207-OR: Cardiac Autonomic Neuropathy (CAN) and HDL Proteomics in Type 1 Diabetes (T1D)

• Published in: Diabetes (New York, N.Y.) Vol. 70; no. Supplement_1
• Main Authors: TOYOSHIMA, MARCOS T., SILVA, AMANDA, SANTANA, MONIQUE DE FATIMA M., RONSEIN, GRAZIELLA E., CORREA-GIANNELLA, MARIA LUCIA, PASSARELLI, MARISA
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2021
• Subjects: Amyloidosis; Antioxidants; Autonomic nervous system; Bikunin; Body mass index; Cholesterol; Diabetes; Diabetes mellitus (insulin dependent); Diabetic neuropathy; High density lipoprotein; Homeostasis; Inflammation; Morbidity; Pathogenesis; Polyneuropathy; Proteins; Proteomes; Proteomics; Thyroid hormones; Transthyretin; Triglycerides; Ultracentrifugation; Vasodilation; Vitamin A
• DOI: 10.2337/db21-207-OR
• ISSN: 0012-1797

CAN is a common complication of diabetes mellitus (DM) strongly related to cardiovascular (CV) disease, contributing to high morbidity and mortality. HDL is inversely related to CV disease due to its ability in removing excess cholesterol from cells and antioxidant, anti-inflammatory and vasodilation actions. Apart from plasma HDL cholesterol (HDLc) and apoA-I levels that are not invariably changed in T1D, HDL proteomics may contribute to understand HDL functionality and its association with CAN. A total of 50 individuals with T1D with or without CAN were selected to assess the proteome of HDL subfractions (HDL2 and HDL3). CAN evaluation was performed by Ewing test using the Poly-Spectrum software. HDL subfractions were isolated by ultracentrifugation and proteomics analyzed by parallel reaction monitoring (PRM). Subjects with T1D with (n = 15) and without CAN (n = 35) did not differ in age, sex, body mass index, age at DM diagnosis, duration of DM, and fructosamine, HbA1c, total cholesterol, HDLc and triglycerides values. A total of 45 proteins were found in association with HDL2 and HDL3; three proteins were highlighted because they were more abundant in HDL2 from T1D with CAN: α1-microglobulin/bikunin precursor (AMBP), α1-acid glycoprotein (Orm1) and transthyretin (TTR) (Mann-Whitney test; P values <0.01, 0.03, 0.04, respectively). Orm1 is an acute inflammatory phase protein that regulates sphingolipid homeostasis related to the pathogenesis of diabetic neuropathy. TTR carries thyroid hormones and retinol binding protein and mutations in the TTR gene causes amyloidosis that includes motor and sensory polyneuropathy, neuropathic pain and autonomic dysfunction. The AMBP gene encodes α1microglobulin and bicunin that relates to T1D complications. In conclusion, three proteins with potential for involvement in the pathophysiology of CAN were more abundant in HDL2 in T1D presenting this chronic complication. Disclosure M. T. Toyoshima: None. A. Silva: None. M. M. Santana: None. G. E. Ronsein: None. M. Correa-giannella: None. M. Passarelli: None. Funding FAPESPCNPq