Insulin Resistance In Children Research Articles

Insulin resistance in children

Insulin resistance (IR) is a clinical condition due to the decline in the efficiency of insulin promoting glucose uptake and utilization. The aim of this review is to provide an overview of the current knowledge on IR in children, focusing on its physiopathology, the most appropriate methods of measurement of IR, the assessment of risk factors, the effects of IR in children, and finally giving indications on screening and treatment. IR has evolved more and more to be a global public health problem associated with several chronic metabolic diseases. Detecting a correct measurement method and specific risk predictors, in order to reduce the incidence of IR, represents a challenging goal.

Insulin-resistance in paediatric age: Its magnitude and implications.

Insulin resistance (IR) is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues. IR is becoming more common in children and adolescents than before. There is a strong association between obesity in children and adolescents, IR, and the metabolic syndrome components. IR shows marked variation among different races, crucial to understanding the possible cardiovascular risk, specifically in high-risk races or ethnic groups. Genetic causes of IR include insulin receptor mutations, mutations that stimulate autoantibody production against insulin receptors, or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules; all induce abnormal energy pathways and end with the development of IR. The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR. Most patients with IR do not develop diabetes mellitus (DM) type-II. However, IR is a crucial risk factor to develop DM type-II in children. Diagnostic standards for IR in children are not yet established due to various causes. Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test. Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance. The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR, enhance insulin sensitivity, and treat possible complications. There are three main lines for treatment: Lifestyle and behavior modification, pharmacotherapy, and surgery. This review will discuss the magnitude, implications, diagnosis, and treatment of IR in children.

The Effect of Screen Addiction and Attention-Deficit Hyperactivity Disorder on Insulin Resistance in Children

The Effect of Screen Addiction and Attention-Deficit Hyperactivity Disorder on Insulin Resistance in Children

Prediction of Insulin Resistance Based on Anthropometric and Clinical Variables in Children with Overweight or Obesity at a Tertiary Center in Northeast Mexico.

Background: This study provides a clinical model to identify children with insulin resistance (IR) in health care units where laboratory tests are not readily available. Methods: A retrospective study of Mexican children aged 2-16 years at an obesity (OB) clinic. A receiver operating characteristic (ROC) curve was used to assess the accuracy of the proposed model consisting of clinical parameters and to establish the cutoff value for the variables (439 children). A second cohort of children with similar characteristics served as the cohort for the validation of the model (577 children). Results: To determine the best model for predicting IR, we performed a multivariate logistic regression analysis, which showed that waist circumference, acanthosis nigricans, and pubertal status are independent predictors of IR, and when integrated, their predictive power increases. Based on this model, we constructed a simplified equation. The predictive tool was constructed using an ROC curve, with an area under the curve of 0.849. A cutoff value of 7.68 was selected based on the Youden Index, with sensitivity and specificity of 78.3% and 83.3%, respectively. Incorporating metabolic laboratory determinations with a cutoff value of 20.64 improved the sensitivity to 94.9%. Conclusions: We developed a simple and affordable method of identifying IR in children with overweight or OB based on anthropometric variables and routine blood tests for metabolic indicators, such as glucose and triglycerides, which can be implemented in underserved sites.

Serum Selenoprotein P level is not indicative of Insulin Resistance in Children and Adolescents with Type 1 Diabetes Mellitus: Single Center Experience

Serum Selenoprotein P level is not indicative of Insulin Resistance in Children and Adolescents with Type 1 Diabetes Mellitus: Single Center Experience

Reduced Free Fatty Acid Receptor 4 Gene Expression is Associated With Extreme Obesity and Insulin Resistance in Children.

Free fatty acid receptor 4 (FFAR4) is a G-protein-coupled membrane receptor highly expressed in macrophages that triggers anti-inflammatory effects and promotes insulin sensitization. We have previously found significant associations between the FFAR4 rs11187533 single nucleotide polymorphism (SNP) and various obesity comorbidity parameters. We aimed to verify the FFAR4 expression levels in children with obesity and the associated comorbidities. Thirty-eight children with obesity were studied. Clinical and anthropometric evaluation was performed. A venous sample under fasting conditions was obtained. Biochemical study included parameters of metabolic risk. DNA was extracted and genotyped for the rs11187533 FFAR4 SNP. Real-time PCR technique was performed to investigate the gene expression. Relative FFAR4 mRNA levels were determined according to the 2-ΔΔCt method. Significant differences in FFAR4 expression levels between the CC and CT-TT genotypes of the rs11187533 FFAR4 SNP were observed (P = 0.034). The minor allele T presented higher levels of FFAR4 expression. We found that a loss of FFAR4 expression was associated with extreme obesity (P = 0.032). The lowest FFAR4 expression levels were observed in children who had higher insulin (P = 0.008) and homeostasis model assessment insulin resistance values (P = 0.012) and lower quantitative insulin-sensitivity check index (P = 0.033). The underexpression of FFAR4 was associated with extreme obesity and parameters indicative of obesity comorbidities in children. This under expression could be partially influenced by the presence of the C allele rs11187533 FFAR4 SNP.

Waist-to-height ratio as a clinical predictor for cardiovascular risks and insulin resistance in children and adolescents with exogenous obesity

BackgroundObesity is one of the most challenging clinical syndromes associated with deleterious health problems. Waist-to-height ratio (WHtR), a newer index for abdominal fat assessment, can be a superior tool in the evaluation of cardiometabolic risk. This study aimed to determine the relation between WHtR and lipid cardiovascular risk ratios and insulin resistance (IR) in children and adolescents with exogenous obesity.ResultsThis analytical cross-sectional study included 80 children and adolescents with exogenous obesity, compared to 80 age- and sex-matched healthy non-overweight non-obese controls. Fasting lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL)), fasting insulin, and fasting blood glucose were done and lipoprotein risk ratios were calculated; TC/HDL, LDL/HDL, non-HDL/HDL, and TG/HDL). In addition, homeostatic model assessment for IR (HOMA IR), triglyceride glucose index (TyG), TyG-BMI, and TyG-WC were calculated. The study group included 55 (34.4%) males and 105 (65.6%) females with a mean age of 13.6 ± 2.22 years. Obese group had significantly higher TC, TG, LDL, non-HDL, LDL/HDL, TC/HDL, non-HDL/HDL, and TG/HDL, with significantly lower HDL. In addition, they had significantly higher FBG, HOMA IR, TyG, TyG-BMI, and TyG-WC indices compared to the control group. There were statistically significant correlations between WHtR and lipid profile, lipid risk ratios and indices of IR. WHtR was found to be an independent predictor of IR by linear regression analysis.ConclusionWHtR can be an excellent, easy, and reliable clinical predictor for cardiovascular risk and IR in children and adolescents with exogenous obesity.

Low birth weight and small for gestational age are associated with complications of childhood and adolescence obesity: Systematic review and meta-analysis.

In recent decades, the incidence of type 2 diabetes (T2D) has increased dramatically in children and adolescents, posing a real public health problem. Beyond unhealthy diets and sedentary lifestyles, growing evidence suggests that some perinatal factors, such as low birth weight (LBW), are associated with higher risk of T2D in adulthood. In this regard, it remains unclear whether the increased risk is already present in childhood and adolescence. We conducted a systematic review and meta-analysis to clarify the association of LBW or being small for gestational age (SGA) with insulin resistance in childhood and adolescence. The systematic review resulted in 28 individual studies, and those with the same outcome were included within two random-effects meta-analyses. Compared with children or adolescents born with adequate size for gestational age, those SGA had 2.33-fold higher risk of T2D (95% confidence interval [CI]: 1.05-5.17). Furthermore, LBW and being SGA were associated with 0.20 higher mean homeostasis model assessment of insulin resistance (HOMA-IR) values (95% CI: 0.02-0.38). Given the high prevalence of preterm babies, from a population perspective, these results may be of great importance as they point to the existence of a potentially vulnerable subgroup of children and adolescents that could benefit from screening tests and early preventive strategies.

Urinary C-peptide and urinary C-peptide creatinine ratio as markers for insulin resistance in obese children and adolescents.

Obesity is associated with insulin resistance (IR). Identifying high-risk obese children affected with IR is crucial to apply preventive management. We aimed to assess the diagnostic value of urinary C-peptide (UCP) and urinary C-peptide creatinine ratio (UCPCR) to diagnoseIR in obese children. This prospective cross-sectional study was performed on 60 children with obesity as the study group. Sixty healthy children of matched age and sex with normal body mass index (BMI) served as the control group. Hemostasis model for the assessment of IR (HOMA-IR), glycated hemoglobin (HbA1c), fasting blood glucose and insulin, UCP, and UCPCR were assessed in all included children. UCP and UCPCR were significantly higher in children with obesity (2.075 ± 0.783) ng/ml, (0.200 ± 0.021) nmol/mmol compared to the control group (1.012 ± 0.465) ng/ml, (0.148 ± 0.016) nmol/mmol, respectively. Both UCP and UCPCR were positively correlated with each other and with HOMA-IR, HbA1c, acanthosis nigricans, waist circumference, and BMI. At cutoff ≥2.45, the sensitivity of UCP to diagnose IR in obese children was 71.4%. At cutoff ≥0.20, the sensitivity of UCPCR to diagnose IR in obese children was 87.6%. UCP and UCPCR are promising surrogate markers of IR in children and adolescents with obesity. However, UCPCR is a better marker than UCP. Obesity is associated with IR. Identifying high-risk obese children affected with IR is crucial to apply preventive management. We aimed to assess the diagnostic value of UCP and UCPCR to detect IR in obese children. To the best of our knowledge, we are the first to use UCP and UCPCR to assess IR in obese children. We found that UCP and UCPCR are practical, easy, dependable noninvasive markers to assess IR in children with obesity and could potentially be useful in epidemiological studies and clinical practice.

Relation of glomerular filtration to insulin resistance and related risk factors in obese children.

Childhood obesity is associated with later development of significant renal morbidity. We evaluated the impact of the degree of insulin sensitivity on estimated glomerular filtration rate (eGFR) and determined the factors associated with eGFR in obese children. We further tested the relation of eGFR to clinical outcomes such as blood pressure and microalbuminuria. We evaluated the relation of whole body insulin sensitivity and estimated glomerular filtration rate (eGFR) across the spectrum of obesity in children and adolescents. eGFR was calculated using the iCARE formula, which has been validated in obese children with varying glucose tolerance. 1080 children and adolescents with overweight and obesity (701 females and 379 males) participated. Insulin sensitivity was a strongly negatively associated with (B = -2.72, p < 0.001) eGFR), even after adjustment for potential confounders. Male sex emerged to be significantly associated with eGFR with boys having greater values than girls (B = 18.82, p < 0.001). Age was a positively associated (B = 2.86, p < 0.001) with eGFR. Whole body and hepatic insulin sensitivity decreased across eGFR quartiles. Adjusted eGFR was tightly positively associated with systolic blood pressure (B = 0.09, p = 0.003) and negatively associated with the presence of microalbuminuria (B = -2.18, p = 0.04). eGFR tends to increase with greater degrees of insulin resistance in children and adolescents representing hyperfiltration and is associated with cardiovascular risk factors. Longitudinal studies are needed to determine the natural history of childhood insulin resistance related hyperfiltration in regards to future kidney disease.

Composition and Functions of the Gut Microbiome in Pediatric Obesity: Relationships with Markers of Insulin Resistance.

The gut microbiome is hypothesized to play a crucial role in the development of obesity and insulin resistance (IR); the pathways linking the microbiome to IR in pediatrics have yet to be precisely characterized. We aimed to determine the relationship between the gut microbiome composition and metabolic functions and IR in children with obesity. In a cross-sectional study, fecal samples from children with obesity (10–16 years old) were collected for taxonomical and functional analysis of the fecal microbiome using shotgun metagenomics. The homeostatic model assessment for insulin resistance (HOMA-IR) was determined using fasting glucose and insulin. Associations between HOMA-IR and α-diversity measures as well as metabolic pathways were evaluated using Spearman correlations; relationships between HOMA-IR and β-diversity were assessed by permutational multivariate analysis of variance. Twenty-one children (nine males; median: age = 12.0 years; BMI z-score = 2.9; HOMA-IR = 3.6) completed the study. HOMA-IR was significantly associated with measures of α-diversity but not with β-diversity. Children with higher HOMA-IR exhibited lower overall species richness, Firmicutes species richness, and overall Proteobacteria species Shannon diversity. Furthermore, HOMA-IR was inversely correlated with the abundance of pathways related to the biosynthesis of lipopolysaccharides, amino acids, and short-chain fatty acids, whereas positive correlations between HOMA-IR and the peptidoglycan biosynthesis pathways were observed. In conclusion, insulin resistance was associated with decreased microbial α-diversity measures and abundance of genes related to the metabolic pathways. Our study provides a framework for understanding the microbial alterations in pediatric obesity.

The Role of Leptin Receptor Gene Polymorphism in the Formation of Insulin Resistance in Children

The Role of Leptin Receptor Gene Polymorphism in the Formation of Insulin Resistance in Children

CHDH-PNPLA3 Gene-Gene Interactions Predict Insulin Resistance in Children with Obesity.

IntroductionInsulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention.PurposeTo evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity.MethodsOne hundred fifty-three children with obesity (73 girls), aged 7–18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene–gene interaction effects were assessed using Multiple Data Reduction Software.ResultsSixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model.ConclusionThe interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.

Contrasting impact of androgens on male and female adiposity, fat distribution and insulin resistance in childhood and adolescence (EarlyBird 75).

To investigate associations between androgens (testosterone, dehydroepiandrosterone sulphate [DHEAS] and androstenedione), adiposity, fat distribution and insulin resistance (IR) during childhood and adolescence. Three hundred and seven children (170 [55.4%] boys; 137 [44.6%] girls) recruited at age 5 and studied annually until age 16: androgens (liquid chromatography tandem-mass spectrometry), anthropometry, body composition (dual-energy x-ray absorptiometry) and IR (homeostasis model assessment). Early adiposity was associated with earlier detection of androstenedione in both sexes, and DHEAS in boys. At puberty, higher androgen levels were associated with favourable metabolic changes in boys, but adverse metabolic effects in girls. In boys, higher free testosterone (FT) was associated with lower body fat and android/gynoid fat ratio (AGR) (both P < .001), but in girls higher total testosterone was associated with higher AGR. In girls only, higher androstenedione (P = .02) and FT (P = .01) was associated with higher IR during puberty. In pre-pubertal children, adiposity is associated with higher secretion of androgen precursors. After pubertal onset, higher testosterone is associated with lower adiposity and AGR in boys, but higher AGR and IR in girls. Therefore, androgens have modest sex-specific associations with children's total body fat, fat distribution and IR.

Daily Branched-Chain Amino Acid Intake and Risks of Obesity and Insulin Resistance in Children: A Cross-Sectional Study.

This study aimed to investigate the association of daily branched-chain amino acid (BCAA) intake with the risks of obesity and insulin resistance in children of mothers with gestational diabetes mellitus (GDM). Daily BCAA intake was calculated by using a validated food frequency questionnaire in 996 children of mothers with GDM. The odds ratios (ORs) (95% CI) of childhood obesity and insulin resistance were obtained using logistic regression models. The multivariable-adjusted ORs for overweight and insulin resistance increased across quartiles of daily BCAA intake (P < 0.05 for trend). Multivariable-adjusted ORs for each 1-SD increase in BCAA intake were 1.37 (1.16-1.62) for overweight and 1.19 (1.02-1.38) for insulin resistance. After additional adjustment of children's daily total energy intake, the OR was still significant for overweight risk but no longer significant for insulin resistance. There were positive associations of daily leucine, isoleucine, and valine intake with the risks for overweight and insulin resistance. Daily BCAA intake was associated with increased risks for overweight and insulin resistance in children of mothers with GDM, but this association was not fully independent of children's daily energy intake. Restriction in dietary BCAA may help prevent childhood obesity and insulin resistance.

Daily Branch Chained Amino Acid Intake and the Risks of Obesity and Insulin Resistance in Children

Abstract Objectives To investigate the association of daily branch chained amino acid intake with the risks of obesity and insulin resistance in children. Methods 996 children of mothers with gestational diabetes mellitus were included. Daily BCAA intake was calculated using a validated food frequency questionnaire. Logistic regression models were used to obtain the odd ratios (ORs) (95% confidence intervals [CI]) of childhood obesity and insulin resistance associated with different levels of daily BCAA intake. Results The multivariable-adjusted ORs across quartiles of daily BCAA intake were 1.00, 2.19, 2.06 and 2.81 (P for trend &amp;lt; 0.001) for overweight, and 1.00, 1.39, 1.52, and 1.71 for insulin resistance (P for trend = 0.018), respectively. When BCAA intake was examined as a continuous variable, multivariable-adjusted ORs for each 1 standard deviation increase in BCAA intake were 1.37 (95% CI 1.16–1.62) for overweight, and 1.19 (95% CI 1.02–1.38) for insulin resistance. There were positive associations of daily leucine, isoleucine and valine intakes with the risks of overweight and insulin resistance. Conclusions Daily intake of BCAA was positively associated with the risks of overweight and insulin resistance in children. Restriction in nutrition ingredient BCAA may be important to prevent childhood obesity and insulin resistance. Funding Sources This study was supported by the European Foundation for the Study of Diabetes (EFSD)/Chinese Diabetes Society (CDS)/Lilly Programme for Collaborative Research between China and Europe. Dr. Hu was partly supported by the grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100790) and the National Institute of General Medical Sciences (U54GM104940) of the National Institutes of Health.

Endocrine-Disrupting Chemicals and Insulin Resistance in Children.

The purpose of this article is to review the evidence linking background exposure to endocrine-disrupting chemicals (EDCs) with insulin resistance in children. Although evidence in children is scarce since very few prospective studies exist even in adults, evidence that EDCs might be involved in the development of insulin resistance and related diseases such as obesity and diabetes is accumulating. We reviewed the literature on both cross-sectional and prospective studies in humans and experimental studies. Epidemiological studies show a statistical link between exposure to pesticides, polychlorinated bisphenyls, bisphenol A, phthalates, aromatic polycyclic hydrocarbides, or dioxins and insulin resistance.

Mitochondrial Nutrient Utilization Underlying the Association Between Metabolites and Insulin Resistance in Adolescents.

A person's intrinsic metabolism, reflected in the metabolome, may describe the relationship between nutrient intake and metabolic health. Untargeted metabolomics was used to identify metabolites associated with metabolic health. Path analysis classified how habitual dietary intake influences body mass index z-score (BMIz) and insulin resistance (IR) through changes in the metabolome. Data on anthropometry, fasting metabolites, C-peptide, and dietary intake were collected from 108 girls and 98 boys aged 8 to 14 years. Sex-stratified linear regression identified metabolites associated with BMIz and homeostatic model assessment of IR using C-peptide (HOMA-CP), accounting for puberty, age, and muscle and fat area. Path analysis identified clusters of metabolites that underlie the relationship between energy-adjusted macronutrient intake with BMIz and HOMA-CP. Metabolites associated with BMIz include positive associations with diglycerides among girls and positive associations with branched chain and aromatic amino acids in boys. Intermediates in fatty acid metabolism, including medium-chain acylcarnitines (AC), were inversely associated with HOMA-CP. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of AC, products of β-oxidation. Approaching significance, fat intake is positively associated with HOMA-CP through increases in levels of dicarboxylic fatty acids, products of omega-oxidation. This cross-sectional analysis suggests that IR in children is associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extramitochondrial fatty acid metabolism, while higher carbohydrate intake appears to lead to decreases in intermediates of β-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake.

The protein S100A4 as a novel marker of insulin resistance in prepubertal and pubertal children with obesity

BackgroundS100A4 is a metastasis-associated protein also reported as a promising marker for dysfunctional white adipose tissue (WAT) and insulin resistance (IR) in adult and adolescent populations. ObjectiveWe aimed to evaluate the association between the protein S100A4 and obesity and IR in children and during pubertal development. Design and methodsThe study design consisted of three cross-sectional populations of 249, 11 and 19 prepubertal children respectively (named study population 1, 2 and 3), and a longitudinal population of 53 girls undergoing sexual maturation (study population 4). All subjects were classified into experimental groups according to their sex, obesity and IR status. All study populations counted on anthropometry, glucose, and lipid metabolism, inflammation and cardiovascular biomarkers as well as S100A4 plasma levels measured. The study population 1 was intended as the discovery population in which to elucidate the relationship between Obesity-IR and S100A4 plasma levels in prepubertal children. The cross-sectional populations 2 and 3 further counted on WAT gene expression data for investigating the molecular basis of this association. Instead, the longitudinal study population 4 presented blood whole-genome DNA methylation data at each temporal record, allowing deepening into the Obesity-IR-S1004 relationship during puberty as well as deciphering plausible epigenetic mechanisms altering S100A4 plasma levels. ResultsS100A4 plasma levels were strongly associated with several metabolic and anthropometric outcomes, namely IR, in prepubertal non-diabetic obese children. We also found highly significant positive associations during the course of puberty between the increase in S100A4 levels and the increase in HOMA-IR (P = 0.0003, FDR = 0.005) and insulin levels (P = 0.0003, FDR = 0.005). Methylation in two-enhancer related CpG sites of the S100A4 region (cg07245635 and cg10447638) was associated with IR biomarkers at the prepubertal stage and with longitudinal changes in these measurements. We further reported an association between visceral WAT (vWAT) S100A4 expression and HOMA-IR, insulin levels and BMI Z-Score, but not with circulating S100A4. ConclusionsWe report for the first time the association of S100A4 with IR and WAT dysfunction in prepubertal populations as well as how the change in plasma S100A4 levels accompanies longitudinal trajectories of IR in children during pubertal development. Moreover, we propose epigenetic changes in two methylation sites and an altered S100A4 vWAT expression as plausible molecular mechanisms underlying this disturbance in obesity.

Cardiorespiratory Fitness, Physical Activity, and Insulin Resistance in Children.

Few studies have investigated the independent and joint associations of cardiorespiratory fitness (CRF) and body fat percentage (BF%) with insulin resistance in children. We investigated the independent and combined associations of CRF and BF% with fasting glycemia and insulin resistance and their interactions with physical activity (PA) and sedentary time among 452 children age 6 to 8 yr. We assessed CRF with a maximal cycle ergometer exercise test and used allometrically scaled maximal power output (Wmax) for lean body mass (LM) and body mass (BM) as measures of CRF. The BF% and LM were measured by dual-energy X-ray absorptiometry, fasting glycemia by fasting plasma glucose, and insulin resistance by fasting serum insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The PA energy expenditure, moderate-to-vigorous PA (MVPA), and sedentary time were assessed by combined movement and heart rate sensor. Wmax/LM was not associated with glucose (β = 0.065, 95% confidence interval [CI] = -0.031 to 0.161), insulin (β = -0.079, 95% CI = -0.172 to 0.015), or HOMA-IR (β = -0.065, 95% CI = -0.161 to 0.030). Wmax/BM was inversely associated with insulin (β = -0.289, 95% CI = -0.377 to -0.200) and HOMA-IR (β = -0.269, 95% CI = -0.359 to -0.180). The BF% was directly associated with insulin (β = 0.409, 95% CI = 0.325 to 0.494) and HOMA-IR (β = 0.390, 95% CI = 0.304 to 0.475). Higher Wmax/BM, but not Wmax/LM, was associated with lower insulin and HOMA-IR in children with higher BF%. Children with higher BF% and who had lower levels of MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. Children with higher BF% together with less MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. Cardiorespiratory fitness appropriately controlled for body size and composition using LM was not related to insulin resistance among children.