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Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome.

ABSTRACT: The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the pediatric population. Irisin, an adipomyokine, is involved in white adipose tissue browning, energy expenditure, insulin sensitivity, and anti-inflammatory pathways. Data on the associations among circulating irisin levels, soluble cell adhesion molecules (sCAMs), and inflammatory cytokines is scarce in children and adolescents with MetS and T2DM. Subjects aged 6-16 years were grouped into T2DM, MetS, and healthy controls. Serum irisin levels were significantly lower in the MetS (6.6 [2.8-18.0] ng/mL) and T2DM (6.8 [2.2-23.2] ng/mL) groups compared with controls (30.3 [24.6-57.1] ng/mL). Negative correlations between irisin and the BMI percentile (R = -0.358), WC percentile (R = -0.308), and triglycerides (R = -0.284) were identified, while positive associations with TC (R = 0.287), HDL-c (R = 0.488), and LDL-c (R = 0.414) were observed. Significant negative correlations were found between irisin and sNCAM (R = -0.382), sICAM-2 (R = -0.300), sVCAM-1 (R = -0.292), MCP-1 (R = -0.308), and IFN-?2 (R = -0.406). Of note, lower concentrations of most sCAMs (sICAM-1, sPSGL-1, sP-selectin, sEpCAM, sICAM-2, sALCAM, sPECAM-1, sCD44, sVCAM-1, sICAM-3, sL-selectin, and sNCAM) were shown in T2DM subjects compared with MetS patients. Lower irisin levels induce a lack of inhibition of oxidative stress and inflammation. In T2DM, higher ROS, AGEs, glucotoxicity, and inflammation trigger endothelial cell apoptosis, which downregulates the sCAM expression as a compensatory mechanism to prevent further vascular damage. In opposition, in subjects with MetS that have not yet developed T2DM and its accompanying stressors, the upregulation of the sCAM expression is ensued.

SUBMITTER: Huerta-Delgado AS

PROVIDER: S-EPMC7492943 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome.

Huerta-Delgado Anna S AS Roffe-Vazquez Daniel N DN Gonzalez-Gil Adrian M AM Villarreal-Calderón José R JR Tamez-Rivera Oscar O Rodriguez-Gutierrez Nora A NA Castillo Elena C EC Silva-Platas Christian C Garcia-Rivas Gerardo G Elizondo-Montemayor Leticia L

Journal of diabetes research 20200904

The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the pediatric population. Irisin, an adipomyokine, is involved in white adipose tissue browning, energy expenditure, insulin sensitivity, and anti-inflammatory pathways. Data on the associations among circulating irisin levels, soluble cell adhesion molecules (sCAMs), and inflammatory cytokines is scarce in children and adolescents with MetS and T2DM. Subjects aged 6-16 years were grouped into T2DM, ...[more]

PMID: 32964051

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Project description: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-1α 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.

Project description:IntroductionThyroid dysfunction is a highly prevalent yet under-recognized complication in hemodialysis patients. In the general population, hypothyroidism has been associated with endothelial dysfunction due to impaired vasodilator synthesis and activity. Little is known about the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with endothelial function in hemodialysis patients.MethodsIn a secondary analysis of 99 patients from the Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) trial, we examined measurements of serum TSH and endothelial function ascertained by fingertip digital thermal monitoring (DTM), a novel method used to measure micro-vascular reactivity, collected within a 90-day period. DTM was used to measure changes in fingertip temperature during and after an ischemic stimulus (blood pressure cuff occlusion) as an indicator of changes in blood flow, and two DTM indices were assessed, namely adjusted (a) Temperature Rebound (TR), defined as the maximum temperature rebound post-cuff deflation, and adjusted (b) Area Under the Temperature Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temperatures. We examined the relationship between serum TSH with impaired TR (separately) and TMP-AUC (both defined as less than the median level of observed values) using multivariable logistic regression.FindingsIn unadjusted and case-mix analyses, higher serum TSH levels (defined as the three highest quartiles) were associated with lower (worse) TR (ref: lowest TSH quartile): ORs (95% CI) 2.64 (1.01-6.88) and 2.85 (1.08-7.57), respectively. In unadjusted and case-mix analyses, higher TSH levels were associated with lower (worse) TMP-AUC: ORs (95% CI) 2.64 (1.01-6.88) and 2.79 (1.06-7.38), respectively.DiscussionIn HD patients, higher serum TSH levels were associated with worse micro-vascular reactivity measured by DTM. Further studies are needed to determine if thyroid hormone supplementation improves endothelial function in hemodialysis patients with lower levels of thyroid function.

Project description:ObjectiveGestational diabetes mellitus (GDM) is a serious complication in pregnancy. Despite controlling the plasma glucose levels with dietary intervention (GDM-D) or insulin therapy (GDM-I), children born of diabetic mothers suffer more long-term complications from childhood to early adulthood. Placental circulation and nutrient exchange play a vital role in fetal development. Additionally, placental endothelial function is an indicator of vascular health, and plays an important role in maintaining placental circulation for nutrient exchange. This study was conducted to assess changes in fetal endothelial dysfunction in GDM under different interventions during pregnancy.MethodsThe primary human umbilical vein endothelial cells (HUVECs) were obtained from normal pregnant women (n = 11), GDM-D (n = 14), and GDM-I (n = 12) patients. LC-MS/MS was used to identify differentially expressed proteins in primary HUVECs among the three groups, after which Bioinformatics analysis was performed. Glucose uptake, ATP level, apoptosis, and differentially expressed proteins were assessed to investigate changes in energy metabolism.ResultsA total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were identified after comparing patients with GDM-D/GDM-I and healthy controls. Of the 142, 64 proteins were upregulated while 77 were downregulated. Bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes and signaling pathways related to cellular processes, biological regulation, and metabolic processes. According to the results from KEGG analysis, there were changes in the PI3K/AKT signaling pathway after comparing the three groups. In addition, there was a decrease in glucose uptake in the GDM-I (P < 0.01) group. In GDM-I, there was a significant decrease in the levels of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3). Moreover, glucose uptake was significantly decreased in GDM-I, although in GDM-D, there was only a decrease in the levels of GLUT1. ATP levels decreased in GDM-I (P < 0.05) and apoptosis occurred in both the GDM-D and GDM-I groups. Compared to the normal controls, the levels of phosphate AKT and phosphate AMPK over total AKT and AMPK were reduced in the GDM-I group.ConclusionIn summary, endothelial dysfunction occurred in pregnancies with GDM even though the plasma glucose levels were controlled, and this dysfunction might be related to the degree of glucose tolerance. The energy dysfunction might be related to the regulation of the AKT/AMPK/mTOR signaling pathway.

Dataset Information

Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome.

Publications

Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome.

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