scholarly journals Plasma metabolites associated with homeostatic model assessment of insulin resistance: metabolite-model design and external validation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pablo Hernández-Alonso ◽  
Jesús García-Gavilán ◽  
Lucía Camacho-Barcia ◽  
Anders Sjödin ◽  
Thea T. Hansen ◽  
...  

Abstract Different plasma metabolites have been related to insulin resistance (IR). However, there is a lack of metabolite models predicting IR with external validation. The aim of this study is to identify a multi-metabolite model associated to the homeostatic model assessment (HOMA)-IR values. We performed a cross-sectional metabolomics analysis of samples collected from overweight and obese subjects from two independent studies. The training step was performed in 236 subjects from the SATIN study and validated in 102 subjects from the GLYNDIET study. Plasma metabolomics profile was analyzed using three different approaches: GC/quadrupole-TOF, LC/quadrupole-TOF, and nuclear magnetic resonance (NMR). Associations between metabolites and HOMA-IR were assessed using elastic net regression analysis with a leave-one-out cross validation (CV) and 100 CV runs. HOMA-IR was analyzed both as linear and categorical (median or lower versus higher than the median). Receiver operating characteristic curves were constructed based on metabolites’ weighted models. A set of 30 metabolites discriminating extremes of HOMA-IR were consistently selected. These metabolites comprised some amino acids, lipid species and different organic acids. The area under the curve (AUC) for the discrimination between HOMA-IR extreme categories was 0.82 (95% CI: 0.74–0.90), based on the multi-metabolite model weighted with the regression coefficients of metabolites in the validation dataset. We identified a set of metabolites discriminating between extremes of HOMA-IR and able to predict HOMA-IR with high accuracy.

2020 ◽  
Author(s):  
Nathan A. Bihlmeyer ◽  
Lydia Coulter Kwee ◽  
Clary B. Clish ◽  
Amy Anderson Deik ◽  
Robert E. Gerszten ◽  
...  

AbstractObesity is an epidemic internationally. While weight loss interventions are efficacious, they are compounded by heterogeneity with regards to clinically relevant metabolic responses. Thus, we sought to identify metabolic pathways and biomarkers that distinguish individuals with obesity who would most benefit from a given type of intervention. Liquid chromatography mass spectrometry-based profiling was used to measure 765 metabolites in baseline plasma from three different weight loss studies: WLM (behavioral intervention, N=443), STRRIDE-PD (exercise trial, N=163), and CBD (surgical cohort, N=125). The primary outcome was percent change in insulin resistance (as measured by the Homeostatic Model Assessment of Insulin Resistance [%ΔHOMA-IR]) over the intervention. Overall, 92 individual metabolites were associated with %ΔHOMA-IR after adjustment for multiple comparisons. Concordantly, the most significant metabolites were triacylglycerols (TAGs; p=2.3e-5) and diacylglycerols (DAGs; p=1.6e-4), with higher TAG and DAG levels associated with a greater improvement in HOMA-IR. In tests of heterogeneity, 50 metabolites changed differently between weight loss interventions; we found amino acids, peptides, and their analogues to be most significant (4.7e-3) in this category. Our results highlight novel metabolic pathways associated with heterogeneity in response to weight loss interventions, and related biomarkers which could be used in future studies of personalized approaches to weight loss interventions.


2013 ◽  
Vol 5 (3) ◽  
pp. 169
Author(s):  
Maria Evi Novianti ◽  
Syakib Bakri ◽  
Mansyur Arif ◽  
Ferry Sandra

BACKGROUND: Not only hypertension, prehypertension has been reported to be linked with increased cardiovascular morbidity and mortality risks as well. Prehypertension has three-fold hypertension and two-fold cardiovascular risks. Pathomechanism that links hypertension with cardiovascular is related with endothelial dysfunction and insulin resistance. Endothelial dysfunction occurs when nitric oxide (NO) biological function was impaired, whereas shown by asymmetric dimethylarginine (ADMA). Subjects with prehypertension had higher insulin resistance events than normotension, whereas shown by homeostatic model assessment-estimated insulin resistance (HOMA-IR). This research was conducted to investigate the correlation of HOMA-IR with ADMA in prehyper- and normo-tension.METHODS: A cross-sectional comparative research was designed. Subjects were recruited and divided into prehyper- and normo-tensive groups. ADMA was measured using ELISA method, while HOMA-IR was calculated by the ratio of fasting insulin and glucose. Spearman 1-tail and Mann Whitney statistical analyses were performed.RESULTS: Comparing to normotensive group, elevated levels of HOMA-IR and ADMA in prehypertensive group were shown, but not significant. In prehypertensive group, we found significant correlation between HOMA-IR and ADMA.CONCLUSION: Insulin resistance and endothelial dysfunction was elevated in prehyper-compared to normotension.KEYWORDS: prehypertension, insulin resistance, endothelial dysfunction, HOMA-IR, ADMA


Author(s):  
Mathuramat Seesen ◽  
Roberto G. Lucchini ◽  
Somkiat Siriruttanapruk ◽  
Ratana Sapbamrer ◽  
Surat Hongsibsong ◽  
...  

Insulin resistance is a risk factor for various diseases. Chronic organophosphate exposure has been reported to be a cause of insulin resistance in animal models. This cross-sectional study aimed to evaluate the association between organophosphate exposure and insulin resistance in pesticide sprayers and nonfarmworkers. Participants aged 40–60 years, consisting of 150 pesticide sprayers and 150 nonfarmworkers, were interviewed and assessed for their homeostatic model assessment of insulin resistance (HOMA-IR) level. Organophosphate (OP) exposure was measured in 37 sprayers and 46 nonfarmworkers by first morning urinary dialkyl phosphate (DAP) metabolites. The DAP metabolite levels were not different in either group except for diethylthiophosphate (DETP; p = 0.03), which was higher in sprayers. No significant association was observed between DAP metabolite levels and HOMA-IR. Wearing a mask while handling pesticides was associated with lower dimethyl metabolites (95% CI = −11.10, −0.17). Work practices of reading pesticide labels (95% CI = −81.47, −14.99) and washing hands after mixing pesticide (95% CI = −39.97, −3.35) correlated with lower diethyl alkylphosphate level. Overall, we did not observe any association between OP exposure and insulin resistance in pesticide sprayers and the general population. However, personal protective equipment (PPE) utilization and work practice were associated with OP exposure level in sprayers.


Author(s):  
Francesca Caroppo ◽  
Alfonso Galderisi ◽  
Laura Ventura ◽  
Anna Belloni Fortina

AbstractPsoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3–10 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was ≥ 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance.Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis. What is Known:• Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.• Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis. What is New:• This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.• In children with psoriasis metabolic syndrome risk factors should be assessed.


2011 ◽  
Vol 57 (2) ◽  
pp. 309-316 ◽  
Author(s):  
Greisa Vila ◽  
Michaela Riedl ◽  
Christian Anderwald ◽  
Michael Resl ◽  
Ammon Handisurya ◽  
...  

BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.


2016 ◽  
Vol 34 (2) ◽  
pp. 234-242 ◽  
Author(s):  
Maria Izabel Siqueira de Andrade ◽  
Juliana Souza Oliveira ◽  
Vanessa Sá Leal ◽  
Niedja Maria da Silva Lima ◽  
Emília Chagas Costa ◽  
...  

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