Hyperinsulinemia in pediatric patients with chronic kidney disease: the role of tumor necrosis factor-α

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 m² body surface area. Patients were grouped by body mass index (BMI) as either non-lean (>85th percentile) or lean (≤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 μU/ml vs 13.4 μU/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)-α. Stepwise regression determined that increased BMI (P = 0.003) and TNF-α (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-α was the only independent predictor of serum insulin (β = 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.