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

• Grant number: 18/10661-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2018
• End date: June 30, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Iracema de Mattos Paranhos Calderon
• Grantee: David Rafael Abreu Reyes
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 16/01743-5 - The new gestational triad: hyperglycemia, urinary incontinence (UI) and biomolecular profile as a long-term predictor for UI: a prospective cohort study: translational research with biodevice with stem cells for muscle regeneration in diabetic rats, AP.TEM

Abstract

The research group "Diabetes and Pregnancy - Clinical and Experimental" at Botucatu-Unesp School of Medicine has been investigating since 2006 the pathophysiology of gestational diabetes (GDM) and mild gestational hyperglycemia (GH), called gestational hyperglycemia in this study (HGG ) and its relationships with pelvic floor muscle dysfunctions (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. Pelvic floor muscles (MAPs) are important structures in the maintenance of pelvic organs such as bladder, uterus and urethrovesical junction, urethral and anal sphincter closure mechanism, vaginal canal mobility and sexuality. The structures and functionality of the Pelvic Floor (PA) can be evaluated by different features during pregnancy, such as 3D Ultrasonography (EMG), electromyography (EMG), and myography evaluating ex vivo contractility. Studies have shown that US 3D is effective in assessing PA in relation to measurements of the diameter and area of the resting hiatus and the evaluation of the functionality, that is, during maximal pelvic contraction and during Valsalva maneuver (intra- abdominal). The EMG is a gold standard examination to analyze recruitment of motor units through the extracellular record of the bioelectrical activity generated by the muscular fibers, which infers on the nervous and muscular capacity and integrity, as well as, to effectively analyze the activity of muscle interaction. Considering the relationship between UI and abdominal rectus muscles (MRAs) and the ethical difficulties of obtaining pelvic floor muscles of pregnant women because it is an invasive procedure, with an ethical bias, since the patient herself does not benefit from the procedure in our point of view it is necessary to verify if the decrease or alteration of the contractile capacity of the muscle by the myography of ex vivo contraction with "gestational hyperglycemic myopathy" ("MHG") in the MRAs obtained at the time of cesarean section. The suggested hypothesis is that there will be differences in the functionality of the MAPs, with an altered result in the group with HG and IU when compared to the control groups. Objectives: To analyze the influence of the functional markers of the gestational hyperglycemic myopathy (MHG) of the MAPs, evaluated by means of the 3DUS, EMG and contractility ex vivo by the myograph, in the prediction of UI 6-12 months postpartum (PP). The null hypothesis is that there will be no differences in the functionality of the MAPs between the group with HG and IU when compared to the control groups. Methodology: C-section will be included primigravidae or cesarean, between 18 and 35 years of age, 24-28th gestational weeks, non-diabetic and without UI prior to current gestation, normotensive, single gestation, without urogynecological surgery, without collagen-related diseases, without malignant neoplasms; without active infection with hepatitis A, B or C virus and / or HIV and without degenerative muscular diseases. Assuming a simple random sampling without replacement, type I error equal to 0.05, test power equal to 0.8, incidence ratio of UI 6 months PP = 8% in the NG-C cohort and absence of confounding, 38 pregnant women per cohort to detect differences above 40% in the proportion of incidence among cohorts. The cohorts will be formed from the combinations between the diagnosis of HGG performed between 24th-28th week and "IUEG" performed at two time points: 24a-28a and 38a -40th gestational week. Therefore, the cohorts will be definitively formed at the end of the 40th week, each pregnant being classified in one of the following cohorts: Cohort 1: Pregnant NGs continents (NG-C); Cohort 2: Urinary incontinence NGs (NG-IU); Cohort 3: Pregnant HGs continents (HGC) and Cohort 4: Pregna

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ALVES, FERNANDA CRISTINA BERGAMO; DE OLIVEIRA, RAFAEL GUILEN; REYES, DAVID RAFAEL ABREU; GARCIA, GABRIELA AZEVEDO; FLORIANO, JULIANA FERREIRA; SHETTY, RAGHAVENDRA HALLUR LAKSHMANA; MARECO, EDSON ASSUNCAO; DAL-PAI-SILVA, MAELI; PAYAO, SPENCER LUIZ MARQUES; SOUZA, FATIMA PEREIRA DE; et al. Transcriptomic Profiling of Rectus Abdominis Muscle in Women with Gestational Diabetes-Induced Myopathy: Characterization of Pathophysiology and Potential Muscle Biomarkers of Pregnancy-Specific Urinary Incontinence. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 21, p. 20-pg., 2022-11-01. (18/10661-8, 19/05710-2, 16/01743-5, 17/21783-4, 18/26305-6, 18/02979-8)

RUDGE, MARILZA V. C.; ALVES, FERNANDA C. B.; HALLUR, RAGHAVENDRA L. S.; OLIVEIRA, RAFAEL G.; VEGA, SOFIA; REYES, DAVID R. A.; FLORIANO, JULIANA F.; PRUDENCIO, CAROLINE B.; GARCIA, GABRIELA A.; REIS, FABIANA V. D. S.; et al. Consequences of the exposome to gestational diabetes mellitus. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1867, n. 2, p. 14-pg., 2023-02-01. (18/02979-8, 16/01743-5, 18/26305-6, 21/10665-6, 17/21783-4, 19/05710-2, 18/10661-8)

REYES, DAVID R. A.; BARBOSA, ANGELICA M. P.; JULIANA, FLORIANO F.; SOFIA, QUIROZ B. C., V; COSTA, SARAH M. B.; HALLUR, RAGHAVENDRA L. S.; ENRIQUEZ, EUSEBIO M. A.; OLIVEIRA, RAFAEL G.; ROSSIGNOLLI, PATRICIA DE SOUZA; PEDRONI, CRISTIANE RODRIGUES; et al. Viability of ex-vivo myography as a diagnostic tool for rectus abdominis muscle electrical activity collected at Cesarean section within a diamater cohort study. BIOMEDICAL ENGINEERING ONLINE, v. 21, n. 1, p. 12-pg., 2022-10-14. (16/01743-5, 18/10661-8)