Mediators of insulin resistance & cardiometabolic risk: Newer insights.
Ontology highlight
ABSTRACT:
SUBMITTER: Bodhini D
PROVIDER: S-EPMC6206760 | biostudies-literature | 2018 Aug
REPOSITORIES: biostudies-literature
Publications
Mediators of insulin resistance & cardiometabolic risk: Newer insights.
Bodhini Dhanasekaran D Mohan Viswanathan V
The Indian journal of medical research 20180801 2
Similar Datasets
Project description:IntroductionRegarding the increased prevalence of obesity among children and adolescents, and the impact of obesity on insulin resistance (IR) and other metabolic disorders, this study was performed to determine the association of cardiometabolic risk factors (CMRFs) with IR in overweight and obese children.MethodIn this cross-sectional study 150 overweight and obese children (BMI ≥ 85th and BMI ≥ 95th age-sex specific percentile) and adolescents were selected via convenient sampling method from Endocrinology clinic in Karaj; Iran in 2020. Anthropometric indices, lipid profile, fasting blood glucose (FBG), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were evaluated. IR was defined as HOMA-IR ≥ 2.6. Multivariable linear and logistic regression model was used to assess the association of CMRFs with insulin level and IR respectively.ResultsThe mean age of children was 10.37 (± 2.6) years. Fifty-four percent of the participants were girls. IR was increased through increasing age (P < 0.001). In the multivariate logistic regression model, by increasing each unit increment in waist circumference (OR: 1.03, 95% CI: 1.01-1.06), wrist circumference (OR: 1.47, 95% CI: 1.06-2.02) total cholesterol (OR: 1.01, 95% CI: 1.003-1.03) and FBG (OR: 1.11, 95% CI: 1.05-1.18) the odds of IR increased significantly. Moreover, in the adjusted linear regression model, HOMA-IR was associated significantly with waist to height ratio (β: 2.45), and FBG (β: 0.02).ConclusionThere was a significant association between some CMRFS with IR in overweight and obese children.
| S-EPMC9761952 | biostudies-literature
Project description:As is well known, adipose tissue is an important site for lipid metabolism and insulin-responsive glucose uptake. The recent discovery of the endocrine function of adipose tissue and the association of obesity with chronic low-grade inflammation in adipose tissue has reinforced the concept of the central role of adipose tissue in mediating obesity-linked insulin resistance and metabolic dysregulation. The study of adipose cells has provided new insights into the mechanism underlying insulin resistance as well as the therapeutic strategies for diabetes. Numerous efforts have been made in identifying key molecular regulators of insulin action and metabolism, including the utilization of advanced proteomics technology. Various proteomic approaches have been applied to identify the adipose secretome, protein-expression profiling and post-translational modifications in adipose cells in the pathological state. In this review, we summarize the recent advances in the proteomics of adipose tissue, and discuss the identified proteins that potentially play important roles in insulin resistance and diabetes.
| S-EPMC2651673 | biostudies-literature
Project description:Many biochemical traits are recognised as risk factors, which contribute to or predict the development of disease. Only a few are in widespread use, usually to assist with treatment decisions and motivate behavioural change. The greatest effort has gone into evaluation of risk factors for cardiovascular disease and/or diabetes, with substantial overlap as 'cardiometabolic' risk. Over the past few years many genome-wide association studies (GWAS) have sought to account for variation in risk factors, with the expectation that identifying relevant polymorphisms would improve our understanding or prediction of disease; others have taken the direct approach of genomic case-control studies for the corresponding diseases. Large GWAS have been published for coronary heart disease and Type 2 diabetes, and also for associated biomarkers or risk factors including body mass index, lipids, C-reactive protein, urate, liver function tests, glucose and insulin. Results are not encouraging for personal risk prediction based on genotyping, mainly because known risk loci only account for a small proportion of risk. Overlap of allelic associations between disease and marker, as found for low density lipoprotein cholesterol and heart disease, supports a causal association, but in other cases genetic studies have cast doubt on accepted risk factors. Some loci show unexpected effects on multiple markers or diseases. An intriguing feature of risk factors is the blurring of categories shown by the correlation between them and the genetic overlap between diseases previously thought of as distinct. GWAS can provide insight into relationships between risk factors, biomarkers and diseases, with potential for new approaches to disease classification.
| S-EPMC3961996 | biostudies-literature
Project description:Obesity is associated with chronic inflammation of various tissues including visceral adipose tissue (VAT), which contributes to insulin resistance. T cells and macrophages infiltrate VAT in obesity and orchestrate this inflammation. Recently, we made the surprising discovery that B cells are important contributors to this process. Thus, some B cells and the antibodies they produce can promote VAT-associated and systemic inflammation, leading to insulin resistance. This report will focus on the properties of these B cells, and how they contribute to insulin resistance through T-cell modulation and production of pathogenic autoantibodies. Understanding the mechanisms by which B cells contribute to insulin resistance should lead to new antibody-based diagnostics and B-cell modulating therapeutics to manage this increasingly prevalent disease.
| S-EPMC4109086 | biostudies-other
Project description:BackgroundWe aimed to define refined body shapes by using multiple anthropometric traits that represent fat distribution, and evaluate their associations with risk of insulin resistance (IR) and cardiometabolic disorders in a Chinese population.MethodsWe performed a cross-sectional analysis in 6570 community-based participants aged ≥ 40 years. Four body circumferences (neck, waist, hip, and thigh) and their ratios were put simultaneously into an open-source Waikato Environment for Knowledge Analysis platform to select the worthiest indicators in determining IR. The ratio of the top 3 fat distribution indicators was used to define the refined body shapes.ResultsWe defined 8 distinct body shapes based on sex-specific combinations of waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and waist-to-neck ratio (WNR), which differed in participants' distribution and risk of IR and related cardiometabolic disorders. In women, as compared to the low WHR-low WTR-low WNR shape, all body shapes were significantly associated with IR and related cardiometabolic disorders; while in men, the low WHR-high WTR-high WNR shape and the higher WHR related shapes were significantly associated with IR and related cardiometabolic disorders. Stratified by WHR, the results were consistent in women; however, no significant associations were detected in men.ConclusionsWe defined 8 distinct body shapes by taking WHR, WTR, and WNR, simultaneously into account, which differed in association with the risk of IR and related cardiometabolic disorders in women. This study suggests that body shapes defined by multiple anthropometric traits could provide a useful, convenient, and easily available method for identifying cardiometabolic risk.
| S-EPMC8650554 | biostudies-literature
Project description:ObjectiveLow-grade chronic inflammation has been hypothesized to underlie the constellation of cardiometabolic risk factors, possibly by inducing insulin resistance. In the present study, we investigated associations between inflammation markers, insulin sensitivity (expressed as the ratio of the M value to the mean plasma insulin concentrations measured during the final 40 min of the clamp [M/I]), and a range of cardiometabolic risk factors in a large, healthy population.Research design and methodsThe Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort includes 1,326 nondiabetic European men and women, aged between 30 and 60 years. We measured cardiometabolic risk factors and performed a hyperinsulinemic-euglycemic clamp. We determined total white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) as markers of chronic inflammation.ResultsWBC and ESR were both strongly associated with M/I. WBC and ESR were further associated with a range of cardiometabolic risk factors. Associations between WBC and HDL cholesterol, triglycerides, heart rate, fasting C-peptide, and insulin and 2-h insulin in men and women and between WBC and 2-h glucose in women remained significant after adjustment for both M/I and waist circumference. Associations between ESR and HDL cholesterol, heart rate, fasting, and 2-h insulin in men and women and between ESR and fat mass in women remained significant after adjustment for M/I and waist circumference.ConclusionsThis study showed that low-grade chronic inflammation is associated with the cardiometabolic risk profile of a healthy population. Insulin resistance, although strongly associated with inflammation, does not seem to play a large intermediary role.
| S-EPMC2699728 | biostudies-literature
Project description:Dysregulated lipid metabolism, characterized by higher levels of circulating triglycerides, higher levels of small, low density lipoprotein, and accumulation of intracellular lipids, is linked to insulin resistance and related complications such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Considering that various metabolic, genetic, and environmental factors are involved in the development of T2DM and CVD, the causalities of these diseases are often confounded. In recent years, Mendelian randomization (MR) studies coupling genetic data in population studies have revealed new insights into the risk factors influencing the development of CVD and T2DM. This review briefly conceptualizes MR and summarizes the genetic traits related to lipid metabolism by evaluating their effects on the indicators of insulin resistance based on the results of recent MR studies. The data from the MR study cases referred to in this review indicate that the causal associations between lipid status and insulin resistance in MR studies are not conclusive. Furthermore, available data on Asian ethnicities, including Korean, are very limited. More genome-wide association studies and MR studies on Asian populations should be conducted to identify Asian- or Korean-specific lipid traits in the development of insulin resistance and T2DM. The present review discusses certain studies that investigated genetic variants related to nutrient intake that can modify lipid metabolism outcomes. Up-to-date inferences on the causal association between lipids and insulin resistance using MR should be interpreted with caution because of several limitations, including pleiotropic effects and lack of information on genotype and ethnicity.
| S-EPMC7379122 | biostudies-literature
Project description:BackgroundIt is known that 15-30% overweight/obese adults do not suffer cardiometabolic consequences. There is limited literature examining factors that can be used to assess cardiometabolic health in overweight/obese children. If such factors can be identified, they would aid in differentiating those most in need for aggressive management.MethodsBaseline data from 7- to 12-year-old, overweight, and obese children enrolled in a weight management program at an urban hospital were analyzed. Homeostatic model assessment for insulin resistance (HOMA-IR) <2.6 was used to define insulin-sensitive and HOMA-IR ≥2.6 was used to defined insulin-resistant participants. Demographics, physical activity measures, and cardiometabolic risk factors were compared between the two phenotypes. Odds ratios (ORs) examining the association between intermediate endpoints (metabolic syndrome [MetS], nonalcoholic fatty liver disease [NAFLD], systemic inflammation, and microalbuminuria) and the two metabolic phenotypes were evaluated.ResultsOf the 362 overweight/obese participants, 157 (43.5%) were insulin sensitive and 204 (56.5%) were insulin resistant. Compared to the insulin-sensitive group, the insulin-resistant group was older (8.6±1.6 vs. 9.9±1.7; p<0.001) and had a higher BMI z-score (1.89±0.42 vs. 2.04±0.42; p=0.001). After multivariable adjustment, compared to the insulin-sensitive group, the insulin-resistant group had higher odds of having MetS (OR, 5.47; 95% confidence interval [CI]: 1.72, 17.35; p=0.004) and NAFLD (OR, 8.66; 95% CI, 2.48, 30.31; p=0.001), but not systemic inflammation (OR, 1.06; 95% CI: 0.56, 2.03; p=0.86) or microalbuminuria (OR, 1.71; 95% CI, 0.49, 6.04; p=0.403).ConclusionsUsing a HOMA-IR value of ≥2.6, clinical providers can identify prepubertal and early pubertal children most at risk. Focusing limited resources on aggressive weight interventions may lead to improvement in cardiometabolic health.
| S-EPMC4485365 | biostudies-literature
Project description:ObjectiveWe sought to characterize associations between aminotransferase levels and cardiometabolic risk after accounting for visceral adipose tissue and insulin resistance.Methods and resultsParticipants (n=2621) from the Framingham Heart Study (mean age 51, 49.8% women) were included. Sex-specific linear and logistic regressions were used to evaluate associations between aminotransferase levels and cardiometabolic risk factors. In multivariable models, increased alanine aminotransferase levels were associated with elevated blood pressure, fasting plasma glucose, and triglycerides and lower high-density lipoprotein levels (all P≤0.007). Furthermore, each 1-SD increase in alanine aminotransferase corresponded to an increased odds of hypertension, diabetes mellitus, the metabolic syndrome, impaired fasting glucose, and insulin resistance estimated by the homeostasis model assessment of insulin resistance (odds ratio, 1.29-1.85, all P≤0.002). Associations with alanine aminotransferase persisted after additional adjustment for visceral adipose tissue, insulin resistance, and body mass index with the exception of high-density lipoprotein cholesterol in both sexes and blood pressure in women. Results were materially unchanged when moderate drinkers were excluded, when the sample was restricted to those with alanine aminotransferase <40 U/L, and when the sample was restricted to those without diabetes mellitus. Similar trends were observed for aspartate aminotransferase levels, but associations were more modest.ConclusionsAminotransferase levels are correlated with multiple cardiometabolic risk factors above and beyond visceral adipose tissue and insulin resistance.
| S-EPMC3593729 | biostudies-literature
Project description:ObjectiveTo assess, among overweight non-hispanic black adolescents the relationship of changes in plasma retinol binding protein 4 (RBP4) over 3 years to changes in insulin resistance (IR) and 4 associated cardiometabolic risks.Study designNested, retrospective study of 51 overweight, post-pubertal non-Hispanic black participants in the Princeton School District Study. Participants were in the top (worsening IR) or bottom (improved IR) quartile for 3-year change in IR. RBP4 was measured by quantitative Western blot with frozen plasma. Regression analyses adjusted for age, sex, and adiposity (baseline and change). Three measures of adiposity were assessed (waist circumference, body mass index, and weight) in separate regression models.ResultsRBP4 increased in one third (n = 17). In logistic regression analyses, increased RBP4 was associated with significantly higher odds of worsening as opposed to improved IR independent of age, sex, or adiposity. Odds ratios were 5.6 (weight, P = .024), 6.0 (BMI, P = .025) and 7.4 (waist circumference, P = .015). Initial RBP4 (beta = 0.81, P = .005) and change in RBP4 (beta = 0.56, P = .046) also predicted change in triglycerides, but not change in high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, or fibrinogen.ConclusionThis retrospective cohort study provides evidence that RBP4 may be a mechanism through which obesity influences insulin resistance and hypertriglyceridemia in overweight postpubertal black youth and suggests utility of RBP4 as a biomarker of risk.
| S-EPMC2770185 | biostudies-literature