Gestational triad hyperglycemia cohort urinary incontinence and clinical molecular and omic profile of hyperglycemic myopathy in the prediction of incontinence and muscle dysfunction and translational research with biodevic for muscle regeneration in rats

Abstract

Introduction: The research group "Diabetes and Pregnancy - Clinical and Experimental" at Botucatu-Unesp Medical School has been investigating since 2006 the pathophysiology of gestational diabetes (GDM) and mild gestational hyperglycemia (GH) and its relationships with muscular dysfunction of the pelvic floor (DMAP) and urinary incontinence (UI) in clinical and experimental studies. After critical analysis in the group and with national and international partners of the results obtained, there were large gaps that need to be filled with more complex preclinical and clinical studies. Objective: To analyze the influence of the association between gestational hyperglycemia (HGG) considering GDM and HGL, "IUEG" and profile (morphological, functional, biochemical, molecular and omic) of "gestational hyperglycemic myopathy" MHG ") of the rectus abdominis muscle (ARM) and pelvic floor muscles (PFM) in the UI 6-12 months postpartum (PP); to analyze the HGG triad, "IUEG" and "MHG" profile, the incidence of UI 6-12 months PP and morphological, functional and biochemical profile, within the four cohorts constituted by the combination between HGG and IUEG; to evaluate the effect of rubber tree latex biodevic with mesenchymal stem cells on regeneration of urethral muscle and ARM after cesarean section in pregnant rats with moderate diabetes in the morphological, microvascular, molecular and omic profile; and to determine the scientific evidence, through the systematic review, of the effectiveness of the exercises on DMAP and "UGT" in pregnant women with HG. Materials and Methods: In the clinical study, the participants will be selected between March 2016 and December 2019 at the FMB UNESP Perinatal Diabetes Research Center, at the Risk Pregnancy Clinic of FAMEMA Maternal and Child Hospital and at Assis Regional Hospital. The total number of participants will be 160 considering the four cohorts that will be constituted. The analysis of the biochemical profile, obtained by the blood tests of the levels of CCL7, Relaxin, Ca, PTH, calcitonin, vitamin D, glucose and insulin will be performed; (EMG) and Ultrasonography (US), EMG and US, at the time of cesarean section, will be performed the ex vivo contractility obtained by the Miographer, and the morphological profiles (Protein and Gene Expression of muscle fibers and extracellular matrix), and Omic (transcriptomic, proteomic and metabolomic). For the experimental study, pregnant Wistar rats, divided into nondiabetic and diabetic groups (n = 20 each), will be used, which will be submitted to the installation of biodevic latex biomembrane coated with mesenchymal stem cells, implanted in the urethral striated musculature and MRA . The Systematic Review study will follow the standards and will be recorded in the Cochrane Collaboration. In the statistical analysis with the software SPSS v21.0, the relations will be considered statistically significant of p <0,05. Expected results: Characterize the "MHG"; that the proposed triad is a predictor of UI and DMAP 6-12 months PP; define markers for diagnosis and in future therapies; to demonstrate the first line of preventive or rehabilitative intervention for muscular dysfunctions and "IUEG"; that the "UGIR" in HGG be considered and included as a public health problem and as clinical intercurrence, becoming a new tool in the definition of maternal long term impact; that biodevic is considered for regeneration of the musculature in future clinical studies; and that this proposed translational approach will bring this research to the frontier of knowledge in the area of Women's Health, since unpublished methodologies of analysis are being applied in the area that complement each other in the approach of problematic of medical / social interest.