The macrophage activation product sCD163 is associated with a less favourable metabolic profile in prepubertal children.

OBJECTIVE: Macrophages are known to be involved in low-grade inflammatory processes such as obesity. soluble cluster of differentiation 163 (sCD163) is shed from the cell surface as specific macrophage activation marker. In prepubertal children, we studied if circulating sCD163 is associated with metabolic and cardiovascular risk markers. METHODS: A population of 236 school-aged Caucasian children (111 girls and 125 boys) aged 8 ± 1 year [81 normal weight (body mass index [BMI]-SDS < 1); 74 overweight (1 ≤ BMI-standard deviation score [SDS] < 2) and 81 with obesity (BMI-SDS ≥ 2)] were studied. BMI, waist circumference, fat mass and visceral fat were measured. Fasting serum sCD163, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, gamma-glutamyl transpeptidase and lipids were quantified. RESULTS: Circulating sCD163 concentrations were higher in children with obesity (p < 0.0001). Associations were observed between circulating sCD163 and a less favourable metabolic profile as judged by higher waist circumference, fat mass, visceral fat, epicardial fat, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, gamma-glutamyl transpeptidase and triglycerides (all between r = 0.173 and r = 0.363; p < 0.05 to p < 0.0001) and lower high-density lipoprotein-cholesterol (r = -0.285, p < 0.0001). In multiple regression analyses, circulating sCD163 was independently associated with HOMA-IR (ß = 0.162, p = 0.016; model R2 = 0.179) and high density lipoprotein-cholesterol/triglycerides ratio (ß = -0.167, p = 0.012; model R2 = 0.209). CONCLUSIONS: Childhood obesity may increase the risk of developing metabolic diseases later in life through chronic macrophage activation having deleterious effects on metabolism.

Uric acid, carotid intima-media thickness and body composition in prepubertal children.

BACKGROUND: Increased uric acid is an independent biomarker for cardiovascular disease in obese adolescents and adults. OBJECTIVE: We investigated whether uric acid relates to carotid intima-media thickness (cIMT) in prepubertal children, and whether body mass index (BMI) and preperitoneal fat modulate this association. METHODS: 359 asymptomatic prepubertal Caucasian children were stratified according to BMI categories (171 with BMI-SDS < 0; 188 with BMI-SDS ≥ 0) and according to preperitoneal fat levels (180 with preperitoneal fat <50th centile; 179 with preperitoneal fat >50th centile). Uric acid levels, insulin resistance (homeostasis model assessment insulin resistance; HOMA-IR), C-reactive protein (CRP), triacylglycerol (TG), systolic blood pressure (SBP), abdominal fat and cIMT (both by ultrasound) were assessed. RESULTS: Uric acid was associated with several cardiovascular risk factors, namely higher HOMA-IR, CRP, TG, BMI, waist, SBP, preperitoneal fat and cIMT (all P < 0.001 to P < 0.0001). Significant BMI and preperitoneal fat interactions were documented in the relationship between uric acid and cIMT (both P < 0.05), as uric acid was preferentially related to cIMT in heavier children (ß = 0.247, P < 0.001, r(2) = 9.1%) and in children with more preperitoneal fat (ß = 0.263, P < 0.0001, r(2) = 11.9%). CONCLUSIONS: Serum uric acid is associated with cIMT in asymptomatic prepubertal children. Both higher BMI and preperitoneal fat aggravate the potential risk of atherosclerotic disease imposed by higher concentrations of uric acid.

Increased serum IgG and IgA in overweight children relate to a less favourable metabolic phenotype.

BACKGROUND: The adaptive immune system has emerged as an unexpected modulator of insulin resistance. B lymphocytes accumulate in adipose tissue and produce pathogenic antibodies that cause insulin resistance. OBJECTIVE: We studied whether circulating immunoglobulins (IgG, IgA and IgM) were related to metabolic risk markers in pre-pubertal children with and without overweight. DESIGN AND METHODS: Subjects were 270 asymptomatic pre-pubertal Caucasian children (145 lean, 125 overweight) recruited in a primary care setting. Assessments included serum IgG, IgA and IgM concentrations (nephelometry), insulin resistance (HOMA-IR) and fasting lipids (triacylglycerol and high-density lipoprotein [HDL]-cholesterol). RESULTS: Overweight children had higher IgG and IgA serum levels than lean children (P ≤ 0.01). Increasing serum IgG and IgA, but not IgM, were associated with a less favourable metabolic phenotype, consisting of higher HOMA-IR and triacylglycerol and lower HDL-cholesterol, particularly in obese children, in whom serum IgG and IgA were both independently associated with HOMA-IR (ß = 0.308, P = 0.017, r2 = 9.5% and ß = 0.361, P = 0.005, r2 = 13.0%, respectively) and triacylglycerol (ß = 0.343, P = 0.006, r2 = 11.1% and ß = 0.354, P = 0.003, r2 = 12.2%, respectively). CONCLUSIONS: Increased circulating IgG and IgA in overweight children are associated with a less favourable metabolic phenotype, particularly in obese children. These results suggest a relationship between adaptive immunity and insulin resistance in childhood obesity.