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Abstract The correlation between diabetes and coronary artery disease (CAD) is well established. Insulin resistance (IR) is considered a primary contributor to elevated CAD risk in diabetic individuals. The triglyceride-glucose (TyG) index serves as a straightforward surrogate marker for insulin resistance. However, few studies have explored their correlations with myocardial infarction and CAD severity. Therefore, our study aimed to investigate the association between the TyG index and the occurrence of myocardial infarction, as well as the severity of coronary artery disease. We conducted a retrospective study involving 3865 consecutive patients who underwent coronary angiography at the First Affiliated Hospital of Zhejiang University, School of Medicine. Of these, 1724 patients were diagnosed with coronary artery disease. Demographic, biochemical, clinical, and angiographic data were gathered. A robust correlation exists between the TyG index and CAD subtypes, suggesting its potential as an independent clinical diagnostic marker. Moreover, the TyG index exhibited a significant positive correlation with disease severity, as assessed by the Gensini score. Elevated TyG index was associated with an increased predisposition to severe CAD, as indicated by the Gensini score, and myocardial infarction, even after adjusting for well-established cardiovascular risk factors.

Abstract Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride–glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (β 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (β −0.57, 95% CI −1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature.

Abstract Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p

Background Polycystic ovary syndrome with insulin resistance (PCOS-IR) is recognized as one of the most challenging subtypes of PCOS to treat due to its intricate pathogenesis and significant individual variability. Although Metformin, as a first-line medication, can ameliorate blood glucose levels and enhance insulin sensitivity, its efficacy in regulating hormonal imbalances and improving ovarian function is limited. Additionally, its gastrointestinal side effects often hinder patient adherence. Objective To evaluate the efficacy and safety of Yishen Quzhuo Formula compared to metformin in the treatment of PCOS-IR. Methods A prospective study enrolled 102 PCOS-IR patients from June 2022 to October 2023 at the Department of Gynecology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients were randomly assigned in a 2∶1 ratio to the experimental group (n=68) treated with Yishen Quzhuo Formula or the control group (n=34) treated with metformin. The comparison was made between the two groups in terms of ovulation rate, pregnancy rate, sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, testosterone (T), anti-Müllerian hormone (AMH) ], glucose and lipid metabolism indicators, BMI, waist-hip ratio (WHR), and incidence of adverse reactions. Results After treatment, the basal body temperature (BBT) ovulation rate in the experimental group increased compared to before treatment (P0.05). After treatment, both groups showed a decrease in LH/FSH compared to before treatment (P0.05). After treatment, the waist circumference of the control group was lower than that of the experimental group (P0.05). During treatment, adverse reactions such as hypoglycemia, fatigue, epigastric discomfort, and diarrhea occurred in patients, with a lower incidence of adverse reactions in the experimental group (5/68, 7.35%) than in the control group (15/31, 48.39%) (χ2=20.404, P

Introduction: The inhibition of the pituitary gland, an increase in the production of catabolic hormones, and the stimulation of the sympathetic nervous system culminate in surgical stress. These factors result in elevated hepatic glycogenesis and gluconeogenesis, decreased skeletal muscle glucose uptake and glycogen synthesis, and hyperglycaemia. Aim: To examine the effects of Subarachnoid Block (SAB) and General Anaesthesia (GA) on perioperative Capillary Blood Glucose (CBG) levels in individuals undergoing surgery lasting 1-3 hours. Materials and Methods: This prospective interventional study included 100 non diabetic patients undergoing surgery of 1-3 hours duration with 50 patients in each group (GA and SAB). CBG was checked 30 minutes before the administration of anaesthesia, 30 and 60 minutes after the induction of anaesthesia, and 30 minutes after shifting to the Post Anaesthesia Care Unit (PACU) in both the GA and SAB groups. Differences in participant characteristics, such as age and CBG levels in the two groups (SAB and GA), were examined using the two-tailed Independent samples t-test and the Chi-square/Fisher’s exact test Results: The mean CBG levels measured 30 minutes before anaesthesia in the GA group were 105.50±21.13 mg/dL, while in the SAB group they were 99.67±19.04 mg/dL, with a p-value of 0.330. However, CBG levels measured 30 minutes after anaesthesia in the GA group were 125.69±22.95 mg/dL, compared to 104.67±20.94 mg/dL in the SAB group, with a p-value of 0.001. At 60 minutes after anaesthesia, CBG levels in the GA group were 152.41±28.97 mg/dL, while in the SAB group they were 99.65±22.69 mg/dL, with a p-value of 0.003. Finally, 30 minutes after shifting to PACU, CBG levels in the GA group were 147.49±27.20 mg/dL, compared to 92.86±24.35 mg/dL in the SAB group, with a p-value of 0.002. Conclusion: CBG levels significantly increased in individuals receiving GA for surgery. This indicates that the hormonal stress response is greater during GA compared to SAB.

Abstract The present study investigated the associations of serum gamma-glutamyl transferase (GGT), a marker of fatty liver and oxidative stress, and ALT/AST, a marker of fatty liver, with percentage trunk fat and postload glucose, insulin resistance, and β-cell function in middle-aged Japanese individuals, whose BMI averaged

Abstract There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner

Abstract Consumption of high-caloric diets contributes to the alarming number of overweight and obese individuals worldwide, which in turn leads to several diseases and multiple organ dysfunction. Not only has the number of calories taken per day but also the type of fat in the diet has an important impact on health. Accordingly, the purpose of the current study was to examine the impact of different types of high-caloric fat diets on the metabolic status and the integrity of the liver and aorta in albino rats. Adult male albino rats were divided into 6 groups: Control group, long chain-saturated fat group (SFD), long chain-monounsaturated fat (MUFAs) group, long chain-polyunsaturated fat (PUFAs) group, medium-chain fat (MCFAs) group, and short-chain fat (SCFAs) group. Body mass index (BMI), Lee index, and visceral fat amount were reported. Serum levels of insulin, liver transaminases, lipid profile, and different oxidative stress and inflammatory markers were evaluated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and adiponectin/leptin ratio were also calculated. Histopathological examinations of liver and aorta with Masson’s trichrome stain, and immune-staining for Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) were also done. SFD group showed significantly elevated liver transaminases, inflammatory markers, HOMA-IR, dyslipidemia, reduced adiponectin, and deficient anti-oxidative response compared to other groups together with disturbed hepatic and aortic architecture. Other treated groups showed an improvement. PUFAs group showed the highest level of improvement. Not all high-fat diets are hazardous. Diets rich in PUFAs, MUFAs, MCFAs, or SCFAs may protect against the hazards of high caloric diet.

Background Chronic kidney disease (CKD) is the eleventh leading cause of death globally, and the burden of disease and economic impact caused by it is increasing rapidly. Its disability and mortality rates have exhibited the highest increase among all chronic diseases. Insulin resistance (IR) and obesity are closely associated with the onset and progression, and triglyceride-glucose (TyG) index can serve as a substitute indicator for IR. Nevertheless, the exact relationship between the TyG index and the development of CKD remains to be fully elucidated. Objective Through a cohort study, we aim to investigate the relationship between triglyceride-glucose (TyG) index and its combination with obesity indices in relation to the occurrence of CKD. Methods This retrospective cohort study selected 4 921 adult participants who underwent annual physical examinations at the Sichuan Provincial People's Hospital Health Management & Physical Examination from January 2015 to November 2022, according to specific inclusion and exclusion criteria. The study cohort was categorized into four groups based on quartiles of the baseline triglyceride-glucose (TyG) index: Q1 (5.43-6.66) , Q2 (6.67-7.04) , Q3 (7.05-7.43) , and Q4 (7.43-9.97) , with sample sizes of 1 230, 1 231, 1 230 and 1 230, respeciyvely Obesity-related indices including waist circumference (WC) , BMI, and waist-to-hip ratio (WHR) , were combined with the TyG index to form TyG-WC, TyG-BMI, and TyG-WHR indices. Based on the quartiles of the baseline TyG-WC index, the study subjects were divided into 4 groups, Q1 (204.49-523.14) , Q2 (523.15-593.21) , Q3 (593.22-657.16) , and Q4 (657.17-992.75) , with sample sizes of 1 230, 1 232, 1 229 and 1 230, respectively. Based on the quartiles of the baseline TyG-BMI index, the study subjects were divided into 4 groups, Q1 (92.43-149.16) , Q2 (149.17-168.43) , Q3 (168.49-188.92) , and Q4 (88.93-306.64) , with sample sizes of 1 228, 1 231, 1 232 and 1 230, respectively. Based on the quartiles of the baseline TyG-WHR index, the study subjects were divided into 4 groups, Q1 (2.76-5.66) , Q2 (5.67-6.26) , Q3 (6.27-6.83) , and Q4 (6.84-9.67) , with sample sizes of 1 230, 1 230, 1 231 and 1 230, respectively. The relationship between the TyG index and its combination with obesity indices and the incidence risk of CKD was examined by a Cox proportional hazards model, while a restricted cubic spline regression (RCS) was used to assess dose-response relationships. Results At the end of follow-up, there were 139 new cases of CKD in the study cohort, with an incidence rate of 2.8%. After accounting for potential confounding factors, the results showed that compared to the TyG index Q1 group, the TyG index Q4 group exhibited a significantly elevated risk of CKD incidence (HR=1.756, 95%CI=1.010-3.054) . Compared to the TyG-WC index Q1 group, the TyG-WC index Q4 group demonstrated a significantly higher risk of CKD incidence (HR=2.532, 95%CI=1.210-5.296) , with P6.93) associated with a greater risk of CKD incidence. The TyG-WC index had a linear dose-response relationship with the risk of CKD incidence (Pnonlinearity=0.078) , with an increasing trend of CKD incidence risk with increasing TyG-WC index values. Conclusion Both TyG and TyG-WC are risk factors for CKD, controlling for TyG and WC can effectively prevent and manage CKD, this finding holds great importance for the prevention and treatment of CKD.

Objective To identify the relationship between physical activity,insulin resistance and cardiovascular risk in individuals with different glucose tolerance status and to provide evidence for exercise intervention in people with different glucose tolerance status. Methods A total of 691 patients with different glucose metabolism status were recruited as subjects of the research. Spearman correlation analysis was used to study the relationship between exercise frequency and insulin resistance, insulin sensitivity, neck circumference (NC) and neck circumference height ratio (NHtR) in the subjects with different glucose metabolism status, the relationship between NC and insulin resistance and insulin sensitivity in different glucose metabolism groups. Results 171(62.9%) Subjects with diabetes were intervened by exercised every day. Spearman correlation analysis showed the correlation between exercise frequency and tri-glyceride triglyceride-glucose index (TyG index) (r=-0.120, P＜0.05) and NC (r=-0.168, P＜0.05) were negatively correlated. In subjects with diabetes, NC was positively correlated with triglycerides(TG) (r=-0.100, P＜0.05), homeostasis model assessment of insulin resistance(HOMA-R) (r=-0.163, P＜0.05), total cholesterol/high-density lipoprotein(TC/HDL-C)(r=-0.214, P＜0.05) and TyG index (r=-0.156, P＜0.05). Conclusions Increased frequency of exercise is associated with reduced NC, improved insulin resistance, and cardiovascular risk factors in subjects of our team with newly diagnosed diabetes. Exercise has no significant effect on insulin resistance of subjects with normal glucose tolerance and pre-diabetes.

Abstract Background To elucidate the relationship between the triglyceride-glycemic index (TyG) and clinical characteristics of pancreatic ductal adenocarcinoma (PDAC). Methods A total of 1,594 individuals diagnosed with pancreatic and periampullary neoplasms were categorized into four groups: PDAC-early (n = 403), locally advanced PDAC (LAPC, n = 315), PDAC-late with distant metastasis (n = 371), and other tumor types (n = 505). TyG-high was defined as a TyG index greater than 8.81 in males and 8.73 in females. Results The prevalence of TyG-high status was highest in PDAC-early (68.48%), followed by LAPC (53.33%), and lowest in PDAC-late (44.47%). TyG-high status significantly predicted worse PDAC prognosis (P = 0.0166), particularly in PDAC-late (P = 0.0420). Despite similar blood glucose levels across PDAC groups (P = 0.897), PDAC-early patients showed significantly higher rates of glycemic disturbances (56.33% vs. 32.28%) and TyG-high status (68.48% vs. 47.13%) compared to those with other tumors. Progressive increases in glycemic disturbances and TyG-high status were observed from benign to pre-malignant lesions and PDAC-early. PDAC-early patients at the pancreatic head exhibited higher rates of glycemic disturbances (58.12% vs. 33.33%, P

Abstract Lipid peroxidation and mitochondrial damage impair insulin sensitivity in skeletal muscle. Sirtuin-1 (SIRT1) protects mitochondria and activates under energy restriction. Dapagliflozin (Dapa) is an antihyperglycaemic agent that belongs to the sodium-glucose cotransporter-2 (SGLT2) inhibitors. Evidence shows that Dapa can induce nutrient deprivation effects, providing additional metabolic benefits. This study investigates whether Dapa can trigger nutrient deprivation to activate SIRT1 and enhance insulin sensitivity in skeletal muscle. We treated diet-induced obese (DIO) mice with Dapa and measured metabolic parameters, lipid accumulation, oxidative stress, mitochondrial function, and glucose utilization in skeletal muscle. β-hydroxybutyric acid (β-HB) was intervened in C2C12 myotubes. The role of SIRT1 was verified by RNA interference. We found that Dapa treatment induced nutrient deprivation state and reduced lipid deposition and oxidative stress, improved mitochondrial function and glucose tolerance in skeletal muscle. The same positive effects were observed after β-HB intervening for C2C12 myotubes, and the promoting effects on glucose utilization were diminished by SIRT1 RNA interference. Thus, Dapa promotes a nutrient deprivation state and enhances skeletal muscle insulin sensitivity via SIRT1 activation. In this study, we identified a novel hypoglycemic mechanism of Dapa and the potential mechanistic targets.

Abstract Insulin resistance (IR) has a strong association with acute ischemic stroke (AIS) occurrence and poor prognosis of afflicted patients. However, the relation between early neurological deterioration (END) risk and IR in elderly and middle-aged patients remains to be thoroughly studied. Here, we investigated the relationship between four indicators of IR and the risk of END in middle-aged patients patients with AIS. The study retrospectively analyzed 1696 elderly and middle-aged patients having AIS between January 2019 and June 2023. Within 7 days of admission, the patients were then stratified relying upon alternations in the National Institutes of Health Stroke Scale. Subsequently, we employed logistic regression analyses for assessing each index correlation with END on the basis of the tertiles of TyG index (TyGI), triglyceride to high-density lipoprotein ratio (TG/HDL), TyG-BMI, alongside IR metabolic score (METS-IR). These four indicators were significantly heightened in the END group (n = 680) in comparison to the non-END group (n = 1016). When grouping using tertiles, the four aforementioned indicators emerged as independent risk factors for END occurrence, whether or not adjusted for confounding factors. The results revealed a progressive elevation in END occurrence risk with the rise in the tertile of each indicator. Finally, we utilized receiver operating characteristic (ROC) curves for assessing the indicators' predictive power. TyG-BMI, TyGI, TG/HDL, and METS-IRs’ area under the curve (AUC) were, respectively, 0.736 (95% CI: 0.712–0.761; P

Abstract The relationship between the triglyceride glucose-body mass index (TyG-BMI) index and Alzheimer’s disease (AD) pathology, cognition, and brain structure remains unclear. This study aimed to investigate these associations, focusing on cerebrospinal fluid (CSF) biomarkers, cognitive measures, and brain imaging data. Eight hundred and fifty-five non-demented participants were included. Linear regression was used to explore associations between the TyG-BMI index and AD pathology, cognition, and brain structure. The association between the TyG-BMI index and AD risk was assessed using Kaplan–Meier and Cox proportional hazards models. Longitudinal relationships were assessed using linear mixed-effects models. Mediation analyses were conducted to examine AD pathology’s potential mediating role between the TyG-BMI index and cognition as well as brain structure. In the linear regression analyses, higher TyG-BMI levels were associated with increased Aβ42 and decreased Tau, pTau, Tau/Aβ42, pTau/Aβ42, and pTau/Tau. Positive correlations were observed with mini-mental state examination (MMSE), memory (MEM), executive function (EF), and the volumes of the hippocampus, entorhinal cortex, and middle temporal regions, while negative correlations were found with Alzheimer’s Disease Assessment Scale (ADAS). Longitudinally, the TyG-BMI index was inversely associated with ADAS, and positively with MMSE, MEM, EF, hippocampus, entorhinal, and middle temporal. High TyG-BMI levels were correlated with lower AD risk (HR 0.996 [0.994, 0.999]). Mediation analyses revealed AD pathology mediated the association between TyG-BMI index and cognition as well as brain structure. Additionally, the TyG-BMI index could mediate cognitive changes by influencing brain structure. The TyG-BMI index is associated with AD pathology, cognition, and brain structure.

Abstract The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1–4 (L1–L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P

Background and aim: Type-2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance (IR) induced by hyperglycaemia and insufficient insulin secretion. We employed a diabetic fly model to examine the effect and molecular mechanism of Atractylodes macrocephala Koidz. and Cuscuta chinensis Lam. (AMK–CCL) extract as traditional Chinese medicine in treating IR and T2DM. Experimental procedure: The contents of the active ingredients (rhamnose, xylose, mannose, and hyperoside) in AMK–CCL extract were determined by high-performance liquid chromatography. Wild-type (Cg-GAL4/+) or diabetic (Cg > InRK1409A) Drosophila flies were divided into the control group or metformin group and AMK–CCL (0.0125, 0.025, 0.05, 0.1 g/ml) groups. Food intake, haemolymph glucose and trehalose, protein, weight, triglycerides (TAG), and glycogen were measured to assess glycolipid metabolism. Phosphatidylinositol-3-kinase (PI3K)/Akt signalling was detected using fluorescent reporters [tGPH, Drosophila forkhead box O (dFoxO)–green fluorescent protein (GFP), Glut1–GFP, 2-NBDG] in vivo. Glut1/3 mRNA levels and Akt phosphorylation levels were detected by quantitative polymerase chain reaction and western blotting, respectively, in vitro. Results: AMK–CCL extract contained 0.038 % rhamnose, 0.017 % xylose, 0.69 % mannose, and 0.039 % hyperoside. AMK–CCL at 0.0125 g/mL significantly suppressed the increase in circulating glucose, and the decrease in body weight, TAG, and glycogen contents of diabetic flies. AMK–CCL improved PI3K activity, Akt phosphorylation, Glut1/3 expression, and glucose uptake in diabetic flies, and also rescued diabetes-induced dFoxO nuclear localisation. Conclusions: These findings indicate that AMK–CCL extract ameliorates IR-induced diabetes via the PI3K/Akt signalling pathway, providing an experimental basis for clinical treatment.

Background In China, there is a significant prevalence of type 2 diabetes patients (T2DM) , who also have an increased risk of developing secondary hyperuricemia (HUA) . Patients with T2DM who develops HUA are at increased risk of developing further problems, which could have detrimental effects on their health. Consequently, it is crucial to promptly identify individuals who have a high risk of developing secondary HUA and to begin early prevention and therapy. Objective Exploring the predictive value of common insulin resistance (IR) surrogates for the HUA in middle-aged and elderly T2DM patients. And employ a subset of these metrics as predictive metrics for the occurrence and progression of HUA. Methods Using stratified random sampling, 479 individuals with type 2 diabetes mellitus (T2DM) and 1 528 patients with non-hyperuricemia (NHUA) were chosen from seven community health service centers in Shenzhen between January and March 2023. Multivariate Logistic regression analysis was used to evaluate the effects of various insulin resistance (IR) metrics and their quartiles on the incidence of HUA in middle-aged and older type 2 diabetic patients. Triglyceride-high density lipoprotein cholesterol (TG/HDL-C) index, non-high density lipoprotein cholesterol ratio (Non-HDL-C/HDL-C) index, triglyceride glucose (TyG) index, triglyceride glucose body mass (TyG-BMI) index, triglyceride glucose waist circumference (TyG-WC) index, and insulin resistance metabolism (METS-IR) index are some of these metrics. The predictive efficacy of several IR substitution measures for HUA in middle-aged and older T2DM patients was assessed using the ROC curve. The CHARLS database's cohort data from 2011 and 2015 were filtered in order to create a nested case-control that would validate the predictive power of different IR alternative indicators for the likelihood of HUA. Results Multivariate Logistic regression study revealed that the METS-IR index, TG/HDL-C index, Non HDL-C/HDL-C index, TyG index, TyG-BMI index, TyG-WC index, and TG/HDL-C index were independent influencing factors for the occurrence of HUA (P

Purpose The present study aimed to determine the serum level of asprosin, a novel glucogenic and orexigenic hormone, in NAFLD and hypothyroidism patients.Methods This is a case–control study that included three groups of age and sex-matched subjects: hypothyroid patients with NAFLD (n = 26), hypothyroid patients without NAFLD (n = 25) and normal control subjects (n = 27). A detailed clinical history was obtained, and an examination was performed. Laboratory tests included fasting plasma glucose and insulin, lipid profile, TSH, free T4, AST, ALT, albumin, and asprosin. The homeostatic model assessment of insulin resistance (HOMA-IR) score was calculated. Abdominal ultrasonography was performed to calculate the hepatorenal index and define participants with NAFLD. The data were statistically analyzed.Results There was a statistically significant difference between the three groups regarding serum asprosin concentration (p

Abstract Rising rates of insulin resistance and an ageing population are set to exact an increasing toll on individuals and society. Here we examine the contribution of age and insulin resistance to the association of cerebral blood flow and glucose metabolism; both critical process in the supply of energy for the brain. Thirty-four younger (20–42 years) and 41 older (66–86 years) healthy adults underwent a simultaneous resting state MR/PET scan, including arterial spin labelling. Rates of cerebral blood flow and glucose metabolism were derived using a functional atlas of 100 brain regions. Older adults had lower cerebral blood flow than younger adults in 95 regions, reducing to 36 regions after controlling for cortical atrophy and blood pressure. Lower cerebral blood flow was also associated with worse working memory and slower reaction time in tasks requiring cognitive flexibility and response inhibition. Younger and older insulin sensitive adults showed small, negative correlations between relatively high rates of regional cerebral blood flow and glucose metabolism. This pattern was inverted in insulin resistant older adults, who showed hypoperfusion and hypometabolism across the cortex, and a positive correlation. In insulin resistant younger adults, the association showed inversion to positive correlations, although not to the extent seen in older adults. Our findings suggest that the normal course of ageing and insulin resistance alter the rates of and associations between cerebral blood flow and glucose metabolism. They underscore the criticality of insulin sensitivity to brain health across the adult lifespan.

Objective: To investigate triglyceride glucose index (TyG index) as a predictor of insulin resistance (IR) in comparison with homeostasis model assessment for insulin resistance (HOMA-IR) for the screening of DM in healthy adult population Study Design: Cross-sectional comparative study. Place and Duration of Study: The study was done at Chemical Pathology & Endocrinology Department, Armed Forces Institute of Pathology, Rawalpindi from 01st June 2022 to 31st May 2023 over a period of one year. Materials and Methods: The study comprised 307 healthy individuals coming for laboratory investigations to our laboratory after routine annual checkup at Combine Military Hospital, Rawalpindi. Individuals of both genders aged between 18 and 35 years were included and initial history of any previous medical condition was taken. All the participants with previous history of any chronic disease were excluded. Healthy individuals who were disease free were included. Blood sample was taken in clot activator and sodium fluoride tube for lipid profile, serum insulin fasting and blood glucose fasting, respectively. Formula used for estimation of HOMA-IR was: The equation used for TyG index was natural log of fasting plasma glucose and triglycerides divided by 2 i.e. .... Results: A comparative analysis was done using SPSS version 29.0 and revealing a significant positive correlation between the TyG index and HOMA-IR with an r value of 0.79 and p value = 0.001 where p value

Obesity has become a global epidemic, intricately linked with metabolic dysfunction and posing significant health risks. This article presents a comprehensive investigation into the complex dynamics of obesity and metabolic disorders, focusing on adipose tissue as an active endocrine organ and its role in chronic inflammation and insulin resistance. Through a thorough literature review and analysis of epidemiological data, this study explores the socioeconomic, lifestyle, and environmental factors influencing obesity prevalence and its associated complications. Case studies from countries with successful intervention programs, expert interviews, and a comparative analysis of strategies implemented worldwide provide valuable insights into effective approaches for addressing obesity and metabolic dysfunction. Drawing on these findings, evidence-based recommendations are proposed for healthcare systems, policymakers, and public health practitioners to combat the multifaceted challenges posed by obesity and promote population health.

Objective: Exercise and physical activity as an essential factor and an integral part in the prevention of standard management of diabetes, however, most people with diabetes are not active enough. The objective of this research was to identify the obstacles hindering the participation of diabetic patients in sports activities in Khuzestan province. Materials and Methods: The study followed an exploratory-applicative approach, utilizing a mixed qualitative-quantitative methodology. The qualitative section involved 18 knowledgeable experts, while the quantitative section included all diabetes patients in Khuzestan province. The sample size for the quantitative section was determined to be 384 patients, based on Morgan's table. Data collection in the qualitative part was conducted through semi-structured interviews, resulting in the extraction of 46 concepts, 19 sub-categories, and 8 main categories over three stages. In the quantitative part, a researcher-designed questionnaire was used, based on the interview findings. The reliability of the questionnaire was assessed using Cronbach's alpha coefficient, which yielded a value of 0.90. Data analysis was performed using SPSS and Smart PLS software. Results: The findings indicated that various factors act as barriers to the participation of diabetic patients in sports activities, including self-actualization (7.79), environmental (6.10), educational and research (5.83), managerial (5.72), cultural (2.85), physical and supportive (2.8), time (2.62), and economic (2.15) factors. Conclusion: Therefore, it is recommended that sports and health officials in the province take measures to alleviate these obstacles and improve the quality of life for diabetic patients.

Abstract Objective Previous studies have shown a clear link between insulin resistance (IR) and an elevated risk of atrial fibrillation (AF). However, the relationship between the estimated glucose disposal rate (eGDR), which serves as a marker for IR, and the risk of AF recurrence after radiofrequency catheter ablation (RFCA) remains uncertain. Therefore, this study aimed to examine the potential association between the eGDR and the risk of AF recurrence following RFCA. Methods This retrospective study was conducted at Nanchang University Affiliated Second Hospital. The study enrolled 899 patients with AF who underwent RFCA between January 2015 and January 2022. The formula used to calculate the eGDR was as follows: 19.02 − (0.22 * body mass index) − (3.26 * hypertension) − (0.61 * HbA1c). Cox proportional hazard regression models and exposure–effect curves were used to explore the correlation between the baseline eGDR and AF recurrence. The ability of the eGDR to predict AF recurrence was evaluated using the area under the receiver operating characteristic curve (AUROC). Results The study observed a median follow-up period of 11.63 months, during which 296 patients experienced AF recurrence. K‒M analyses revealed that the cumulative incidence AF recurrence rate was significantly greater in the group with the lowest eGDR (log-rank p

Background: Diabetes mellitus (DM) is a major public health concern worldwide. Although there are many possible causes of diabetes, the three most prevalent ones are insulin resistance, pancreatic cell damage, and insulin insufficiency. Visfatin, an adipocytokine with insulin-mimicking characteristics, and chemerin, an adipokine responsible for maintaining normal cholesterol and glucose levels, are linked to inflammation and immunological dysfunction in metabolic illnesses. Hence, in this study, we aimed to evaluate the possible association between type 2 diabetes mellitus (T2DM) and the adipokines visfatin and chemerin. Methods and Results: This study was conducted at the Al-Salam Teaching Hospital in Mosul from December 1, 2022, to the end of June 2023. The study included 65 patients of both sexes with T2DM aged between 35 and 80. Twenty-five healthy individuals of both sexes were chosen for a control group. Visfatin and chemerin levels in the serum were measured using an ELISA kit (Koma biotech, ELISA, USA) per the manufacturer's instructions. The levels of visfatin and chemerin in T2DM patients were significantly higher than in controls (1.478±0.631ng/ml and 158.768±36.941pg/ml vs. 0.538±0.151ng/ml and 71.272±12.994pg/ml, respectively, P=0.000 in both cases). The study showed no significant difference in the levels of chemerin and visfatin between females and males in T2DM patients. Among men, the visfatin levels were significantly higher in T2DM patients with diabetic retinopathy than in T2DM patients with such complications as cardiovascular disease and diabetic nephropathy. These features also occurred among women. Men and women with T2DM did not differ in the chemerin levels, depending on the nature of the diabetes complication. Conclusion: T2DM patients are characterized by significantly higher visfatin and chemerin levels than healthy controls. No differences in the levels of these adipokines that depend on the gender of diabetic patients have been found.

Introduction: Helicobacter pylori (H. pylori), despite its high prevalence in the Indian population, has been subjected to limited studies concerning its potential role as a risk factor for Metabolic Syndrome (MetS) and Insulin Resistance (IR). Proposed mechanisms include inflammatory mediators, atherogenic lipid profiles, and vasoconstriction. Aim: To determine the association between H. pylori infection and MetS components, focusing on Highly sensitive C-Reactive Protein (hs-CRP) levels, to enhance understanding and management of these conditions. Materials and Methods: This cross-sectional study was conducted at the Department of Medicine, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune, Maharashtra, India spanning from September 2017 to August 2019. This study involved 100 dyspeptic patients aged 18 years or older undergoing upper Gastrointestinal (GI) endoscopy. Data collection included fasting/postprandial blood parameters, serum lipids, hs-CRP, and H. pylori detection via both rapid urease test and Histopathological Examination (HPE). Physical assessments covered height, weight, Waist Circumference (WC), and blood pressure. MetS was evaluated using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Statistical analysis employed unpaired t-tests, Chi-square tests, and Fisher-Exact tests using IBM Statistical Package for Social Sciences (SPSS) version 21.0. Results: The study of 100 dyspeptic patients, predominantly females, revealed a significant association between H. pylori infection and MetS (p-value

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits and has anti-inflammatory, anti-oxidant, and anti-MetS properties. This study aims to systematically review the effects of apigenin against MetS and the relevant molecular and cellular mechanisms of action, pharmacokinetics features, and potential structure-activity relationship. Electronic databases including Scopus, PubMed, Science Direct and Cochrane Library were searched for in vivo, and in vitro, and human studies with the following keywords: “apigenin” and “metabolic syndrome or insulin resistance syndrome”, “fatty liver”, “hypertension or blood pressure”, “diabetes or blood glucose”, “dyslipidemia”, “heart or cardiovascular ” and “obesity” in title/abstract. Data were collected from 2000 until 2021 (up to April). Only papers published in the English language were included. Forty-six full-text articles out of 1016 retrieved papers were reviewed and underwent quality assessment by investigators. Anti-obesity activity of apigenin is mainly through attenuating adipocyte differentiation by suppressing the mitotic clonal expansion and the adipogenesis-related factors. Its anti-diabetic effects can be exerted through inhibition of protein tyrosine phosphatase1B expression, maintaining the activity of anti-oxidant enzymes, reducing intracellular ROS production, cellular DNA damage, protein carbonylation, and attenuating β-cell apoptosis. Moreover, apigenin could attenuate dyslipidemia and subsequent atherosclerotic conditions through down-regulating sterol regulatory element-binding proteins (SREBP)-1c, SREBP-2, stearyl-CoA desaturase-1, and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Apigenin as a dietary bioactive compound would be a promising candidate for improving MetS and its components.

Abstract Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P

Abstract Physical activity promotes various metabolic benefits by balancing pro and anti-inflammatory adipokines. Recent studies suggest that asprosin might be involved in progression of metabolic syndrome (MetS), however, the underlying mechanisms have not been understood yet. This study aimed to evaluate the effects of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and further detraining on MetS indices, insulin resistance, serum and the liver levels of asprosin, and AMP-activated protein kinase (AMPK) pathway in menopause-induced MetS model of rats. A total of 64 Wistar rats were used in this study and divided into eight groups: Sham1, OVX1 (ovariectomized), Sham2, OVX2, OVX + HIIT, OVX + MICT, OVX + HIIT + Det (detraining), and OVX + MICT + Det. Animals performed the protocols, and then serum concentrations of asprosin, TNF-α, insulin, fasting blood glucose, and lipid profiles (TC, LDL, TG, and HDL) were assessed. Additionally, the liver expression of asprosin, AMPK, and P-AMPK was measured by western blotting. Both HIIT and MICT caused a significant decrease in weight, waist circumference, BMI (P = 0.001), and serum levels of glucose, insulin, asprosin (P = 0.001), triglyceride, total cholesterol, low-density lipoprotein (LDL), and TNF-α (P = 0.001), but an increase in the liver AMPK, P-AMPK, and P-AMPK/AMPK (P = 0.001), compared with OVX2 noexercised group. MICT was superior to HIIT in reducing serum asprosin, TNF-a, TG, LDL (P = 0.001), insulin, fasting blood glucose, HOMA-IR, and QUEKI index (P = 0.001), but an increase in the liver AMPK, and p-AMPK (P = 0.001). Although after two months of de-training almost all indices returned to the pre exercise values (P

In the contemporary reality pharmacological correction of the early carbohydrate metabolism disorders is the main method for the type 2 diabetes prevention. Taking into account the main role of insulin resistance in the prediabetes development it can be supposed that pharmacological agents directly activating the insulin receptor are the pathogenic-base therapy for prediabetes treatment. Such kind of this pathogenic therapy is Subetta® – a representative of the class of biological drugs created using the based graduated technology. Due to the absent of the direct comparative trials of Subetta® versus metformin in the efficacy of the type 2 diabetes prevention in prediabetes patients, was performed an analysis of the effectiveness of these two drugs using the adjusted indirect comparison method of the results of the randomized double-blind placebo-controlled clinical trial of Subetta® efficacy and safety in impaired glucose tolerance patients with the results of several metformin studies similar in inclusion and efficacy criteria. The results indicate greater Subetta® efficacy in the treatment of glucose intolerance and metformin's – in the impaired fasting glucose treatment, which can be explained by the differences in the action mechanisms of these two drugs for prediabetes treatment.

Background: Insulin resistance plays a crucial role in the onset of type 2 diabetes, with body mass index (BMI) being a significant determinant. Aims and Objectives: This study examines the link between BMI and insulin resistance in pre-diabetic individuals to inform strategies for early diabetes intervention. Materials and Methods: This cross-sectional study involved 100 pre-diabetic participants. Data on demographic characteristics, BMI, insulin resistance (measured by the Homeostatic Model Assessment for Insulin Resistance, HOMA-IR), lipid profiles, and blood pressure (BP) were collected. Participants were categorized into normal weight, overweight, and obese groups to explore the relationship between BMI and insulin resistance and its impact on metabolic and cardiovascular health. Results: The average participant age was 45.8 years (SD=12.3), with a slight majority being female (52%) and an average BMI of 28.4 kg/m² (SD=4.5). A significant positive correlation (r=0.64, P

Background: Metabolic syndrome (MetS) in obese is a fairly common entity. However, excluding the waist circumference (WC) criteria, other components of the MetS are also seen in lean or nonobese people. Our study aimed to determine the prevalence of lean MetS among newly diagnosed MetS cases and compare the biochemical parameters and insulin resistance in lean versus overweight/obese MetS. Methods: A cross-sectional, observational study was conducted over 12 months and included adult patients of either sex, newly diagnosed with MetS. Fever cases, infections such as tuberculosis/HIV/chronic infectious disease, chronic inflammatory diseases, those having endocrine causes of obesity such as Cushing syndrome, known cases of ischemic heart disease, and those on antiobesity medications were excluded. Diagnosed MetS patients were categorized as lean or obese based on the standard criteria. A convenient sample of 50 was considered for either group (lean MetS vs. obese MetS). Included patients were investigated for lipid, liver, glycemic, and insulin resistance profiles. Other parameters included serum uric acid, thyroid function, whole abdomen ultrasound, electrocardiography, two-dimensional echocardiography (ECHO), fibroscan, and polysomnography for obstructive sleep apnea (OSA). Results: The prevalence of lean MetS was 9.87%. Variables such as body mass index, WC, low-density lipoprotein, and systolic blood pressure were significantly higher in the obese MetS in comparison to the lean MetS group. Fasting insulin was also significantly higher in the obese MetS compared to lean MetS. Biochemical measures such as aspartate aminotransferase and alanine transferase were significantly higher for the obese MetS, while the change was nonsignificant for other biochemical measures. Except for complications such as polycystic ovary syndrome, acanthoses nigricans, and gallstones which were significantly higher in the obese MetS group, the rest of the complications were similar in both groups. Conclusion: MetS among nonobese or lean subjects differs in certain aspects from those with obesity. As lean MetS is an emerging entity, clinicians must be aware of it to avoid morbidity.

Diabetic nephropathy is one of microvascular complications of diabetic nephropathy （DN） and the main cause of end-stage renal disease. Inflammation， oxidative stress， endothelial and podocyte dysfunction and metabolic abnormalities play critical roles in the pathogenesis of DN. Increasing evidence has demonstrated that omentin-1 exerts a variety of biological effects and can play a role in kidney protection. In DN patients， omentin-1 levels are generally reduced， which impairs anti-inflammation， anti-oxidative stress， endothelial cell and podocyte function and insulin resistance， and further aggravates the progression of nephropathy. In this article， the protection mechanism of omentin-1 in DN was illustrated from its role in the regulation of inflammation， oxidative stress， improvement of endothelial cell and podocyte function， and improvement of insulin resistance， aiming to provide novel ideas for the diagnosis and treatment of DN.

Objective: The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome(PCOS) is an important medical issue in human reproduction. Some of the oxidative phosphorylation (OXPHOS) geneshave been previously studied in granulosa and muscle cells of PCOS patients. Cumulus cells (CCs) remain close to theoocyte even after ovulation. This research has been designed to compare the expression of OXPHOS genes in CCs ofPCOS, with or without insulin resistance.Materials and Methods: In this experimental study, patients were included in PCOS insulin-resistant, PCOS insulinsensitive(IS), and control (fertile women with male infertility history) groups. The expression of NCF2, TXNIP, UCP2,NDUFB6, ATP5H, COX7C, NDUFA3, SDHA, and SDHB was studied by real-time polymerase chain reaction (PCR),aand normalization was performed considering HPRT1 and CYC1 as reference genes. One-way ANOVA and Tukey testwere used for data analysis.Results: The results showed that the expression of NCF2, TXNIP, UCP2, and ATP5H was significantly higher in theIR group than IS and control groups (P

Abstract Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic β-cell function (Pβf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes. These treatments increased the abundance of GM SCFA-producing bacteria M (Fusicatenibacter and Blautia) and LM (Roseburia, Bifidobacterium, and [Eubacterium] hallii group). We performed a mediation analysis with structural equation models (SEM). In conclusion, M and LM therapies improve insulin sensitivity and Pβf in prediabetics. GM is partially associated with these improvements since the SEM models suggest a weak association between specific bacterial genera and improvements in IS and Pβf.

Objectives: This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). Materials and Methods: This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. Results: The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). Conclusion: LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

Abstract The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = − 22.07 mg/dl (95% CI − 27.17, − 16.97), HbA1c [MD = − 0.53% (95% CI − 0.67, − 0.38)], HOMA-IR [MD = − 1.26 (95% CI − 2.16, − 0.37)], and fasting insulin [MD = − 19.83 pmol/L (95% CI − 29.54, − 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D. PROSPERO registration no. CRD42023412603.

Abstract Background The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk. Methods The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan–Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count. Results During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan–Meier curves. The adjusted HR (95% CI) for incident CVD in Q2–Q4, compared with Q1, was 1.47 (1.12–1.93), 1.91 (1.44–2.54) and 2.24 (1.63–3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease. Conclusions The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.

Abstract Bisphenol-A (BPA) is widely used in food packaging and household products, leading to daily human exposure and potential health risks including metabolic diseases like type 2 diabetes mellitus (T2DM). Understanding BPA's mechanisms and developing intervention strategies is urgent. Centella asiatica, a traditional herbal medicine containing pentacyclic triterpenoids, shows promise due to its antioxidant and anti-inflammatory properties, utilized for centuries in Ayurvedic therapy. We investigated the effect of Centella asiatica (CA) ethanol extract on BPA-induced pancreatic islet toxicity in male Swiss albino mice. BPA administration (10 and 100 μg/kg body weight, twice daily) for 21 days caused glucose homeostasis disturbances, insulin resistance, and islet dysfunction, which were partially mitigated by CA supplementation (200 and 400 mg/kg body weight). Additionally, heightened oxidative stress, elevated levels of proinflammatory cytokines, loss of mitochondrial membrane potential (MMP), abnormal cell cycle, and increased apoptosis were implicated in the detrimental impact of BPA on the endocrine pancreas which were effectively counteracted by CA supplementation. In summary, CA demonstrated a significant ability to mitigate BPA-induced apoptosis, modulate redox homeostasis, alleviate inflammation, preserve MMP, and regulate the cell cycle. As a result, CA emerged as a potent agent in neutralizing the diabetogenic effects of BPA to a considerable extent.

Abstract Background The metabolically demanding nature of immune response requires nutrients to be preferentially directed towards the immune system at the expense of peripheral tissues. We study the mechanisms by which this metabolic reprograming occurs using the parasitoid infection of Drosophila larvae. To overcome such an immune challenge hemocytes differentiate into lamellocytes, which encapsulate and melanize the parasitoid egg. Hemocytes acquire the energy for this process by expressing JAK/STAT ligands upd2 and upd3, which activates JAK/STAT signaling in muscles and redirects carbohydrates away from muscles in favor of immune cells. Methods Immune response of Drosophila larvae was induced by parasitoid wasp infestation. Carbohydrate levels, larval locomotion and gene expression of key proteins were compared between control and infected animals. Efficacy of lamellocyte production and resistance to wasp infection was observed for RNAi and mutant animals. Results Absence of upd/JAK/STAT signaling leads to an impaired immune response and increased mortality. We demonstrate how JAK/STAT signaling in muscles leads to suppression of insulin signaling through activation of ImpL2, the inhibitor of Drosophila insulin like peptides. Conclusions Our findings reveal cross-talk between immune cells and muscles mediates a metabolic shift, redirecting carbohydrates towards immune cells. We emphasize the crucial function of muscles during immune response and show the benefits of insulin resistance as an adaptive mechanism that is necessary for survival.

Diabetes, a chronic condition characterized by an inability to maintain normal glucose levels significantly accounts for enhancing the cost of healthcare expenditure. Managing diabetes using a standard medication protocol more often leads to progressive failure in effectively treating the associated complications. The recent trends involve understanding of diabetes's genetic architecture and its consequences have provided the background for application of precision medicine for customizing protocols for preventing and managing the diabetes therapy. Further, utilizing the electronic health data and genetic information for assisting care and planning therapeutic protocol for monogenic form of diabetes is well-executed example of genomic medicine. The present write-up emphasized recent advances about the causes and effects of diabetes genetics. This also drive to the need for the further investigation for ensuring the appropriate knowledge to enable patients and healthcare providers to make informed decisions for obtaining the best possible outcome.

Background: Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking. Methods: We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using two-sample Mendelian randomization and mice models. Results: Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7 and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2 hr glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice. Conclusions: Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes. Funding: South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes’ legat til forskning og bekjempelse av sukkersyke. The UK Biobank resource reference 53641. Australian National Health and Medical Research Council Investigator Grant (APP2017942). Australian Research Council Discovery Early Career Award (DE220101226). Research Council of Norway (Project grant: 325640 and Mobility grant: 287198). The Medical Student Research Program at the University of Oslo. Novo Nordisk Fonden Excellence Emerging Grant in Endocrinology and Metabolism 2023 (NNF23OC0082123). Clinical trial number: clinicaltrials.gov: NCT01803568.

Abstract Metabolic disorders, including obesity, dyslipidemia, diabetes, nonalcoholic fatty liver disease, and metabolic syndrome, are characterized by insulin resistance, abnormalities in circulating cholesterol and lipid profiles, and hypertension. The most common pathophysiologies of metabolic disorders are glucose/lipid metabolism dysregulation, insulin resistance, inflammatory response, and oxidative stress. Although several agents have been approved for the treatment of metabolic disorders, there is still a strong demand for more efficacious drugs with less side effects. Natural products have been critical sources of drug research and discovery for decades. However, the usefulness of bioactive natural products is often limited by incomplete understanding of their direct cellular targets. In this review, we highlight the current understanding of the established and emerging molecular mechanisms of metabolic disorders. We further summarize the therapeutic effects and underlying mechanisms of natural products on metabolic disorders, with highlights on their direct cellular targets, which are mainly implicated in the regulation of glucose/lipid metabolism, insulin resistance, metabolic inflammation, and oxidative stress. Finally, this review also covers the clinical studies of natural products in metabolic disorders. These progresses are expected to facilitate the application of these natural products and their derivatives in the development of novel drugs against metabolic disorders.

Background: Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition of increasing prevalence, is closely related to various metabolic disorders. Hemoglobin, a protein that transports oxygen in red blood cells, is the focus of this study, which seeks to investigate its potential association with NAFLD. Methods: We selected 6,516 eligible adult participants from the United States using the 2017–2020 National Health and Nutrition Examination Survey database for cross-sectional analyses. We analyzed the association of hemoglobin with NAFLD using weighted logistic regression models. Results: The study performed a weighted logistic regression modeling analysis, which verified that hemoglobin levels were positively associated with NAFLD, especially in the higher hemoglobin quartile groups. Subgroup analyses revealed no significant interactions, demonstrating the robustness of the model. The analysis of mediation effects showed that Gamma-Glutamyl Transferase, Alanine Aminotransferase, and triglycerides were important mediating variables in the relationship between hemoglobin and NAFLD. Conclusion: Increased hemoglobin levels were found to be significantly and independently associated with an increased NAFLD risk. This insight is crucial for the risk assessment and early detection of NAFLD, underscoring the need for heightened vigilance in individuals with higher hemoglobin levels.

Background: The triglyceride-glucose (TyG) index has been recommended as a practical surrogate of insulin resistance (IR). However, the association between the TyG index and hyperuricemia among adults with hypertension remains to be elucidated. Methods: We included and analyzed 3134 HTN patients and 4233 non-HTN participants from the cross-sectional 2013–2018 U.S. National Health and Nutrition Examination Surveys (NHANES). Multivariable logistic regression and restricted cubic splines (RCS) were used to explore the association between the TyG index and hyperuricemia. Stratifed analyses were performed to assess the association in populations with different subgroups of hypertension. Results: The prevalence of hyperuricemia was higher in HTN patients (28.00 %) than in non-HTN participants (12.47 %). The multivariable logistic regression showed that the TyG index was significantly associated with hyperuricemia. After multivariable adjustment, higher TyG index levels were found to be associated with a higher prevalence of hyperuricemia in HTN patients (OR: 2.39, 95 % CI: 1.37–4.17, Ptrend 0.05). In the subgroup analysis suggested that the positive association seemed to be strong among male, alcohol use, and diabetes group (P for interaction

Background Insulin resistance is associated with the development and progression of various cancers. However, the epidemiological evidence for the association between insulin resistance and prostate cancer is still limited. Objectives To investigate the associations between insulin resistance and prostate cancer prevalence. Methods A total of 451 patients who were pathologically diagnosed with prostate cancer in the First Affiliated Hospital of Xinjiang Medical University were selected as the case population; 1,863 participants who conducted physical examinations during the same period were selected as the control population. The metabolic score for insulin resistance (METS-IR) was calculated as a substitute indicator for evaluating insulin resistance. The Chi-square test and Mann-Whitney U test were performed to compare the basic information of the case population and control population. Univariate and multivariate logistic regression analyses to define factors that may influence prostate cancer prevalence. The generalized additive model (GAM) was applied to fit the relationship between METS-IR and prostate cancer. Interaction tests based on generalized additive model (GAM) and contour plots were also carried out to analyze the interaction effect of each factor with METS-IR on prostate cancer. Results METS-IR as both a continuous and categorical variable suggested that METS-IR was negatively associated with prostate cancer prevalence. Smoothed curves fitted by generalized additive model (GAM) displayed a nonlinear correlation between METS-IR and prostate cancer prevalence (P < 0.001), and presented that METS-IR was negatively associated with the odds ratio (OR) of prostate cancer. The interaction based on the generalized additive model (GAM) revealed that METS-IR interacted with low-density lipoprotein cholesterol (LDL-c) to influence the prostate cancer prevalence (P = 0.004). Contour plots showed that the highest prevalence probability of prostate cancer was achieved when METS-IR was minimal and low-density lipoprotein cholesterol (LDL-c) or total cholesterol (TC) was maximal. Conclusions METS-IR is nonlinearly and negatively associated with the prevalence of prostate cancer. The interaction between METS-IR and low-density lipoprotein cholesterol (LDL-c) has an impact on the prevalence of prostate cancer. The study suggests that the causal relationship between insulin resistance and prostate cancer still needs more research to confirm.

From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the Spag7 gene linked to metabolic dysfunction in mice. Here, we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a ‘thrifty phenotype’ is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.

Polycystic ovary syndrome (PCOS) is a popular illness in women after puberty age. It’s described via overdone androgen production, and ovulation unrest while elevating metabolic syndrome. PCOS was usually diagnosed by Ultrasound or blood test to check the androgens and other hormone levels. There are many causes of having pathogenesis of POCS which was related to abnormalities in hormone levels, insulin resistance, obesity, and others. the symptoms of PCOS could include irregular periods, excess body hair, weight gain, oily skin, and infertility. Due to the variety of symptoms, the POCS has many different types of treatment options, for instant use of medications or lifestyle changes such as weight loss. Many medications are used to treat PCOS like organic compounds and have proven effective in treating PCOS as well as many metallic elements will aid medicinal chemists in planning, organizing, and implementing new approaches toward the discovery of novel drugs. One of the most important medications which were used to treat PCOS is clomiphene citrate and that is commonly used for the treatment of infertility. This review highlights to the causes and treatments of PCOS and gives many examples of recent research that uses drugs and metallic elements as a medication.

Abstract We aimed to identify the key potential insulin resistance (IR)-related genes and investigate their correlation with immune cell infiltration in type 2 diabetes (T2D). The GSE78721 dataset (68 diabetic patients and 62 controls) was downloaded from the Gene Expression Omnibus database and utilized for single-sample gene set enrichment analysis. IR-related genes were obtained from the Comparative Toxicology Genetics Database, and the final IR-differentially expressed genes (DEGs) were screened by intersecting with the DEGs obtained from the GSE78721 datasets. Functional enrichment analysis was performed, and the networks of the target gene with microRNA, transcription factor, and drug were constructed. Hub genes were identified based on a protein–protein interaction network. Least absolute shrinkage and selection operator regression and Random Forest and Boruta analysis were combined to screen diagnostic biomarkers in T2D, which were validated using the GSE76894 (19 diabetic patients and 84 controls) and GSE9006 (12 diabetic patients and 24 controls) datasets. Quantitative real-time polymerase chain reaction was performed to validate the biomarker expression in IR mice and control mice. In addition, infiltration of immune cells in T2D and their correlation with the identified markers were computed using CIBERSORT. We identified differential immune gene set regulatory T-cells in the GSE78721 dataset, and T2D samples were assigned into three clusters based on immune infiltration. A total of 2094 IR-DEGs were primarily enriched in response to endoplasmic reticulum stress. Importantly, HDAC9 and ARRDC4 were identified as markers of T2D and associated with different levels of immune cell infiltration. HDAC9 mRNA level were higher in the IR mice than in control mice, while ARRDC4 showed the opposite trend. In summary, we discovered potential vital biomarkers that contribute to immune cell infiltration associated with IR, which offers a new sight of immunotherapy for T2D.

Abstract Background Dihydromyricetin (DHM), a flavonoid compound of natural origin, has been identified in high concentrations in ampelopsis grossedentata and has a broad spectrum of biological and pharmacological functions, particularly in regulating glucose and lipid metabolism. The objective of this research was to examine how DHM affected nonalcoholic fatty liver disease (NAFLD) and its underlying mechanisms involved in the progression of NAFLD in a rat model subjected to a high-fat diet (HFD). Additionally, the study examines the underlying mechanisms in a cellular model of steatohepatitis using palmitic acid (PA)-treated HepG2 cells, with a focus on the potential correlation between autophagy and hepatic insulin resistance (IR) in the progress of NAFLD. Methods SD rats were exposed to a HFD for a period of eight weeks, followed by a treatment with DHM (at doses of 50, 100, and 200 mg·kg−1·d−1) for additional six weeks. The HepG2 cells received a 0.5 mM PA treatment for 24 h, either alone or in conjunction with DHM (10 µM). The histopathological alterations were assessed by the use of Hematoxylin–eosin (H&E) staining. The quantification of glycogen content and lipid buildup in the liver was conducted by the use of PAS and Oil Red O staining techniques. Serum lipid and liver enzyme levels were also measured. Autophagic vesicle and autolysosome morphology was studied using electron microscopy. RT-qPCR and/or western blotting techniques were used to measure IR- and autophagy-related factors levels. Results The administration of DHM demonstrated efficacy in ameliorating hepatic steatosis, as seen in both in vivo and in vitro experimental models. Moreover, DHM administration significantly increased GLUT2 expression, decreased G6Pase and PEPCK expression, and improved IR in the hepatic tissue of rats fed a HFD and in cells exhibiting steatosis. DHM treatment elevated Beclin 1, ATG 5, and LC3-II levels in hepatic steatosis models, correlating with autolysosome formation. The expression of AMPK levels and its downstream target PGC-1α, and PPARα were decreased in HFD-fed rats and PA-treated hepatocytes, which were reversed through DHM treatment. AMPK/ PGC-1α and PPARα knockdown reduced the impact of DHM on hepatic autophagy, IR and accumulation of hepatic lipid. Conclusions Our findings revealed that AMPK/ PGC-1α, PPARα-dependent autophagy pathways in the pathophysiology of IR and hepatic steatosis has been shown, suggesting that DHM might potentially serve as a promising treatment option for addressing this disease. Graphical Abstract

Abstract Continuous glucose monitoring (CGM) device adoption in non- and pre-diabetics for preventive healthcare has uncovered a paucity of benchmarking data on glycemic control and insulin resistance for the high-risk Indian/South Asian demographic. Furthermore, the correlational efficacy between digital applications-derived health scores and glycemic indices lacks clear supportive evidence. In this study, we acquired glycemic variability (GV) using the Ultrahuman (UH) M1 CGM, and activity metrics via the Fitbit wearable for Indians/South Asians with normal glucose control (non-diabetics) and those with pre-diabetes (N = 53 non-diabetics, 52 pre-diabetics) for 14 days. We examined whether CGM metrics could differentiate between the two groups, assessed the relationship of the UH metabolic score (MetSc) with clinical biomarkers of dysglycemia (OGTT, HbA1c) and insulin resistance (HOMA-IR); and tested which GV metrics maximally correlated with inflammation (Hs-CRP), stress (cortisol), sleep, step count and heart rate. We found significant inter-group differences for mean glucose levels, restricted time in range (70–110 mg/dL), and GV-by-SD, all of which improved across days. Inflammation was strongly linked with specific GV metrics in pre-diabetics, while sleep and activity correlated modestly in non-diabetics. Finally, MetSc displayed strong inverse relationships with insulin resistance and dysglycemia markers. These findings present initial guidance GV data of non- and pre-diabetic Indians and indicate that digitally-derived metabolic scores can positively influence glucose management.