Dataset Information

Association between Irisin, hs-CRP, and Metabolic Status in Children and Adolescents with Type 2 Diabetes Mellitus.

ABSTRACT: Proinflammatory cytokines and the novel myokine irisin, a cleavage product of FNDC5, have been found to play a role in obesity and type 2 diabetes mellitus (T2DM). Irisin has been shown to increase browning of adipose tissue, thermogenesis, energy expenditure, and insulin sensitivity, yet its association with inflammatory markers is still limited. Circulating irisin has been found to be increased in obesity, while in adult subjects with T2DM decreased levels have been found. However, data establishing the association of circulating irisin in children and adolescents with T2DM has not been described in the literature. The objective of this study was to determine irisin plasma concentration and its association with metabolic and adiposity markers and with hs-CRP, a surrogate marker of inflammation used in clinical practice, in a pediatric population with T2DM. A cross-sample of 40 Mexican children and adolescents aged 7-17 were recruited, 20 diagnosed with T2DM and 20 healthy controls. Plasma irisin levels were found to be lower in the T2DM group compared with controls, which could be attributed to a reduced PGC-1? activity in muscle tissue with a consequent decrease in FNDC5 and irisin expression. Irisin concentration was found to be positively correlated with HDL-c, LDL-c, and total cholesterol, while negatively correlated with BMI, waist circumference, and triglycerides. However, after multiple regression analysis, only HDL-c correlation remained significant. hs-CRP was higher in the T2DM group and positively associated with adiposity markers, unfavorable lipid profile, insulin levels, and HOMA-IR, but no association with irisin was found. Given the favorable metabolic effects attributed to irisin, the low plasma levels found in children and adolescents with T2DM could exacerbate the inflammatory and metabolic imbalances and the intrinsic cardiovascular risk of this disease. We propose an "irisin-proinflammatory/anti-inflammatory axis" to explain the role of irisin as a metabolic regulator in obesity and T2DM.

SUBMITTER: Elizondo-Montemayor L

PROVIDER: S-EPMC6446111 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association between Irisin, hs-CRP, and Metabolic Status in Children and Adolescents with Type 2 Diabetes Mellitus.

Elizondo-Montemayor Leticia L Gonzalez-Gil Adrian M AM Tamez-Rivera Oscar O Toledo-Salinas Carla C Peschard-Franco Mariana M Rodríguez-Gutiérrez Nora A NA Silva-Platas Christian C Garcia-Rivas Gerardo G

Mediators of inflammation 20190320

Proinflammatory cytokines and the novel myokine irisin, a cleavage product of FNDC5, have been found to play a role in obesity and type 2 diabetes mellitus (T2DM). Irisin has been shown to increase browning of adipose tissue, thermogenesis, energy expenditure, and insulin sensitivity, yet its association with inflammatory markers is still limited. Circulating irisin has been found to be increased in obesity, while in adult subjects with T2DM decreased levels have been found. However, data establ ...[more]

PMID: 31015797

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Project description:BACKGROUND:Type 1 diabetes mellitus (T1DM) is one of the most common pediatric diseases and its incidence is rising in many countries. Recently, it has been shown that metabolites other than glucose play an important role in insulin deficiency and the development of diabetes. The aim of our study was to look for discriminating variation in the concentrations of small-molecule metabolites in the plasma of T1DM children as compared to non-diabetic matched controls using proton nuclear magnetic resonance (1H-NMR)-based metabolomics. METHODS:A cross-sectional study was set-up to examine the metabolic profile in fasting plasma samples from seven children with poorly controlled T1DM and seven non-diabetic controls aged 8-18 years, and matched for gender, age and BMI-SDS. The obtained plasma 1H-NMR spectra were rationally divided into 110 integration regions, representing the metabolic phenotype. These integration regions reflect the relative metabolite concentrations and were used as statistical variables to construct (train) a classification model in discriminating between T1DM patients and controls. RESULTS:The total amount of variation explained by the model between the groups is 81.0% [R2Y(cum)] and within the groups is 75.8% [R2X(cum)]. The predictive ability of the model [Q2(cum)] obtained by cross-validation is 50.7%, indicating that the discrimination between the groups on the basis of the metabolic phenotype is valid. Besides the expected higher concentration of glucose, the relative concentrations of lipids (triglycerides, phospholipids and cholinated phospholipids) are clearly lower in the plasma of T1DM patients as compared to controls. Also the concentrations of the amino acids serine, tryptophan and cysteine are slightly decreased. CONCLUSIONS:The present study demonstrates that metabolic profiling of plasma by 1H-NMR spectroscopy allows to discriminate between T1DM patients and controls. The metabolites that significantly differ between both groups might point to disturbances in biochemical pathways including (1) choline deficiency, (2) increased gluconeogenesis, and (3) glomerular hyperfiltration. Although the sample size of this study is still somewhat limited and a validation should be performed, the proof of principle looks promising and justifies a deeper investigation of the diagnostic possibilities of 1H-NMR metabolomics in follow-up studies. Trial registration NCT03014908. Registered 06/01/2017. Retrospectively registered.

Dataset Information

Association between Irisin, hs-CRP, and Metabolic Status in Children and Adolescents with Type 2 Diabetes Mellitus.

Publications

Association between Irisin, hs-CRP, and Metabolic Status in Children and Adolescents with Type 2 Diabetes Mellitus.

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