The role of Gestational Diabetes Mellitus and pelvic floor 3D-ultrasound assessment during pregnancy predicting urinary incontinence: a prospective cohort study.

Postpartum urinary incontinence may have a severe impact on women's health. Despite pregnancy and parturition being the most recognized risk factors, methods to identify new pregnant predictor risk factors are needed. Our study investigated the Gestational Diabetes Mellitus, clinical and pelvic floor 3D-ultrasound markers in pregnant women as predictors for 6-18 months of urinary incontinence. This prospective cohort study included nulliparous pregnant women submitted to Gestational Diabetes Mellitus screening in the second trimester. Pelvic floor 3D Ultrasound was performed at the second and third trimesters of gestation to evaluate the pelvic floor muscles and functions. Clinical data, the ICIQ-SF, and ISI questionnaires for urinary incontinence were applied in the third trimester and 6-18 months postpartum. Univariate analysis (P < .20) to extract risk factors variables and multivariate logistic regression analysis (P < .05) to obtain the adjusted relative ratio for urinary incontinence were performed. A total of 93 participants concluded the follow-up. Using the variables obtained by univariate analysis and after adjustments for potential confounders, multivariate analysis revealed that Gestational Diabetes Mellitus exposure was a solid and independent risk factor for 6-18 months of urinary incontinence (Adjusted RR 8.08; 95%CI 1.17-55.87; P:0.034). In addition, a higher Hiatal area observed in distension maneuver from the second to third trimester was negatively associated (Adjusted RR 0.96; 95%CI 0.93-0.99; P:0.023). In conclusion, Gestational Diabetes Mellitus was positively associated with 6-18 months of urinary incontinence, and higher Hiatal area distension was negatively associated.

Risk factors for postpartum urinary incontinence: The impact of early-onset and late-onset Gestational Diabetes Mellitus in a nested case-control study.

BACKGROUND: Gestational Diabetes Mellitus (GDM) and many other clinical variables have been associated with postpartum urinary incontinence (UI). However, the data are still restricted, and no study explored early- or late-onset GDM as a risk factor for this condition. We aimed to identify independent risk factors for postpartum UI, focusing on GDM and its early or late onset. METHODS: A nested case control derived from the Diamater cohort study included 517 pregnant women who submitted to a planned C-section and followed by 6-18 months after delivery according to the timing of GDM diagnosis: early-onset GDM (before 20 weeks) and late-onset GDM(24-28 weeks) and the occurrence of UI. RESULTS: Univariate analysis showed that the risk for 6-18 months postpartum UI was 49% higher in non-Caucasian ethnicity (1.49,1.02-2.18), 3,3 times higher in previous bariatric surgery [3.37,1.36-8.21], 39% higher in GDM women (1.39,1.01-1.93), and 5% higher for each BMI score in prepregnancy (1.05, 1.03-1.08) and at the end of pregnancy (1.05,1.02-1.08). Multivariate logistic regression analysis indicates that prepregnancy BMI was the only independent factor associated with the 6-18 months postpartum UI (adj 1.05, 95 %CI 1.02-1.08, P <.001). After stratifying, a second univariate and multivariate analysis were done according to the prepregnancy BMI cutoff score of 25. Thus, a significant association between GDM and postpartum UI in prepregnancy overweight women (RR: 1.91; 95 %CI 1.25-2.90, P =.003) and no association between GDM and 6-18 months postpartum UI in normal prepregnancy BMI (RR: 0.78, 95 %CI 0.39-1.54, P =.482) were found. After multivariate regression, the early-onset-GDM remained the unique independent adjusted risk factor for 6-18 months postpartum UI analysis (adjRR 2.15, 95 %CI 1.33-3.46, P =.002). CONCLUSION: After a planned C-section, we observed a 6-18 months postpartum UI higher occurrence after GDM, either in early-onset GDM or late-onset GDM. In addition, being overweight (BMI > 25) among women with early-onset GDM was associated with postpartum UI.

Consequences of the exposome to gestational diabetes mellitus.

The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including those from the environment, diet, behaviour, and endogenous processes. The exposome concept and the 2030 Agenda for the Sustainable Development Goals (SDGs) from the United Nations are the basis for understanding the aetiology and consequences of non-communicable diseases, including gestational diabetes mellitus (GDM). Pregnancy may be developed in an environment with adverse factors part of the immediate internal medium for fetus development and the external medium to which the pregnant woman is exposed. The placenta is the interface between maternal and fetal compartments and acts as a protective barrier or easing agent to transfer exposome from mother to fetus. Under and over-nutrition in utero, exposure to adverse environmental pollutants such as heavy metals, endocrine-disrupting chemicals, pesticides, drugs, pharmaceuticals, lifestyle, air pollutants, and tobacco smoke plays a determinant role in the development of GDM. This phenomenon is worsened by metabolic stress postnatally, such as obesity which increases the risk of GDM and other diseases. Clinical risk factors for GDM development include its aetiology. It is proposed that knowledge-based interventions to change the potential interdependent ecto-exposome and endo-exposome could avoid the occurrence and consequences of GDM.

Viability of ex-vivo myography as a diagnostic tool for rectus abdominis muscle electrical activity collected at Cesarean section within a diamater cohort study.

BACKGROUND: Ex-vivo myography enables the assessment of muscle electrical activity response. This study explored the viability of determining the physiological responses in muscles without tendon, as rectus abdominis muscle (RAM), through ex-vivo myography to assess its potential as a diagnostic tool. RESULTS: All tested RAM samples (five different samples) show patterns of electrical activity. A positive response was observed in 100% of the programmed stimulation. RAM 3 showed greater weight (0.47 g), length (1.66 cm), and width (0.77 cm) compared to RAM 1, RAM 2, RAM 4 and RAM 5 with more sustained electrical activity over time, a higher percentage of fatigue was analyzed at half the time of the electrical activity. The order of electrical activity (Mn) was RAM 3 > RAM 5 > RAM 1 > RAM 4 > RAM 2. No electrical activity was recorded in the Sham group. CONCLUSIONS: This study shows that it is feasible to assess the physiological responses of striated muscle without tendon as RAM, obtained at C-section, under ex vivo myography. These results could be recorded, properly analyzed, and demonstrated its potential as a diagnostic tool for rectus abdominis muscle electrical activity.

Reversal of diabetic-induced myopathy by swimming exercise in pregnant rats: a translational intervention study.

Gestational diabetes mellitus (GDM) plus rectus abdominis muscle (RAM) myopathy predicts long-term urinary incontinence (UI). Atrophic and stiff RAM are characteristics of diabetes-induced myopathy (DiM) in pregnant rats. This study aimed to determine whether swimming exercise (SE) has a therapeutic effect in mild hyperglycemic pregnant rats model. We hypothesized that SE training might help to reverse RAM DiM. Mild hyperglycemic pregnant rats model was obtained by a unique subcutaneous injection of 100 mg/kg streptozotocin (diabetic group) or citrate buffer (non-diabetic group) on the first day of life in Wistar female newborns. At 90 days of life, the rats are mated and randomly allocated to remain sedentary or subjected to a SE protocol. The SE protocol started at gestational day 0 and consisted of 60 min/day for 6 days/week in a period of 20 days in a swim tunnel. On day 21, rats were sacrificed, and RAM was collected and studied by picrosirius red, immunohistochemistry, and transmission electron microscopy. The SE protocol increased the fiber area and diameter, and the slow-twitch and fast-twitch fiber area and diameter in the diabetic exercised group, a finding was also seen in control sedentary animals. There was a decreased type I collagen but not type III collagen area and showed a similar type I/type III ratio compared with the control sedentary group. In conclusion, SE during pregnancy reversed the RAM DiM in pregnant rats. These findings may be a potential protocol to consider in patients with RAM damage caused by GDM.

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

AIM: This study aimed to assess, for the first time, the dynamic morphometry of pelvic floor muscles (PFM) using three-dimensional transperineal ultrasound (3D-TPUS) and its progression at two-time points of gestation between women with and without gestational diabetes mellitus (GDM), and whether the PFM dysfunction is connected to GDM. METHODS: The study comprised 83 consecutive pregnant women with (n = 38) and without (n = 45) GDM screened at 24-30 and 38-40 weeks of gestation. 3D-TPUS and a mobility test were used to quantify PFM dynamic morphometry during maximum contraction and the Valsalva maneuver. RESULTS: When compared to the control group, GDM women had no significant variations in all levator hiatal dimensions at 24-30 weeks of gestation. Meanwhile, women with GDM experienced an increase in levator hiatal area (LHa) (p < 0.000) during PFM contraction and enlargement in LHa (p < 0.001) during Valsalva maneuver (p = 0.010) at 38-40 weeks of gestation. As a result, the mobility index among GDM women had a lower value (p = 0.000). The dynamic morphometry development of PFM in GDM women at two stages during pregnancy revealed a substantial decrease (p = 0.000) in all LHa dimensions of contraction, distension, and mobility. CONCLUSIONS: Using 3D-TPUS, we found that GDM women had a specific pattern of PFM functional changes in the third trimester of pregnancy. These initial findings revealed alterations in PFM functionality, such as decreased contractility, distensibility, or mobility. This dysfunctional PFM could contribute to the long-term development of pelvic floor dysfunction years after a GDM pregnancy.

Impact of gestational diabetes on pelvic floor: A prospective cohort study with three-dimensional ultrasound during two-time points in pregnancy.

AIM: To evaluate the pelvic floor (PF) biometry using three-dimensional ultrasound (US) at two-time points of gestational in pregnant women with gestational diabetes mellitus (GDM). METHODS: A prospective cohort study conducted at the Perinatal Diabetes Research Center including 44 pregnant women with GDM and 66 pregnant women without GDM at 24 to 28 weeks of gestation. Three-dimensional transperineal US was performed at 24 to 28 and 34 to 38 weeks of gestation in the lithotomy position at rest. The axial plane of the minimal Levator hiatal dimensions was used to determine Levator ani muscle and Hiatal area (HA) biometry at 24 to 28 and 34 to 38 weeks of gestation. RESULTS: Of the 110 pregnant women, 100 (90.9%) completed the follow-up at 34 to 38 weeks of gestation. The evaluation by US showed a negative biometric change between the two-time points, during pregnancy in women with GDM; in the HA (ß coefficient: estimative of effect in biometric progression according to GDM diagnosis, using the non-GDM group as reference = -6.76; P = .020), anteroposterior diameter (ß = -5.07; P = .019), and Levator ani thickness (ß = -12.34; P = .005). CONCLUSIONS: Pregnant women with GDM had a significantly lower than expected percentage of changes in biometry of Levator ani thickness and HA from 24 to 28 to 34 to 38 weeks of gestation when compared with the group of pregnant women without GDM. GDM alters the morphology of PF structures assessed by three-dimension US. This reported complication may be implicated in adverse birth outcomes and may play a role in the development of PF dysfunction.

Deleterious effects of gestational diabetes mellitus on the characteristics of the rectus abdominis muscle associated with pregnancy-specific urinary incontinence.

AIMS: To evaluate the effects of gestational diabetes mellitus (GDM) on the structural characteristics of the rectus abdominis muscle (RAM) and its indirect effects on pregnancy-specific urinary incontinence (PSUI). METHODS: A total of 92 pregnant women were divided into four groups, according to their clinical conditions: non-GDM continent, non-GDM associated PSUI, GDM continent and GDM associated PSUI. The muscle morphometry (histochemistry and immunohistochemistry) for the fiber types and collagen fiber distribution, the ultrastructural analysis (transmission electron microscopy), the protein expression of fiber types and calcium signaling (Western blotting), and the content of types I and III collagen fiber (ELISA) in RAM collected at delivery were assessed. RESULTS: The GDM groups presented a significantly increased number of slow fibers and slow-twitch oxidative fiber expression; decreased fiber area, number of fast fibers, and area of collagen; an increase in central nuclei; ultrastructural alterations with focal lesion areas such as myeloid structures, sarcomere disorganization, and mitochondrial alteration. The PSUI groups presented a considerable decrease in types I and III collagen contents and the localization of collagen fiber. CONCLUSIONS: Our data reveal that GDM causes morphological, biochemical and physiological changes in the RAM, and this might predispose women to PSUI.

Pregnancy-specific urinary incontinence in women with gestational hyperglycaemia worsens the occurrence and severity of urinary incontinence and quality of life over the first year post partum.

OBJECTIVE: To determine the occurrence and severity of pregnancy-specific urinary incontinence (PSUI) in women with gestational hyperglycaemia, and its impact on quality of life (QoL) over the first year post partum. STUDY DESIGN: Three hundred and eighty-eight pregnant women with PSUI were distributed into two groups (normoglycaemic and hyperglycaemic) and analysed at five timepoints during pregnancy and the first year post partum. Gestational hyperglycaemia was defined according to the criteria of the American Diabetes Association and the glucose profile test. Relationships with outcome were analysed using Chi-squared test for categorical variables and Student's t-test for quantitative variables. RESULTS: The overall prevalence rate of PSUI was 54.1 %, with prevalence rates of 43.3 % and 56.7 % in normoglycaemic and hyperglycaemic Brazilian pregnant women, respectively. Women with gestational hyperglycaemia had a higher amount of urine loss (p < 0.0027), frequency of UI (p < 0.0014), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0003) and total scores on the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-SF) and Incontinence Severity Index (ISI) (p<0.0001) at the two timepoints during pregnancy; and a higher amount of urine loss (p = 0.0079), frequency of UI (p = 0.0382), impact of UI on QoL (p < 0.0001), severity of UI (p = 0.0053) and questionnaire scores (p < 0.0001 for ICIQ-SF and p = 0.003 for ISI) over the first year post partum. CONCLUSIONS: PSUI in women with gestational hyperglycaemia worsens the occurrence and severity of UI, and the impact of UI on QoL over the first year post partum. These results emphasize the interaction between PSUI, gestational hyperglycaemia and long-term maternal outcome.

Alterations in the structural characteristics of rectus abdominis muscles caused by diabetes and pregnancy: A comparative study of the rat model and women.

BACKGROUND AND OBJECTIVE: In the present study, we compared the effect of diabetic pregnancy on the rectus abdominis muscle (RAM) in humans and rats. We hypothesized that our animal model could provide valuable information about alterations in the RAM of women with Gestational Diabetes (GDM). METHOD: Newborns female rats (n = 10/group) were administered streptozotocin (100 mg/kg body weight) subcutaneously and were mated on reaching adulthood, to develop the mild hyperglycemic pregnant (MHP) rat model. At the end of pregnancy, the mothers were sacrificed, and the RAM tissue was collected. Pregnant women without GDM (non-GDM group; n = 10) and those diagnosed with GDM (GDM group; n = 8) and undergoing treatment were recruited, and RAM samples were obtained at C-section. The RAM architecture and the distribution of the fast and slow fibers and collagen were studied by immunohistochemistry. RESULTS: No statistically significant differences in the maternal and fetal characters were observed between the groups in both rats and women. However, significant changes in RAM architecture were observed. Diabetes in pregnancy increased the abundance of slow fibers and decreased fast fiber number and area in both rats and women. A decrease in collagen distribution was observed in GDM women; however, a similar change was not observed in the MHP rats. CONCLUSION: Our results indicated that pregnancy- associated diabetes- induced similar structural adaptations in the RAM of women and rats with slight alterations in fiber type number and area. These findings suggest that the MHP rat model can be used for studying the effects of pregnancy-associated diabetes on the fiber structure of RAM.

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

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.

Impact of Gestational Diabetes Mellitus on Sexual Function: A Case-Control Study.

Background: The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide, and this condition may be compromising female sexual function. However, there are controversial findings regarding the impact of GDM diagnosis and proposed treatments on sexual function during pregnancy. Therefore, this study seeks to elucidate the impact of GDM on sexual function in pregnant women by making a comparison between GDM and non-GDM groups using pregnancy sexual response inventory (PSRI). Materials and Methods: A case-control study involved 303 [168 women without GDM (control group) and 108 women diagnosed with GDM (case group)] Brazilian pregnant women at the Perinatal Diabetes Research Centre-Universidade Estadual Paulista, Brazil. PSRI was used to collect the data. The sexual function was scored in 10 domains as composite and specific scores by domains, categorized into quartiles (0 < 25 "very low," 25 < 50 "low," 50 < 75 "high," and 75-100 "very high"), for "before pregnancy" and "during pregnancy." The obtained data were subjected to statistical analysis using Student's t-, F-, and chi-square tests. Results: GDM women (PSRI composite score <50) are at risk of decreased sexual function during pregnancy, while non-GDM women are not at risk (PSRI composite score >50). There were no significant differences in the sexual functions between the two groups before pregnancy (p > 0.0001). After GDM diagnosis and proposed treatment, the differences were significant (p < 0.0001), notably in the frequency, arousal, orgasm, satisfaction, and dyspareunia score. Conclusions: This study showed that GDM diagnosis and proposed treatment resulted in decreased sexual functions during pregnancy.

Negative impact of gestational diabetes mellitus on progress of pelvic floor muscle electromyography activity: Cohort study.

BACKGROUND AND OBJECTIVE: Pelvic floor muscles are involved in postural stability, in maintenance intra-abdominal pressure, and on mechanical support for pelvic organ. Gestational Diabetes Mellitus' (GDM) pregnancies complicated by fetal macrosomia, large placenta and polyhydramnios contribute for abrupt and intense increase in maternal intra-abdominal pressure. Our objective was analyze the impact of GDM on pelvic floor muscle (PFM) electromyography (EMG) activity progress from 24-30 to 36-38 weeks of gestation. We conducted a prospective cohort study. PFM EMG was performed in nulliparous or primiparous women with one previous elective cesarean delivery and with or not GDM diagnosed by the American Diabetes Association criteria. A careful explanation of the muscle anatomy and functionality of the PFM was given before EMG assessment. The outcome measures were PFM recruitment and progress from 24-30 to 36-38 weeks of gestation analyzed by the normalized root mean square (RMS) during rest-activity, fast and hold pelvic floor muscle contraction. RESULTS: Fifty-two pregnant women were assigned to 2 groups: the GDM (n = 26) and normoglycemic (NG) (n = 26). The demographic and obstetric data showed homogeneity between the groups. PFM activity progress was decreased in rest-activity (P = 0.042) and hold contraction (P = 0.044) at 36-38 weeks of gestation in the GDM group relative to that in the NG group. CONCLUSION: GDM group showed a progressive decrease in EMG-PFM activity during rest-activity and hold contractions from 24-30 to 36-38 weeks of gestation.

Prenatal exposure to gestational diabetes mellitus increases developmental defects in the enamel of offspring.

BACKGROUND AND OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with short- and long-term maternal and perinatal repercussions. Our objective was to evaluate the long-term consequences of intrauterine exposure to hyperglycemia on Developmental Defects of Enamel (DDE) in offspring. RESULTS: Overall, 50 children of women with GDM and 250 children of normoglycemic women participated, the latter serving as controls. Children were examined at the age between 3 and 12 years. In addition to physical examination, two independent observers examined and rated photographs to identify specific types of DDE in a blinded fashion. Among offspring of mothers with GDM, rates of DDE (all types combined) and hypoplasia (specific type) were significantly higher (p<0.001, p = 0.04), in comparison to offspring of normoglycemic mothers. Considering only the affected teeth (1060 in GDM category; 5499 in controls), rates of DDE (all types combined) were significantly higher for total teeth (p <0.001) and deciduous teeth (p<0.001), but not permanent teeth. In specific types of DDE involving deciduous teeth, rates of demarcate opacity were significantly higher (p<0.001; canine and 2nd mandibular molars) and hypoplasia (p <0.001; 2nd maxillary molars and 2nd mandibular molars). In permanent teeth, the rate of diffuse opacity in association with GDM was significantly higher (p<0.001; maxillary central incisors and 1st maxillary molars). CONCLUSION: GDM was associated with the adverse effects of DDE on offspring. This study lays the foundation for future studies to determine the impact of GDM on long-term risk of DDE.

The influence of hyperglycemia on the remodeling of urethral connective tissue in pregnant rats.

OBJECTIVE: To analyze the distribution and quantification of the key structural extracellular matrix components of the urethral tissue in a rat model of hyperglycemia and pregnancy. STUDY DESIGN: A total of 120 female Wistar rats were distributed into the following four experimental groups: virgin, pregnant, hyperglycemic and hyperglycemic + pregnant groups. The urethra was harvested for histochemical, morphometric, immunohistochemical, Western blot and glycosaminoglycan analyses. All protocols were approved by the Institutional Animal Care and Use Committee of Botucatu Medical School (process number 828-2010). RESULTS: The hyperglycemic + pregnant group showed significantly increased stiffness in urethral tissue. The total striated muscle was decreased, with increased deposition of collagen fibers around the muscle fibers and a change in the organization of the collagen fibrils. An increase in the relative collagen type I/III ratio and a decrease in total glycosaminoglycans were also observed. CONCLUSIONS: This study provides the first line of experimental evidence supporting a metabolic relationship between hyperglycemia and urethral remodeling of connective tissue in pregnant rats. The different organization of the collagen fibrils and the profile of glycosaminoglycans found in urethral samples suggest that the pathology of the urethral fibromuscular system could be related to hyperglycemia-induced pelvic floor dysfunction in women, which has direct clinical implications with the possibility to develop new multidisciplinary treatments for improving the health care of these women.