Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity.
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ABSTRACT:
SUBMITTER: Khan MS
PROVIDER: S-EPMC8748903 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ContextPlasma total cysteine (tCys) independently relates to fat mass in adults. Dietary cyst(e)ine promotes adiposity and decreases glucose tolerance in some rodent models, but alleviates insulin resistance in others.ObjectiveTo investigate whether the association of tCys with body fat extends to children at particular risk of obesity, and whether tCys is associated with insulin resistance and obesity-associated inflammation.MethodsWe explored the cross-sectional relations of fasting plasma tCys and related metabolites with body composition measured by dual-energy X-ray absorptiometry in 984 Hispanic children and adolescents aged 4-19 years from the Viva La Familia Study. Linear and logistic regression and dose-response curves were used to evaluate relations of tCys with obesity, insulin resistance and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-?), monocyte chemoattractant protein-1 (MCP-1) and C-reactive protein (CRP).ResultstCys, methionine and total homocysteine (tHcy) increased with age. Upper tCys quartile was independently associated with a 5-fold increased risk of obesity (95% CI 3.5-8.0, P<0.001), and 2-fold risk of insulin resistance (95% CI: 1.6-5.0, P<0.001; adjusted for body fat%). Within the overweight/obese subgroup, but not in normal-weight children, tCys accounted for 9% of the variability in body fat% (partial r = 0.30, P<0.001; adjusted for age and gender). tCys correlated positively with serum non-esterified fatty acids and leptin, partly independent of body fat, but was not associated with serum IL-6, TNF-? or MCP-1. A positive correlation with CRP disappeared after adjustment for BMI.ConclusiontCys is independently associated with obesity and insulin resistance in Hispanic children and adolescents, highlighting a previously underappreciated link between the sulfur amino acid metabolic pathway and obesity and cardiometabolic risk.
| S-EPMC3439485 | biostudies-literature
Project description:BackgroundHigh intake of sugar-sweetened beverages (SSB) has been suggested to contribute to the pediatric obesity epidemic, however, how the home food environment influence children's intake of SSB among Hispanic families is still poorly understood.ObjectivesTo evaluate the relationships between the home food environment and Hispanic children's diet in relation to weight status and insulin resistance (IR).MethodsA food frequency questionnaire was administered to 187 Hispanic children (ages 10 to 14 years) and anthropometrics were measured. IR was estimated from fasting insulin and glucose levels using the homeostasis model assessment of insulin resistance (HOMAIR ). Parents reported on family demographics and the home food environment. A structural equation modelling approach was applied to examine the hypothesized relationships among variables.ResultsThe prevalence of childhood overweight and obesity was 52.8% and it was positively associated with HOMAIR (β = 0.687, P < .0001). Children's SSB consumption was positively associated with children's body mass index z-score (β = 0.151, P < 0.05) and subsequently to HOMAIR . Children's SSB consumption was predicted by home availability (β = 0.191) and parental intake of SSB (β = 0.419) (P < 0.05). The model fit indices [χ(2) = 45.821 (d.f. = 30, P > 0.01 and < 0.05), χ(2) /d.f. = 1.53, root mean square error of approximation = 0.053 (90% confidence interval = 0.016, 0.082), comparative fit index = 0.904] suggested a satisfactory goodness-of-fit.ConclusionsThe home food environment and parental diet seem to play an important role in the children's access to and intake of SSB, which in turn predicted children's weight status.
| S-EPMC4558387 | biostudies-literature
Project description:Obesity is a critical health concern, and identifying new biomarkers has become essential for better understanding the progression to disease such as type 2 diabetes. DNA methylation has become a useful epigenetic biomarker in part due to its susceptibility to disease influence. Detecting methylation changes in blood is important as it is an easily accessible, compared to the insulin responsive tissue skeletal muscle. The aim of our study was to identify methylation changes in whole blood that were strongly associated with obesity associated insulin resistance. Whole blood was obtained from lean (n=10; BMI= 23.6±0.7 kg/m2) and obese (n=10; BMI= 34.4±1.3 kg/m2) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed the next generation technique, reduced representation bisulfite sequencing (RRBS) on isolated genomic DNA. There were 49 significantly altered differentially methylated cytosines (DMCs; q<0.05). Of these, solute carrier family 19 member 1 (SLC19A1) was also identified using a differentially methylated region approach. The sites for this gene were significantly correlated (P<0.05) with body mass index, body fat percent, and the clamp Rd. Moreover, the decrease in SLC19A1 methylation was similar to the change previously found in skeletal muscle. Pyrosequencing confirmed the changes in methylation at Chr.21:46,957,915 in both tissues. These results demonstrate that the methylation status of SLC19A1 provides a new potential epigenetic biomarker for obesity related insulin resistance.
2016-10-01 | GSE85928 | GEO
Project description:BackgroundLittle is known about the normal eating time periods in adolescents with obesity and how these patterns change throughout development. As the obesity epidemic continues to rise in adolescence, it becomes imperative to understand developmentally appropriate eating behaviours and to create weight management strategies that build on those innate patterns and preferences. The purpose of this study was to determine the most common habitual eating windows observed in adolescents with obesity.MethodsParticipants were 101 Hispanic adolescents (mean age 14.8 ± 2.1 years; 48 male/53 female) with obesity (BMI ≥95th percentile) who were recruited as part of a larger clinical trial. Dietary intake and meal timing was determined using multiple pass 24-hours recalls. Histograms were utilized to determine the natural distribution of percent consumption of total kilocalories, carbohydrates and added sugar per hour.ResultsThe majority of total kilocalories (65.4%), carbohydrates (65.3%) and added sugar (59.1%) occurred between 11:00 and 19:00. Adolescents were 2.5 to 2.9 times more likely to consume kilocalories, carbohydrates, and added sugar during the 8-hour window between 11:00 am and 19:00 pm than other time windows examined (all P < .001). The consumption of these calories did not differ between weekdays and weekend (P > .05) or by sex.ConclusionsIn this cohort, more than 60% of calories, carbohydrates and added sugar were consumed between 11:00 am and 19:00 pm, which is concordant with an afternoon/evening chronotype that is common in adolescents. Our findings support this 8-hour period as a practical window for weight loss interventions that target pre-specified eating periods in this population.
| S-EPMC8178160 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:Nonalcoholic fatty liver disease (NAFLD) disproportionately affects Hispanic boys. Further, obesity and insulin resistance are major risk factors for NAFLD. No gene localization studies had been performed on children with biopsy-proven NAFLD. This study aims to identify genomic variants associated with increased adiposity and insulin resistance in a population of children with varying histologic severity of NAFLD. METHODS:We conducted a genome-wide association scan (GWAS) including 624,297 single-nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in 234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research Network Studies. Traits were examined quantitatively using linear regression. SNPs with P value <10 and a minor allele frequency >5% were considered potentially significant. RESULTS:Evaluated subjects had a median age of 12.0 years, body mass index (BMI) of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The prevalence of NAFL, borderline NASH, and definite NASH were 23%, 53%, and 22%, respectively. The GWAS identified 10 SNPs that were associated with BMI z score, 6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver gluconeogenesis. In addition, the GWAS identified 9 novel variants associated with insulin resistance: HOMA-IR (6) and HbA1c (3). CONCLUSIONS:This study of Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic syndrome revealed novel genetic variants that are associated with obesity and insulin resistance.
| S-EPMC5916321 | biostudies-literature
Project description:Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m2) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m2) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; q < 0.05) that were altered in obese compared with lean participants. We identified 2 sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5' untranslated region of solute carrier family 19 member 1 (SLC19A1) with decreased methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These 2 DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, P = 0.003; r = 0.66; P = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915-46,958,001 in SLC19A1 of -34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood SLC19A1 methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0.10 vs. obese 0.18 ± 0.06) and skeletal muscle (lean 0.71 ± 0.10 vs. obese 0.30 ± 0.11). Our findings demonstrate a new potential epigenetic biomarker, SLC19A1, for obesity and its underlying insulin resistance.
| S-EPMC5398771 | biostudies-literature
Project description:We have performed gene expression microarray analysis to profile transcriptomic signatures between insulin resistance high risk subjects and insulin resistance low risk subjects Participants enrolled in this study were recruited in the overnight fasted state, then the collection and processing of glucose (fasting, 30, 60 and 120 minutes) and insulin from blood samples, hemoglobin A1c (HbA1c) , assessment of medical history, socio-demographic characteristics, lifestyle factors, blood pressure and anthropometric and body composition measurements were conducted. During baseline visit, participants were asked to refrain from eating, drinking and oral hygiene procedures for at least 1-hour prior to saliva collection.5 ml of unstimulated whole saliva samples were consistently collected, stabilized and preserved, the sample supernatants were reserved at -80°C prior to assay. Based on the homeostasis model assessment of insulin resistance (HOMA-IR), using the formula [HOMA-IR= (fasting glucose*fasting insulin)/405], participants were divided into 2 groups: IR high risk group (HOMA-IR value ?2.5) and IR low risk group (HOMA-IR value <2.5). Total RNA was extracted from saliva and subjected to gene expression microarray analysis using Affymetrix human genome 2.0 plus array
2015-04-10 | E-GEOD-67738 | biostudies-arrayexpress
Project description:BackgroundThe burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics.AimsTo determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful.MethodsA two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period.ResultsSeven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics.ConclusionsLimonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed.
| S-EPMC4588000 | biostudies-literature
Project description:We have performed gene expression microarray analysis to profile transcriptomic signatures between insulin resistance high risk subjects and insulin resistance low risk subjects
2015-04-10 | GSE67738 | GEO
Project description:ObjectivesInsulin resistance (IR) in adolescents with obesity is associated with a sex-dependent metabolic 'signature' comprising the branched-chain amino acids (BCAAs), glutamate/glutamine, C3/C5 acylcarnitines and uric acid. Here, we compared the levels of branched-chain α-keto acids (BCKAs) and glutamate/glutamine, which are the byproducts of BCAA catabolism and uric acid among adolescents with obesity prior to and following a 6-month lifestyle-intervention program.MethodsFasting plasma samples from 33 adolescents with obesity (16 males, 17 females, aged 12-18 year) were analysed by flow-injection tandem MS and LC-MS/MS. Multiple linear regression models were used to correlate changes in BCKAs, glutamate/glutamine and uric acid with changes in weight and insulin sensitivity as assessed by HOMA-IR, adiponectin and the ratio of triglyceride (TG) to HDL. In predictive models, BCKAs, glutamate/glutamine and uric acid at baseline were used as explanatory variables.ResultsBaseline BCKAs, glutamate/glutamine and uric acid were higher in males than females despite comparable BMI-metrics. Following lifestyle-intervention, α-keto-β-methylvalerate (α-KMV, a metabolic by product of isoleucine) decreased in males but not in females. The ratio of BCKA/BCAA trended lower in males. In the cohort as a whole, BCKAs correlated positively with the ratio of TG to HDL at baseline and HOMA-IR at 6-month-follow-up. Glutamate/glutamine was positively associated with HOMA-IR at baseline and 6-month-follow-up. A reduction in BCKAs was associated with an increase in adiponectin, and those with higher BCKAs at baseline had higher adiponectin levels at 6-month-follow-up. Interestingly those adolescents with higher uric acid levels at baseline had greater reduction in weight.ConclusionsBCKAs and glutamate/glutamine may serve as biomarkers of IR in adolescents with obesity, and uric acid might serve as a predictor of weight loss in response to lifestyle-intervention. Differential regulation of BCAA catabolism in adolescent males and females implicates critical roles for sex steroids in metabolic homeostasis.
| S-EPMC9836245 | biostudies-literature