Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome
Anna Sofia Huerta Delgado, Daniel N. Roffe-Vazquez, Adrian M. González-Gil, José R. Villarreal-Calderón, Oscar Tamez‐Rivera, Nora A. Rodríguez-Gutiérrez, Elena C. Castillo, Christian Silva‐Platas, Gerardo García‐Rivas, Leticia Elizondo‐Montemayor
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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.358</mml:mn></mml:math>), WC percentile (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.308</mml:mn></mml:math>), and triglycerides (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.284</mml:mn></mml:math>) were identified, while positive associations with TC (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mn>0.287</mml:mn></mml:math>), HDL-c (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mn>0.488</mml:mn></mml:math>), and LDL-c (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mn>0.414</mml:mn></mml:math>) were observed. Significant negative correlations were found between irisin and sNCAM (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.382</mml:mn></mml:math>), sICAM-2 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.300</mml:mn></mml:math>), sVCAM-1 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.292</mml:mn></mml:math>), MCP-1 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.308</mml:mn></mml:math>), and IFN- α 2 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M11"><mml:mi>R</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.406</mml:mn></mml:math>). 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.