Epigenetic marks associated with gestational diabetes mellitus across two time points during pregnancy.

An adverse intrauterine or periconceptional environment, such as hyperglycemia during pregnancy, can affect the DNA methylation pattern both in mothers and their offspring. In this study, we explored the epigenetic profile in maternal peripheral blood samples through pregnancy to find potential epigenetic biomarkers for gestational diabetes mellitus (GDM), as well as candidate genes involved in GDM development. We performed an epigenome-wide association study in maternal peripheral blood samples in 32 pregnant women (16 with GDM and 16 non-GDM) at pregnancy week 24-28 and 36-38. Biochemical, anthropometric, and obstetrical variables were collected from all the participants. The main results were validated in an independent cohort with different ethnic origin (European = 307; South Asians = 165). Two hundred and seventy-two CpGs sites remained significantly different between GDM and non-GDM pregnant women across two time points during pregnancy. The significant CpG sites were related to pathways associated with type I diabetes mellitus, insulin resistance and secretion. Cg01459453 (SELP gene) was the most differentiated in the GDM group versus non-GDM (73.6 vs. 60.9, p = 1.06E-11; FDR = 7.87E-06). Three CpG sites (cg01459453, cg15329406, and cg04095097) were able to discriminate between GDM cases and controls (AUC = 1; p = 1.26E-09). Three differentially methylated positions (DMPs) were replicated in an independent cohort. To conclude, epigenetic marks during pregnancy differed between GDM cases and controls suggesting a role for these genes in GDM development. Three CpGs were able to discriminate GDM and non-GDM groups with high specificity and sensitivity, which may be biomarker candidates for diagnosis or prediction of GDM.

Epigenome wide association study in peripheral blood of pregnant women identifies potential metabolic pathways related to gestational diabetes.

Gestational diabetes mellitus (GDM) increases the risk of developing metabolic disorders in both pregnant women and their offspring. Factors such as nutrition or the intrauterine environment may play an important role, through epigenetic mechanisms, in the development of GDM. The aim of this work is to identify epigenetic marks involved in the mechanisms or pathways related to gestational diabetes. A total of 32 pregnant women were selected, 16 of them with GDM and 16 non-GDM. DNA methylation pattern was obtained from Illumina Methylation Epic BeadChip, from peripheral blood samples at the diagnostic visit (26-28 weeks). Differential methylated positions (DMPs) were extracted using ChAMP and limma package in R 2.9.10, with a threshold of FDR <0.05, deltabeta >|5|% and B >0. A total of 1.141 DMPs were found, and 714 were annotated in genes. A functional analysis was performed, and we found 23 genes significantly related to carbohydrate metabolism. Finally, a total of 27 DMPs were correlated with biochemical variables such as glucose levels at different points of oral glucose tolerance test, fasting glucose, cholesterol, HOMAIR and HbA1c, at different visits during pregnancy and postpartum. Our results show that there is a differentiated methylation pattern between GDM and non-GDM. Furthermore, the genes annotated to the DMPs could be implicated in the development of GDM as well as in alterations in related metabolic variables.

Changes in Oxidative Stress and Intestinal Permeability during Pregnancy in Women with Gestational Diabetes Mellitus Treated with Metformin or Insulin and Healthy Controls: A Randomized Controlled Trial.

Both oxidative stress and intestinal permeability are increased in hyperglycemic situations and have been shown to be reduced by metformin in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to elucidate the effect of metformin on oxidative stress and intestinal permeability in women with gestational diabetes mellitus (GDM) treated with metformin compared to those treated with insulin and healthy controls. A total of 120 women were included from August 2016 to February 2022: 41 received metformin (MET group), 38 received insulin (INS group), and 41 were healthy controls. Baseline and antenatal visits were carried out at 25.4 ± 4.8 and 36.1 ± 0.8 weeks of pregnancy, respectively. Advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and zonulin levels were measured at every visit. Zonulin levels from baseline to prepartum visit increased significantly in both healthy controls (0.6 ± 0.9 to 1.2 ± 1.7 ng/mL, p = 0.004) and the INS group (0.4 ± 0.3 to 0.6 ± 0.5 ng/mL, p = 0.034) but did not significantly change in the MET group (0.4 ± 0.4 to 0.5 ± 0.4 ng/mL, p = 0.202). However, TAC and AOPP levels significantly increased in women with GDM, both in the INS and MET groups but not in the healthy controls. In conclusion, in our population, metformin has been shown to avoid an increase in intestinal permeability but failed to avoid an increase in oxidative stress related to hyperglycemia.

Metformin action over gut microbiota is related to weight and glycemic control in gestational diabetes mellitus: A randomized trial.

BACKGROUND: Metformin, which is known to produce profound changes in gut microbiota, is being increasingly used in gestational diabetes mellitus (GDM). The aim of this study was to elucidate the differences in gut microbiota composition and function in women with GDM treated with metformin compared to those treated with insulin. METHODS: From May to December 2018, 58 women with GDM were randomized to receive insulin (INS; n = 28) or metformin (MET; n = 30) at the University Hospital Virgen de la Victoria, Málaga, Spain. Basal visits, with at least 1 follow-up visit and prepartum visit, were performed. At the basal and prepartum visits, blood and stool samples were collected. The gut microbiota profile was determined through 16S rRNA analysis. RESULTS: Compared to INS, women on MET presented a lower mean postprandial glycemia and a lower increase in weight and body mass index (BMI). Firmicutes and Peptostreptococcaceae abundance declined, while Proteobacteria and Enterobacteriaceae abundance increased in the MET group. We found inverse correlations between changes in the abundance of Proteobacteria and mean postprandial glycemia (p = 0.023), as well as between Enterobacteriaceae and a rise in BMI and weight gain (p = 0.031 and p = 0.036, respectively). Regarding the metabolic profile of gut microbiota, predicted metabolic pathways related to propionate degradation and ubiquinol biosynthesis predominated in the MET group. CONCLUSION: Metformin in GDM affects the composition and metabolic profile of gut microbiota. These changes could mediate, at least in part, its clinical effects. Studies designed to assess how these changes influence metabolic control during and after pregnancy are necessary.

Insulin Requirement for Gestational Diabetes Control Is Related to Higher Vitamin D Levels up to 1 Year Postpartum: A Prospective Cohort Study.

Vitamin D deficiency is highly prevalent in pregnant women and has been related to a higher risk of gestational diabetes mellitus (GDM). The aim of this study is to analyze vitamin D status evolution in a population of pregnant women with and without GDM. Two-hundred women were included from January 2019 to February 2022 as follows: Control group -CG-, Lifestyle group -LG- (GDM not requiring insulin), and Insulin group -IG- (GDM requiring insulin). Visits were carried out at baseline, antenatal, postpartum, and 1 year after birth. Vitamin D levels, weight, and insulin resistance were measured at every visit. Data about the season, vitamin D supplementation, Mediterranean diet adherence, and physical activity were included. In the three groups, 134 women were included in the CG, 43 in the LG, and 23 in the IG. Vitamin D levels were similar among the groups at baseline, but they were significantly higher in the LG and IG in comparison with the CG at the antenatal visit and significantly higher in the IG vs. CG and LG at the postpartum and 1 year after birth visits. Vitamin D levels were independently related to vitamin D supplementation and the season at baseline, to the season and belonging to the LG or IG at the antenatal visit, and were only independently associated with belonging to the IG at postpartum and 1 year after birth visits. In conclusion, in our population, women with GDM requiring insulin had higher levels of vitamin D in comparison with those not requiring insulin and healthy controls at postpartum and 1 year after pregnancy. Requiring insulin during pregnancy seems to be a factor that independently determines the levels of vitamin D until 1 year after birth. More studies are required to reproduce these data in other populations and to elucidate the mechanisms underlying these findings.

Impact of the Gestational Diabetes Diagnostic Criteria during the Pandemic: An Observational Study.

OBJECTIVE: To analyze the effect of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence and obstetrical and perinatal outcomes, in comparison to usual diagnostic approaches. METHODS: Data from women referred to GDM diagnosis from 1 September to 30 November 2019 were retrospectively collected (2019-group). The same data from the same period in 2020 were prospectively collected (2020-group). In both cases, a two-step diagnostic approach was used, the first step being a screening test (1 h 50 goral glucose tolerance test, OGTT). In 2019 it was followed by a 100 gr OGTT for diagnosis. In 2020, this was replaced by a blood test for the measurement of plasma glucose and HbA1c, according to alternative GDM diagnostic criteria during the COVID-19 pandemic. RESULTS: From 237 women in the 2019 group, 40 (16.9%) were diagnosed with GDM, while from 255 women in the 2020 group, 37 (14.5%) had GDM (p = 0.470). More women in the 2020 group, in comparison to the 2019 group, were nulligravid (41.9% vs. 47.2%, p = 0.013), had a personal history of GDM (11.4% vs. 4.6%, p = 0.013) and had macrosomia in previous pregnancies (10.2% vs. 2.1%, p = 0.001). Obstetrical and perinatal outcomes were similar when comparing women with GDM to non-GDM women in the 2019 and 2020 groups and between GDM women and non-GDM women. CONCLUSION: In a Spanish population, GDM prevalence during the COVID-19 pandemic using the alternative diagnostic criteria was similar to that found in 2019 using the usual diagnostic criteria. Despite women referred for GDM diagnosis during the pandemic having more GDM risk factors, obstetrical and perinatal outcomes were comparable to those observed before the pandemic.

Relationship between environmental temperature and the diagnosis and treatment of gestational diabetes mellitus: An observational retrospective study.

INTRODUCTION: Environmental temperature has been described to affect plasma glucose levels after oral glucose tolerance testing (OGTT). AIMS: We evaluated the relationship between seasons and environmental temperature and gestational diabetes mellitus (GDM) diagnosis and treatment. METHODS: We analyzed data from 2374 women retrospectively. GDM was diagnosed in 473 patients by a 100-g OGTT. OGTT results and needing of insulin therapy were evaluated in relation to seasons and environmental temperature (mean temperature and temperature change) the day of the OGTT and the preceding 14 and 28 days. RESULTS: We found significant seasonal differences in the percentage of GDM: 24.4% in summer vs. 15.6% in autumn (p < 0.01). The odds ratio (OR) for being diagnosed with GDM was 1.78 in summer relative to autumn, after controlling for age. A higher mean temperature the day of the OGTT and the preceding 14 and 28 days increased the risk of being diagnosed with GDM the months in which temperature was rising (March-August) but not the months in which temperature was decreasing (September-February). We observed a negative correlation between temperature and fasting glucose and a positive correlation with post-load glucose. Neither the season nor the environmental temperature affected the risk of requiring insulin therapy. CONCLUSIONS: There is a higher prevalence of GDM diagnosis at warmer seasons and at rising temperatures the 2-4 weeks prior to the OGTT. The impact of temperature is different between fasting and post-load glucose.

Comparison of the Effects of Goat Dairy and Cow Dairy Based Breakfasts on Satiety, Appetite Hormones, and Metabolic Profile.

The satiating effects of cow dairy have been thoroughly investigated; however, the effects of goat dairy on appetite have not been reported so far. Our study investigates the satiating effect of two breakfasts based on goat or cow dairy and their association with appetite related hormones and metabolic profile. Healthy adults consumed two breakfasts based on goat (G-Breakfast) or cow (C-Breakfast) dairy products. Blood samples were taken and VAS tests were performed at different time points. Blood metabolites were measured and Combined Satiety Index (CSI) and areas under the curves (AUC) were calculated. Desire to eat rating was significantly lower (breakfast & time interaction p < 0.01) and hunger rating tended to be lower (breakfast & time interaction p = 0.06) after the G-breakfast. None of the blood parameters studied were different between breakfasts; however, AUCGLP-1 was inversely associated with the AUChunger and AUCdesire-to-eat after the G-Breakfast, whereas triglyceride levels were directly associated with AUCCSI after the C-Breakfast. Our results suggest a slightly higher satiating effect of goat dairy when compared to cow dairy products, and pointed to a potential association of GLP-1 and triglyceride levels with the mechanisms by which dairy products might affect satiety after the G-Breakfast and C-Breakfast, respectively.