Insulin Resistance Research Articles

Association between triglyceride glucose combined with body mass index and hypertension in the NHANES 2017 to 2020

Abstract Triglyceride glucose-body mass index (TyG-BMI), as a new surrogate index for evaluating insulin resistance (IR), has rarely been studied with the incidence rate of hypertension (HTN). This study aims to explore the correlation between TyG-BMI and HTN in American adults, to find a cost-effective and convenient marker to guide early prevention of HTN. We performed this cross-sectional study based on the NHANES database from 2017 to 2020. A multivariate logistic regression model was used to analyze the correlation between TyG-BMI and the prevalence of HTN. Additionally, stratified analysis was performed to test the robustness of the results. 3,069 eligible participants were included in our study (48.8% male, mean age 50.0 ± 17.2 years), and multivariate logistic regression analysis showed that TyG-BMI was maintained positively correlated with HTN after fully adjusting covariates. For every 10-unit increase in the TyG-BMI, the risk of HTN increases by 4.3% (95% CI: 1.007–1.08, P = 0.018). When TyG-BMI was represented as a Quartile, the relationship between TyG-BMI and increased risk of HTN remained significant, which were statistically significant for each model. Stratified analyses suggested that the correlation between TyG-BMI and HTN was more pronounced in those aged 60 years or older (P < 0.05). The correlation between TyG-BMI and HTN remained stable in all strata except the age subgroup (P > 0.05). TyG-BMI is significantly associated with HTN among American adults. Early monitoring of TyG-BMI may help to monitor early the risk of hypertension.

ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis

ATGL links insulin dysregulation to insulin resistance in adolescents with obesity and hepatosteatosis

Full-length 16S rRNA Sequencing Reveals Gut Microbiome Signatures Predictive of MASLD in children with obesity

BackgroundThe gut microbiota plays a crucial role in metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation sequencing technologies are essential for exploring the gut microbiome. While recent advancements in full-length 16S (FL16S) rRNA sequencing offer better taxonomic resolution, whether they establish stronger associations with the risk of MASLD remains to be determined.MethodThis study utilized long-read FL16S and short-read V3-V4 16S rRNA sequencing to profile gut microbiome compositions in age-, sex-, and BMI-matched case–control pairs of obese children with and without MASLD. A random forest predictive model was employed, using gut-microbiota features selected based on the top 35 most abundant taxa or a linear discriminant analysis score greater than 3. The model's performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC) through a tenfold cross-validation method.ResultsSubjects with MASLD exhibited significantly elevated serum alanine aminotransferase, triglycerides, and homeostasis model assessment of insulin resistance levels compared to controls. At the genus level, the gut microbiome compositions detected by both FL16S and V3-V4 sequencing were similar, predominantly comprising Phocaeicola and Bacteroides, followed by Prevotella, Bifidobacterium, Parabacteroides, and Blautia. The AUC for the model based on FL16S sequencing data (86.98%) was significantly higher than that based on V3-V4 sequencing data (70.27%), as determined by DeLong's test (p = 0.008).ConclusionFL16S rRNA sequencing data demonstrates stronger associations with the risk of MASLD in obese children, highlighting its potential for real-world clinical applications.

Transient extreme insulin resistance in a critically ill patient: A case report

BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients, typically managed with insulin infusion. However, the occurrence of transient extreme insulin resistance (EIR) requiring exceptional high-dose insulin is rare. CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest, subsequently developing transient EIR following a new episode of sepsis. Remarkably, insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour (a total of 18224 units on that day), and it was promptly titrated down to zero upon achieving the target glucose level. CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR, which is typically transient. Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.

Elevated Serum Ferritin and Insulin Resistance in Libyan Women with Polycystic Ovary Syndrome: A Retrospective Case-Control Study

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder associated with metabolic and hormonal disturbances, including insulin resistance (IR) and altered iron metabolism. This retrospective case-control study aimed to evaluate serum ferritin levels and insulin resistance in 196 Libyan women (98 PCOS cases and 98 controls) attending the Tripoli Fertility Center. Anthropometric, biochemical, and hormonal parameters were assessed, including body mass index (BMI), waist circumference (WC), lipid profile, and hormonal levels. Results revealed significantly higher BMI, WC, and IR (HOMA-IR) in the PCOS group compared to controls (p < 0.001). Elevated ferritin levels were also observed in PCOS patients (p = 0.001), with a weak but significant correlation between ferritin and IR (r = 0.104, p = 0.01). The PCOS group exhibited a more atherogenic lipid profile, with lower HDL-cholesterol (p < 0.0001) and higher LDL-cholesterol (p < 0.0001). Hormonal analysis showed elevated luteinizing hormone (LH) and a reduced FSH/LH ratio (p < 0.0001), consistent with PCOS pathophysiology. intricate relationship between metabolic dysfunction, hormonal imbalances, and altered iron metabolism in women with PCOS.

The Interplay between Diabetes and Malnutrition in Rural Uganda: Pathophysiology, Challenges, and Interventions

The coexistence of diabetes mellitus and malnutrition in rural Uganda presents a significant public health challenge. Diabetes, particularly type 2 diabetes (T2D), has emerged as a growing concern in sub-Saharan Africa, including rural Uganda, where it often overlaps with malnutrition, manifesting as both undernutrition (e.g., protein-energy malnutrition and micronutrient deficiencies) and overnutrition (e.g., obesity and excessive consumption of processed foods). This review explores the pathophysiology of the diabetes-malnutrition nexus, emphasizing how undernutrition exacerbates insulin resistance and glucose dysregulation, while overnutrition contributes to obesity and chronic inflammation, further complicating diabetes management. The healthcare challenges in rural Uganda, including limited access to care, high costs of medications, and low levels of health literacy, exacerbate these dual burdens. The review discusses potential interventions, such as community-based strategies, sustainable agriculture, biofortification, and policy reforms aimed at strengthening healthcare services and improving nutrition. Future research needs to focus on affordable dietary interventions, long-term effects of malnutrition on diabetes progression, and cost-effective management strategies. A coordinated, multi-pronged approach that includes education, improved healthcare infrastructure, and culturally tailored nutritional support is essential for managing diabetes and malnutrition in rural Uganda. Keywords: Diabetes mellitus, type 2 diabetes, malnutrition, undernutrition, overnutrition, rural Uganda.

Insulin resistance and cancer: molecular links and clinical perspectives.

The association between insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cancer is increasingly recognized and poses an escalating global health challenge, as the incidence of these conditions continues to rise. Studies indicate that individuals with T2DM have a 10-20% increased risk of developing various solid tumors, including colorectal, breast, pancreatic, and liver cancers. The relative risk (RR) varies depending on cancer type, with pancreatic and liver cancers showing a particularly strong association (RR 2.0-2.5), while colorectal and breast cancers demonstrate a moderate increase (RR 1.2-1.5). Understanding these epidemiological trends is crucial for developing integrated management strategies. Given the global rise in T2DM and cancer cases, exploring the complex relationship between these conditions is critical. IR contributes to hyperglycemia, chronic inflammation, and altered lipid metabolism. Together, these factors create a pro-tumorigenic environment conducive to cancer development and progression. In individuals with IR, hyperinsulinemia triggers the insulin-insulin-like growth factor (IGF1R) signaling pathway, activating cancer-associated pathways such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PIK3CA), which promote cell proliferation and survival, thereby supporting tumor growth. Both IR and T2DM are linked to increased morbidity and mortality in patients with cancer. By providing an in-depth analysis of the molecular links between insulin resistance and cancer, this review offers valuable insights into the role of metabolic dysfunction in tumor progression. Addressing insulin resistance as a co-morbidity may open new avenues for risk assessment, early intervention, and the development of integrated treatment strategies to improve patient outcomes.

Insulin resistance-induced mitochondrial dysfunction and pyroptosis in trophoblasts: protective role of metformin

BackgroundGestational diabetes mellitus (GDM) affects up to 14% of pregnancies globally, with insulin resistance (IR) playing a critical but often underappreciated role in its pathogenesis. Yet the specific impact of insulin at IR levels on mitochondrial function and pyroptosis in first-trimester trophoblasts remains unclear. Metformin use in GDM pregnancies is rising, but its impact on placental mitochondrial function is uncertain. This study aimed to investigate the impact of IR, a key feature of GDM, on mitochondrial dysfunction and pyroptosis in trophoblasts and to evaluate the protective effects of metformin.MethodsDual staining assays using TUNEL and caspase-1, and enzyme-linked immunosorbent assay were conducted to assess pyroptosis and pyroptosis-related inflammatory markers in placentas from 42 GDM patients and 39 controls. In vitro, HTR-8/SVneo trophoblast cells were treated with IR-level insulin concentrations, and a concentration gradient of metformin to evaluate the mitochondrial damage, pyroptosis, and cell viability.ResultsThere was a significant increase in pyroptosis in GDM placenta, as well as pyroptosis-related inflammatory markers, IL-1β and IL-18. Placental IL-1β and IL-18 levels were strongly correlated with IR indices, especially in GDM cases. Moreover, IR-level insulin concentrations induced mitochondrial dysfunction and activated the NLRP3 inflammasome, triggering pyroptosis in HTR-8/SVneo trophoblasts. Metformin, particularly at therapeutic doses (10–100 µM), mitigated IR-induced mitochondrial damage by promoting mitochondrial biogenesis and reducing pyroptosis via suppressing the ROS/TXNIP/NLRP3 pathway. Metformin-treated cells exhibited enhanced mitochondrial respiration, restored membrane potential homeostasis, and reduced oxidative stress.ConclusionIR, independent of hyperglycemia, drives placental inflammation and trophoblastic injury via pyroptosis. Targeting the ROS/TXNIP/NLRP3 pathway with metformin or other therapeutic agents offers potential therapeutic value in managing IR-related complications in GDM.

Surrogate markers of insulin resistance and coronary artery disease in type 2 diabetes: U-shaped TyG association and insights from machine learning integration

BackgroundSurrogate insulin resistance (IR) indices are simpler and more practical alternatives to insulin-based IR indicators for clinical use. This study explored the association between surrogate IR indices, including triglyceride-glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), triglyceride glucose-waist to height ratio (TyG-WHtR), metabolic score for insulin resistance (METS-IR), and the triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, and coronary artery disease (CAD) in patients with type 2 diabetes (T2D).MethodsPatients with T2D were enrolled in this study and divided into two groups, matched for age and diabetes duration: those with CAD and those without CAD. The association between surrogate IR indices and CAD was evaluated using restricted cubic spline (RCS) and multivariable logistic regression and their discriminative ability was assessed via Receiver operating characteristic (ROC) curve analysis. Additionally, machine learning models, including Logistic Regression, Random Forest, eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Support Vector Machine (SVM), were employed to predict CAD presence using multiple surrogate IR indices and their components.ResultsAll surrogate IR indices exhibited non-linear associations with CAD. TyG demonstrated a U-shaped relationship, where both extremely low and high levels were associated with higher odds of CAD compared to intermediate levels. The surrogate IR indices showed a relatively strong discriminative ability for CAD, with AUC values exceeding 0.708 across all indices. The TG/HDL-C ratio displayed the highest AUC (0.721), accuracy (68%), and sensitivity (71%), whereas TyG-WC showed the highest specificity (78%). Machine learning algorithms (except logistic regression) demonstrated greater discriminative power than individual IR indices. Random forest and XGBoost revealed the best performance when using either multiple surrogate IR indices or their components.ConclusionsSurrogate IR indices could be used as valuable tools for evaluating cardiometabolic risk in patients with T2D, who are at high risk for CAD. Integrating machine learning models further improved CAD prediction, underscoring their potential for better risk stratification. The observed association between these indices and CAD in T2D may help clarify the complex pathophysiology of CAD and offer insights for future research.

Cross-sectional study of the association between triglyceride glucose-body mass index and obstructive sleep apnea risk

BACKGROUND The triglyceride glucose-body mass index (TyG-BMI) is a novel indicator of insulin resistance (IR). Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent complete or partial collapse of the pharyngeal airway during sleep; however, the relationship between these two conditions remains unexplored. We hypothesized that a higher TyG-BMI is associated with the occurrence of OSA. AIM To assess the association between TyG-BMI and OSA in adults in the United States. METHODS A cross-sectional study was conducted utilizing data from the National Health and Nutrition Examination Surveys spanning from 2005-2008 to 2015-2018. TyG-BMI was calculated as Ln [triglyceride (mg/dL) × fasting blood glucose (mg/ dL)/2] × BMI. Restricted cubic splines were used to analyze the risk of TyG-BMI and OSA occurrence. To identify potential nonlinear relationships, we combined Cox proportional hazard regression with smooth curve fitting. We also conducted sensitivity and subgroup analyses to verify the robustness of our findings. RESULTS We included 16794 participants in the final analysis. Multivariate regression analysis showed that participants with a higher TyG-BMI had a higher OSA incidence. After adjusting for all covariates, TyG-BMI was positively correlated with the prevalence of OSA (odds ratio: 1.28; 95% confidence interval: 1.17, 1.40; P < 0.001); no significant nonlinear relationship was observed. Subgroup analysis showed no strong correlation between TyG-BMI and OSA in patients with diabetes. The correlation between TyG-BMI and OSA was influenced by age, sex, smoking status, marital status, hypertensive stratification, and obesity; these subgroups played a moderating role between TyG-BMI and OSA. Even after adjusting for all covariates, there was a positive association between TYG-BMI and OSA prevalence. CONCLUSION A higher TyG-BMI index is linked to higher chances of developing OSA. As TyG-BMI is an indicator of IR, managing IR may help reduce the risk of OSA.

Estimated glucose processing rates and the association of chronic kidney disease and proteinuria in non-diabetic adults.

The study, which was based on NHANES data (1999-2018), included 21,234 nondiabetic individuals aged 20years and older to investigate the associations between the estimated glucose disposal rate (eGDR) and the risk of chronic kidney disease (CKD) and proteinuria. CKD was defined as an estimated glomerular filtration rate (eGFR) less than 60mL/min/1.73 m2, and proteinuria was defined as a urinary albumin-to-creatinine ratio (UACR) exceeding 30mg/g. The results demonstrated a significant inverse association between eGDR levels and the risks of CKD and proteinuria. After adjusting for potential confounders, the association between eGDR and CKD showed that, compared with those for Q1, the adjusted odds ratios (ORs) for Q2, Q3, and Q4 were 0.82 (95% CI: 0.61-1.11), 0.62 (95% CI: 0.39-0.98), and 0.55 (95% CI: 0.28-1.05), respectively. For the relationship between eGDR and proteinuria, the adjusted ORs for Q2, Q3, and Q4 were 0.54 (95% CI: 0.42-0.69), 0.41 (95% CI: 0.27-0.62), and 0.65 (95% CI: 0.43-0.98), respectively. Moreover, each standard deviation increase in eGDR was associated with a 9% reduction in CKD risk (OR: 0.91, 95% CI: 0.85-0.98) and a 13% reduction in proteinuria risk (OR: 0.87, 95% CI: 0.82-0.93). Further adjustments via restricted cubic spline (RCS) regression analysis revealed a significant nonlinear relationship between eGDR and CKD and a U-shaped relationship between eGDR and proteinuria. A lower risk of proteinuria was observed when eGDR levels were between 8.70 and 9.91. These findings, combined with those of previous studies, suggest that eGDR may serve as a potential alternative metric for insulin resistance (IR). In nondiabetic individuals, the eGDR was significantly associated with the risk of CKD and proteinuria, with a notable nonlinear pattern in these relationships.

Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis.

The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5-8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5-8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble control. We treated the scramble control and INSRe5-8 KO HSCs with insulin or TGFβ and profiled hundreds of kinase activities using the PamGene PamStation kinome technology. Our analysis showed that serine/threonine kinase (STK) activities were reduced, and most of the protein-tyrosine kinase (PTK) activities were increased in the INSRe5-8 KO compared to the Scramble control HSCs. To study gene transcripts altered in activated Scramble control and INSRe5-8 KO HSCs, we treated them with TGFβ for 24 h. We isolated RNA for sequencing and found that the INSRe5-8 KO cells, compared to control HSCs, had altered transcriptional responsiveness to TGFβ stimulation, collagen-activated signaling, smooth muscle cell differentiation pathways, SMAD protein signaling, collagen metabolic process, integrin-mediated cell adhesion, and notch signaling. This study demonstrates that reduced INSR responsiveness enhances HSC growth and selectively mediates TGFβ-induced HSC activation. These findings provide new insights into the development of more effective treatments for liver fibrosis.

Triglyceride-glucose related indices as predictors for major adverse cardiovascular events and overall mortality in type-2 diabetes mellitus patients

BACKGROUND Recent studies have indicated that triglyceride glucose (TyG)-waist height ratio (WHtR) and TyG-waist circumference (TyG-WC) are effective indicators for evaluating insulin resistance. However, research on the association in TyG-WHtR, TyG-WC, and the risk and prognosis of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) cases are limited. AIM To clarify the relation in TyG-WHtR, TyG-WC, and the risk of MACEs and overall mortality in T2DM patients. METHODS Information for this investigation was obtained from Action to Control Cardiovascular Risk in Diabetes (ACCORD)/ACCORD Follow-On (ACCORDION) study database. The Cox regression model was applied to assess the relation among TyG-WHtR, TyG-WC and future MACEs risk and overall mortality in T2DM cases. The RCS analysis was utilized to explore the nonlinear correlation. Subgroup and interaction analyses were conducted to prove the robustness. The receiver operating characteristic curves were applied to analysis the additional predicting value of TyG-WHtR and TyG-WC. RESULTS After full adjustment for confounding variables, the highest baseline TyG-WHtR cohort respectively exhibited a 1.353-fold and 1.420-fold higher risk for MACEs and overall mortality, than the lowest quartile group. Similarly, the highest baseline TyG-WC cohort showed a 1.314-fold and 1.480-fold higher risk for MACEs and overall mortality, respectively. Each 1 SD increase in TyG-WHtR was significantly related to an 11.7% increase in MACEs and a 14.9% enhance in overall mortality. Each 1 SD increase in TyG-WC corresponded to an 11.5% in MACEs and a 16.6% increase in overall mortality. Including these two indexes in conventional models significantly improved the predictive power for MACEs and overall mortality. CONCLUSION TyG-WHtR and TyG-WC were promising predictors of MACEs and overall mortality risk in T2DM cases.

Characteristics in patients with unexplained recurrent spontaneous abortion and the impact on immune, coagulation, and inflammatory profiles

Objective Unexplained Recurrent Spontaneous Abortion (RSA) impacts the physical and psychological well-being of women of reproductive age. This study aimed to reveal the potential mechanisms behind unexplained RSA from the perspective of glucose and lipid metabolic profiles before conception and their relationship with immune, coagulation, and inflammatory markers. Methods A retrospective analysis was conducted on 100 patients with unexplained recurrent spontaneous abortion at our gynecology department from June 2022 to June 2023. According to whether abnormal glucose and lipid metabolism exist, patients were grouped into normal group and abnormal group. The study compared the glucose and lipid metabolic characteristics, immune status, coagulation, and inflammatory parameters between two groups. Results The Abnormal Group exhibited higher fasting blood glucose, 2-hour oral glucose tolerance test, homeostatic model assessment of insulin resistance, total cholesterol, and LDL cholesterol, along with lower levels of HDL cholesterol. Additionally, alterations in immune profile parameters, including lower levels of CD4+ T cells, CD8+ T cells, B cells, NK cells, and elevated IL-6, were observed in the Abnormal Group. Regarding coagulation and inflammatory profile parameters, the Abnormal Group demonstrated prolonged prothrombin time, activated partial thromboplastin time, elevated fibrinogen and D-dimer levels, and increased platelet count, along with elevated C-reactive protein, TNF-α, and IL-1β levels. Correlation analysis revealed significant associations between the pre-pregnancy metabolic characteristics and immune, coagulation, and inflammatory profile parameters. Conclusion Abnormal glucose and lipid metabolism may lead to or exacerbate unexplained RSA in some patients, and therapeutic interventions targeting glucose and lipid metabolism hold promise for improving pregnancy outcomes in this population.

The effect of garlic and stevia extract with aerobic exercise on hypothalamic leptin and ghrelin receptor mRNA expression and insulin resistance in obese rats

BackgroundObesity has recently become the most prevalent diet-related disease worldwide. This study aimed to investigate the effects of aerobic exercise, stevia, and garlic extract on leptin and ghrelin receptor mRNA, as well as the interactions between insulin and glucose in relation to these genes.MethodsA total of 50 male Wistar rats were split into two groups: one group was fed regular rodent food, while the other was fed a high-fat diet for 12 weeks to induce obesity. The obese rats were then divided into six groups of five (N = 5) based on Lee’s index: an obese control group (OC), obese treated with garlic, stevia (OGS), obese aerobic exercise (OE), obese garlic and aerobic exercise (OGE), Obese stevia and aerobic exercise (OSE), and a Normal weight group (NC). The exercise groups participated in a gradually increasing aerobic walking program, whereas the stevia and garlic groups received daily oral doses of their respective extracts. The expression of leptin and ghrelin receptor genes in the hypothalamus was measured using real-time PCR, and insulin resistance was calculated using the HOMA/IR formula. Statistical analysis was conducted using ANOVA, with a significance level set at P < 0.05.ResultsThe obese (O) rats experienced a significant increase in body weight compared with the control (C) rats (p = 0.013), whereas the treated rats showed no significant changes in weight. Leptin receptor mRNA levels were significantly lower in O rats than in C rats (p = 0.00), but increased significantly in the OS (p = 0.000) and OSE (p = 0.034) groups compared with obese rats. Ghrelin receptor mRNA levels were significantly higher in the O group than in the C group (p = 0.035), but decreased in all treatment groups, with the OE (p = 0.001), OGE (p = 0.001), and OSE (p = 0.004) groups showing the greatest reductions. Insulin resistance increased slightly in the O group compared with the C group (p = 0.112), but was lowest in the OS group among all groups (p = 0.018).ConclusionsStevia significantly improved leptin and ghrelin receptor mRNA expression, glucose levels, and insulin resistance in obese rats, showing its potential as an effective dietary intervention for managing obesity.

FVB but Not B6 Mice Carrying the Thr92Ala-Dio2 Polymorphism Have Impaired Thyroid Hormonogenesis and Goiter.

The Thr92Ala-Dio2 polymorphism is prevalent worldwide, with about 50% of the population carrying at least one allele. The Ala92-Dio2 allele encodes a less active D2 enzyme and has been associated with neurodegenerative diseases, hypertension, and insulin resistance. To understand why its phenotypic effects are variable across different populations, in this study, we examined the impact of genetic background on the Thr92Ala-Dio2 polymorphism. We focused on the thyroid gland of two genetically distant mouse strains, the C57BL/6J (B6) and the FVB/N (FVB). While the B6-Ala92-Dio2 mice have no meaningful phenotype, the FVB-Ala92-Dio2 exhibit a goiter (about 2.3-fold heavier thyroid) with an about 1.7-fold enlarged thyroid follicular area and impaired hormonogenesis with reduced thyroglobulin content of T4 and T3, 35-50%-lower serum T4 and about 3-fold elevated serum TSH levels. Notably, the FVB-Ala92-Dio2 thyroid glands showed transcriptional evidence of endoplasmic reticulum (ER) stress, unfolded protein response (UPR), autophagy, and apoptosis. Female FVB-Ala92-Dio2 mice exhibited a more pronounced thyroid phenotype than males. These findings underscore the critical role of genetic background in modulating the phenotype outcomes of the Thr92Ala-Dio2 polymorphism and highlight its potential implications for understanding variable disease susceptibility in human populations.

The association between triglyceride-glucose index and its combination with post-stroke depression: NHANES 2005–2018

BackgroundGrowing evidence indicates a link between insulin resistance and post-stroke depression (PSD). This study employed the triglyceride glucose (TyG) index as a measure of insulin resistance to investigate its relationship with PSD.MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2005–2018). PSD was assessed using data from patient health questionnaires, while the TyG index was calculated based on fasting venous blood glucose and fasting triglyceride levels. The formula used for the TyG index is ln[triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Participants were categorized into four groups according to the TyG index quartiles. A weighted multivariable logistic regression model was applied to examine the relationship between the TyG index and PSD.ResultsA total of 1217 patients were included in the study, of which 232 were diagnosed with PSD. The TyG index was divided into quartiles (Q1-Q4) for analysis. After adjusting for potential confounders, we found a significant positive association between the highest quartile of the TyG index (Q4: ≥9.33) and PSD (OR = 2.51, 95% CI: 1.04–6.07, p = 0.041). This suggests that in the U.S. adult stroke population, individuals with higher TyG indices are more likely to experience depressive symptoms. Subgroup analysis further confirmed a stable and independent positive association between the TyG index and PSD (all trend p > 0.05).ConclusionIn this large cross-sectional study, our results suggest that among US adults who have experienced a stroke, those with higher TyG index levels are more likely to exhibit depressive symptoms. This provides a novel approach for the clinical prevention of PSD. Patients with higher TyG indices in the stroke population may require closer psychological health monitoring and timely intervention. Additionally, since the TyG index is calculated using only fasting blood glucose and triglyceride levels, it can help identify high-risk PSD patients, particularly in regions with limited healthcare resources.

Metabolic Profiles Associate with Mortality and Neurological Outcomes in Out-of-Hospital Cardiac Arrest Patients.

Metabolic Profiles Associate with Mortality and Neurological Outcomes in Out-of-Hospital Cardiac Arrest Patients.

Diabetes, obesity, and cardiovascular disease-what is the impact of lifestyle modification?

Diabetes, obesity, and cardiovascular disease (CVD) represent an escalating global health challenge, contributing significantly to morbidity, mortality, and healthcare costs. Evidence from large cohort studies and clinical trials underscores the impact of diabetes and obesity as major risk factors for CVD, causing systemic inflammation, insulin resistance, and neurohormonal activation. Frequently, asedentary lifestyle and unbalanced dietary habits are associated with these risk factors. Physical activity and exercise training interventions, aMediterranean and plant-based diet, smoking cessation, and reduction of alcohol have shown promise in mitigating these risks. The implementation of lifestyle and pharmacotherapy have emerged as new pillars of preventive medicine. This review discusses the evidence of lifestyle interventions to reduce the burden of diabetes, obesity, and CVD. It is highlighted that only amultifaceted, sustained approach integrating lifestyle interventions and pharmacological strategies can reduce the burden of disease and improve long-term outcomes.

Controlled induction of type 2 diabetes in mice using high fat diet and osmotic-mini pump infused streptozotocin

Type 2 diabetes (T2D) is a progressive metabolic disorder characterised by obesity, insulin resistance, impaired glucose tolerance, and hyperglycaemia. The long time-course of T2D in humans makes accurate modelling of sustained T2D in animal models difficult. The goal of this study was to develop and characterise an accurate and reproducible, non-transgenic model of sustained T2D in mice. Adult, male C57BL/6 mice were placed on a high-fat diet (HFD) for 17 weeks. From weeks 3–5, osmotic mini-pumps were implanted subcutaneously to slowly infuse streptozotocin (STZ; 200–350 mg/kg) for 14-days after which mini-pumps were removed. Body weight, blood glucose concentration, and glucose tolerance were monitored for 12 weeks post STZ treatment. Our data demonstrate that the combination of HFD and 200 mg/kg STZ delivered by mini-pump leads to increased blood glucose concentrations and impaired glucose tolerance, while maintaining obesity and hepatic dyslipidaemia. In week 17, plasma insulin concentration was assessed and showed that with STZ treatment, mice still produce insulin, but that this is reduced compared with mice on HFD only. Lastly, we examined pancreas sections using immunohistochemistry and show that there is no overt loss of beta cell mass. In conclusion, we demonstrate development of a reproducible in vivo model of T2D in mice that replicates a number of key pathophysiological changes seen in humans with T2D.