospital, Cardiothoracic Academy.

Ninety-three patients (of both sexes) with uncontrolled diabetes presenting for urgent CABG were categorized into 2 groups.

The dipeptiven group (n = 46) was given an infusion of dipeptiven 1.5 mL/kg body weight dissolved in normal saline (200 mL) over 3 hours before surgery. The control group (n = 47) received a normal saline infusion (200 mL).

The dipeptiven group demonstrated statistically significant lower intraoperative (173.74 ± 19.97 mg/dL v 198.22 ±14.64 mg/dL) and postoperative (162.36 ±13.11 mg/dL v 176.13 ±14.86 mg/dL) mean blood glucose levels. In addition, dipeptiven infusion was found to reduce mean total insulin requirements intraoperatively by 3.64 ± 0.56 units/h and postoperatively by 37.109 ± 4.30 units/24 h in comparison to placebo (50.98 ± 16.55 units/24 h and 5.10 ± 2.28 units/h, respectively).

A preoperative infusion of dipeptiven can contribute to ameliorating stress hyperglycemia in uncontrolled diabetic patients undergoing urgent CABG.

Obesity is characterized by chronic inflammation, insulin resistance, and gut microbiota dysbiosis. Dioscorea opposita Thunb. is a traditional food and medicine homolog from China. In the present study, polysaccharides isolated from a water extract of Dioscorea opposita Thunb. (DOTPs) were prepared. We showed that DOTPs reduced body weight, accumulation of fat tissues, insulin resistance, and inflammation in high-fat diet (HFD)-fed mice. Further experiments showed that DOTPs could regulate the composition of the gut microbiota in HFD mice. DOTPs supplementation in HFD-fed mice resulted in the reduction of the Firmicutes-to-Bacteroidetes ratio. We further demonstrated that DOTPs supplementation enhanced bacterial levels of Akkermansia and reduced levels of Ruminiclostridium_9. A significant reduction of glycolysis metabolism related to obesity and gut microbiota dysbiosis was also observed upon administration of DOTPs. Our results suggest that DOTPs can produce significant anti-obesity effects, by inhibiting systematic inflammation and ameliorating gut microbiota dysbiosis in diet-induced obese mice.

Despite the role of BMI as a classical obesity index, other indexes reflecting mainly abdominal obesity, usually outperform BMI in terms of metabolic complications prediction.

The aim of the present study is to compare the usefulness of different adiposity indexes for the identification of metabolic disturbances in patients with obesity.

In the study, we included 461 patients - group 1 with obesity (n = 182), group 2 with prediabetes (n = 193), and group 3 with newly diagnosed type 2 diabetes (n = 86). Different anthropometric and adiposity indexes were calculated - WHR, WSR, VAI, ABSI, BRI, Hip index, WWI, LAP.

VAI and LAP had the highest predictive value for the presence of carbohydrate disturbances. VAI also showed the strongest correlation with Framingham and SCORE compared to other adiposity indexes.

VAI and LAP are most useful for the identification of metabolic disturbances and cardiovascular risk in patients with obesity.