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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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

Triglyceride-Glucose Index (TyG index) and HbA1c are metabolic risk factors associated with insulin resistance (IR), which have been confirmed to be independently correlated with the incidence of hypertension. However, there is limited research specifically focusing on the interaction between these two metabolic risk factors in hypertensive populations. Currently, it remains unclear how the metabolic indicators TyG index and HbA1c affect BP control in individuals with hypertension. This study aims to investigate the value and interaction of TyG index and HbA1c in blood pressure (BP) control among hypertensive patients. The results are conducive to enhancing the effectiveness of clinical BP control for individuals with hypertension. This cohort study included 99,336 adults diagnosed with hypertension. Participants were grouped according to the median of TyG index and HbA1c. The main endpoint is inadequate BP control. Multivariable-adjusted risk ratios and multivariable Cox regression analysis were used to represent the relationship between BP control levels and metabolic risk factors. Finally, we evaluated the interaction between TyG index and HbA1c in the population with inadequate BP control. This study confirmed that TyG index and HbA1c, as metabolic risk factors, are independently associated with poor BP control (P < 0.05). In multivariable Cox regression analysis, it was found that TyG index and HbA1c were significantly associated with poor BP control. In the male elderly population, HbA1c was significantly associated with poor BP control (P = 0.029). [ABSTRACT FROM AUTHOR]

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 < 23.0 kg/m2. Pancreatic β-cell function was assessed using the disposition index calculated by a product of the insulinogenic index (IGI) and Matsuda insulin sensitivity index, a biomarker of early-phase glucose-stimulated insulin secretion and whole-body insulin sensitivity, respectively. Multivariate linear regression analyses revealed that the disposition index was associated inversely with GGT independently of percentage trunk fat, homeostasis model assessment insulin resistance (HOMA-IR), a marker of insulin resistance, and Matsuda index. When IGI was included instead of the disposition index, IGI (inversely) and HOMA-IR were associated with GGT independently of percentage trunk fat and Matsuda index. When the area under the glucose concentration curve (AUCg) during an oral glucose tolerance test was included instead of the disposition index, AUCg and HOMA-IR emerged as independent determinants of GGT. ALT/AST was associated with HOMA-IR alone. Results suggest a different pathophysiologic basis between GGT and ALT/AST in predicting diabetic risk in non-obese Japanese. [ABSTRACT FROM AUTHOR]

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 < 0.9), and microalbuminuria (UACR > 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 < 0.01), peripheral artery disease (P for no-liner < 0.01), and microalbuminuria (P for no-liner < 0.01). Further segmented regression analyses revealed that in study subjects with HOMA-IR < 5, we found that HOMA-IR was associated with an increased OR for arteriosclerosis (OR: 1.36, 95% CI (1.28, 1.45), P < 0.01), peripheral artery disease (OR: 1.33, 95% CI (1.10, 1.60), P < 0.01) and microalbuminuria (OR: 1.59, 95% CI (1.49, 1.70), P < 0.01). HOMA-IR is an independent risk factor for vascular damage, both macrovascular and microvascular. The phenomenon of saturation of HOMA-IR with vascular damage needs further investigation. [ABSTRACT FROM AUTHOR]

Klotho, an anti-aging protein, is believed to participate in metabolic diseases and play a potential protective role by regulating insulin sensitivity. This study aimed to explore the relationship between the triglyceride-glucose (TyG) index (a simple marker of insulin resistance) and serum soluble Klotho (S-Klotho) levels. The cross-sectional study comprised 5237 adults aged 40–79 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The serum levels of S-Klotho were measured by enzyme-linked immunosorbent assay. The association between the TyG index and S-Klotho levels was investigated by multiple linear regression models, smoothed curve fitting, segmented linear regression models, subgroup analyses, and interaction tests. The TyG index was inversely associated with serum S-Klotho level after full adjustment (β = − 45.11, 95% CI (− 79.53, − 10.69), P = 0.011). Furthermore, we also found a non-linear correlation and saturation phenomenon between the TyG index and serum S-Klotho levels, with a turning point of 9.56. In addition, a significant interaction effect of sex was found between the two (P for interaction < 0.001), with a more pronounced association observed in females. Further studies are required to explore the mechanisms and verify the correlation. [ABSTRACT FROM AUTHOR]

Dietary intake of live microbes may benefit human health, but less is known about the role in insulin resistance. This study was developed with the goal of evaluating potential relationships between IR and dietary live microbes. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged to collect data from 6,333 subjects 18 + years of age. The Sanders system for the classification of dietary live microbe intake (containing Low (< 104 CFU/g), Medium (104–107 CFU/g), or High (> 107 CFU/g) levels of live microbes) was then used to separate these patients into three groups (low, medium, or high). Fasting blood glucose and insulin levels were used to approximate IR based on the homeostasis model of insulin resistance (HOMA-IR). Weighted linear regressions were used to assess the relationship between IR and live microbe intake. After fully adjusting for confounding factors, subjects in the groups exhibiting medium and high levels of live microbe intake exhibited HOMA-IR scores that were below those of subjects in the low group. The relationship between live microbe intake and HOMA-IR scores was also potentially impacted by ethnicity. In summary, a negative correlation was detected between dietary live microbe intake and HOMA-IR values. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Associations of adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acids) with body fat mass and distribution and appendicular skeletal muscle mass (ASM) were compared with results of homeostasis-model assessment-insulin resistance (HOMA-IR) in 284 Japanese female university students and 148 their biological mothers whose BMI averaged < 23 kg/m2. Although mothers compared with daughters had higher BMI, body fat percentage, trunk fat to body fat (TF/BF) ratio and lower leg fat to body fat (LF/BF), AT-IR and HOMA-IR did not differ. We had multivariable linear regression analyses which included TF/BF ratio, LF/BF ratio, weight-adjusted ASM (%ASM), height-adjusted ASM index (ASMI), fat mass index (FMI), and body fat percentage. In young women, AT-IR was independently associated with LF/BF ratio (Standardized β [Sβ]: − 0.139, p = 0.019) and ASMI (Sβ: − 0.167, p = 0.005). In middle-aged women, LF/BF ratio (Sβ: − 0.177, p = 0.049) and %ASM (Sβ: − 0.205, p = 0.02) emerged as independent determinants of AT-IR. HOMA-IR was associated with TF/BF ratio and FMI, a proxy of abdominal and general adiposity, respectively, in both young and middle-aged women. The inverse association of AT-IR with leg fat may support the notion that limited peripheral adipose storage capacity and small skeletal muscle size are important etiological components in insulin-resistant cardiometabolic disease in Japanese women. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 < 0.001), 0. 694 (95% CI: 0.668–0.721; P < 0.001), 0.684 (95% CI: 0.658–0.711; P < 0.001), and 0.722 (95% CI: 0.697–0.747; P < 0.001). IR is associated with END risk in middle-aged AIS patients. TyG-BMI, TyGI, TG/HDL, and METS-IR are independent risk factors of END in elderly and middle-aged AIS patients. Simultaneously, these four IR indicators have significant predictive power for END. [ABSTRACT FROM AUTHOR]

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 < 0.05), and the probability of major osteoporotic fracture in the next 10 years (PMOF) was significantly higher than that in T2DM group (P < 0.001). However, with the prolongation of the course of T2DM, the BMD significantly decreased, while fracture risk and the prevalence of osteoporosis significantly increased (P < 0.05). We also found that the BMD of L1-4, LFN and LHJ were negatively correlated with homeostatic model assessment-insulin resistance (HOMA-IR) (P = 0.028, P = 0.01 and P = 0.047, respectively). The results also showed that the BMD of LHJ was positively correlated with indirect bilirubin (IBIL) (P = 0.018). Although the BMD was lower in the non-T2DM group than in the T2DM group, the prolongation of the course of T2DM associated with the lower BMD. And the higher prevalence of osteoporosis and fracture risk significantly associated with the prolongation of the course of T2DM. In addition, BMD was significantly associated with insulin resistance (IR) and bilirubin levels in T2DM patients. Registration number: China Clinical Trials Registry: MR-51-23-051741; https://www.medicalresearch.org.cn/search/research/researchView?id=c0e5f868-eca9-4c68-af58-d73460c34028. [ABSTRACT FROM AUTHOR]

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

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.

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

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.

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

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 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.

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. [ABSTRACT FROM AUTHOR]

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 < 0.05), which was attributed to an increased percentage of fat mass. Plasma concentrations of IL-6, insulin, and HOMA-IR were also elevated in the HFI group. Both the HFP and HFI groups showed hypertrophied adipocytes and pancreatic islets, increased alpha and beta cell masses, hepatic steatosis, low expression of genes related to beta-oxidation, and upregulated lipogenesis. In conclusion, the consumption of interesterified palm oil alters inflammatory and glucose profiles. [ABSTRACT FROM AUTHOR]

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 < 0.05). The findings suggest that MICT effectively alleviates MetS induced by menopause, at least partly through the activation of liver signaling of P-AMPK and the reduction of asprosin and TNF-α. These results have practical implications for the development of exercise interventions targeting MetS in menopausal individuals, emphasizing the potential benefits of MICT in mitigating MetS-related complications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Limited research has explored the effectiveness of insulin resistance (IR) in forecasting metabolic syndrome (MetS) risk, especially within the Iranian population afflicted with type 2 diabetes mellitus (T2DM). The present investigation aimed to assess the efficacy of IR indices in predicting the risk of MetS among T2DM patients. Convenient sampling was utilized to select four hundred subjects with T2DM. Metabolic factors and IR indices, including the Waist Circumference-Triglyceride Index (WTI), Triglyceride and Glucose Index (TyG index), the product of TyG index and abdominal obesity indices, and the Metabolic Score for Insulin Resistance (METS-IR), were evaluated. Logistic regression, coupled with modeling, was employed to explore the risk of MetS. The predictive performance of the indices for MetS stratified by sex was evaluated via receiver operating characteristic (ROC) curve analysis and estimation of the area under the curve (AUC) values. The TyG-Waist Circumference (TyG-WC) index exhibited the largest AUCs in both males (0.91) and females (0.93), while the TyG-Body Mass Index (TyG-BMI) demonstrated the smallest AUCs (0.77 in males and 0.74 in females). All indices significantly predicted the risk of MetS in all subjects before and after adjustment (p < 0.001 for all). The TyG-WC index demonstrated the highest odds ratios for MetS (8.06, 95% CI 5.41–12.00). In conclusion, all IR indices assessed in this study effectively predicted the risk of MetS among Iranian patients with T2DM, with the TyG-WC index emerging as the most robust predictor across both genders. [ABSTRACT FROM AUTHOR]

Dietary factors such as food texture affect feeding behavior and energy metabolism, potentially causing obesity and type 2 diabetes. We previously found that rats fed soft pellets (SPs) were neither hyperphagic nor overweight but demonstrated glucose intolerance, insulin resistance, and hyperplasia of pancreatic β-cells. In the present study, we investigated the mechanism of muscle atrophy in rats that had been fed SPs on a 3-h time-restricted feeding schedule for 24 weeks. As expected, the SP rats were normal weight; however, they developed insulin resistance, glucose intolerance, and fat accumulation. In addition, skeletal muscles of SP rats were histologically atrophic and demonstrated disrupted insulin signaling. Furthermore, we learned that the muscle atrophy of the SP rats developed via the IL-6–STAT3–SOCS3 and ubiquitin–proteasome pathways. Our data show that the dietary habit of consuming soft foods can lead to not only glucose intolerance or insulin resistance but also muscle atrophy. [ABSTRACT FROM AUTHOR]

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 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.

Abstract The dietary inflammatory index (DII) is a measure of the inflammatory potential of the diet and is closely associated with insulin resistance (IR) and stroke. And IR may play an important role in the development of stroke. Therefore, this study aimed to evaluate the relationship between DII and stroke risk while delving into the potential role of IR in this association. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, performing weighted univariate analyses, logistic regression, and mediation analyses. At baseline, 3.89% of participants developed stroke, and we observed stroke patients exhibited higher DII scores. After adjusting for covariates, compared to participants in the first quartile of DII scores, those in the third quartile and fourth quartile had increased odds of experiencing a stroke (OR: 1.78, 95% CI: 1.18–2.68) and (OR: 1.70, 95% CI: 1.16–2.50), respectively. Moreover, a significant dose–response relationship was observed (P-trend

Abstract The relationship between remnant cholesterol (RC) and homeostasis model assessment-insulin resistance (HOMA-IR) in the context of metabolic-associated fatty liver disease (MAFLD) remains an area of ambiguity. This investigation was designed to elucidate the potential association between RC and HOMA-IR in a cohort of American adults diagnosed with MAFLD. Data from 5533 participants were procured from the 2017–2018 US National Health and Nutrition Examination (NHANES) databases. A weighted linear regression model was employed to analyze the association between RC and HOMA-IR in the context of MAFLD. Preliminary analysis revealed that 44.67% of the participants were diagnosed with MAFLD, with a higher prevalence observed in individuals aged 50–64 years (31.84%, p

To assess cardiometabolic profiles and proteomics to identify biomarkers associated with the metabolically healthy and unhealthy obesity. Young adults (N = 156) enrolled were classified as not having obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) based on NCEP ATP-III criteria. Plasma proteomics at study entry were measured using Olink Cardiometabolic Explore panel. Linear regression was used to assess associations between proteomics and obesity groups as well as cardiometabolic traits of glucose, insulin, and lipid profiles at baseline and follow-up visits. Enriched biological pathways were further identified based on the significant proteomic features. Among the baseline 95 (61%) and 61 (39%) participants classified as not having obesity and having obesity (8 MHO and 53 MUHO), respectively. Eighty of the participants were followed-up with an average 4.6 years. Forty-one proteins were associated with obesity (FDR < 0.05), 29 of which had strong associations with insulin-related traits and lipid profiles (FDR < 0.05). Inflammation, immunomodulation, extracellular matrix remodeling and endoplasmic reticulum lumen functions were enriched by 40 proteins. In this study population, obesity and MHO were associated with insulin resistance and dysregulated lipid profiles. The underlying mechanism included elevated inflammation and deteriorated extracellular matrix remodeling function. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

The relationship between remnant cholesterol (RC) and homeostasis model assessment-insulin resistance (HOMA-IR) in the context of metabolic-associated fatty liver disease (MAFLD) remains an area of ambiguity. This investigation was designed to elucidate the potential association between RC and HOMA-IR in a cohort of American adults diagnosed with MAFLD. Data from 5533 participants were procured from the 2017–2018 US National Health and Nutrition Examination (NHANES) databases. A weighted linear regression model was employed to analyze the association between RC and HOMA-IR in the context of MAFLD. Preliminary analysis revealed that 44.67% of the participants were diagnosed with MAFLD, with a higher prevalence observed in individuals aged 50–64 years (31.84%, p < 0.0001) and in males compared to females (53.48% vs. 46.52%, p < 0.0001). A positive correlation was identified between RC and HOMA-IR in MAFLD patients. The threshold effect analysis model indicated a breakpoint at RC = 30 mg/dl, with a more pronounced positive correlation when RC < 30 mg/dl (β = 0.17, p < 0.001). Receiver operating characteristic analysis further demonstrated that among all lipid parameters, RC exhibited the largest area under the curve. The study findings suggest a positive correlation between RC and HOMA-IR in MAFLD patients, indicating that elevated RC may serve as an independent risk factor for MAFLD. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the association of nutrient patterns (NPs) with metabolic health status and serum levels of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults. This cross-sectional survey was performed on 527 adults aged 20–60 years in Isfahan, Iran. To evaluate dietary intake, a validated 168-item semi-quantitative food frequency questionnaire (FFQ) was used. Participants were categorized as metabolically healthy (MH) and metabolically unhealthy (MU) according to their glycemic and lipid profile, insulin resistance (IR), and inflammation status. An overnight fasting blood sample was collected from each participant and serum levels of BDNF and adropin were assessed. A total of 42.50% of participants were recognized as MU. Three NPs were recognized by factor analysis that labeled as "high animal protein" (NP1), "high vegetable" (NP2), and "high carbohydrate" (NP3) patterns. Moderate adherence to NP2 was related to a lower risk of MU (ORT2 vs. T1 = 0.38, 95% CI: 0.18–0.76). Moreover, high adherence of NP2 (T3 vs. T1) was inversely associated with hypertriglyceridemia (OR = 0.27, 95% CI: 0.11–0.65; P-trend < 0.001) and high hs-CRP values (OR = 0.29, 95% CI: 0.09–1.00; P-trend = 0.03). No significant association was observed between adherence of NP1 and NP3 with MU in crude and adjusted models. However, negative associations were found between moderate adherence to NP3 and insulin resistance (IR) (OR = 0.23, 95% CI: 0.06–0.91) as well as high adherence to NP1 and hypertension (OR = 0.23, 95% CI: 0.09–0.61; P-trend < 0.001). NPs were not associated with serum BDNF and adropin values. [ABSTRACT FROM AUTHOR]

Prior studies have mainly focused on the association of one specific nutrient with insulin resistance (IR) and endothelial dysfunction and limited studies have assessed the association with different nutrient patterns (NPs). We examined the association between various NPs and IR and endothelial dysfunction among Iranian women. This cross-sectional study was carried out on a sample of 368 female nurses. A 106-items food frequency questionnaire (FFQ) was applied for dietary assessments. Using factor analysis, the relationships between NPs and markers of insulin resistance (HOMA-IR, HOMA-β, and QUICKY), and endothelial dysfunction (E-selectin, sICAM-1, and sVCAM-1) were assessed. Mean age and body mass index of participants were respectively 35.21 years and 24.04 kg/m2. Three major NPs were identified. NP1, named as "dairy, fruits, and vegetables" had high values of potassium, folate, vitamins A and C, magnesium, and beta carotene. No significant association was observed between this NP and insulin resistance or endothelial dysfunction indices. The second NP was full of chromium, selenium, copper, vitamin B6, monounsaturated fatty acid (MUFA), thiamin, vitamin D, and iron. Adherence to NP2 (named "legumes, nuts, and protein foods") was associated with lower values of insulin (6.8 ± 1.1 versus 8.4 ± 1.1, P = 0.01), homeostasis model assessment-Insulin resistance (HOMA-IR) (1.3 ± 0.2 versus 1.7 ± 0.2, P = 0.02), and vascular adhesion molecule 1 (VCAM-1) (444.2 ± 27.9 versus 475.8 ± 28.4, P = 0.03). However, adherence to the third NP, rich in saturated fatty acid (SFA), cholesterol, sodium, zinc, vitamin E, and B12, described as "animal fat and meat + vitamin E", was associated with higher amounts of homeostasis model assessment-β (HOMA-β) (531.3 ± 176.2 versus 48.7 ± 179.8, P = 0.03). In conclusion, following the NP2, correlated with higher intakes of chromium, selenium, copper, vitamin B6, MUFA and thiamin was associated with lower values of insulin, HOMA-IR, and sVCAM-1. Adherence to NP3, rich in SFA, cholesterol, vitamin E, vitamin B12, and zinc was associated with higher levels of HOMA-β. [ABSTRACT FROM AUTHOR]

The role of inflammation in disease promotion is significant, yet the precise association between a newly identified inflammatory biomarker and insulin resistance (IR) and mortality remains uncertain. We aim to explore the potential correlation between systemic immune-inflammation index (SII) and these factors. We used data from 2011 to 2016 of National Health and Nutrition Examination Survey, and multivariate logistic regression and restricted cubic spline were employed. Subgroup and interaction analysis were conducted to recognize the consistency of the results. The association between SII and mortality was described by survival analysis. 6734 participants were enrolled, of whom 49.3% (3318) exhibited IR and 7.02% experienced mortality. Multivariate logistic regression revealed that individuals in the highest quartile (Q4) of SII had a significantly increased risk of IR compared to those in the lowest quartile (Q1). We then identified a linear association between SII and IR with an inflection point of 407, but may be influenced by gender. Similarly, compared to Q1, people whose SII at Q4 showed a higher all-cause and cardiovascular mortality. It showed a significant association between SII and both all-cause and cardiovascular mortality, but the results need to be interpreted with caution. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) development is associated with insulin resistance and obesity, with the progression of visceral adipose tissue playing a crucial role. Excessive adipose tissue is accompanied by an increase in the asprosin (ASP), which is responsible for carbohydrate metabolism and the regulation of hunger and satiety. Exercise affects the release of ASP, which may regulate metabolism accordingly. Due to the inconclusive results of the effect of exercise on ASP concentration in men with MetS, 12-week interventions were carried out in the following groups: EG1—aerobic training (n = 21, age: 34.21 ± 6.06, WC; waist circumference: 114.7 ± 10.93) and EG2—a combination of aerobic and resistance training (n = 21, age: 37.37 ± 7.08, WC: 114.8 ± 11.64) and compared with a control group (CG) of men with MetS without any intervention (n = 20, age: 38.26 ± 7.43, WC: 115.3 ± 10.54). Body composition, indicators of carbohydrate-lipid metabolism, and ASP were assessed four times: before the intervention, at 6 and 12 weeks of training, and 4 weeks after the training sessions. A comparison of the intervention influence on changes in the analyzed variables between the groups was performed using ANOVA test for dependent groups with post-hoc comparison. The effect size (ES) was also assessed using squared eta (η2). The implementation of aerobic training resulted in a decrease in ASP concentration (p = 0.03) within 6 weeks of the intervention, while in the CG a gradual increase in ASP was confirmed (p < 0.001). Aerobic-resistance training did not induce significant changes in ASP concentration but resulted in an increase in fat-free mass/fat mass (FFM/FM) ratio (p < 0.001), and a decrease (p = 0.04) in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Changes in the visceral adipose tissue level indicate a gradual decrease in both the EG1 (p = 0.01) and EG2 (p = 0.04) groups. Both aerobic and aerobic-resistance exercises may have a regulatory effect, mainly by reducing visceral adipose tissue, on the improvement of metabolic disorders. [ABSTRACT FROM AUTHOR]

There is variability in the metabolic health status among individuals presenting with obesity; some may be metabolically healthy, while others may have developed the metabolic syndrome, a cluster including insulin resistance, hypertension, dyslipidemia, and increased risk of cardiovascular disease and type 2 diabetes. The mechanisms contributing to this metabolic heterogeneity are not fully understood. To address this question, plasma samples from 48 individuals with BMI ≥ 35 kg/m2 were examined (27 with and 21 without metabolic syndrome). Fasting plasma samples were subjected to Olink proteomics analysis for 184 cardiometabolic and inflammation-enriched proteins. Data analysis showed a clear differentiation between the two groups with distinct plasma protein expression profiles. Twenty-four proteins were differentially expressed (DEPs) between the two groups. Pathways related to immune cell migration, leukocyte chemotaxis, chemokine signaling, mucosal inflammatory response, tissue repair and remodeling were enriched in the group with metabolic syndrome. Functional analysis of DEPs revealed upregulation of 15 immunological pathways. The study identifies some of the pathways that are altered and reflect metabolic health in individuals with obesity. This provides valuable insights into some of the underlying mechanisms and can lead to identification of therapeutic targets to improve metabolic health in individuals with obesity. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) plays an important role in the development of non-alcoholic fatty liver disease (NAFLD). IR markers are divided into two types: (1) insulin-based IR marker, homeostatic model assessment of IR (HOMA-IR); and (2) non-insulin-based IR markers, such as triglyceride-glucose (TyG) index, TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), and metabolic score for IR (METS-IR). The non-insulin-based IR markers are often associated with lipids. The aim of this study was to analyse the association between IR markers and NAFLD in non-diabetic population. Baseline data of NAFLD and non-NAFLD groups were compared. Logistic regression was used to evaluate the relationship between five IR markers and NAFLD risk. The odds ratios (ORs) and 95% confidence intervals (CIs) of IR markers were calculated. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the ability of different IR markers to detect NAFLD. Subgroup analyses were performed in obese and non-obese subgroups. This study found a positive correlation between NAFLD risk and elevation in five IR markers (HOMA-IR, TyG, TyG-BMI, TG/HDL-c, and METS-IR). In non-obese subjects, the AUC of TyG-BMI was larger than that of the other four IR markers to detect NAFLD. The AUC of HOMA-IR was larger than that of the other four IR markers to detect NAFLD in obese subjects. In non-diabetic population, the five IR markers are associated with the risk of NAFLD, including non-obese and obese NAFLD. TyG-BMI and HOMA-IR can be used to detect non-obese and obese NAFLD, respectively, with better detection ability compared with the other IR markers. [ABSTRACT FROM AUTHOR]

The occurrence of heart failure following acute myocardial infarction (AMI) significantly increases the risk of post-infarction mortality. Alkaline phosphatase (AP) is considered to be an independent predictor of cardiovascular disease (CVD) and adverse outcomes. Furthermore, in recent years, alkaline phosphatase has been associated with insulin resistance (IR). Our aim was to investigate the correlation between IR substitutes (triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio), AP, and LV dysfunction in patients admitted after AMI. The retrospective study included 810 patients who underwent coronary angiography for myocardial infarction at the First Hospital of Hebei Medical University from August 2018 to December 2021. Patients were categorized into three groups based on their serum AP levels. Clinical characteristics at admission, cardiac echocardiography findings, coronary angiography results, and biochemical markers such as serum AP levels and triglycerides (TG) were recorded during hospitalization. Left ventricular ejection fraction (LVEF) was assessed using cardiac echocardiography conducted from the time of admission until the coronary angiography procedure. A total of 774 patients with AMI were included in this study. The TyG index is significantly correlated with the TG/HDL-C ratio. (R = 0.739, P < 0.001). Binary logistic regression analysis revealed that elevated serum AP (OR 2.598, 95% CI 1.331–5.071, P = 0.005), presence of the left anterior descending (LAD) artery as the infarct-related artery (IRA) (OR 2.452, 95% CI 1.352–4.449, P = 0.003), and triglyceride (TG) levels (OR 0.652, 95% CI 0.429–0.992, P = 0.046) were protective risk factor for an admission LVEF < 40% following AMI. The serum alkaline phosphatase and LAD as IRA are independent risk factors for severe reduction in LVEF during hospitalization for AMI. Conversely, triglyceride are independent protective factor for severe reduction in LVEF during AMI hospitalization. [ABSTRACT FROM AUTHOR]

Visceral adipose tissue (VAT) is a well-established risk factor for the development of diabetes in individuals with prediabetes. We aimed to evaluate various adiposity and metabolic indices, including visceral adipose tissue (VAT) volume measured by CT, in individuals with prediabetes, based on their different subtypes. This retrospective study included 78 prediabetes individuals aged ≥ 20 years whose VAT volumes were evaluated by CT. Individuals were classified into prediabetes subtypes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG and IGT (C-IFG/IGT). We conducted a comparison of the patients' adiposity indices and their associations with one other, as well as with insulin resistance, based on the different prediabetes subtypes. Individuals with C-IFG/IGT had higher levels of visceral obesity than those with IFG or IGT. VAT volume was more strongly associated with insulin resistance than other adiposity indices, regardless of prediabetes subtypes. Additionally, VAT volume and liver attenuation index showed a significant correlation with the other indices studied across the prediabetes subtypes. CT-based measurement of VAT volume may be a valuable tool for evaluating metabolic risk factors among individuals with prediabetes. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the relationship between serum uric acid (SUA) and the triglyceride-glucose (TyG) index, which is a more effective indicator of insulin resistance. The study participants included 1700 children and adolescents with short stature who were recruited at the Affiliated Hospital of Jining Medical University in China between March 2013 and April 2021. A positive association between SUA levels and the TyG index was detected by univariate analysis (p < 0.001). Furthermore, a nonlinear relationship was detected between SUA and the TyG index, whose point was 6.55 mg/dL. There was a positive association between SUA and the TyG index when the SUA level was greater than 6.55 mg/dL (β 0.17, 95% CI: 0.07, 0.27; P < 0.001). However, we did not observe a significant relationship between SUA and the TyG index when the SUA level was less than 6.55 mg/dL (β 0.02, 95% CI: − 0.01, 0.05; P = 0.091). In addition, a stratified analysis was performed to appraise changes in this relationship for different sexes. The relationship between SUA and the TyG index in males and females is consistent with that in the general population, showing a nonlinear relationship. However, the inflection points of SUA level were significantly higher in males than in females, and the inflection points were approximately 6.72 and 5.88 mg/dL, respectively. This study revealed a nonlinear relationship between SUA and the TyG index in children with short stature. The nonlinear relationship remained in gender stratification analysis, but the inflection point of SUA level was higher in men. Further studies are needed to establish a causal relationship between SUA levels and the TyG index in children with short stature. [ABSTRACT FROM AUTHOR]