38-LB: Discovery Analysis of MicroRNAs (miRs) Associated with Microvascular Complications in Adults with Type 1 Diabetes

Abstract

Objective: Despite therapeutic advances, type 1 diabetes (T1D) is associated with a risk of development of micro- and macrovascular complications. Early treatment of complications is associated with a more favorable prognosis, hence biomarkers to enable early detection and to monitor treatments may be useful. Methods: Plasma (EDTA) samples were obtained from 30 adult (M/F = 20/10) individuals with T1D, age 42±16 years, T1D duration 24±11 years, HbA1c 7.5±1.2% and BMI 26.5±4.0 kg/m2 (15 with microvascular complications (retinopathy or nephropathy) - CX+, and 15 without complications - CX-) and compared with 15 nondiabetic controls (CON, matched age, gender, smoking and BMI). T1D CX+ and CX- individuals were matched for age, gender, diabetes duration, smoking, BMI, HbA1c and insulin therapy modality (CSII/MDI). In these discovery cohort samples, profiling of 754 miRs was done using a high throughput probe based quantitative PCR on nanofluidics Open Array platform . Results were analyzed using independent T test, Mann-Whitney test and classification trees. Statistical analysis was undertaken using R (ver. 3.5.1) and XLStat (ver. 2018.6). Results: Of 754 available miRs on the array, 186 miRs were detectable in plasma. Using an unbiased approach expression of 32 miRs differed significantly in CON vs. T1D and 16 miRs were differentially expressed between CX+ and CX- T1D subjects. Using a Random Forest wrapper algorithm 5 miRs were identified with importance for segregating CX+ vs. CX- status: miR-483-5p, miR-328, miR-1274B, miR-7 and miR-30a-5p. In logistic regression those 5 miRs provided a ROC curve with AUC=0.90 for the CX+ vs. CX- discrimination. Conclusion: In a discovery analysis of well- matched CX+ and CX- selected miRs provided good discrimination between T1D CX status. Validation studies in a larger cohort of cross-sectional and longitudinal samples are in progress. Disclosure A.S. Januszewski: None. E.S. Scott: None. M. Joglekar: None. L. Carroll: None. R. Farr: None. W. Wong: None. D.N. O’Neal: None. C. Karschimkus: None. G. Fulcher: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Research & Development, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. A. Hardikar: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. Funding Sydney Medical School Foundation; National Health and Medical Research Council of Australia