Increased carotid intima-media thickness in pre-pubertal children with constitutional leanness and severe obesity: the speculative role of insulin sensitivity, oxidant status, and chronic inflammation

Abstract

In order to characterize whether different degrees of adipose tissue storage may be associated with markers of early atherosclerosis, we evaluated oxidant-antioxidant status and inflammatory markers and determined carotid intima-media thickness (cIMT) in healthy constitutional lean and obese pre-pubertal children. Eighty healthy pre-pubertal lean and obese children were recruited and compared with 40 age, gender, and pubertal stage-matched normal controls. Anthropometric measurements, oxidant (urinary isoprostanes (PGF-2alpha), lag phase, and malondialdehyde (MDA)) and antioxidant status (vitamin E), inflammatory markers (high sensitive C-reactive protein (hs-CRP)), and insulin sensitivity (fasting glucose-insulin ratio, homeostasis model assessment of insulin resistance (HOMA-IR)) were investigated. Furthermore, cIMT was measured by high-resolution ultrasound. hs-CRP was not different between lean and control subjects (P=0.45), while higher values were found in obese compared with lean and control children (P<0.001 and P<0.001 respectively). PGF-2alpha and MDA were higher while lag phase shorter in lean and obese subjects compared with controls (lean P<0.001; P<0.001; P<0.001 and obese P<0.001; P<0.001; P<0.001 respectively), while no differences were documented between lean and obese subjects (P=0.78, P=0.019, and P=0.53 respectively). Compared with controls, cIMT was increased in lean and in obese subjects (P=0.001; P=0.004), while no differences were documented between obese and lean subjects (P=0.1). In a multiple stepwise linear regression analysis, cIMT was related with PGF-2alpha (beta=0.641, P<0.001) and HOMA-IR (beta=0.307; P<0.001). Pre-pubertal lean and obese children present increased oxidative stress and impaired inflammation and insulin sensitivity, which in turn seem to result in similar impaired endothelial dysfunction and early signs of atherosclerosis, already in childhood.