Urinary cytokine response to asymptomatic bacteriuria in type 1 diabetic children and young adults

Abstract

It has been reported that urinary interleukin-6 (IL-6) and IL-8 levels are decreased in adult diabetic women with asymptomatic bacteriuria (ASB) when compared with non-diabetic women with ASB. Such impaired cytokine excretion might play a role in the higher prevalence of ASB among diabetic subjects. The aim of this study was to examine the urinary IL profile in children and young adults with type 1 diabetes mellitus (T1DM) with and without ASB. Midstream clean voiding urine samples were collected and cultured from 133 patients with T1DM (age: 15.6 +/- 5.7 yr) and 178 controls (14.1 +/- 4.7 yr) for two consecutive days. ASB was diagnosed in the case of >or=10(5) bacteria/mL. The urinary IL-6 and IL-8 concentrations were determined, and the presence of leukocyturia was also recorded. The prevalence of ASB was 16.5% in diabetic subjects and 2.8% in controls (p = 0.001). There was no difference between the diabetic and the control groups in the prevalence of 'IL-6-uria' (21.9 vs. 18.0%; p = 0.41), but IL-8 was more frequently detectable in the diabetic group (47.4 vs. 27.5%; p = 0.001). In individuals with ASB, the IL-8 level was similar in the diabetic (median: 70.0 pg/mg creatinine) and control group (42.3 pg/mg creatinine; p = 0.8). Indeed, the IL-8 levels were higher in diabetic subjects with ASB as compared with those without it (70.0 vs. <3.1 pg/mg creatinine; p = 0.001), and there was a significant association between the urinary IL-8 concentration and the bacterial count (p = 0.001). Diabetic patients with leukocyturia had higher IL-8 concentration than those without it (20.9 vs. <3.1 pg/mg creatinine; p = 0.003). Weak significant correlation was found between urinary IL-8 and hemoglobin A1c (HbA1c) (r = 0.4; p = 0.002). The sensitivity and specificity of leukocyturia were 50 and 89.9% in the whole population and those of IL-8 were 74.1 and 67.5%, respectively. In diabetic patients, 36.4% of the bacteriuria were gram-negative and 63.6% gram-positive. Our results suggest that diabetic children with ASB mount an IL-8 response to pathogens, which is comparable to non-diabetic children with bacteriuria. Thus, early in the natural history of diabetes, there are no significant changes in the IL response of children with ASB, as previously reported in adults.