Homeostasis Model Assessment Of Insulin Resistance Research Articles

Hepatic insulin resistance affects the efficacy of metformin in patients with newly diagnosed type 2 diabetes: A Sub-Analysis of the MARCH trial

AimOur study aimed to analyze how hepatic insulin resistance (IR) influences the efficacy of 48 weeks of metformin treatment in newly diagnosed type 2 diabetes patients. MethodsWe chose 291 participants who were allocated to a 48-week metformin treatment in the “Metformin and Acarbose in Chinese as initial Hypoglycemic treatment” (MARCH) trial and calculated their hepatic insulin resistance indexes (HIRI). We equally grouped the subjects into tertiles: low, medium, and high HIRI groups based on baseline HIRI; Low, medium, and high ΔHIRI groups based on the decreasing extent of HIRI after a 48-week metformin treatment. ResultsMultiple linear regression showed that baseline HIRI was positively associated with the rising degree of Matsuda index and the falling range of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HIRI. Furthermore, baseline fasting insulin, homeostatic model assessment of β cell function (HOMA-β), HOMA-IR, and HIRI were positively associated with the decreasing extent of HIRI, while baseline Matsuda index had a negative association with the falling extent of HIRI. ConclusionsPatients with higher levels of hepatic IR obtained better curative effects from metformin in terms of glycemic control, insulin saving, insulin sensitivity enhancement, and IR improvement. Higher fasting blood glucose, fasting insulin, HOMA-β, IR, and lower Matsuda index were indicators of better hepatic IR improvement.

Slow-velocity eccentric-only resistance training improves symptoms of type 2 diabetic mellitus patients by regulating plasma MMP-2 and -9.

This study investigated the intervention effect of slow-velocity eccentric-only resistance training on type 2 diabetic mellitus (T2DM) patients based on the role of matrix metalloproteinase-2 and -9 (MMP-2 and -9) in regulating extracellular matrix homeostasis. 50 T2DM patients were randomly divided into the slow-velocity eccentric-only resistance training group (E) and control group (C). The E group performed eccentric-only resistance training 3 times a week, every other day for 10 weeks, while the C group did not. Blood samples were collected before and after training, and subjects were tested for changes in clinical parameters, insulin resistance indices [fasting insulin, homeostatic model assessment insulin resistance (HOMA-IR)], MMP-2 and -9, and hydroxyproline, and muscle strength (12-RM), respectively. After 10 weeks of training, the E group showed significant decreases in fasting glucose (P < .05), insulin (P < .05), insulin resistance indices (P < .05), hemoglobin A1c (HbA1c) (P < .01), triglycerides (P = .06) and MMP-2 (P < .05), while total cholesterol (P < .05), MMP-9 (P < .05), hydroxyproline (P < .01), Creatine Kinase (CK) (P < .05), and muscle strength (P < .001) significantly increased. There were no significant changes in the count of neutrophil, lymphocyte and platelet, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). Compared with the C group, the E group showed a trend of a significant decrease in triglyceride (P < .05), lymphocyte count (P < .05), fasting glucose (P = .07), and plasma MMP-2 (P < .05), while MMP-9 (P < .05), hydroxyproline (P < .001), and muscle strength (P < .01) significantly increased. However, no significant changes were observed in insulin and insulin resistance indices, HbA1c, total cholesterol, HDL-c, LDL-c, CK, and other inflammatory indicators. Slow-velocity eccentric-only resistance training was beneficial for T2DM, but the potential role of MMP-2 and -9 in regulating extracellular matrix homeostasis is very different in T2DM patients.

Altered Body Composition and Cytokine Production in Patients with Elevated HOMA-IR after SARS-CoV-2 Infection: A 12-Month Longitudinal Study.

Altered body composition and cytokine production due to SARS-CoV-2 antigens may affect homeostasis model assessment for insulin resistance (HOMA-IR) after SARS-CoV-2 infection. To elucidate this phenomenon, we conducted a longitudinal study involving 47 COVID-19 patients, who were followed up for 12 months. During recruitment, body composition and glucose indices were measured, and heparin blood samples were collected for measuring cytokine production. HOMA-IR was considered an elevated or non-elevated group based on the ratio between HOMA-IR at 12 months and 1 month of convalescence. Those with elevated HOMA-IR had a significantly higher body mass index, body fat percentage, and visceral fat rating and had a lower lean mass and lean/fat mass ratio than their counterparts. During the convalescent period, the elevated HOMA-IR group had lower TNFα, IFNγ, IL-2, IL-10, and granzyme B expression levels but had higher TNFα/IL-10, IFNγ/IL-10, IL-2/IL-10, and granzyme B/IL-10 ratios than the other group. The reduced cytokine production and pro-/anti-inflammatory imbalance in patients with elevated HOMA-IR may suggest immune cell dysfunction toward SARS-CoV-2. Patients with elevated HOMA-IR after SARS-CoV-2 infection may experience an increase in BMI and body fat percentage, leading to increased immune dysfunction and chronic inflammatory condition. A nutritional approach and promotion of physical activity may help reduce HOMA-IR and ameliorate glucose indices in these patients.

The U-shape relationship between insulin resistance-related indexes and chronic kidney disease: a retrospective cohort study from National Health and Nutrition Examination Survey 2007–2016

BackgroundThere is ongoing debate on the correlation between chronic kidney disease (CKD) and insulin resistance (IR)-related indices. Our objective was to explore the prognostic ability of IR-related indexes for the prevalence of CKD, as well as the mortality from all causes and cardiovascular disease (CVD) in CKD patients.MethodsThe data used in this study came from the National Health and Nutrition Examination Survey (NHANES). Binary logistic regression analysis, Cox proportional hazards model, and restricted cubic spline (RCS) were used to analyze the relationship between IR-related indexes, including metabolic score of IR (METS-IR), homeostatic model assessment for IR (HOMA-IR), triglyceride glucose index (TyG), triglyceride glucose-waist-to-height ratio (TyG-WHtR), triglyceride glucose-body mass index (TyG-BMI), with CKD and its all-cause mortality and CVD mortality. Subgroup analysis was performed to test the stability of the results. Finally, the predictive power of IR-related indexes for CKD was tested by the receiver operating characteristic (ROC) curve.ResultsAmong the recruited 10,660 participants, 15.42% were CKD patients. All IR-related indexes were found to be nonlinearly correlated to the prevalence of CKD in the study. When the TyG index was higher than 9.05, it was positively associated with CKD (OR: 1.77, 95% CI 1.44–2.18). Moreover, increased TyG-WHtR level was correlated with a greater prevalence of CKD when it was higher than 4.3 (OR: 1.31, 95% CI 1.19–1.45). Other IR-related indexes (METS-IR, HOMA-IR, and TyG-BMI) showed fewer notable correlations with CKD. The association of IR-related indexes and the prevalence of CKD remained consistent in most subgroups (P for interactions > 0.05). TyG-WHtR was also the predictor of all-cause mortality in CKD patients (HR: 1.34, 95% CI 1.14–1.58), while other IR-related indexes were not correlated with the all-cause mortality or CVD mortality in CKD patients (P > 0.05). Otherwise, ROC curves showed that TyG-WHtR had more robust diagnostic efficacy than other IR-related indexes (METS-IR, HOMA-IR, TyG, and TyG-BMI) in predicting CKD (area under the curve: 0.630, 95% CI 0.615–0.644).ConclusionsIR-related biomarkers (METS-IR, HOMA-IR, TyG, and TyG-BMI) were positively correlated with the prevalence of CKD. Moreover, TyG-WHtR enhanced CKD and its all-cause mortality prediction. In patients with elevated levels of IR-related indexes, the early detection and intervention of IR may reduce the occurrence of CKD and the prognosis of CKD patients.

Effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome: a randomized controlled trial

ObjectiveThe aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS).MethodsA total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment, including body mass index (BMI), waist to hip ratio (WHR), oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters.ResultsThe serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P < 0.05). The BMI, WHR, insulin concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group (P < 0.05). The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower compared with control group (obesity) (P < 0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) (P < 0.05). No significant difference was observed in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (P > 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05).ConclusionVitamin D supplementation had beneficial effects on metabolic parameters in PCOS women, especially in women with obesity or insulin resistance.

Adipose tissue insulin resistance index was inversely associated with gluteofemoral fat and skeletal muscle mass in Japanese women

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.

Decreased serum levels of 25-OH vitamin D and vitamin K in patients with type 2 diabetes mellitus.

Insulin resistance and/or insulin secretion dysfunction are crucial causes of type 2 diabetes mellitus (T2DM). Although some studies have suggested potential roles for vitamins D and K in glucose metabolism and insulin sensitivity, there is limited and inconclusive research on their levels in T2DM patients and their relationship with blood glucose levels and insulin resistance. Additionally, there is a lack of large-scale clinical trials and comprehensive studies investigating the combined effects of vitamins D and K on T2DM. A total of 195 participants with newly diagnosed T2DM were included in the research group, while 180 volunteers undergoing physical examinations in our hospital served as the control group. Fasting plasma glucose (FPG) was estimated using the glucose-oxidase technique, and fasting serum insulin (FINS) was evaluated by radioimmunoassay. FPG and FINS were used to calculate the homeostasis model assessment-insulin resistance (HOMA-IR). Serum vitamin D levels were measured using 25-hydroxyvitamin D, and vitamin K levels were evaluated using phylloquinone (VK1) and menaquinone (VK2) via ultra-high performance liquid chromatography and tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of these vitamins for T2DM. Circulating levels of 25-hydroxyvitamin D (25.95 ± 10.42 ng/mL), VK1 (1.24 ± 0.89 ng/mL), and VK2 (0.2 ± 0.21 ng/mL) in T2DM patients were significantly lower than in the control group (37.46 ± 13.95 ng/mL for 25-hydroxyvitamin D, 1.99 ± 1.39 ng/mL for VK1, and 0.33 ± 0.22 ng/mL for VK2; p<0.001 for all comparisons). ROC analysis indicated that 25-hydroxyvitamin D, VK1, and VK2 could predict the occurrence of T2DM, with AUC values of 0.75, 0.69, and 0.71, respectively. In T2DM patients, 25-hydroxyvitamin D levels were positively correlated with VK1 (r=0.43, p<0.001) and VK2 (r=0.40, p<0.001) levels. FPG and HOMA-IR in T2DM patients were negatively correlated with circulating levels of 25-hydroxyvitamin D (r=-0.57, p<0.001), VK1 (r=-0.44, p<0.001), and VK2 (r=-0.36, p<0.001). Circulating levels of vitamins D and K are lower in T2DM patients and show significant correlations with blood glucose levels and insulin resistance. These findings suggest that measurements of 25-hydroxyvitamin D, VK1, and VK2 could have predictive value for T2DM, highlighting the potential roles of these vitamins in T2DM management.

Longitudinal changes in mitochondrial-associated measures and insulin resistance in youth with perinatally-acquired HIV in the U.S

HIV infection and its treatment are associated with mitochondrial dysfunction and metabolic derangement. However, longitudinal changes in oxidative phosphorylation activities [Complex I (C1) and Complex IV (C4)], or venous lactate/pyruvate ratios (LPR), and their relationships with insulin resistance (IR), remain unclear in youth living with perinatally-acquired HIV (YPHIV). We measured venous LPR, C1, and C4 activities in blood cells and homeostatic model assessment for IR (HOMA-IR) over two years. Limited longitudinal differences in mitochondrial-related measures and IR were observed in YPHIV vs youth perinatally HIV-exposed but uninfected. There were no systematic differences in C1, C4, or HOMA-IR between the groups.

The Efficacy and Safety of DLBS3233, A Combined Bioactive Fraction of Cinnamomum burmanii and Lagerstroemia speciosa Plants on The Endocrine-Metabolic Profile of Women with Polycystic Ovary Syndrome: A Randomized Clinical Trial.

A bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa, DLBS3233, has recently been used for type-2-diabetes treatment due to its favorable effect on insulin sensitivity. The insulin resistance leading to metabolic syndrome is closely linked to hyperandrogenemia in polycystic ovary syndrome (PCOS). This study evaluated the metabolic and reproductive efficacy and safety of DLBS3233 in insulin-resistant PCOS women. This was a 2-arm, randomized, double-blind, controlled, noninferiority clinical study over a 6-month therapy with DLBS3233 100-mg daily in comparison to metformin-XR 750 mg twice daily, involving 124 PCOS women with insulin resistance. The primary efficacy endpoint was the improvement of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Secondary endpoints were improvements in other metabolic and reproductive parameters. Safety endpoints were based on blood pressure, heart rate, electrocardiogram findings, liver and renal function, and adverse events. After 6 months, HOMA-IR improvement in DLBS3233-treated group (-1.03 ± 0.50) and metformin-XR (-1.19 ± 0.50) were comparable, with a between-group difference fell within the pre-set non-inferiority margin (0.16; 95% confidence interval (CI): -1.24, 1.56; P=0.3168). The HOMA-IR in both groups were significantly improved from baseline. On all secondary endpoints, both groups showed comparable effects. Markedly fewer adverse events occurred in the DLBS3233 treated group than in the Metformin-XR-treated group and most were mild clinically and had been resolved by the end of the study. Treatment with DLBS3233 100-mg daily in PCOS women demonstrated comparable efficacy to metformin- XR 750-mg twice daily in improving insulin resistance. However, the non-inferiority of DLBS3233 to metformin- XR remains inconclusive. DLBS3233 was more tolerable than metformin-XR (registration number: NCT01733459).

The biological variation of insulin resistance markers: data from the European Biological Variation Study (EuBIVAS).

An insulin resistant state is characteristic of patients with type 2 diabetes, polycystic ovary syndrome, and metabolic syndrome. Identification of insulin resistance (IR) is most readily achievable using formulae combining plasma insulin and glucose results. In this study, we have used data from the European Biological Variation Study (EuBIVAS) to examine the biological variability (BV) of IR using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and the Quantitative Insulin sensitivity Check Index (QUICKI). Ninety EuBIVAS non-diabetic subjects (52F, 38M) from five countries had fasting HOMA-IR and QUICKI calculated from plasma glucose and insulin samples collected concurrently on 10weekly occasions. The within-subject (CVI) and between-subject (CVG) BV estimates with 95 % CIs were obtained by CV-ANOVA after analysis of trends, variance homogeneity and outlier removal. The CVI of HOMA-IR was 26.7 % (95 % CI 25.5-28.3), driven largely by variability in plasma insulin and the CVI for QUICKI was 4.1 % (95 % CI 3.9-4.3), reflecting this formula's logarithmic transformation of glucose and insulin values. No differences in values or BV components were observed between subgroups of men or women below and above 50 years. The EuBIVAS, by utilising a rigorous experimental protocol, has produced robust BV estimates for two of the most commonly used markers of insulin resistance in non-diabetic subjects. This has shown that HOMA-IR, in particular, is highly variable in the same individual which limits the value of single measurements.

Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females.

Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer's disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.5 kg/m2 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9 years) maintaining nutritional ketosis (NK) for an average of 3.9 years (± 2.3) who underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Ketosis suppression significantly increased insulin, 1.83-fold (p = 0.0006); glucose, 1.17-fold (p = 0.0088); homeostasis model assessment for insulin resistance (HOMA-IR), 2.13-fold (p = 0.0008); leptin, 3.35-fold (p = 0.0010); total osteocalcin, 1.63-fold (p = 0.0138); and uncarboxylated osteocalcin, 1.98-fold (p = 0.0417) and significantly decreased beta-hydroxybutyrate, 13.50-fold (p = 0.0012) and glucagon-like peptide-1 (GLP-1), 2.40-fold (p = 0.0209). Sustained NK showed no adverse health effects and may mitigate hyperinsulinemia. All biomarkers returned to basal P1 levels after removing the intervention for SuK, indicating that metabolic flexibility was maintained with long-term euketonaemia.

Serum Levels of Adipolin and Adiponectin and Their Correlation with Perinatal Outcomes in Gestational Diabetes Mellitus.

Objectives: This study aimed to investigate the serum level of adipolin and adiponectin in healthy pregnant women and pregnant women with gestational diabetes mellitus (GDM) during the second trimester, the prepartum period, and in the newborns of these patients. Methods: A total of 55 women diagnosed with GDM and 110 healthy pregnant women were included in this study. Pearson's and Spearman's correlation coefficients were calculated to determine the association of adipolin and adiponectin with anthropometric markers of obesity (body mass index (BMI), mid-upper arm circumference (MUAC), tricipital skinfold thickness (TST)), inflammation markers (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)), and maternal glucose homeostasis parameters (fasting glucose, insulin, C peptide, glycosylated hemoglobin A1c (HbA1c), Insulin Resistance-Homeostatic Model Assessment (IR HOMA)). Results: There were no statistical differences between the adipolin value in patients with GDM compared to healthy patients (p = 0.65 at diagnosis and p = 0.50 prepartum) and in newborns from mothers with GDM compared to healthy mothers (p = 0.24). Adipolin levels are significantly higher in patients with GDM who gave birth via cesarean section (p = 0.01). In patients with GDM, the adipolin level correlates positively with HgA1c in the prepartum period. We found a positive correlation between the maternal adipolin values at diagnosis and prepartum and neonatal adipolin (respectively: r = 0.556, p = 0.001; r = 0.332, p = 0.013). Adiponectin levels were significantly lower in patients with GDM at diagnosis and prepartum (p = 0.0009 and p = 0.02), but their levels increased prepartum (5267 ± 2114 ng/mL vs. 6312 ± 3150 ng/mL p = 0.0006). Newborns of mothers with GDM had lower adiponectin levels than newborns of healthy mothers (p < 0.0001). The maternal adiponectin value correlates negatively with maternal BMI, MUAC, and IR HOMA in both groups at diagnosis and prepartum. There were no differences between the groups in terms of cesarean rate (p > 0.99). The relative risk of occurrence of adverse events in patients with GDM compared to healthy ones was 2.15 (95% CI 1.416 to 3.182), and the odds ratio for macrosomia was 4.66 (95% CI 1.591 to 12.69). Conclusions: There was no difference in adipolin levels between mothers with GDM and healthy mothers during the second trimester and the prepartum period. Adipolin is known to enhance insulin sensitivity and reduce inflammation, but unlike adiponectin, it does not appear to contribute to the development of GDM.

High triglyceride-glucose index and HOMA-IR are associated with different cardiometabolic profile in adults from the ELSA-Brasil study

Background and aimsInsulin resistance (IR) is a risk factor for several cardiometabolic disorders; however, there is conflicting evidence about the reliability of certain IR markers. In this context, the triglyceride-glucose index (TyG) has been proposed as a surrogate marker for IR. This study aimed to compare the TyG index and homeostasis model assessment of insulin resistance (HOMA-IR). Methods and resultsA cross-sectional analysis was conducted using baseline data from 11,314 adults (aged 35–74 years) from the ELSA-Brasil study. The correlation between TyG and HOMA-IR, their interrater reliability, and their predictive value in identifying metabolic syndrome (MetS) were assessed. The mean TyG and HOMA-IR in our sample were 8.81 ± 0.52 and 2.78 ± 1.58 for men, and 8.53 ± 0.48 and 2.49 ± 1.38 for women, respectively. TyG and HOMA-IR showed a weak to moderate correlation with each other (Pearson’s r for men: 0.395 and 0.409 for women, p-value <0.05) and other markers of glycemic metabolism. Additionally, the area under the curve for the prediction of MetS was greater for TyG than HOMA-IR, regardless of sex (TyG: 0.836 for men and 0.826 for women; HOMA-IR: 0.775 for men and 0.787 for women). The concordance between these markers was low (Coheńs kappa coefficient: 0.307 for men and 0.306 for women). Individuals with increased TyG exhibited mainly anthropometrical and glycemic metabolic alterations, whereas those with elevated HOMA-IR displayed mostly lipid-associated metabolic alterations. ConclusionTyG and HOMA-IR might indicate different profiles of cardiometabolic disorders, showing poor agreement in classifying individuals (normal vs. altered) and a weak correlation. Therefore, further studies are needed to investigate the role of TyG as a surrogate marker of IR.

Metabolic score for insulin resistance (METS-IR) predicts all-cause and cardiovascular mortality in the general population: evidence from NHANES 2001–2018

BackgroundThe prevalence of obesity-associated insulin resistance (IR) is increasing along with the increase in obesity rates. In this study, we compared the predictive utility of four alternative indexes of IR [triglyceride glucose index (TyG index), metabolic score for insulin resistance (METS-IR), the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and homeostatic model assessment of insulin resistance (HOMA-IR)] for all-cause mortality and cardiovascular mortality in the general population based on key variables screened by the Boruta algorithm. The aim was to find the best replacement index of IR.MethodsIn this study, 14,653 participants were screened from the National Health and Nutrition Examination Survey (2001–2018). And TyG index, METS-IR, TG/HDL-C and HOMA-IR were calculated separately for each participant according to the given formula. The predictive values of IR replacement indexes for all-cause mortality and cardiovascular mortality in the general population were assessed.ResultsOver a median follow-up period of 116 months, a total of 2085 (10.23%) all-cause deaths and 549 (2.61%) cardiovascular disease (CVD) related deaths were recorded. Multivariate Cox regression and restricted cubic splines analysis showed that among the four indexes, only METS-IR was significantly associated with both all-cause and CVD mortality, and both showed non-linear associations with an approximate “U-shape”. Specifically, baseline METS-IR lower than the inflection point (41.33) was negatively associated with mortality [hazard ratio (HR) 0.972, 95% CI 0.950–0.997 for all-cause mortality]. In contrast, baseline METS-IR higher than the inflection point (41.33) was positively associated with mortality (HR 1.019, 95% CI 1.011–1.026 for all-cause mortality and HR 1.028, 95% CI 1.014–1.043 for CVD mortality). We further stratified the METS-IR and showed that significant associations between METS-IR levels and all-cause and cardiovascular mortality were predominantly present in the nonelderly population aged < 65 years.ConclusionsIn conjunction with the results of the Boruta algorithm, METS-IR demonstrated a more significant association with all-cause and cardiovascular mortality in the U.S. population compared to the other three alternative IR indexes (TyG index, TG/HDL-C and HOMA-IR), particularly evident in individuals under 65 years old.

A study on the association between insulin resistance and genome-wide DNA methylation based on Shanghai monozygotic twins

Objective: To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study. Methods: Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters. Results: A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 (β=0.74%, P=1.51×10-7, OR=1.06, 95%CI: 1.03-1.09) and ch.17.49619327-SPOP (β=0.23%, P=7.54×10-7, OR=1.17, 95%CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated (β=-0.39%, P<0.001) and hypermethylated (β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions: IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

The correlation between hepatic controlled attenuation parameter (CAP) value and insulin resistance (IR) was stronger than that between body mass index, visceral fat area and IR

BackgroundHepatic controlled attenuation parameter (CAP) is a novel marker for quantifying hepatic fat accumulation. Insulin resistance (IR) plays a major role in the pathogenesis and natural history of hepatic steatosis. This study aimed to investigate the possible relationship between CAP value and IR.MethodsThis study included a total of 420 patients with overweight or obesity who came to the obesity clinic at Tianjin Union Medical Center. Vibration-controlled transient elastography examination was conducted to detect CAP and liver stiffness measurement (LSM) values. Body composition, including visceral fat area (VFA), and body fat mass (BFM), was evaluated by the direct segmental multi-frequency bioelectrical impedance analysis (BIA). The associations between CAP value, body mass index (BMI), VFA, BFM and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed.ResultsCAP value was positively associated with HOMA-IR (r = 0.568, P < 0.001), the strength of which was much stronger than BMI, VFA, and BFM. In multivariate linear regression, CAP value and HOMA-IR showed a significant positive association (adjusted β = 0.015, 95% CI 0.007–0.022, P < 0.001). Subgroup analysis suggested no significant interaction between CAP value and HOMA-IR across age, BMI, LSM, hypertension, and sex groups (all P for interaction > 0.05).ConclusionsHepatic CAP value is more remarkably than other obesity markers associated with HOMA-IR in individuals with overweight or obesity, regardless of age, BMI, LSM, hypertension, and sex.

Associations of insulin sensitivity and immune inflammatory responses with child blood lead (Pb) and PM2.5 exposure at an e-waste recycling area during the COVID-19 lockdown.

Fine particular matter (PM2.5) and lead (Pb) exposure can induce insulin resistance, elevating the likelihood of diabetes onset. Nonetheless, the underlying mechanism remains ambiguous. Consequently, we assessed the association of PM2.5 and Pb exposure with insulin resistance and inflammation biomarkers in children. A total of 235 children aged 3-7years in a kindergarten in e-waste recycling areas were enrolled before and during the Corona Virus Disease 2019 (COVID-19) lockdown. Daily PM2.5 data was collected and used to calculate the individual PM2.5 daily exposure dose (DED-PM2.5). Concentrations of whole blood Pb, fasting blood glucose, serum insulin, and high mobility group box 1 (HMGB1) in serum were measured. Compared with that before COVID-19, the COVID-19 lockdown group had lower DED-PM2.5 and blood Pb, higher serum HMGB1, and lower blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR) index. Decreased DED-PM2.5 and blood Pb levels were linked to decreased levels of fasting blood glucose and increased serum HMGB1 in all children. Increased serum HMGB1 levels were linked to reduced levels of blood glucose and HOMA-IR. Due to the implementation of COVID-19 prevention and control measures, e-waste dismantling activities and exposure levels of PM2.5 and Pb declined, which probably reduced the association of PM2.5 and Pb on insulin sensitivity and diabetes risk, but a high level of risk of chronic low-grade inflammation remained. Our findings add new evidence for the associations among PM2.5 and Pb exposure, systemic inflammation and insulin resistance, which could be a possible explanation for diabetes related to environmental exposure.

Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder

BackgroundThe understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI).Methods67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[−]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance).ResultsMDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia.ConclusionIR appears to be linked to depressive symptoms characteristic of the “metabolic” MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI.

The Prospect of Probiotics to Treat Metabolic Syndrome

Metabolic syndrome remains as a major health problem in the world today, with a prevalence of 23.4% in people aged 26-82 years. A high-fat, high-carbohydrate diet and lack of physical activity are considered as one of the triggers for metabolic syndrome. Dysbiosis is a condition where there is an imbalance between pathogenic and non-pathogenic bacteria in the human gut. Currently, an association has been found between dysbiosis and metabolic syndrome. Dysbiosis causes the generation of fermentation products in the form of active metabolites that can modulate hormones and other physiological functions. In metabolic syndrome, low-grade inflammation, energy metabolism, and disruption of the gut brain axis are thought to be the main mechanisms of the development of metabolic syndrome due to dysbiosis. Probiotics may be a promising therapeutic agent in the treatment of metabolic syndrome, by improving dysbiosis to eubiosis. Based on previously conducted clinical trials, it is currently known that probiotics can improve lipid profiles, fasting blood glucose, homeostatic model assessment for insulin resistance (HOMA-IR), vascular cell adhesion molecule 1 (VCAM-1), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and body mass index (BMI). However, the results found are still varied, so a dose ranging study is needed to determine the duration, bacterial composition and dose of probiotics as a therapeutic agent for metabolic syndrome. Keywords: insulin resistance, dysbiosis, gut-brain axis

Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD). In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol-1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol-1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6-week interventions: (1) exercise training (EX; 70%-75% maximum heart rate; four sessions/week; n = 13) or (2) non-exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA-IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin-18 (CK18) M65, among others. In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA-IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = -0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate-intensity exercise training.