Search Results (1,478)

Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and insulin resistance (IR) mediate this association. Methods: This retrospective study included 577 women diagnosed with PCOS at a tertiary academic center from 2010 to 2018. Clinical data included age at diagnosis, BMI, and diagnoses of hypertension, non-alcoholic fatty liver disease, and metabolic syndrome. Laboratory measures included total testosterone, sex hormone-binding globulin, anti-Müllerian hormone, luteinizing hormone, fasting glucose, insulin, and triglycerides (TG). Derived indices included a free androgen index (FAI), homeostasis model assessment of insulin resistance (HOMA-IR), and fasting glucose-to-insulin ratio. PTCs were identified through imaging or surgical findings. Structural equation modeling (SEM) assessed direct and indirect relationships between FAI, BMI, HOMA-IR, and PTCs, while adjusting for diagnostic age. Results: PTCs were identified in 2.77% of participants. BMI, FAI, TG, and IR indices were significantly higher for women with PTCs than those without PTCs. SEM revealed significant indirect effects of FAI on PTCs via BMI and HOMA-IR. The direct effect was negative, resulting in a non-significant total effect. A sensitivity model using HOMA-IR as the predictor showed a significant direct effect on PTCs without mediation via FAI. Conclusions: Biochemical HA may influence PTC development in PCOS through metabolic pathways, establishing the need to consider metabolic context when evaluating adnexal cysts in hyperandrogenic women. Full article

Blood flow restriction training (BFRT) offers notable advantages, including simplicity and time efficiency. However, no meta-analysis has yet comprehensively evaluated its effects on glucose and lipid metabolism in overweight or obese adults. This meta-analysis examines the potential efficacy of BFRT in improving glycemic and lipid control in overweight/obese adults. The literature was searched in six databases, with the search period up to 31 March 2025. A total of eight randomized controlled trials involving 267 participants were identified. Data were analyzed using Stata 18.0 and RevMan 5.4 with random effects models. Outcomes included fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles, and risk of bias and publication bias (Egger’s test) were assessed. BFRT significantly reduced FBG (Hedges’ g = −1.13, 95% CI: −1.65 to −0.62, p < 0.01; I² = 66.34%) and HOMA-IR (Hedges’ g = −0.98, 95% CI: −1.35 to −0.61, p < 0.01; I² = 17.33%) compared with the controls. However, no significant changes were observed in lipid profiles. Our analysis demonstrates that BFRT exhibits the favorable effect of improving glucose metabolism in overweight/obese adults; however, current evidence does not support significant advantages of BFRT for lipid metabolism improvement. Full article

Background: Menopause increases the risk of cardiovascular diseases (CVD) accompanied by a decline in muscle function. Myokines, released by skeletal muscle, could play a significant role in cardiovascular health. Objectives and Methods: This study aimed to investigate the changes induced by a 16-week resistance training (RT) program and/or the docosahexaenoic acid (DHA)-rich n-3 PUFA supplementation on myokine and cytokine circulating levels and to study their associations with parameters of body composition, muscle function, and glucose and lipid serum markers in postmenopausal women with overweight/obesity. Results: At baseline, interleukin-6 (IL-6) levels were positively correlated with body fat and with tumor necrosis factor-alpha (TNF-α) levels and negatively associated with meterorin-like (METRNL) levels. Moreover, METRNL was inversely associated with insulin levels and with HOMA-IR. After the intervention, muscle quality improved with either treatment but more notably in response to RT. N-3 supplementation caused significant improvements in cardiometabolic health markers. TNF-α decreased in all experimental groups. Myostatin levels decreased in the RT and in the n-3 groups, and IL-6 increased in the n-3+RT group. Lastly, no interactions between treatments were observed. Conclusions: In postmenopausal women with overweight or obesity, RT could help improve skeletal muscle function, while DHA-rich n-3 supplementation might decrease CVD risk and might potentially improve muscle function. The modulation of myokine levels could be underlying some of the effects of DHA or RT; however, further research is necessary. Full article

Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article

Background/Objectives: Primary liver cancer (PLC), encompassing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), constitutes a growing global health concern. Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) and Type 2 diabetes mellitus (T2DM) represent a recurrent epidemiological overlap. Individuals with MASLD and T2DM (MASLD-T2DM) are at a higher risk of PLC. This scoping review highlights the epidemiological burden, the classic and novel pathogenetic frontiers, and the potential strategies optimizing the management of PLC in MASLD-T2DM. Methods: A systematic search of the PubMed, Medline, and SCOPUS electronic databases was conducted to identify evidence investigating the pathogenetic mechanisms linking MASLD and T2DM to hepatic carcinogenesis, highlighting the most relevant targets and the relatively emerging therapeutic strategies. The search algorithm included in sequence the filter words: “MASLD”, “liver steatosis”, “obesity”, “metabolic syndrome”, “body composition”, “insulin resistance”, “inflammation”, “oxidative stress”, “metabolic dysfunction”, “microbiota”, “glucose”, “immunometabolism”, “trained immunity”. Results: In the MASD-T2DM setting, insulin resistance (IR) and IR-induced mechanisms (including chronic inflammation, insulin/IGF-1 axis dysregulation, and autophagy), simultaneously with the alterations of gut microbiota composition and functioning, represent crucial pathogenetic factors in hepatocarcinogenesis. Besides, the glucose-related metabolic reprogramming emerged as a crucial pathogenetic moment contributing to cancer progression and immune evasion. In this scenario, lifestyle changes, simultaneously with antidiabetic drugs targeting IR-related effects and gut-liver axis, in parallel with novel approaches modulating immunometabolic pathways, represent promising strategies. Conclusions: Metabolic dysfunction, classically featuring MASLD-T2DM, constitutes a continuously expanding global issue, as well as a critical driver in PLC progression, demanding integrated and personalized interventions to reduce the future burden of disease. Full article

Background: Obesity and its complications have increased in both adults and children, with pediatric populations developing metabolic disorders at earlier ages. Long non-coding RNAs, particularly MEG3, are involved in obesity through regulation of lipogenic genes including ATF4, FTO, SREBP1, FASN, and ACACA. However, data on MEG3 expression in pediatric obesity are limited. This study evaluated MEG3, FTO, and ATF4 expression in PBMCs from children with obesity and their associations with added sugar intake and lipid metabolism genes. Methods: In this cross-sectional study 71 children within the age range of 6 to 12 years were included (28 normal weight and 43 with obesity). Anthropometrical and clinical parameters and dietary added sugar consumption were analyzed. Real-time PCR was performed to assess MEG3, FTO, ATF4, SREBP1, FASN, and ACACA gene expression in peripheral blood mononuclear cells. Results: The expression of MEG3, ATF4, FTO, SREBP1, FASN, and ACACA was decreased in children with obesity. MEG3 and FTO showed sex-dependent expression in children without obesity, while additional sex-related differences were observed for SREBP1, FASN, ACACA, FTO, and MEG3 in children with obesity. MEG3 was associated with the expression of SREBP1, FASN, ACACA, FTO, and ATF4. In insulin-resistant (IR) children, MEG3, ATF4, FTO, ACACA, and SREBP1 were reduced, while FASN was increased. Added sugar intake negatively correlated with FTO, SREBP1, and ACACA. Conclusions: The MEG3, FTO, and ATF4 expression was altered in children with obesity, showing sex- and IR-related differences. Added sugar intake correlated negatively with lipogenic gene expression. Full article

Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination and their relevance to metabolic health. We examined recent in vitro, animal, and human studies focusing on how germination enhances the nutritional and functional properties of grains, particularly through the synthesis of compounds such as γ-aminobutyric acid, polyphenols, flavonoids, and antioxidants, while reducing anti-nutritional factors. These bioactive compounds have been shown to modulate metabolic and inflammatory pathways by inhibiting carbohydrate-digesting enzymes, suppressing pro-inflammatory cytokines, improving redox balance, and influencing gut microbiota composition. Collectively, these effects contribute to improved insulin sensitivity and glycemic control. The findings suggest that sprouted grains serve not only as functional food ingredients but also as accessible dietary tools for preventing or alleviating IR. Their role in delivering multiple bioactive molecules through a simple, environmentally friendly process highlights their promise in developing future nutrition-based strategies for metabolic disease prevention. Full article

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Resveratrol (RSV), a polyphenol found in a variety of berries and wines, is known for its anti-inflammatory, anticancer, and antioxidant properties. It has been suggested that RSV may play a role in the regulation of metabolic disorders, including diabetes and insulin resistance. However, in recent years, it has been reported to completely inhibit Akt kinase function in liver cells. Akt is a central protein involved in the metabolic function of insulin and is regulated by the phosphatidylinositol-3-kinase (PI3K) pathway. In this study, we examined the effect of RSV on insulin-induced insulin receptor (IR) phosphorylation and proteins involved in the PI3K/Akt pathway in a hepatic cell model, clone 9 (C9), and in hepatoma cells, Hepa 1-6 (H1-6). In both cell lines, RSV inhibited tyrosine phosphorylation of IR and insulin-induced activation of Akt. We also evaluated the effect of RSV on the activation of protein tyrosine phosphatase 1B (PTP1B), which is associated with IR dephosphorylation, and found that RSV increased PTP1B-Tyr¹⁵² phosphorylation in a time- and concentration-dependent manner. Furthermore, we found that the protein kinase C (PKC) inhibitors BIM and Gö6976 prevented the inhibition of Akt phosphorylation by RSV and increased the phosphorylation of Ser/Thr residues in IR, suggesting that PKC is involved in the inhibition of the insulin pathway by RSV. Thus, classical PKC isoforms impair the PI3K/Akt pathway at the IR and GSK3 and GS downstream levels; however, IRS-Tyr⁶³² phosphorylation remains unaffected. These results suggest that RSV can lead to insulin resistance by activating PTP1B and PKC, consequently affecting glucose homeostasis in hepatic cells. Full article

Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed whether metabolic improvements from dietary intervention were accompanied by changes in lung function. Methods: This cross-sectional analysis included 184 individuals (101 with T2D, 33 with prediabetes, and 50 glucose-tolerant individuals). Lung function parameters—vital capacity (VC), total lung capacity by plethysmography (TLC-B), and diffusion capacity for carbon monoxide (TL_CO)—were assessed alongside metabolic markers including HOMA2-IR, fatty liver index (FLI), NAFLD score, and Fibrosis-4 index (FIB-4). In a subset of 54 T2D participants, lung function was reassessed after six months following either a fasting-mimicking diet (FMD, n = 14), Mediterranean diet (n = 13), or no dietary intervention (n = 27). Results: T2D participants had significantly lower VC and TLC-B compared to glucose-tolerant and prediabetic individuals, with 18–21% falling below clinical thresholds for RLD. Lung volumes were negatively correlated with HOMA2-IR, FLI, NAFLD score, and FIB-4 across the cohort and within the T2D group. Although the FMD intervention led to significant improvements in HOMA2-IR and FLI, no corresponding changes in lung function were observed over the six-month period. Conclusions: Restrictive lung impairment in T2D is associated with insulin resistance and markers of liver steatosis and fibrosis. While short-term dietary interventions can improve metabolic parameters, their effect on lung function may require a longer duration or additional interventions and targeted follow-up. These findings highlight the relevance of pulmonary assessment in individuals with metabolic dysfunction. Full article

Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article

Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO₂ were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO₂, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article

Insulin resistance is a fundamental pathophysiological mechanism contributing to the development of type 2 diabetes and metabolic syndrome. Recently, attention has focused on mitochondria’s role in glucose and lipid metabolism. Mitochondrial dysfunction is strongly associated with impaired energy metabolism and elevated oxidative stress. We investigated the mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in insulin-sensitive (IS) and insulin-resistant (IR) individuals. Twenty-seven paired adipose tissue biopsies were obtained during elective abdominal surgery. DNA and RNA were extracted, and mtDNA copy number was quantified using Real-Time PCR. We found that mtDNA content in VAT was approximately two-fold lower than in SAT. Furthermore, in IR individuals, mtDNA copy number was significantly reduced in both SAT and VAT compared to IS subjects. A strong positive correlation was observed between mtDNA content in VAT and body mass index (BMI), and a negative correlation was found with the QUICKI index. Additionally, mtDNA copy number in VAT positively correlated with the expression of several genes involved in insulin signalling, lipid metabolism, and other metabolic pathways. These findings underscore the central role of mitochondrial function in VAT in the context of metabolic disorders and suggest that targeting mitochondrial regulation in this tissue may represent a promising therapeutic approach. Full article

Background/Objectives: Unhealthy lifestyles are closely linked to insulin resistance (IR) and adiposity. However, the mediating role of adiposity in the relationship between lifestyle factors and IR is not yet fully understood. Mediation analysis may help clarify the role of adiposity in the relationship between lifestyle factors and IR. Therefore, we aimed to explore the bidirectional relationship between adiposity and IR, and to evaluate the relationship between lifestyle factors and adiposity-mediated IR in Mexican adults. Methods: A longitudinal analysis was conducted using data from the Health Workers Cohort Study, with measurements taken every six years from 2004 to 2018. This study included 1134 participants aged from 18 to 70 years. Lifestyle factors were assessed using a self-administered questionnaire. IR was assessed using the Homeostasis Model Assessment (HOMA). Adiposity was measured through body mass index (BMI), waist circumference (WC), and body fat proportion (BFP), and BMI was used as the marker indicator to set the metric of adiposity. We fitted structural equation models with a cross-lagged specification to examine the relationships between adiposity and ln(HOMA). In our analysis, we considered baseline adiposity and ln(HOMA) as mediators of the relation between lifestyle factors and future adiposity and ln(HOMA). Models were stratified by sex and adjusted by baseline age. Results: Results from the cross-lagged panel model showed that, for both men and women, adiposity predicted subsequent increases in HOMA (+5.3% IC95%: 1.8%, 9.0% in men; +6.0% IC95%: 4.2%, 7.8% in women). In men, baseline adiposity acted as a mediator between lifestyle variables (physical activity, tobacco consumption, and sleep duration) and HOMA. Conclusions: Our results suggest that understanding both the relationship between adiposity and HOMA and the mediating effects of adiposity is crucial for developing effective interventions to reduce IR in the Mexican population. Full article

Background/Objectives: After diagnosis, it is common for women with breast cancer to gain weight, which is associated with worse clinical outcomes. However, traditional measures such as body weight, BMI, and waist circumference do not detect key changes in body composition, such as fat redistribution or muscle loss. The objective of this exploratory study was to assess the evolution of body composition and muscle strength after one year of treatment, and their relationship with metabolic biomarkers. Methods: Prospective observational study in newly diagnosed breast cancer patients. Body composition was assessed using bioelectrical impedance analysis (BIA) and ultrasound (US); muscle strength was measured by handgrip dynamometry. Biomarkers analyzed included glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), total cholesterol (and its fractions), triglycerides, C-reactive protein (CRP), 6-interleukin (IL-6), vitamin D, myostatin, and fibroblast growth factor 21 (FGF-21). Results: Sixty-one women (mean age 58 years) were included. After one year, fat mass and related parameters significantly increased, while skeletal muscle mass and muscle strength decreased. Sarcopenic obesity prevalence rose from 1.16% to 4.9%. No significant changes were found in biomarkers, but positive correlations were observed between fat parameters and insulin, HOMA-IR, and triglycerides, and negative correlations with HDL-cholesterol. Conclusions: BIA and US can detect unfavorable changes in body composition that are not reflected in conventional measurements. At one year post-diagnosis, women showed increased fat accumulation, muscle loss, and reduced strength, even without significant metabolic biomarker changes. Further research is warranted to elucidate the long-term clinical implications of these findings and the external validity in larger cohorts. Full article