Serum α-KL, a potential early marker of diabetes complications in youth with T1D, is regulated by miRNA 192

Despite the wealth of information on biomarkers of diabetes complications in adults with type 1 diabetes, data in the pediatric population is limited. Diabetic nephropathy (DN), the leading cause of mortality in type 1 diabetes T1D), could be potentially missed in youth, as albuminuria, the current "gold" standard, may be transient and may not reflect permanent renal impairment. Soluble alpha KL has emerged as a potential marker of early diabetic nephropathy. Seventy-nine pediatric patients with type 1 diabetes meeting ISPAD criteria for nephropathy screening were consecutively recruited (90% Caucasian, 51% male, mean age 16.1 ± 3.1 years, duration of T1D 7.2 ± 3.9 years, 2-year average HbA1c 8.0 ± 1.3%, and serum and urine samples were collected for analysis. Serum Klotho (KL) and circulating miRNA levels of select miRNA involved in the pathogenesis of DN were estimated. KL had a strong inverse correlation with diabetes duration and HbA1c, two important risk factors in the development of diabetes complications. Serum miR-192 were negatively associated with KL among children with prolonged duration of diabetes (≥12 years) after adjustment for age and sex. In cell culture, overexpression of miR-192 significantly downregulated KL mRNA and protein levels, and reduced KL levels in the media. miR-192 mimic reduced luciferase activity in a reporter containing the KL 3' UTR (60% compared to controls, p