Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence.

Serotonin and interleukin 10 (IL-10) may play a role in gestational diabetes mellitus. Hyperglycemic environment, the detrusor musculature of the bladder and pelvic floor muscles may become damaged, leading to urination problems and urine viscosity in pregnant women with gestational diabetes mellitus and pregnancy-specific urinary incontinence. Urine and blood samples were collected from pregnant women between 24 and 28 weeks of gestation. The serotonin concentration and cytokine IL-10 levels were evaluated in plasma and urine. In the total blood and urine, the viscosity was evaluated in the presence and absence of exogenous serotonin and IL-10. The plasma serotonin levels decreased, while the urine serotonin levels increased in the normoglycemic incontinent (NG-I), hyperglycemic continent (GDM-C), and hyperglycemic incontinent (GDM-I) groups. The IL-10 in the plasma decreased in the GDM-I group and was higher in the urine in the NG-I and GDM-I groups. The blood viscosity was higher, independently of urinary incontinence, in the GDM groups. The serotonin increased the blood viscosity from women with GDM-C and urine in the NG-I, GDM-C, and GDM-I groups. Blood and urine in the presence of IL-10 showed a similar viscosity in all groups studied. Also, no difference was observed in the viscosity in either the blood or urine when in the presence of serotonin and IL-10. These findings suggest that serotonin and IL-10 have the potential to reduce blood viscosity in pregnant women with gestational diabetes and specific urinary incontinence, maintaining values similar to those in normoglycemic women's blood.

Impact of Obesity and Hyperglycemia on Pregnancy-specific Urinary Incontinence.

OBJECTIVE: The lack of data on the impact of hyperglycemia and obesity on the prevalence of pregnancy-specific urinary incontinence (PSUI) led us to conduct a cross-sectional study on the prevalence and characteristics of PSUI using validated questionnaires and clinical data. METHODS: This cross-sectional study included 539 women with a gestational age of 34 weeks who visited a tertiary university hospital between 2015 and 2018. The main outcome measures were the prevalence of PSUI, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Incontinence Severity Index (ISI) questionnaires. The women were classified into four groups: normoglycemic lean, normoglycemic obese, hyperglycemic lean, and hyperglycemic obese. The differences between groups were tested using descriptive statistics. Associations were estimated using logistic regression analysis and presented as unadjusted and adjusted odds ratios. RESULTS: Prevalence rates of PSUI were no different between groups. However, significant difference in hyperglycemic groups worse scores for severe and very severe PSUI. When adjusted data for confound factors was compared with normoglycemic lean group, the hyperglycemic obese group had significantly higher odds for severe and very severe forms of UI using ICIQ-SF (aOR 3.157; 95% CI 1.308 to 7.263) and ISI (aOR 20.324; 95% CI 2.265 to 182.329) questionnaires and highest perceived impact of PSUI (aOR 4.449; 95% CI 1.591 to 12.442). CONCLUSION: Our data indicate that obesity and hyperglycemia during pregnancy significantly increase the odds of severe forms and perceived impact of PSUI. Therefore, further effective preventive and curative treatments are greatly needed.

OBJETIVO: A falta de dados sobre o impacto da hiperglicemia e obesidade na prevalência de incontinência urinária específica da gravidez (IAPS) nos levou a realizar um estudo transversal sobre a prevalência e características da IAPS usando questionários validados e dados clínicos. MéTODOS: Este estudo transversal incluiu 539 mulheres com idade gestacional de 34 semanas que visitaram um hospital universitário terciário entre 2015 e 2018. As principais medidas de desfecho foram a prevalência de PSUI, o formulário curto do International Consultation on Incontinence Questionnaire (ICIQ-SF) e os questionários do Incontinence Severity Index (ISI). As mulheres foram classificadas em quatro grupos: magras normoglicêmicas, obesas normoglicêmicas, magras hiperglicêmicas e obesas hiperglicêmicas. As diferenças entre os grupos foram testadas por meio de estatística descritiva. As associações foram estimadas usando análise de regressão logística e apresentadas como odds ratio não ajustadas e ajustadas. RESULTADOS: As taxas de prevalência de PSUI não foram diferentes entre os grupos. No entanto, houve diferença significativa nos grupos hiperglicêmicos com piores escores para PSUI grave e muito grave. Quando os dados ajustados para fatores de confusão foram comparados ao grupo magro normoglicêmico, o grupo obeso hiperglicêmico teve chances significativamente maiores de formas graves e muito graves de IU usando ICIQ-SF (aOR 3,157; IC 95% 1,308 a 7,263) e ISI (aOR 20,324; 95% CI 2,265 a 182,329) questionários e maior impacto percebido de PSUI (aOR 4,449; 95% CI 1,591 a 12,442). CONCLUSãO: Nossos dados indicam que a obesidade e a hiperglicemia durante a gravidez aumentam significativamente as chances de formas graves e o impacto percebido da PSUI. Portanto, tratamentos preventivos e curativos mais eficazes são extremamente necessários.

Impact of Obesity and Hyperglycemia on Pregnancy-specific Urinary Incontinence / Impacto da obesidade e hiperglicemia na incontinência urinária específica da gravidez

Abstract Objective The lack of data on the impact of hyperglycemia and obesity on the prevalence of pregnancy-specific urinary incontinence (PSUI) led us to conduct a cross-sectional study on the prevalence and characteristics of PSUI using validated questionnaires and clinical data. Methods This cross-sectional study included 539 women with a gestational age of 34 weeks who visited a tertiary university hospital between 2015 and 2018. The main outcome measures were the prevalence of PSUI, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Incontinence Severity Index (ISI) questionnaires. The women were classified into four groups: normoglycemic lean, normoglycemic obese, hyperglycemic lean, and hyperglycemic obese. The differences between groups were tested using descriptive statistics. Associations were estimated using logistic regression analysis and presented as unadjusted and adjusted odds ratios. Results Prevalence rates of PSUI were no different between groups. However, significant difference in hyperglycemic groups worse scores for severe and very severe PSUI. When adjusted data for confound factors was compared with normoglycemic lean group, the hyperglycemic obese group had significantly higher odds for severe and very severe forms of UI using ICIQ-SF (aOR 3.157; 95% CI 1.308 to 7.263) and ISI (aOR 20.324; 95% CI 2.265 to 182.329) questionnaires and highest perceived impact of PSUI (aOR 4.449; 95% CI 1.591 to 12.442). Conclusion Our data indicate that obesity and hyperglycemia during pregnancy significantly increase the odds of severe forms and perceived impact of PSUI. Therefore, further effective preventive and curative treatments are greatly needed.

Resumo Objetivo A falta de dados sobre o impacto da hiperglicemia e obesidade na prevalência de incontinência urinária específica da gravidez (IAPS) nos levou a realizar um estudo transversal sobre a prevalência e características da IAPS usando questionários validados e dados clínicos. Métodos Este estudo transversal incluiu 539 mulheres com idade gestacional de 34 semanas que visitaram um hospital universitário terciário entre 2015 e 2018. As principais medidas de desfecho foram a prevalência de PSUI, o formulário curto do International Consultation on Incontinence Questionnaire (ICIQ-SF) e os questionários do Incontinence Severity Index (ISI). As mulheres foram classificadas em quatro grupos: magras normoglicêmicas, obesas normoglicêmicas, magras hiperglicêmicas e obesas hiperglicêmicas. As diferenças entre os grupos foram testadas por meio de estatística descritiva. As associações foram estimadas usando análise de regressão logística e apresentadas como odds ratio não ajustadas e ajustadas. Resultados As taxas de prevalência de PSUI não foram diferentes entre os grupos. No entanto, houve diferença significativa nos grupos hiperglicêmicos com piores escores para PSUI grave e muito grave. Quando os dados ajustados para fatores de confusão foram comparados ao grupo magro normoglicêmico, o grupo obeso hiperglicêmico teve chances significativamente maiores de formas graves e muito graves de IU usando ICIQ-SF (aOR 3,157; IC 95% 1,308 a 7,263) e ISI (aOR 20,324; 95% CI 2,265 a 182,329) questionários e maior impacto percebido de PSUI (aOR 4,449; 95% CI 1,591 a 12,442). Conclusão Nossos dados indicam que a obesidade e a hiperglicemia durante a gravidez aumentam significativamente as chances de formas graves e o impacto percebido da PSUI. Portanto, tratamentos preventivos e curativos mais eficazes são extremamente necessários.

Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus.

Gestational diabetes mellitus is an important public health problem and has been associated with the development of pregnancy-specific urinary incontinence. The interaction is related to hyperglycemia, and inflammatory and hormonal patterns, which favor functional alterations in different organs and systems. Several genes associated with human diseases have been identified and partially characterized. Most of these genes are known to cause monogenic diseases. However, about 3 % of diseases do not fit the monogenic theory due to the complex interactions between multiple genes and environmental factors, as in chronic metabolic diseases such as diabetes. The nutritional, immunological, and hormonal patterns associated with changes in maternal metabolism may influence and contribute to greater susceptibility to urinary tract disorders. However, early systematic reviews have not yielded consistent findings for these associations. This literature review summarizes important new findings from integrating nutrigenomics, hormones, and cytokines in women with Gestational diabetes mellitus and pregnancy-specific urinary incontinence. Changes in maternal metabolism due to hyperglycemia can generate an inflammatory environment with increased inflammatory cytokines. This environment modulated by inflammation can alter tryptophan uptake through food and thus influence the production of serotonin and melatonin. As these hormones seem to have protective effects against smooth muscle dysfunction and to restore the impaired contractility of the detrusor muscle, it is assumed that these changes may favor the onset of urinary incontinence specific to pregnancy.

Assessment of Pelvic Floor Disorders due to the Gestational Diabetes Mellitus Using Three-Dimensional Ultrasonography: A Narrative Review.

Gestational diabetes mellitus (GDM)is an entity with evolving conceptual nuances that deserve full consideration. Gestational diabetes leads to complications and adverse effects on the mother's and infants' health during and after pregnancy. Women also have a higher prevalence of urinary incontinence (UI) related to the hyperglycemic status during pregnancy. However, the exact pathophysiological mechanism is still uncertain. We conducted a narrative review discussing the impact of GDM on the women's pelvic floor and performed image assessment using three-dimensional ultrasonography to evaluate and predict future UI.

O diabetes gestacional (DG)é uma entidade com nuances conceituais em evolução que merecem total consideração. O DG leva a complicações e efeitos adversos na saúde da mãe e do bebê durante e após a gravidez. As mulheres também apresentam maior prevalência de incontinência urinária (IU) relacionada ao estado hiperglicêmico durante a gravidez. No entanto, o mecanismo fisiopatológico exato ainda é incerto. Realizamos uma revisão narrativa discutindo o impacto do DG no assoalho pélvico das mulheres e utilizamos o exame de ultrassonografia tridimensional para avaliar e predizer a ocorrência de IU.

Assessment of Pelvic Floor Disorders due to the Gestational Diabetes Mellitus Using Three-Dimensional Ultrasonography: A Narrative Review / Avaliação das desordens do assoalho pélvico decorrentes do diabetes gestacional usando a ultrassonografia tridimensional: Uma revisão narrativa

Abstract Gestational diabetes mellitus (GDM)is an entity with evolving conceptual nuances that deserve full consideration. Gestational diabetes leads to complications and adverse effects on the mother's and infants' health during and after pregnancy. Women also have a higher prevalence of urinary incontinence (UI) related to the hyperglycemic status during pregnancy. However, the exact pathophysiological mechanism is still uncertain. We conducted a narrative review discussing the impact of GDM on the women's pelvic floor and performed image assessment using three-dimensional ultrasonography to evaluate and predict future UI.

Resumo O diabetes gestacional (DG)é uma entidade com nuances conceituais em evolução que merecem total consideração. O DG leva a complicações e efeitos adversos na saúde da mãe e do bebê durante e após a gravidez. As mulheres também apresentam maior prevalência de incontinência urinária (IU) relacionada ao estado hiperglicêmico durante a gravidez. No entanto, o mecanismo fisiopatológico exato ainda é incerto. Realizamos uma revisão narrativa discutindo o impacto do DG no assoalho pélvico das mulheres e utilizamos o exame de ultrassonografia tridimensional para avaliar e predizer a ocorrência de IU.

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.

Gestational diabetes mellitus (GDM) is recognized as a "window of opportunity" for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.

Maternal care of the whole litter improves the success rate of diabetes in pregnancy in rats.

Induction of diabetes mellitus by streptozotocin (STZ) in rats at birth is of high mortality and low success rate when male puppies are separated from females, prioritizing females breastfeeding. Cross-parental care of the entire litter and SZT-induced diabetes up to 12 h post-birth become with high success rate, low animal death, and females with glycaemia >140 mg/dL on the 90 postnatal day. Cross-parental care is more effective in STZ-induction of diabetes, which is maintained during pregnancy (diabetes in pregnancy), than the conventional protocol of male separation at birth.

Gestational diabetes is associated with alteration on pelvic floor muscle activation pattern during pregnancy and postpartum: Prospective cohort using electromyography assessment.

Background and objective: Gestational diabetes mellitus (GDM) is a comorbidity which may cause acute and lifelong disorders to mother and child. Alterations in muscular and connective tissues have been associated with GDM in translation studies, characterizing gestational diabetic myopathy. Pregnancy-specific urinary incontinence and sexual disabilities, disorders that depend on the pelvic floor muscle (PFM) integrity, are also associated with GDM both during and after pregnancy. The aim was to compare PFM activation patterns between GDM and non-GDM women from 24-30 gestational weeks to 18-24 months postpartum during a standard clinical test during gestation and postpartum. Methods: We conducted a prospective three-time-point cohort study from gestation (24-30 weeks-T1, and 36-38 weeks-T2) to 18-24 months postpartum (T3). PFM electromyography was recorded in primigravida or primiparous women with one previous elective c-section with or without the diagnosis of GDM according to the American Diabetes Association criteria. A careful explanation of the muscle anatomy and functionality of the PFM was given to participants before EMG assessment. The outcome measures were PFM activation patterns assessed during pregnancy and postpartum, comparing intra and between groups. PFM activation patterns were assessed by normalized electromyography signal at rest and during 1-second (sec) phasic, 10-sec hold, and 60-sec sustained contractions. Results: Demographic and obstetric data showed homogeneity between groups. The GDM group achieved peak PFM EMG amplitudes similarly to the non-GDM group, but they took longer to return to baseline levels during the ~1-sec contraction (flicks). During 10-sec hold contractions, the GDM group sustained lower levels of PFM activation than the non-GDM group at both 36-38 weeks of gestation and 18-24 months postpartum when compared to the non-GDM group. Conclusion: The results suggest that GDM impaired PFM control mainly on 1-sec flicks and 10-sec hold contraction, which appears to develop during late pregnancy and extends long-term postpartum. This motor behavior may play a role on pelvic floor dysfunctions.

Relaxin-2 during pregnancy according to glycemia, continence status, and pelvic floor muscle function.

INTRODUCTION AND HYPOTHESIS: To investigate relaxin-2 concentration comparing gestational diabetes mellitus (GDM) and non-GDM patients during pregnancy according to urinary incontinence (UI) and pelvic function status. METHODS: This is a cross-sectional study evaluating 282 pregnant women from 24 weeks of gestation. The participants were divided into two groups, non-GDM and GDM, according to American Diabetes Association's diabetes mellitus gestational threshold. In addition, according to subanalysis, both groups were subdivided according to the presence of pregnancy-specific urinary incontinence: non-GDM continent, non-GDM incontinent, GDM continent, and GDM incontinent. All participants filled in questionnaires on clinical, obstetric, and urinary continence status (International Consultation on Incontinence Questionnaire-Short Form, ICIQ-SF, and Incontinence Severity Index, ISI), followed by pelvic floor muscle evaluation by the PERFECT scheme in which strength, endurance, and speed of contractions were evaluated. RESULTS: Serum relaxin-2 concentrations were significantly lower in pregnant women with pregnancy-specific urinary incontinence in both non-GDM and GDM patients, but GDM showed the lowest concentration. In addition, the stratification of the groups according to pelvic floor muscle strength showed that pregnant patients with GDM and modified Oxford scale 0-2 had significantly lower levels than those who were non-GDM and GDM with Modified Oxford Scale 3-5. Relaxin-2 level was much lower in GDM incontinent pregnant women with MOS 0-2 compared to the other three groups. CONCLUSIONS: Lower relaxin-2 concentration was associated with the presence of pregnancy-specific urinary incontinence, but the combination of GDM, pregnancy-specific urinary incontinence, and lower levels of pelvic floor strength led to lower levels of relaxin-2 compared to the other three groups.

Pro-angiogenic approach for skeletal muscle regeneration.

The angiogenesis process is a phenomenon in which numerous molecules participate in the stimulation of the new vessels' formation from pre-existing vessels. Angiogenesis is a crucial step in tissue regeneration and recovery of organ and tissue function. Muscle diseases affect millions of people worldwide overcome the ability of skeletal muscle to self-repair. Pro-angiogenic therapies are key in skeletal muscle regeneration where both myogenesis and angiogenesis occur. These therapies have been based on mesenchymal stem cells (MSCs), exosomes, microRNAs (miRs) and delivery of biological factors. The use of different calls of biomaterials is another approach, including ceramics, composites, and polymers. Natural polymers are use due its bioactivity and biocompatibility in addition to its use as scaffolds and in drug delivery systems. One of these polymers is the natural rubber latex (NRL) which is biocompatible, bioactive, versatile, low-costing, and capable of promoting tissue regeneration and angiogenesis. In this review, the advances in the field of pro-angiogenic therapies are discussed.

Supplementation of Vitamin D in the Postdelivery Period of Women with Previous Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM). METHODS: Randomized clinical trials of pregnant women with GDM of any chronological, gestational age and parity, with no history of previous disease who received vitamin D supplementation in the prenatal and/or postpartum period and were evaluated in the postpartum period were included. The PubMed, EMBASE, Cochrane, and LILACS databases were consulted until July 2019. Serum vitamin D concentration (25-hydroxyvitamin D in nmol/L), fasting blood glucose, glycated hemoglobin, serum calcium concentration, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), parathyroid hormone (PTH) and body mass index (BMI) were evaluated. Similar results in at least two trials were plotted using the RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. The quality of the evidence was generated according to the classification, development, and evaluation of the classification of the recommendations. RESULTS: Four studies were included in the present review (200 women). The findings indicate that there is no difference in the postpartum period in women diagnosed with previous GDM who received vitamin D supplementation in the prenatal and/or in the postpartum period, showing only that there was a significant increase in the concentration of vitamin D (relative risk [RR]: 1.85; 95% confidence interval [CI]: 1.02-2.68). CONCLUSION: This increase in the concentration of vitamin D should be interpreted with caution, since the assessment of the quality of the evidence was very low. For the other analyzed outcomes, there was no significance between the intervention and control groups, and the outcomes, when analyzed in their strength of evidence, were considered very low and low in their evaluation.

OBJETIVO: Avaliar os efeitos da suplementação de vitamina D no pós-parto de mulheres com diabetes mellitus gestacional (DGM) anterior. MéTODOS: Foram incluídos ensaios clínicos randomizados com gestantes com GDM de qualquer idade cronológica, gestacional e paridade, sem história de doença prévia, que receberam suplementação de vitamina D no pré-natal e/ou no pós-parto e foram avaliadas no pós-parto. As bases de dados consultadas foram PubMed, EMBASE, Cochrane e LILACS, até julho de 2019. Foram avaliados concentração sérica da vitamina D (25-hidroxivitamina D em nmol/L), glicemia de jejum, hemoglobina glicada, concentração sérica de cálcio, modelo de avaliação da homeostase de resistência à insulina (HOMA-IR, na sigla em inglês), índice qualitativo de verificação da sensibilidade à insulina (QUICKI, na sigla em inglês), hormônio da paratireoide (PTH) e índice de massa corpórea (IMC). Resultados semelhantes em pelo menos dois ensaios foram plotados no software RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. A qualidade das evidências foi gerada de acordo com a classificação, o desenvolvimento e a avaliação da classificação das recomendações. RESULTADOS: Quatro estudos foram incluídos na presente revisão (200 mulheres). Os achados indicam que não há diferença no período pós-parto em mulheres com diagnóstico prévio de DMG que receberam suplementação de vitamina D no período pré-natal e/ou pós-parto, mostrando apenas que houve um aumento significativo na concentração de vitamina D (risco relativo [RR]: 1,85; IC [intervalo de confiança] 95%: 1,02­2,68). CONCLUSãO: Este aumento na concentração de vitamina D deve ser interpretado com cautela, uma vez que a avaliação da qualidade das evidências foi muito baixa. Para os demais desfechos analisados, não houve significância entre os grupos intervenção e controle, e os desfechos, quando analisados em sua força da evidência, foram considerados muito baixa e baixa em sua avaliação. PROSPERO: CRD42018110729.

Supplementation of Vitamin D in the Postdelivery Period of Women with Previous Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Trials / Suplementacão da vitamina D no período pós-parto de mulheres com diabetes mellitus gestacional anterior: revisão sistemática de ensaios clínicos randomizados

Abstract Objective To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM). Methods Randomized clinical trials of pregnant women with GDM of any chronological, gestational age and parity, with no history of previous disease who received vitamin D supplementation in the prenatal and/or postpartum period and were evaluated in the postpartum period were included. The PubMed, EMBASE, Cochrane, and LILACS databases were consulted until July 2019. Serum vitamin D concentration (25- hydroxyvitamin D in nmol/L), fasting blood glucose, glycated hemoglobin, serum calcium concentration, homeostatic model assessment of insulin resistance (HOMAIR), quantitative insulin sensitivity check index (QUICKI), parathyroid hormone (PTH) and body mass index (BMI) were evaluated. Similar results in at least two trials were plotted using the RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. The quality of the evidence was generated according to the classification, development, and evaluation of the classification of the recommendations. Results Four studies were included in the present review (200 women). The findings indicate that there is no difference in the postpartum period in women diagnosed with previous GDM who received vitamin D supplementation in the prenatal and/or in the postpartum period, showing only that there was a significant increase in the concentration of vitamin D (relative risk [RR]: 1.85; 95% confidence interval [CI]: 1.02-2.68). Conclusion This increase in the concentration of vitamin D should be interpreted with caution, since the assessment of the quality of the evidence was very low. For the other analyzed outcomes, there was no significance between the intervention and control groups, and the outcomes, when analyzed in their strength of evidence, were considered very low and low in their evaluation.

Resumo Objetivo Avaliar os efeitos da suplementação de vitamina D no pós-parto de mulheres com diabetes mellitus gestacional (DGM) anterior. Métodos Foram incluídos ensaios clínicos randomizados com gestantes com GDM de qualquer idade cronológica, gestacional e paridade, sem história de doença prévia, que receberam suplementação de vitamina D no pré-natal e/ou no pós-parto e foram avaliadas no pós-parto. As bases de dados consultadas foram PubMed, EMBASE, Cochrane e LILACS, até julho de 2019. Foram avaliados concentração sérica da vitamina D (25-hidroxivitamina D em nmol/L), glicemia de jejum, hemoglobina glicada, concentração sérica de cálcio, modelo de avaliação da homeostase de resistência à insulina (HOMA-IR, na sigla em inglês), índice qualitativo de verificação da sensibilidade à insulina (QUICKI, na sigla em inglês), hormônio da paratireoide (PTH) e índice de massa corpórea (IMC). Resultados semelhantes em pelo menos dois ensaios foram plotados no software RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. A qualidade das evidências foi gerada de acordo com a classificação, o desenvolvimento e a avaliação da classificação das recomendações. Resultados Quatro estudos foram incluídos na presente revisão (200 mulheres). Os achados indicam que não há diferença no período pós-parto em mulheres com diagnóstico prévio de DMG que receberam suplementação de vitamina D no período pré-natal e/ou pós-parto, mostrando apenas que houve um aumento significativo na concentração de vitamina D (risco relativo [RR]: 1,85; IC [intervalo de confiança] 95%: 1,02-2,68). Conclusão Este aumento na concentração de vitamina D deve ser interpretado com cautela, uma vez que a avaliação da qualidade das evidências foi muito baixa. Para os demais desfechos analisados, não houve significância entre os grupos intervenção e controle, e os desfechos, quando analisados em sua força da evidência, foram considerados muito baixa e baixa em sua avaliação. PROSPERO CRD42018110729

Highly absorptive dressing composed of natural latex loaded with alginate for exudate control and healing of diabetic wounds.

Wounds can take longer to heal in diabetic patients, increasing the risk of infections and other complications. The most common wounds in diabetic patients are diabetic foot ulcers, a severe complication associated with diabetes mellitus. The United States alone spends $18.7 billion annually on care for these wounds including pain and infection management. If improperly managed, infected lesions may require amputation. The enormous cost associated with wound care and the dire consequences if not cared for properly, emphasize the need to develop strategies to accelerate the healing of diabetic foot wounds. Natural rubber latex (NRL), extracted from Hevea brasiliensis (the rubber tree), has been widely applied as a carrier system for several pharmacologically active compounds. Furthermore, it has been shown to encourage angiogenesis, facilitate cell adhesion, and accelerate wound healing. When NRL dressings are applied to wounds of diabetic patients, exudate release is upregulated. The production of exudate is essential to wound healing as it provides the nutrients, proteins, cells, and environment required for regeneration. Despite its benefits, it is necessary to control excess exudate to avoid prolonged healing resulting from dermatitis, maceration of the wound edges, and lesion growth. In order to solve the problem of excessive exudate release induced by NRL membrane application, we aimed to regulate humidity by absorbing excess exudate and increase water vapor transmission. We developed a highly absorptive, permeable, alginate loaded NRL dressing. Adding alginate to NRL membranes, swelling was increased up to 80-fold, absorbing 4.80 g of water per gram of dry membrane. Moreover, water vapor transmission was improved drastically as the material transmitted 480% more water vapor than pure NRL membranes. Furthermore, in vitro tests demonstrated not only that the membranes are biocompatible, but that they also enhance cell proliferation. Through a cell proliferation assay, we observed that fibroblast proliferation was improved by the presence of NRL while the keratinocytes benefit from the presence of alginate. The NRL-alginate dressings have great potential to improve diabetic wound care by accelerating the healing process.

Effectiveness of the pelvic floor muscle training on muscular dysfunction and pregnancy specific urinary incontinence in pregnant women with gestational diabetes mellitus: A systematic review protocol.

BACKGROUND: There is ample evidence that gestational diabetes mellitus has a direct influence on urinary incontinence and pelvic floor muscles. There are no standardized pelvic floor muscle exercise programs in the literature for the physiotherapy and differ in the type of exercise, intensity, type and duration of application, and the frequency and duration of treatment sessions. The aim of this systematic review will be to investigate that Pelvic Floor Muscle Training can prevent and/or decrease the pregnancy specific urinary incontinence in women with gestational diabetes mellitus or gestational hyperglycemia. METHODS: We will perform a systematic review according to the Cochrane methodology of Randomized Controlled Trials. An overall search strategy will be developed and adapted for Embase, MEDLINE, LILACS, and CENTRAL databases, with the date of consultation until June 2020. The MeSH terms used will be "Pregnancy", "Hyperglycemia", "Diabetes Mellitus, Type 2", "Diabetes Mellitus, Type 1", "Pregnancy in Diabetics", "Diabetes, Gestational", "Urinary Incontinence", "Pelvic Floor Muscle Strength". Primary outcomes: improvement or cure of pregnancy specific urinary incontinence (which can be assessed by questionnaires, and tools such as tampon test, voiding diary, urodynamic study). Secondary outcomes: improvement of pelvic floor muscle strength (pelvic floor functional assessment, perineometer, electromyography, functional ultrasonography), improved quality of life (questionnaires), presence or absence of postpartum Urinary Incontinence and adverse effects. Quality assessment by Cochrane instrument. Metanalysis if plausible, will be performed by the software Review Manager 5.3. DISCUSSION: The present study will be the first to analyze the effectiveness of pelvic floor exercises in pregnant women with Gestational Diabetes Mellitus or Hyperglycemia, who suffer from pregnancy specific urinary incontinence. Randomized Controlled Trials design will be chosen because they present the highest level of evidence. It is expected to obtain robust and conclusive evidence to support clinical practice, in addition to promoting studies on the theme and contributing to new studies. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42017065281.

Exosomes Could Offer New Options to Combat the Long-Term Complications Inflicted by Gestational Diabetes Mellitus.

Gestational diabetes Mellitus (GDM) is a complex clinical condition that promotes pelvic floor myopathy, thus predisposing sufferers to urinary incontinence (UI). GDM usually regresses after birth. Nonetheless, a GDM history is associated with higher risk of subsequently developing type 2 diabetes, cardiovascular diseases (CVD) and UI. Some aspects of the pathophysiology of GDM remain unclear and the associated pathologies (outcomes) are poorly addressed, simultaneously raising public health costs and diminishing women's quality of life. Exosomes are small extracellular vesicles produced and actively secreted by cells as part of their intercellular communication system. Exosomes are heterogenous in their cargo and depending on the cell sources and environment, they can mediate both pathogenetic and therapeutic functions. With the advancement in knowledge of exosomes, new perspectives have emerged to support the mechanistic understanding, prediction/diagnosis and ultimately, treatment of the post-GMD outcomes. Here, we will review recent advances in knowledge of the role of exosomes in GDM and related areas and discuss the possibilities for translating exosomes as therapeutic agents in the GDM clinical setting.

Streptozotocin-induced leukocyte DNA damage in rats.

Although several studies using peripheral blood samples suggest that DNA damage is caused by streptozotocin (STZ) per se, our hypothesis is that DNA damage is caused by STZ-induced glycemic changes. Thus, we aimed at evaluating DNA damage levels in peripheral blood samples from rats at different time points within the first 24 h after a single intravenous dose of STZ. Female Wistar rats (control, n = 8; STZ, n = 7) were administered a single STZ intravenous injection (40 mg/kg body weight). Blood samples were collected from the tail vein for genotoxicity analysis by comet assay and glycemia assessment before STZ administration (time point zero) and at 2, 4, 6, 8, 12, and 24 h afterward. At 2 h, there was initial hyperglycemia associated with STZ-induced glycogenolysis that caused an increase in leukocyte DNA damage levels. At 4 h, glycemic and DNA damage levels were normalized. However, at 6 and 8 h, we observed hypoglycemia concomitant with increased DNA damage levels. From 10 h onward up to 24 h, DNA damage persisted and hyperglycemia appeared. Thus, DNA damage increased soon after both hypoglycemia and hyperglycemia, which were not directly induced by STZ owing to its known short life. In conclusion, increased peripheral blood DNA damage levels within 24 h after STZ administration in rats are associated with abnormal glycemic levels and their complications rather than with STZ per se.

Altered maternal metabolism during mild gestational hyperglycemia as a predictor of adverse perinatal outcomes: A comprehensive analysis.

Mild gestational hyperglycemia (MGH), as assessed using the normal oral glucose tolerance test (OGTT) and detection of an altered glycemic profile, is associated with adverse perinatal outcome. This study described the results of 40 years of research conducted at the Perinatal Diabetes Research Centre at São Paulo State University (UNESP), Brazil, on the maternal MGH environment and placental markers. This study also described the unidirectional relationship between MGH and excessive fetal growth, also supplying moderator analysis. In addition to hyperglycemia, MGH is associated with an increased incidence of hypertension, metabolic syndrome, persistent insulin resistance after pregnancy, and high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Structural changes and functional abnormalities resulting from MGH were observed in placenta. The fully adjusted model concluded that the predictor variable (MGH), which creates a complex environment for the fetus, has a direct effect on excessive birth weight and produces a z-score for ratios of birth weight to gestational age of ≥2. Maternal age, pre-pregnancy BMI, number of previous pregnancies, numbers of prenatal visits, and 1 h OGTT are moderator variables that impact MGH and excessive fetal growth. These results show that maternal MGH has some characteristics associated with similar long-term T2DM development and similar adverse perinatal results to those of gestational diabetes mellitus (GDM) mothers, making it an intermediate maternal and placental marker between normoglycemic and GDM mothers.

Prenatal care satisfaction: perception of caregivers with diabetes mellitus.

OBJECTIVE: to understand the satisfaction of pregnant women with diabetes who took insulin during pregnancy and prenatal care performed through outpatient and inpatient follow-up. METHOD: a qualitative approach with analysis of 30 pregnant women who underwent prenatal care and participated in a clinical trial study carried out by the research group of the Perinatal Diabetes Research Center of the Hospital das Clínicas, of the Faculdade de Medicina de Botucatu. The data were collected through interviews and analyzed from content analysis. RESULTS: from the category Satisfaction, the following subcategories emerged: facilities and difficulties faced in prenatal care performed through outpatient or inpatient follow-up, demonstrating that the pregnant women were satisfied with the prenatal care offered regardless of the type of follow-up. CONCLUSION: there was satisfaction in both care, but in outpatient care some structural, technical and administrative difficulties were identified, requiring reassessment, in order to guarantee service agility.