Unhealthy Levels of Phthalates and Bisphenol A in Mexican Pregnant Women with Gestational Diabetes and Its Association to Altered Expression of miRNAs Involved with Metabolic Disease.

Several studies indicate that bisphenol A (BPA) and phthalates may have a role in the development of metabolic diseases using different molecular pathways, including epigenetic regulatory mechanisms. However, it is unclear whether exposure to these chemicals modifies serum levels of miRNAs associated with gestational diabetes mellitus (GDM) risk. In the present study, we evaluated the serum levels of miRNAs associated with GDM (miR-9-5p, miR-16-5p, miR-29a-3p and miR-330-3p) and urinary levels of phthalate metabolites (mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono(2-ethyl hexyl) phthalate (MEHP)) and bisphenol A in GDM patients and women without GDM during the second trimester of gestation. We observed higher levels of miR-9-5p, miR-29a-3p and miR-330-3p in sera of patients with GDM compared to non-diabetic subjects. Phthalates were detected in 97-100% of urine samples, while BPA only in 40%. Urinary MEHP and BPA concentrations were remarkably higher in both study groups compared to previously reported data. Unadjusted MEHP levels and adjusted BPA levels were higher in non-diabetics than in GDM patients (p = 0.03, p = 0.02). We found positive correlations between adjusted urinary MBzP levels and miR-16-5p expression levels (p < 0.05), adjusted MEHP concentrations and miR-29a-3p expression levels (p < 0.05). We also found negative correlations between unadjusted and adjusted MBP concentrations and miR-29a-3p expression levels (p < 0.0001, p < 0.05), unadjusted MiBP concentrations and miR-29a-3p expression levels (p < 0.01). Urinary MEHP levels reflect a striking exposure to di(2-ethylhexyl) phthalate (DEHP) in pregnant Mexican women. This study highlights the need for a regulatory strategy in the manufacture of several items containing endocrine disruptors in order to avoid involuntary ingestion of these compounds in the Mexican population.

Urinary Metabolites Altered during the Third Trimester in Pregnancies Complicated by Gestational Diabetes Mellitus: Relationship with Potential Upcoming Metabolic Disorders.

Gestational diabetes mellitus (GDM) is a disorder in pregnancy with highest impact in the future life of both mother and newborn. Increasing incidence, economic impact, and potential for severe GDM-related pregnancy complications are some factors that have motivated the deep study of physiopathology, risk factors for developing GDM, and potential biomarkers for its diagnosis. In the present pilot study, we analyzed the urinary metabolome profile of GDM patients in the 3rd trimester of pregnancy, when GDM is already established and the patients are under dietary and pharmacological control. An untargeted metabolomics method based on liquid chromatography⁻mass spectrometry analysis was developed to identify differentially expressed metabolites in the GDM group. We identified 14 metabolites that are significantly upregulated in the urine of GDM patients, and, more importantly, we identified those related with the steroid hormone biosynthesis and tryptophan (TRP) metabolism pathways, which are associated with GDM pathophysiology. Thus, these metabolites could be screened as potential prognostic biomarkers of type two diabetes mellitus, coronary artery disease and chronic renal failure in future follow-up studies with GDM patients.

Urinary Inorganic Arsenic Concentration and Gestational Diabetes Mellitus in Pregnant Women from Arica, Chile.

Introduction: The association of total arsenic exposure with impaired glucose tolerance and gestational diabetes has been shown; however, evidence regarding urinary inorganic arsenic in pregnant women is still limited. Our aim was to evaluate the association between urinary inorganic arsenic concentration and gestational diabetes among pregnant women living in Arica, Chile. Methods: Cross-sectional study of pregnant women receiving care at primary health centers in urban Arica. The exposure was urinary inorganic arsenic concentration, while gestational diabetes was the outcome. The association was evaluated using multiple logistic regression models adjusted by age, education level, ethnicity, and pre-pregnancy body mass index. Results: 244 pregnant women were surveyed. The median urinary inorganic arsenic was 14.95 μg/L, and the prevalence of gestational diabetes was 8.6%. After adjusting, we did not find a significant association between gestational diabetes and inorganic arsenic exposure tertiles (Odds ratio (OR) 2.98, 95% CI = 0.87⁻10.18), (OR 1.07, 95% CI = 0.26⁻4.33). Conclusion: This study did not provide evidence on the relationship between urinary inorganic arsenic concentration and gestational diabetes. Further research is needed to elucidate the factors underlying this association.

Diabetes na gestação e incontinência urinária: uma associação pouco reconhecida / Diabetes in pregnancy and urinary incontinence: a little acknowledged association

Incontinência Urinária (IU) feminina é definida como toda perda involuntária de urina. É uma condição frequente, de alto custo econômico para o governo e que implica em danos físicos, psicológicos, sociais e pior qualidade de vida para as mulheres. Inúmeros são os fatores de risco envolvidos no desenvolvimento da IU, porém a associação com o diabetes mellitus (DM) é de grande interesse atualmente. DM afeta múltiplos sistemas orgânicos, incluindo o sistema urinário em aproximadamente 52% dos pacientes diabéticos e dos que apresentam apenas hiperglicemia, porém ainda não é totalmente explicada a associação entre diabetes mellitus gestacional e IU. O profissional de saúde deve estar atento a esse novo parâmetro e procurar analisá-lo de forma mais pormenorizada para que medidas profiláticas e terapêuticas sejam estabelecidas.Há necessidade de delinear a cronologia da relação entre DMG e as complicações urinárias, a relação entre o diabetes controlado e a incidência de incontinência e modalidades de tratamento efetivo para pacientes diabéticos com sintomas no trato urinário inferior.

Urinary incontinence (UI) in women is defined as any involuntary urine loss. This is a frequent condition of high economic cost to the government that also results in women’s physical, psychological and social damage and impaired quality of life. Various risk factors are involved in UI development; however, association with diabetes mellitus (DM) is of great interest at present. DM affects multiple organ systems, including the urinary system in approximately 52% of diabetic patients and in those showing only hyperglycemia; however, the association between gestational diabetes mellitus and UI has not been fully explained. Health care professionals must be attentive to this new parameter and attempt to analyze it in more detail so that prophylactic and therapeutic measures can be established. It is necessary to delineate the chronology of the relation ship between gestational diabetes mellitus and urinary complications, the relationship between controlled diabetes and the incidence of incontinence as well as effective treatment modalities for diabetic patients with symptoms in the lower urinary tract.

Increased tissue kallikrein amidase activity in urine of patients with type 1 diabetes under insulin therapy, and in those with gestational diabetes mellitus not under insulin therapy.

Human tissue kallikrein (hK1) is reduced in hypertension, cardiovascular and renal diseases. There is little information on the participation of hK1 in type 1 diabetes mellitus (DM), type 2 DM, and gestational diabetes mellitus (GDM), respectively. The aim of this study was to evaluate the roles of insulin and hyperglycemia on urinary hK1 activity in type 1 DM and in GDM. Forty-three type 1 DM patients (5-35 years, disease duration ≤ 5years, receiving insulin, HbA(1c)>7.6%) were selected. Forty-three healthy individuals, paired according to gender and age, were used as controls. Thirty GDM patients (18-42 years, between the 24th and 37th week of pregnancy, recently diagnosed, not under insulin therapy) were also selected. Thirty healthy pregnant (18-42years, between the 24th and 37th week of pregnancy) and 30 healthy non-pregnant women (18-42years) were selected as controls. Random midstream urine was used. hK1 amidase activity was estimated with D-Val-Leu-Arg-Nan substrate. Creatinine was determined by Jaffe's method. hK1 specific amidase activity was expressed as µM/(minmg creatinine) to correct for differences in urine flow rate. hK1 specific amidase activity was significantly higher in the urine of type 1 DM than in controls, and in the urine of GDM patients than in healthy pregnant women and healthy non-pregnant women, respectively. The data suggest that hyperglycemia, rather than insulin, is involved in the mechanism of increased hK1 specific amidase activity in both type 1 DM and GDM patients, respectively.