Serum Sclerostin as a Marker of Microvascular and Macrovascular Complications among Children and Adolescents with Type 1 Diabetes Mellitus

Abstract Background: Chronically uncontrolled diabetes mellitus (DM) is linked to long-term micro and macrovascular adverse outcomes, through speeding up atherosclerosis and peripheral vascular diseases. Owing to the early cardiac and renal involvement, an early diagnostic biomarker is required. Sclerostin is a Wnt-signaling inhibitor, having a pathophysiological role in vasculopathy, and could be used as a vasculopathy marker, nevertheless, few data are available in pediatric patients with type 1 diabetes mellitus (T1DM). We aimed at assessing its serum level, and the relation to diabetic microvascular and macrovascular complications. Methods: a case control study on pediatric and adolescent patients with T1DM, and healthy controls. Patients were divided according to proteinuria into non-diabetic nephropathy (DN), and DN group. Patients’ clinicodemographic, and anthropometric measurements were obtained, with withdrawal of fasting serum lipid profile, kidney function test, and serum sclerostin. Carotid intimal media thickness (CIMT), a marker of subclinical atherosclerosis, was measured. Results: We included 75 comparable subjects, where median (IQR) serum sclerostin levels was significantly higher in DN, compared to non-DN, and controls [90.83 (82.32 – 115.1), vs 33.29 (28.37 – 38.53), vs 13.5 (10.32 – 15.72) ng/ml respectively, p< 0.001]. Similarly, median (IQR) CIMT was significantly higher in DN, than non-DN and controls [1.1 (0.8 – 1.3), vs 0.11 (0.1 – 0.2), vs 0.11 (0.1 – 0.2) mm, p<0.001]. Serum sclerostin level correlated positively with disease duration, higher HgbA1c%, albuminuria level, and CIMT in all patients. The cut off values of serum sclerostin > 60.0 ng/ml and CIMT >0.3 mm were able to detect DN. Conclusions: Serum Sclerostin levels could serve as a potential biomarker for micro and macrovascular complications in pediatric patients with T1DM.