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-α2 (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.

Effect of Sitagliptin on Serum Irisin Levels in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

“…We also found that the serum irisin levels were lower in patients with T2DM than in the control group. Moreover, consistent with other studies, serum irisin levels were negatively correlated with TG, FBG and HbA1c while positively correlated with HDL-C and HOMA-β [ 4 , 15 , 18 ]. Mechanistically, it has been reported that irisin exerts metabolic benefits via distinct mechanisms.…”

Novel adipokine asprosin modulates browning and adipogenesis in white adipose tissue

“…The browned white adipocytes begin to express uncoupling protein-1 (UCP1), a specific marker of brown adipose tissue, making white adipose tissue more likely to generate heat and increase the body’s energy consumption. In addition to the change of environmental temperature, many factors such as inflammation, oxidative stress and autophagy can affect the white adipose browning ( Huerta-Delgado et al 2020 , Yamamuro et al 2020 ). Browning of white adipose tissue is currently considered as a new approach to weight loss, insulin sensitivity and glucose tolerance, with potential therapeutic effects in the treatment of obesity and cardiovascular diseases.…”

Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

“…Oxidative stress and the inflammatory state act overtime, promoting endothelial dysfunction. Hyperglycemia contributes to the production of advanced glycation end products (AGES), which, together with reactive oxygen species, cause endothelial damage, while adhesion molecules and immune cells are attracted to the vascular bed [ 94 ]. This environment constitutes fertile soil for atherosclerosis’s chronic inflammatory process, a prelude to several cardiovascular conditions [ 8 ].…”