Uric Acid-Induced Inflammation Is Mediated by the Parathyroid Hormone:25-Hydroxyvitamin D Ratio in Obese Adolescents

Background: Elevated serum uric acid (SUA) level is strongly associated with prevalence of metabolic syndrome (MS), elevated parathyroid hormone (PTH) levels, and 25-hydroxyvitamin D [25(OH)D] insufficiency in adults. We examined the relationship among SUA, [25(OH)D], PTH, and inflammation in obese adolescents, in obese adolescents with and without MS. Methods: Body mass index, body composition, 25(OH)D, PTH, fasting lipids, glucose, high-sensitivity C-reactive protein (hs-CRP), SUA, hemoglobin A(1c) (HbA(1c)), insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR) were evaluated in 152 obese adolescents. Results: Hyperuricemia [SUA >= 6.0 mg/dL (357 mu M)] was present in 54.6% of entire cohort without significant ethnic/racial differences. While SUA was negatively correlated with high-density lipoprotein cholesterol (HDL-C) and 25(OH)D (P < 0.01), it was positively correlated with fat mass (FM), PTH, PTH:25(OH)D, and hs-CRP (P < 0.01). Vitamin D deficiency [25(OH)D <50 nM] was present in 47.4% of subjects, and PTH and 25(OH)D were inversely correlated (P < 0.0001). FM was negatively correlated with 25(OH)D (r = -0.29; P < 0.001), but was positively correlated with PTH (P < 0.0001). MS was identified in 53.3% of cohort with higher FM, SUA, hs-CRP, HOMA-IR, PTH, and PTH:25(OH)D ratio than the non-MS subgroup (P < 0.001) with similar 25(OH)D status. Multiple regression analysis showed that the PTH:25(OH)D ratio mediated the relationship between SUA and hs-CRP (beta = 0.19, P < 0.05 to beta = 0.15, P = 0.19). Conclusions: Hyperuricemia is strongly associated with PTH and hs-CRP levels independent of vitamin D status. The relationship between SUA and low-grade inflammation is mediated by the PTH:25(OH)D ratio in obese adolescents.