Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus

Abstract

Background: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/ RAM hyperglycemic myopathy will be evaluated. Methods: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. Discussion: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Pelvic floor muscle dysfunction at 3D transperineal ultrasound in maternal exposure to gestational diabetes mellitus: A prospective cohort study during pregnancy

“…What we do know is that the central features of PFM muscles in diabetic pregnant rats are thinning, atrophy, disorganization, disruption in the circular annulus associated with the co‐localization of fast and slow fibers, and a steady decrease in the proportion of fast versus slow fibers of PFM and RAM muscles. Furthermore, translational research in diabetic pregnant rats revealed increased collagen deposition, severe fibrosis, lipid droplets, and numerous subsarcolemmal and intermyofibrillar mitochondria, but also an increased collagen type I/III ratio and a decrease in total glycosaminoglycan in urethral tissue 10,24 …”

“…9 These major findings from the literature review on hyperglycemia in pregnant rats and PFM and/or RAM myopathy prompted us to ponder if this may occur in GDM women. 10 These investigations, however, did not look at changes in the contractility and distensibility of the levator hiatus during PFM contraction and the Valsalva maneuver employing 3D transperineal ultrasound (3D-TPUS). Additionally, ultrasonography is the objective method as a standard diagnostic tool in functional urogynecology research.…”

Pro-angiogenic approach for skeletal muscle regeneration

“…Women with pregnancy complicated by gestational diabetes mellitus have high risk to develop the gestational diabetic myopathy (GDMy) characterized by pelvic floor skeletal muscle severe atrophy leading to urinary incontinence [335][336][337]. GDMy is a condition poorly addressed still waiting for an efficient therapy.…”

The Role of Gestational Diabetes Mellitus and Pelvic Floor 3D-Ultrasound Markers at the Second and Third Trimester of Pregnancy Predicting 6-18 Months Postpartum Urinary Incontinence: Preliminary Results From a Prospective Cohort

“…Both combined disorders seem to have hyperglycemic Pelvic Floor Muscle (PFM) and Rectus Abdominis Muscle (RAM) myopathy as the underlying mechanism. [1,[4][5][6][7] Speci cally, current clinical and experimental studies suggest that Pregnancy Speci c-UI (PS-UI) is the earliest symptom of hyperglycemic PFM and RAM myopathy during pregnancy, despite overlooked complaints during prenatal care assistance. [5,[7][8][9][10] Nevertheless, a previous study showed that PS-UI, the severity of long-term UI, and the negative impact of UI on quality of life are more signi cant among GDM pregnant women in the rst year postpartum.…”

“…The triad proposed by Rudge et al, characterized by hyperglycemic PFM, RAM myopathy, and PS-UI, impacts long-term UI's prevalence and severity. [4] The development of a predictive test during pregnancy for long-term UI collaborates to identify a high-risk population accurately.…”