Metabolic, inflammatory, endothelial and haemostatic markers in a group of Italian obese children and adolescents

Abstract

Childhood obesity and its related comorbidities are increasingly recognised in children, predisposing them to early cardiovascular disease and metabolic syndrome. The objective of the study was to investigate markers of metabolism, inflammation and haemostasis in a group of Italian obese children and adolescents. Fifty-nine obese and 40 non-obese subjects were recruited. Fasting glucose and insulin, total cholesterol, HDL and LDL cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha (TNF-α), and adiponectin were measured. Hypercoagulability was assessed by measuring the circulating levels of thrombin-antithrombin complex (TAT), D: -dimer, fibrinogen, plasminogen activator inhibitor 1 (PAI-1) and von Willebrand Factor (vWF). A significant degree of insulin resistance was present in obese subjects compared with controls (p < 0.0001). The obese showed higher levels of total cholesterol, LDL cholesterol and triglycerides, and lower levels of HDL cholesterol than controls (p < 0.0001). Circulating levels of hsCRP and TNF-α were significantly higher in obese than in controls while serum adiponectin levels were significantly lower in obese than non-obese subjects (p < 0.001; p = 0.031; p < 0.0001, respectively). vWF, TAT, D-dimer, fibrinogen and PAI-1 levels were significant higher in obese subjects compared with control group (p = 0.02; p < 0.0001; p = 0.0037; p < 0.0001; p = 0.017, respectively). In conclusion, our results suggest that childhood obesity per se is associated with a proinflammatory and prothrombotic state.

Endothelial and Metabolic Function Interactions in Overweight/Obese Children:

“…D-dimers, fibrinogen, and vWFAg levels did not reach a significant correlation with vascular parameters. These results were in contrast with some previous literature studies, 11,[49][50][51][52] which reported the influence of such parameters on endothelial function and on vascular wall morphological structure. In fact, OrenesPiñero et al 53) pointed out the correlation between BMI and coagulation parameters, observing an increased prothrombotic status in adult subjects suffering from increased body weight.…”

“…Adiponectin protein is probably an insulin modulator and plays a protective role against inflammation and atherosclerosis, stimulating the production of endothelial nitric oxide and inhibiting the accumulation of lipids in macrophages [7][8][9][10] . Several studies showed that hypoadiponectinemia is associated with greater BMI, waist circumference, and insulin resistance in obese children 11,12) . High molecular weight adiponectin acts on cardiac muscular cells protecting them from ischemia/ reperfusion damages by improving cyclooxygenases-2 activity and promoting nitric oxide (NO) production; it obstacles the promotion of cardiac fibrosis and the morphological and structural alterations derived from hypertrophic stimuli, while it ameliorates contractile function by inducing calcium influx into myotubes.…”

“…Abdominal obesity lowers serum levels of adiponectin since childhood 13) . The early endothelial damage associated with obesity is confirmed by the high levels of von Willebrand factor (vWF Ag), D-dimer concentration, thrombin-antithrombin complex (TAT), plasminogen activator inhibitor 1 (PAI-1), and fibrinogen 11,14) . vWF Ag and PAI-1 are two haemostatic markers of endothelial dysfunction.…”

“…TAT is an index of hypercoagulability and increased thrombin generation; instead, D-dimer concentration correlates with an increased fibrin turnover. Therefore, the excess of adiposity may cause an imbalance in the haemostatic system where more fibrin is produced and deposited, less is degraded or both 11) . Non-invasive techniques can evaluate preclinical atherosclerosis, such as the ultrasound common carotid artery intima-media thickness (C-IMT), flowmediated dilatation (FMD) of brachial artery, and anteroposterior diameter of infra-renal abdominal aorta (APAO).…”

Is triglyceride to high-density lipoprotein cholesterol ratio a surrogates for insulin resistance in youth?

“…Otherwise not all obese persons will develop IR, endothelial dysfunction, MS and cardiometabolic diseases, and paradoxically, a high number of non-obese individuals do suffer from these conditions [30]. A number of biomarkers described in literature, such as highmolecular weight subfraction of adiponectin, tumour necrosis factor alpha (TNF-), plasminogen activator inhibitor 1 (PAI-1), von Willebrand Factor (vWF), cytokines related to IR, inflammation, atherosclerosis, type 2 diabetes, dyslipidemia and hypertension [30][31][32] are not available for clinical practice. Furthermore the measurement of small low-LDL-C (phenotype B), which is associated with a fourfold atherogenic risk [33], or even insulin dosage that is closely related to IR are difficult to measure.…”