Hyperinsulinemia in Pediatric Patients with Chronic Kidney Disease: the Role of Tumor Necrosis Factor-alpha

We sought to determine the prevalence of hyperinsulinemia and insulin resistance in pediatric patients with chronic kidney disease (CKD) stages 2-4. Data were collected on 43 subjects, aged 6-21 years with mean glomerular filtration rate (GFR) = 47 ml/min per 1.73 m(2) body surface area. Patients were grouped by body mass index (BMI) as either non-lean (>85th percentile) or lean (<or=85th percentile). Fourteen (33%) subjects had hyperinsulinemia, and seven (16%) had elevated homeostasis model assessment of insulin resistance (HOMA-IR). Non-lean subjects had a higher serum insulin level (21.0 microU/ml vs 13.4 microU/ml, P < 0.0001) and HOMA-IR (4.9 vs 3.2, P < 0.001) than lean subjects had. The prevalence of hyperinsulinemia was higher in non-lean patients (40%) than in lean patients (29%) but was not statistically significant. High HOMA-IR was present in six (40%) non-lean subjects and in one lean subject (P < 0.001). Correlation analysis demonstrated that serum insulin level was significantly associated with BMI, leptin and tumor necrosis factor (TNF)-alpha. Stepwise regression determined that increased BMI (P = 0.003) and TNF-alpha (P = 0.01) independently predicted higher insulin level in the whole cohort. Separate analysis for lean subjects showed no significant associations between serum insulin level and BMI; TNF-alpha was the only independent predictor of serum insulin (beta = 1.11, P = 0.01). We conclude that hyperinsulinemia and insulin resistance are frequent in pediatric CKD. In lean patients inflammation appears to be an important determinant of serum insulin level.