Characterization of metabolic syndrome in patients with systemic autoimmune myopathies

• Grant number: 24/17776-6
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: April 30, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Samuel Katsuyuki Shinjo
• Grantee: Samuel Katsuyuki Shinjo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Sueli Mieko Oba Shinjo

Abstract

Systemic autoimmune myopathies (SAMs) - including dermatomyositis (DM), polymyositis (PM), immune-mediated necrotizing myopathy (IMNM), and anti-synthetase syndrome (ASyS) - are rare, chronic, and highly disabling diseases that primarily affect striated skeletal muscle. These conditions are associated with significant functional impairment, reduced quality of life, and increased morbidity, including cardiovascular disease. Our research group was among the first to demonstrate a high prevalence of metabolic syndrome (MetS) in patients with SAMs. However, this finding was based on a retrospective cohort (2011-2015) composed of patients from a tertiary referral center who were treated with high-dose, long-term glucocorticoids and presented marked functional limitations, physical inactivity, and muscle mass loss. In recent years, advances in the understanding of the pathophysiology, phenotypic stratification, and therapeutic approaches - including the use of several immunosuppressants, reduced glucocorticoid exposure, and implementation of physical rehabilitation programs - may have substantially altered the metabolic and functional profile of these patients. Therefore, a contemporary reassessment of MetS and its determinants in the context of SAMs is not only timely but necessary. In this context, the present study proposes a comprehensive cross-sectional investigation with the following objectives: (A) primary: to determine the current prevalence of metabolic syndrome (MetS) in patients with various SAMs (DM, PM, ASyS, and IMNM); (ii) secondary: (B1) to compare patients with SAM and healthy controls regarding: (a) clinical and laboratory determinants of MetS, including comorbidities, biomarkers, and cardiometabolic risk factors; (b) body composition; (c) sarcopenia prevalence and associated risk factors; (d) bone health, including bone mineral density and osteometabolic profile. (B1) to map metabolic and inflammatory signalizng pathways in skeletal muscle biopsies by RNA-seq (transcriptome analysis); (B3) to assess the impact of current glucocorticoid exposure on clinical, metabolic, musculoskeletal, and molecular parameters.This novel, integrated approach - combining clinical, functional, and molecular assessments in a contemporary SAM cohort - aims to refine screening, prevention, and intervention strategies, reduce irreversible dysfunction and premature morbidity and mortality, and enhance personalized patient care. (AU)