Immunological Adaptations to Pregnancy in Women with Type 1 Diabetes.
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ABSTRACT:
SUBMITTER: Groen B
PROVIDER: S-EPMC4585728 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:AIMS/HYPOTHESIS:The aim of this study was to explore the association between type 1 diabetes and reproductive health indicators in women, focusing on termination of pregnancy and sterilisation. METHODS:We conducted a registry-based cohort study involving 2281 women with childhood-onset type 1 diabetes, matched for age and birthplace with women without diabetes: two control participants for each woman with diabetes. We compared the frequencies of termination of pregnancy and sterilisation over a 25 year period between women with type 1 diabetes and women without, and estimated standardised incidence ratios (SIRs). Smoothed age and period effects in the incidence of termination of pregnancy or sterilisation were tested statistically. RESULTS:There were more terminations of pregnancy (SIR 1.67; 95% CI 1.51, 1.86) and sterilisations (SIR 1.69; 95% CI 1.56, 1.83) in women with diabetes than in control women. During recent years, sterilisations in women with diabetes have decreased and the difference compared with control women has vanished. The indications for both procedures showed a statistically highly significant difference: maternal medical indications were almost absent (< 1%) in procedures among control women, but comprised 23.6% of terminations of pregnancy and 22.9% of sterilisations in women with diabetes. CONCLUSIONS/INTERPRETATION:The indications for termination of pregnancy and sterilisation are different in women with diabetes compared with other women. Pregnancies in women with type 1 diabetes are still terminated more often than in women without diabetes, but the difference in sterilisation rates has disappeared during recent years.
| S-EPMC6448903 | biostudies-other
Project description:AimsTo examine maternal fear of hypoglycaemia, glycaemia and pregnancy outcomes in women with impaired and normal awareness of hypoglycaemia.MethodsA pre-planned sub-study of 214 pregnant women with type 1 diabetes who participated in the CONCEPTT trial. Participants completed hypoglycaemia fear surveys (HFS-II) at baseline. Logistic regression and Poisson regression analyses were used to obtain an adjusted estimate for the rate ratio relating awareness to the number of severe hypoglycaemic episodes, and for several neonatal outcomes in relation to the total HFS-II score. The role of continuous glucose monitoring (CGM) use was examined.ResultsOverall, 30% of participants reported impaired awareness of hypoglycaemia (n = 64). Women with impaired awareness of hypoglycaemia had more episodes of severe hypoglycaemia (mean 0.44 vs. 0.08, p < 0.001) (12-34 weeks gestation) and scored higher on the HFS-II scale (43.7 vs. 36.0, p 0.008), indicating more fear of hypoglycaemia. They spent more time below range (CGM <3.5 mmol/L) and exhibited more glycaemic variability at 12 weeks gestation. Higher overall HFS-II scores were associated with a higher risk of maternal severe hypoglycaemia episodes (Rate Ratio 1.78, 95% CI 1.39-2.27). Women with impaired awareness of hypoglycaemia had less maternal weight gain but there were no differences in neonatal outcomes between women with impaired awareness of hypoglycaemia and normal hypoglycaemia awareness. Higher HFS-II scores were associated with more nephropathy (Odds Ratio 1.91, 95% CI 1.06-3.4). CGM use after 12 weeks was not associated with the number of episodes of severe hypoglycaemia (RR 0.75, 95% CI 0.49-1.15; p = 0.18).ConclusionsIn pregnant women with type 1 diabetes, impaired awareness of hypoglycaemia is associated with more maternal severe hypoglycaemia episodes and more fear of hypoglycaemia. Having impaired awareness of hypoglycaemia and/or fear of hypoglycaemia should alert clinicians to this increased risk. Reassuringly, there was no increase in adverse neonatal outcomes.
| S-EPMC9305507 | biostudies-literature
Project description:OBJECTIVE:To examine time trends in US pregnant women with type 1 diabetes mellitus for maternal characteristics and pregnancy outcomes. STUDY DESIGN:We abstracted clinical data from the medical records of 700 pregnant women from 2004 to 2017. For each time period, means and percentages were calculated. P values for trend were calculated using linear and logistic regression. RESULTS:HbA1c in each trimester was unchanged across the analysis period. The prevalence of nephropathy decreased from 4.8% to 0% (P?=?0.002). Excessive gestational weight gain increased (P?=?0.01). Gestation length also increased (P?=?0.01), as did vaginal deliveries (P?=?0.03). There were no change in birthweight over time (P?=?0.07) and the percentage of neonates with macrosomia and large for gestational age (LGA) neonates also remained unchanged. CONCLUSION:Obstetric guideline changes may have improved gestation length and mode of delivery; however, other outcomes need more attention, including excessive gestational weight gain, macrosomia, and LGA.
| S-EPMC7375951 | biostudies-literature
Project description:Approximately, 35% of women with Gestational Diabetes (GDM) progress to Type 2 Diabetes (T2D) within 10 years. However, links between GDM and T2D are not well understood. We used a well-characterised GDM prospective cohort of 1035 women following up to 8 years postpartum. Lipidomics profiling covering >1000 lipids was performed on fasting plasma samples from participants 6-9 week postpartum (171 incident T2D vs. 179 controls). We discovered 311 lipids positively and 70 lipids negatively associated with T2D risk. The upregulation of glycerolipid metabolism involving triacylglycerol and diacylglycerol biosynthesis suggested activated lipid storage before diabetes onset. In contrast, decreased sphingomyelines, hexosylceramide and lactosylceramide indicated impaired sphingolipid metabolism. Additionally, a lipid signature was identified to effectively predict future diabetes risk. These findings demonstrate an underlying dyslipidemia during the early postpartum in those GDM women who progress to T2D and suggest endogenous lipogenesis may be a driving force for future diabetes onset.
| S-EPMC7417169 | biostudies-literature
Project description:The aim of this study was to verify the incidence on the development of type 2 diabetes in women with previous gestational diabetes with and without periodontitis after a three-year time interval.Initial sample of this follow-up study consisted of 90 women diagnosed with gestational diabetes who underwent periodontal examination. After three years, 49 women were subjected to new periodontal examination and biological, behavioral, and social data of interest were collected. Additionally, the quantification of the C-reactive protein in blood samples was performed. Fasting glucose and glycated hemoglobin levels were requested. Saliva samples were collected for quantification of interleukin 6 and 10, tumor necrosis factor α, matrix metalloproteinase 2 and 9.The incidence of type 2 diabetes mellitus was 18.4% and of periodontitis was 10.2%. There was no significant difference in the incidence of type 2 diabetes mellitus among women with and without periodontitis. It was observed impact of C-reactive protein in the development of type 2 diabetes mellitus. However, it was not observed impact of periodontitis on the development of type 2 diabetes mellitus among women with previous gestational diabetes.It was not observed impact of periodontitis on the development of type 2 diabetes among women with previous gestational diabetes. The impact of C-reactive protein in the development of type 2 diabetes mellitus highlights the importance of an inflammatory process in the diabetes pathogenesis.
| S-EPMC5393533 | biostudies-other
Project description:Current approaches aiming to cure type 1 diabetes (T1D) have made a negligible number of patients insulin-independent. In this review, we revisit the role of stem cell (SC)-based applications in curing T1D. The optimal therapeutic approach for T1D should ideally preserve the remaining β-cells, restore β-cell function, and protect the replaced insulin-producing cells from autoimmunity. SCs possess immunological and regenerative properties that could be harnessed to improve the treatment of T1D; indeed, SCs may reestablish peripheral tolerance toward β-cells through reshaping of the immune response and inhibition of autoreactive T-cell function. Furthermore, SC-derived insulin-producing cells are capable of engrafting and reversing hyperglycemia in mice. Bone marrow mesenchymal SCs display a hypoimmunogenic phenotype as well as a broad range of immunomodulatory capabilities, they have been shown to cure newly diabetic nonobese diabetic (NOD) mice, and they are currently undergoing evaluation in two clinical trials. Cord blood SCs have been shown to facilitate the generation of regulatory T cells, thereby reverting hyperglycemia in NOD mice. T1D patients treated with cord blood SCs also did not show any adverse reaction in the absence of major effects on glycometabolic control. Although hematopoietic SCs rarely revert hyperglycemia in NOD mice, they exhibit profound immunomodulatory properties in humans; newly hyperglycemic T1D patients have been successfully reverted to normoglycemia with autologous nonmyeloablative hematopoietic SC transplantation. Finally, embryonic SCs also offer exciting prospects because they are able to generate glucose-responsive insulin-producing cells. Easy enthusiasm should be mitigated mainly because of the potential oncogenicity of SCs.
| S-EPMC3591677 | biostudies-literature
Project description:The incidence of both gestational and pre-gestational diabetes is increasing worldwide. The main cause of this increase is likely the concomitant increase in the incidence of global obesity, but in the case of gestational diabetes, changes in the diagnostic criteria are also a contributing factor. The adverse outcomes associated with pre-gestational diabetes are well known and have led clinicians to implement various strategies that include increased fetal surveillance and induction of labour at various gestational ages. In many cases these same strategies have been applied in clinical practice also to women with gestational diabetes despite there being differences in the type and magnitude of perinatal complications associated with this diagnosis. Despite the widespread application of these clinical practices, there is a paucity of quality data in the medical literature to guide the clinician in choosing a strategy for fetal surveillance and timing of delivery in both gestational diabetes and pre-gestational diabetes pregnancies. In the following review, we will discuss the rationale and consequences of planned delivery in gestational diabetes and pre-gestational diabetes, the evidence supporting different strategies for delivery and finally highlight future targets for research in this area.
| S-EPMC4934937 | biostudies-other
Project description:The incidence of type 2 diabetes in pregnancy is rising and rates of serious adverse maternal and fetal outcomes remain high. Metformin is a biguanide that is used as first-line treatment for non-pregnant patients with type 2 diabetes. We hypothesize that metformin use in pregnancy, as an adjunct to insulin, will decrease adverse outcomes by reducing maternal hyperglycemia, maternal insulin doses, maternal weight gain and gestational hypertension/pre-eclampsia. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. Our aim is to compare the effectiveness of the addition of metformin to insulin, to standard care (insulin plus placebo) in women with type 2 diabetes in pregnancy.The MiTy trial is a multi-centre randomized trial currently enrolling pregnant women with type 2 diabetes, who are on insulin, between the ages of 18-45, with a gestational age of 6 weeks 0 days to 22 weeks 6 days. In this randomized, double-masked, parallel placebo-controlled trial, after giving informed consent, women are randomized to receive either metformin 1,000 mg twice daily or placebo twice daily. A web-based block randomization system is used to assign women to metformin or placebo in a 1:1 ratio, stratified for site and body mass index. The primary outcome is a composite neonatal outcome of pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, or neonatal intensive care unit admission longer than 24 h. Secondary outcomes are large for gestational age, cord blood gas pH?<?7.0, congenital anomalies, hyperbilirubinemia, sepsis, hyperinsulinemia, shoulder dystocia, fetal fat mass, as well as maternal outcomes: maternal weight gain, maternal insulin doses, maternal glycemic control, maternal hypoglycemia, gestational hypertension, preeclampsia, cesarean section, number of hospitalizations during pregnancy, and duration of hospital stays. The trial aims to enroll 500 participants.The results of this trial will inform endocrinologists, obstetricians, family doctors, and other healthcare professionals caring for women with type 2 diabetes in pregnancy, as to the benefits of adding metformin to insulin in this high risk population.ClinicalTrials.gov Identifier: no. NCT01353391 . Registered February 6, 2009.
| S-EPMC4952061 | biostudies-literature
Project description:AimTo describe trends in modifiable and non-modifiable unfavorable factors affecting pregnancy outcomes, over time (years 2004-2017), in women with diabetes of childbearing age from an English primary care perspective.MethodsWe identified women with diabetes aged 16-45 years from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network, an English primary care sentinel database. Repeated annual cross-sectional analyses (2004-2017) assessed the prevalence of unfavorable factors for pregnancy, such as obesity, poor glycaemic control, microalbuminuria, hypertension, use of medications for treating diabetes, and associated comorbidities not recommended for pregnancy.ResultsWe identified 3,218 women (61.5% with Type 2 diabetes) in 2004 and 6,657 (65.0% with Type 2 diabetes) in 2017. The proportion of women with ideal glycaemic control for conception (HbA1c<6.5%) increased over time, in patients with Type 1 diabetes from 9.0% (7.1%-11.0%) to 19.1% (17.2%-21.1%), and in those with Type 2 diabetes from 27.2% (24.6%-29.9%) to 35.4% (33.6%-37.1%). The proportion of women with Type 2 diabetes prescribed medications different from insulin and metformin rose from 22.3% (20.5%-24.2%) to 27.3% (26.0%-28.6%).In 2017, 14.0% (12.6%-15.4%) of women with Type 1 and 30.7% (29.3%-32.0%) with Type 2 diabetes were prescribed angiotensin-modulating antihypertensives or statins. We captured at least one unfavorable factor for pregnancy in 50.9% (48.8%-52.9%) of women with Type 1 diabetes and 70.7% (69.3%-72.0%) of women with Type 2 diabetes. Only one third of women with Type 1 diabetes (32.2%, 30.3%-34.0%) and a quarter of those with Type 2 diabetes (23.1%, 21.9%-24.4%) were prescribed hormonal contraception. Contraception was prescribed more frequently to women with unfavorable factors for pregnancy compared to those without, however, the difference was significant only for women with Type 1 diabetes.ConclusionsDespite significant improvements in general diabetes care, the majority of women with Type 1 or Type 2 diabetes have unfavorable, although mostly modifiable, factors for the start of pregnancy. Good diabetes care for women of childbearing age should include taking into consideration a possible pregnancy.
| S-EPMC7937966 | biostudies-literature
Project description:BackgroundWomen with history of hypertensive disorders of pregnancy (HDP) are at increased risk of early onset cardiovascular disease and type 2 diabetes (T2D). We aimed to investigate the extent to which HDP is also associated with midlife development of T2D and hypertension above and beyond established risk factors.MethodsWe included parous women who attended population-based structured clinical visits at age 50 and 60 years in Sweden 1991-2013 (N?=?6587). Women with prior diabetes mellitus, stroke, or ischemic heart disease at age 50 years were excluded. Data on reproductive history were collected from registries. To study the association between history of HDP and the between-visits development of T2D, hypertension, and clinical risk factors of cardiometabolic disease (body mass index (BMI), blood pressure, and total cholesterol), we utilized multivariable adjusted regression models (logistic, log binomial, and linear regression, respectively). Models included data on outcome risk factors at age 50 years, e.g. BMI, 75 g 2 h oral glucose tolerance test result, and mean arterial pressure, respectively.ResultsBetween ages 50 and 60 years, 5.8% of initially disease-free women developed T2D and 31.6% developed hypertension. History of HDP was associated with increased risk of developing T2D between age 50 and 60 years even when adjusting for risk factors, including BMI, at age 50 years (odds ratio (OR) 1.96, 95% confidence interval (CI) 1.29-2.98). By contrast, the higher risk of developing hypertension observed in women with history of HDP (relative risk (RR) 1.47, 95% CI 1.22-1.78) was attenuated when adjusted for risk factors (RR 1.09, 95% CI 0.94-1.25). Participants with a history of HDP had higher mean BMI and blood pressure at age 50 years, with levels roughly corresponding to those observed at age 60 years in unaffected women.ConclusionsWomen with history of HDP are not only at higher risk of cardiometabolic disease during their reproductive years, but HDP is also associated with midlife T2D development above and beyond established risk factors.
| S-EPMC6130069 | biostudies-literature