Homeostasis Model Assessment Of Insulin Resistance Research Articles

Prognostic Implications of Insulin Resistance in Heart Failure in Japan.

Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index ≥ 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59-77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4-37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39-2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28-2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28-2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations.

Control of Weıght, Insulın Resıstance and Oxıdatıve Stress in Rats Fed Hıgh-Fat Dıet Usıng Aframomum melegueta (Allıgator Pepper)

Consumptions of diets rich in fat is very predominant due to the sensational values it adds to the foods. If overconsumed, such foods lead to metabolic diseases. Inclusion of alligator pepper in the diets as means of ameliorating such diseases was investigated. Thirty-six (36) Wistar rats were divided into 6 groups. Groups 1, 2, 3 and 4 received standard diet, high fat diet (HFD), 1% and 2% alligator pepper-supplemented standard diet respectively. Groups 5 and 6 got 1% and 2% alligator pepper-supplemented HFD respectively. The groups were fed ad libitum for 8 weeks. Blood glucose level, body weights, activities of antioxidant enzymes and serum concentrations of malondialdehyde (MDA) and insulin were determined. homeostasis model assessment of insulin resistance (HOMA-IR) was computed. The groups that received alligator pepper-supplemented HFD had significantly (p&lt;0.05) higher final average weight, insulin level and HOMA-IR in comparison with the control but lower ın these parameters when compared with the HFD-group. All the groups fed supplemented diets had significantly (p&lt;0.05) higher serum catalase activities in comparison with the HFD group. Also, all, except the group fed 1% alligator pepper-supplemented HFD had significantly (p&lt;0.05) higher superoxide dismutase activities than the HFD group. It is concluded that including the pepper in the standard diet may have no special advantages in respects of the studied parameters, but could decrease weight gain, improve insulin sensitivity and oxidative stress defense mechanism in rats fed HFD.

Quercetin Alleviates Insulin Resistance and Repairs Intestinal Barrier in db/db Mice by Modulating Gut Microbiota.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease which seriously affects public health. Gut microbiota remains a dynamic balance state in healthy individuals, and its disorder may affect health status and even results in metabolic diseases. Quercetin, a natural flavonoid, has been shown to have biological activities that can be used in the prevention and treatment of metabolic diseases. This study aimed to explore the mechanism of quercetin in alleviating T2DM based on gut microbiota. db/db mice were adopted as the model for T2DM in this study. After 10 weeks of administration, quercetin could significantly decrease the levels of body weight, fasting blood glucose (FBG), serum insulin (INS), the homeostasis model assessment of insulin resistance (HOMA-IR), monocyte chemoattractant protein-1 (MCP-1), D-lactic acid (D-LA), and lipopolysaccharide (LPS) in db/db mice. 16S rRNA gene sequencing and untargeted metabolomics analysis were performed to compare the differences of gut microbiota and metabolites among the groups. The results demonstrated that quercetin decreased the abundance of Proteobacteria, Bacteroides, Escherichia-Shigella and Escherichia_coli. Moreover, metabolomics analysis showed that the levels of L-Dopa and S-Adenosyl-L-methionine (SAM) were significantly increased, but 3-Methoxytyramine (3-MET), L-Aspartic acid, L-Glutamic acid, and Androstenedione were significantly decreased under quercetin intervention. Taken together, quercetin could exert its hypoglycemic effect, alleviate insulin resistance, repair the intestinal barrier, remodel the intestinal microbiota, and alter the metabolites of db/db mice.

Serum selenium and fasting blood glucose: a cross-sectional study in women of different menopause status

BackgroundThis cross-sectional study aims to explore whether there exists an interaction between selenium and menopause concerning type 2 diabetes (T2D) prevalence and its related indicators such as fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR).Methods150 women aged 35–60 years old were finally analyzed in this study. Multivariate linear or logistic regression modeling was conducted to explore the association of selenium and the prevalence of T2D besides its related indicators. Subgroup analyses were conducted based on menopause status to assess the potential impact on the relationship.ResultsIn the fully adjusted model, serum selenium was positively associated with FBG (β: 0.03, CI: 0.01–0.05) and the prevalence of T2D (OR: 1.04, CI: 1.00–1.08). After stratifying the data by menopause status, compared with the postmenopausal women group, as the serum selenium concentrations increased, the FBG concentrations were significantly higher in the premenopausal women group (p for interaction = 0.0020).ConclusionsThe present study found serum selenium was positively associated with FBG and the prevalence of T2D. Furthermore, the relationship between serum selenium and FBG was different in the premenopausal and postmenopausal women. More studies are still needed in the future to verify the relationship as well as to explore the specific mechanisms.

The positive association between hyperuricemia and polycystic ovary syndrome and analysis of related factors.

To examine the potential association between polycystic ovary syndrome (PCOS) and hyperuricemia and to elucidate the underlying contributory factors. Retrospective study on 603 women with PCOS and 604 women without PCOS. Anthropometric features, reproductive hormone profiles, and metabolic parameters were measured and compared between two groups of patients. Examinations of correlations between SUA levels and other parameters were conducted to discern potential correlations. Both serum uric acid levels and the incidence of hyperuricemia exhibited statistically significant elevations in women with PCOS when compared to their counterparts without PCOS. Nonetheless, this statistical difference was not found between the obese subgroup after stratifying study subjects by body mass index (BMI). Pearson's correlation analysis underscored the prominence of BMI as a robust factor influencing SUA levels in women, regardless of their PCOS status. Furthermore, multivariable linear regression model demonstrated significant positive associations between SUA levels and several variables, namely dehydroepiandrosterone sulfate (DHEA-S), free androgen index (FAI), total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), area under the curve for insulin (AUC-I), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, it is noteworthy that the prevalence of hyperuricemia exhibited a positive association with fasting plasma glucose (FPG) levels, while conversely, it displayed a negative association with estradiol (E2) levels. PCOS is associated with a significant elevation of SUA level and hyperuricemia prevalence. HA, IR, and dyslipidemia may be the mediators in the pathogenesis of hyperuricemia in women with PCOS.

Unveiling Systemic Immune Inflammation Index Correlations in Women with Polycystic Ovary Syndrome: A Cross-sectional Study

Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-age women that imposes metabolic and cardiovascular risks. Systemic immune inflammation index (SII), an inflammatory biomarker calculated from a complete blood count, was linked to many metabolic and cardiovascular illnesses. Objective: To evaluate the SII correlation with clinical, biochemical, and hormonal parameters characteristic of PCOS cases for screening and diagnostic values. Methods: For fifty PCOS patients who were eligible, we did a cross-sectional study and collected three types of information on each person: demographic information like age, menstrual cycle length, and body mass index (BMI); hormonal information like LH/FSH ratio, testosterone, and fasting insulin; and biochemical information like the homeostasis model assessment of insulin resistance (HOMA-IR), serum cholesterol, serum HDL, and serum LDL. The systemic inflammatory index (SII) was calculated from a complete blood count. Results: We found a strong positive correlation between SII and BMI, LH/FSH ratio, testosterone, fasting serum insulin, HOMA-IR, cholesterol, and LDL. However, the correlation between SII, HDL and menstrual cycle days was negative. Regarding the other parameters (HOMA-IR, testosterone, cholesterol, BMI, and LH/FSH ratio), the best subset regression model figures out how strongly SII is linked to each one. Conclusions: SII was strongly and significantly correlated to PCOS clinical, biochemical, and hormonal parameters, which makes it recommendable for screening. Its feasibility, affordability, and meaningful correlation inspired therapeutic and prognostic applications in practice.

Relationship between serum 1, 5-anhydroglucitol level and insulin resistance, microvascular complications in type 2 diabetes mellitus

Objective: To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, n=490), complication group 1 (1 microvascular complications, n=217), and complication group 2 (2 or more microvascular complications, n=129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. Results: The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant (F=537.470, 791.690, 136.340, P<0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) μg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) μg/ml] and complication group 2 [30.42 (12.53, 47.26) μg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant (H=210.020, P<0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients (r=-0.431, -0.372, -0.546, P<0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes (OR=2.261, 95%CI: 1.564-3.269), increased HbA1c (OR=2.040, 95%CI: 1.456-2.858), and increased HOMA-IR (OR=2.158, 95%CI: 1.484-3.137) and decreased 1, 5-AG (OR=2.512, 95%CI: 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients (P<0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95%CI: 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95%CI: 0.692-0.767). Conclusion: Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study.

The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women. This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer. Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87). The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Normalization of impaired glucose tolerance after kidney transplantation is associated with improved β-cell function.

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with β-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). β-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = -0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in β-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Improvements in BUN after transplantation were associated with improvements in β-cell function.NEW & NOTEWORTHY In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in β-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus.

Association of systemic immune-inflammation index with insulin resistance and prediabetes: a cross-sectional study.

Previous research suggested a relationship between the Systemic Immune-Inflammation Index (SII) and multiple adverse health conditions. However, the role of SII in prediabetes and insulin resistance (IR) remains poorly understood. Therefore, this study aims to explore the potential relationship between SII and prediabetes and IR, providing data support for effective diabetes prevention by reducing systemic inflammation. Linear regression models were used to assess the correlation between continuous SII and risk markers for type 2 diabetes (T2D). Subsequently, multivariate logistic regression models and subgroup analyses were employed to evaluate the association between SII tertiles and prediabetes and IR, controlling for various confounding factors. Finally, restricted cubic spline graphs were used to analyze the nonlinear relationship between SII and IR and prediabetes. After controlling for multiple potential confounders, SII was positively correlated with fasting blood glucose (FBG) (β: 0.100; 95% CI: 0.040 to 0.160), fasting serum insulin (FSI) (β: 1.042; 95% CI: 0.200 to 1.885), and homeostasis model assessment of insulin resistance (HOMA-IR) (β: 0.273; 95% CI: 0.022 to 0.523). Compared to participants with lower SII, those in the highest tertile had increased odds of prediabetes (OR: 1.17; 95% CI: 1.02-1.34; p for trend < 0.05) and IR (OR: 1.35; 95% CI: 1.18 to 1.51; p for trend<0.001). Our study results demonstrate an elevated association between SII levels and both IR and prediabetes, indicating SII as a straightforward and cost-effective method identifying individuals with IR and prediabetes.

Role of secreted frizzled-related protein 4 in prediabetes and type 2 diabetes: a cross sectional study

BackgroundType 2 diabetes (T2D) has become an epidemic. Delays in diagnosis and as a consequent late treatment has resulted in high prevalence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4), has been recently identified as a potential early biomarker of T2D related to obesity, due to its association with low grade inflammation in adipose tissue and impaired glucose metabolism. We aimed to evaluate the role of SFRP4 in prediabetes and T2D in a Mexican population.MethodsThis was a cross-sectional study that included 80 subjects with T2D, 50 subjects with prediabetes and 50 healthy individuals. Fasting SFRP4 and insulin concentrations were measured by ELISA. Human serum IL-10, IL-6, IL-1β and IL-8 levels were quantified by flow cytometry. Genotyping was performed by TaqMan® probes.ResultsPrediabetes and T2D patients had significantly higher SFRP4 levels than controls (P < 0.05). In turn, prediabetes subjects had higher SFRP4 concentrations than control subjects (P < 0.05). Additionally, the prediabetes and T2D groups had higher concentrations of proinflammatory molecules such as IL-6, IL-1β and IL-8, and lower concentrations of IL-10, an anti-inflammatory cytokine, than controls (P < 0.001). The serum SFRP4 concentrations were positively correlated with parameters that are elevated in prediabetes and T2D states, such as, HbA1c and homeostasis model assessment insulin resistance (HOMA-IR), (r = 0.168 and 0.248, respectively, P < 0.05). Also, serum SFRP4 concentrations were positively correlated with concentrations of pro-inflammatory molecules (CRP, IL-6, IL-1β and IL-8) and negatively correlated with the anti-inflammatory molecule IL-10, even after adjusting for body mass index and age (P < 0.001). The genetic variant rs4720265 was correlated with low HDL concentrations in T2D (P < 0.05).ConclusionsSFRP4 correlates positively with the stage of prediabetes, suggesting that it may be an early biomarker to predict the risk of developing diabetes in people with high serum concentrations of SFRP4, although further longitudinal studies are required.

Biochemical and Anthropometric Indices of Insulin Resistance in Obese and Overweight Children with Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.

Low levels of Vitamin D during pregnancy associated with gestational diabetes mellitus and low birth weight: results from the MAASTHI birth cohort.

India has a high prevalence of Vitamin D insufficiency among women of childbearing age. In this study, we aimed to evaluate the potential relationship between Vitamin D deficiency and gestational diabetes mellitus (GDM) and low birth weight (LBW) of newborns in the "Maternal antecedents of adiposity and studying the transgenerational role of hyperglycaemia and insulin" (MAASTHI) birth cohort. A prospective cohort study involving 230 participants was conducted in public hospitals located in urban Bengaluru, India. Healthy pregnant women who visited these hospitals for antenatal care (ANC) and who were between 14 and 36 weeks of gestational age were recruited after obtaining their informed consent. An oral glucose tolerance test (OGTT) was administered between 24 and 36 weeks of pregnancy and blood samples were preserved at -80°C for Vitamin D analysis. Follow-up at birth included recording the child's birth weight. We found that 178 (77.4%) of the study participants were vitamin D deficient, 44 (19.1%) were diagnosed with GDM, and 64 (27.8%) gave birth to LBW babies. Women in the lowest quartile of serum Vitamin D levels had three times higher odds of developing GDM than women in the higher quartiles [OR = 3.22 (95% CI: 1.03, 10.07), p = 0.04] after adjusting for age, parity, socioeconomic status, season, and adiposity. For every one-unit increase in Vitamin D levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) decreased by nearly 18%. Furthermore, causal mediation analysis showed that a decrease in one unit of Vitamin D is associated with a decrease of 0.015 units of fasting blood sugar (FBS) and 0.019 units of postprandial blood sugar (PPBS) as it flows through the mediator variable insulin resistance. Vitamin D-deficient women were twice at risk of giving birth to LBW babies (OR 2.04, 95% CI 0.99, 4.19, p = 0.05). Low levels of Vitamin D during pregnancy are associated with a greater risk of pregnant women developing GDM and giving birth to LBW babies in urban Bengaluru.

Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities

Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes. To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities. This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled. Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died. The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness. A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group. The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities. Chinese Clinical Trial Register: ChiCTR1900023241.

Triglyceride-Fasting Glucose Index and Homeostatic Model Assessment for Insulin Resistance as Predictors of Type 2 Diabetes Mellitus in South Indians With Normal Body Mass Index.

Early detection of type 2 diabetes mellitus (T2DM) is imperative to prevent the complications associated with the disease. Current guidelines for diagnosis rely on the assessment of serum glucose (fasting and post-prandial) and glycosylated hemoglobin (HbA1c) levels. Insulin resistance, a phenomenon associated with T2DM, has been observed before the changes in these metrics. The homeostatic model assessment for insulin resistance (HOMA-IR) has been widely used to assess the degree of insulin resistance. The triglyceride-fasting glucose (TyG) index is a newer marker of insulin resistance that merits further study. Aim: The study aimed to assess the validity of the TyG index and HOMA-IR as markers for the development of T2DM in non-obese individuals. Materials and methods:One hundred eight non-obese patients without T2DM were included in this prospective cohort study and followed up for eight years. Anthropometric and biochemical parameters, including fasting glucose levels, HbA1c, fasting serum insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG), were measured at enrolment and eight years follow-up, and HOMA-IR and TyG index were calculated. Results:Twenty participants out of 108 (18.5%) developed T2DM over eight years. On performing the area under the curve (AUC)-receiver operating characteristic curve analysis, TyG of >8.61 and HOMA-IR of >1.5 had the highest validity (ability) to predict new-onset T2DM in the study population (TyG: AUC: 0.612 (95% CI: 0.514-0.705); HOMA-IR: AUC: 0.529 (95% CI: 0.431-0.626)); however, this was not statistically significant. Conclusion:At an eight-year follow-up, TyG and HOMA-IR were unreliable predictors of the development of T2DM in non-obese individuals.

Role of Hentriacontane on dexamethasone-induced insulin resistance in rats

BackgroundThe worldwide incidence of morbidity and mortality linked to diabetes mellitus is on the ascent, with insulin resistance (IR) standing out as a key characteristic. Given the restricted safety and effectiveness observed in current therapeutic approaches, there exists a demand for novel anti-diabetic pharmaceuticals. This study aims to explore the impact of Hentriacontane, a naturally occurring long-chain alkane hydrocarbon, in an experimental model of IR induced by dexamethasone. The animals were administered dexamethasone (0.08 mg/kg b.w. s.c.) for six weeks to produce IR in the experimental animals. The animals distributed into five groups (n = 6) were: Normal group, IR group, IR + Hentriacontane low dose (2 mg/kg b.w./day p.o.), IR + Hentriacontane high dose (5 mg/kg b.w./day p.o.), and IR + Metformin (250 mg/kg b.w./day p.o.). Following the experimental period, blood/serum samples were taken for the assessment of various biochemical parameters, and a histopathological investigation of the pancreas was carried out. ResultsThe inhibitory concentration (IC50) value of Hentriacontane in various in-vitro assays targeting anti-diabetic and anti-oxidant effects indicates its efficacy in mitigating diabetes and scavenging free radicals. Findings from in-vivo studies demonstrate that this phytoconstituent notably lowers fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels in dexamethasone-induced diabetic rats. Administration of hentriacontane effectively counteracts dexamethasone-induced impairments in oral glucose tolerance tests. Further, Hentriacontane normalizes lipid profiles and restores beta-cell function in diabetic rats. ConclusionThis study has provided scientific support and evidence that Hentriacontane has a positive hypoglycemic impact on insulin-resistant rats induced by dexamethasone. Additional studies are required to ascertain the most effective dosage, duration of therapy and molecular mode of action.

SORBS1 expression as a biomarker for obesity and breast cancer prognosis: Insights from genomic analysis and survival outcomes.

e13050 Background: Obesity is a known risk factor for breast cancer development and poorer survival. Correlation between the expression of the adaptor protein SORBS1 (Sorbin and SH3 domain-containing protein 1) and body mass index (BMI). Methods: Bioinformatics analysis. Results: We analyzed published datasets and plotted SORBS1 expression against patient BMI. Our findings show a negative correlation between SORBS1 expression and BMI in both datasets (R = -0.42, p = 0.00087, and R = -0.45 p = 0.00083, respectively). We also observed a negative correlation between SORBS1 expression and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R = -0.43, p = 0.00016). Additionally, we examined BMI-associated variants of the SORBS1 gene in the Qatar Biobank cohort of 15k individuals. We identified a total of 26 variants that were associated with an elevated risk for BMI in this population at a nominal significance. The top risk variant associated with the BMI is a missense variant (rs35480352; beta=0.058, p-value = 3.3e-03) with a frequency of 9.1% for the risk allele in our population. These results suggest that SORBS1 expression decreases with obesity and diabetes. This is significant because obesity is a known risk factor for breast cancer development and poorer survival. We also examined the SORBS1 gene expression in breast adenocarcinoma using UCSC TOIL RNA-seq recompute and TCGA-BRCA genomic and methylation data. Out of the 963 patients analyzed, only 12 (1.2%) showed any SORBS1 gene alteration, such as mutation (0.7%), amplification (0.2%), or deep deletion (0.3%), indicating a low occurrence of genomic alterations. Furthermore, our findings revealed no significant difference in SORBS1 methylation levels between the tumor and matched normal samples, indicating that the SORBS1 gene is not hypermethylated in breast carcinoma. Interestingly, our comparison of SORBS1 expression values between tumor and normal samples indicated significant under-expression in BRCA (log2FC = -2.7, p = 1.07E-127). SORBS1 expression was found to vary across various clinical stages (p = 0.0082, Kruskal-Wallis rank test), exhibiting a decline in advanced cancer stages. Moreover, we detected a significant difference in SORBS1 expression among different molecular subtypes (p &lt; 2E-16, Kruskal-Wallis rank test), with a lower expression level in more aggressive subtypes like HER2. Patients were classified into two groups according to their SORBS1 expression levels, using the median expression as a threshold: high and low. Conclusions: Our findings showed that the SORBS1 low group had substantially lower overall survival (log-rank p = 0.0024) and progression-free survival rates (log-rank p = 0.028). Silencing of SORBS1 in MCF-7 and MDA-MB-231 cells increased cell proliferation, migration, and invasion, underscoring its importance in breast cancer prognosis and as a target for intervention.

Increased Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) value is not related to glomerular filtration rate in healthy non-diabetic young adults

Increased Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) value is not related to glomerular filtration rate in healthy non-diabetic young adults

HOMA-IR as a Predictor of PAI-1 Levels in Women with Severe Obesity.

Obesity is a chronic inflammatory disorder that increases the risk of cardiovascular diseases (CVDs). Given the high CVD mortality rate among individuals with obesity, early screening should be considered. Plasminogen activator inhibitor (PAI-1), a cytokine that links obesity and CVDs, represents a promising biomarker. However, PAI-1 is not part of the clinical routine due to its high cost. Therefore, it is necessary to find good predictors that would allow an indirect assessment of PAI-1. This study enrolled 47 women with severe obesity (SO). The obtained anthropometric measurements included weight, height, neck (NC), waist (WC), and hip circumference (HC). Blood samples were collected to analyse glucose and lipid profiles, C-reactive protein, liver markers, adiponectin, and PAI-1 (determined by ELISA immunoassay). Homeostasis model assessment-adiponectin (HOMA-AD), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), triglyceride-glucose index (TyG), and atherogenic index of plasma (AIP) were calculated. The women were grouped according to PAI-1 levels. The data were analysed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%. Women with SO who have higher levels of PAI-1 have lower values of high-density lipoprotein cholesterol (HDL) (p = 0.037) and QUICKI (0.020) and higher values of HOMA-AD (0.046) and HOMA-IR (0.037). HOMA-IR was demonstrated to be a good predictor of PAI-1 in this sample (B = 0.2791; p = 0.017). HOMA-IR could be used as a predictor of PAI-1 levels, pointing out the relevance of assessing glycaemic parameters for the prevention of CVDs in women with SO.

Is Curcumin Intake Really Effective for Chronic Inflammatory Metabolic Disease? A Review of Meta-Analyses of Randomized Controlled Trials.

This review aimed to examine the effects of curcumin on chronic inflammatory metabolic disease by extensively evaluating meta-analyses of randomized controlled trials (RCTs). We performed a literature search of meta-analyses of RCTs published in English in PubMed®/MEDLINE up to 31 July 2023. We identified 54 meta-analyses of curcumin RCTs for inflammation, antioxidant, glucose control, lipids, anthropometric parameters, blood pressure, endothelial function, depression, and cognitive function. A reduction in C-reactive protein (CRP) levels was observed in seven of ten meta-analyses of RCTs. In five of eight meta-analyses, curcumin intake significantly lowered interleukin 6 (IL-6) levels. In six of nine meta-analyses, curcumin intake significantly lowered tumor necrosis factor α (TNF-α) levels. In five of six meta-analyses, curcumin intake significantly lowered malondialdehyde (MDA) levels. In 14 of 15 meta-analyses, curcumin intake significantly reduced fasting blood glucose (FBG) levels. In 12 of 12 meta-analyses, curcumin intake significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR). In seven of eight meta-analyses, curcumin intake significantly reduced glycated hemoglobin (HbA1c) levels. In eight of ten meta-analyses, curcumin intake significantly reduced insulin levels. In 14 of 19 meta-analyses, curcumin intake significantly reduced total cholesterol (TC) levels. Curcumin intake plays a protective effect on chronic inflammatory metabolic disease, possibly via improved levels of glucose homeostasis, MDA, TC, and inflammation (CRP, IL-6, TNF-α, and adiponectin). The safety and efficacy of curcumin as a natural product support the potential for the prevention and treatment of chronic inflammatory metabolic diseases.