Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy.

BACKGROUND: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. METHODS: To identify DMRs, we employed the bump hunter method in samples from young (9-16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28-33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. RESULTS: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. CONCLUSIONS: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.

Hemoglobin A1c Trajectories During Pregnancy and Adverse Outcomes in Women With Type 2 Diabetes: A Danish National Population-Based Cohort Study.

OBJECTIVE: To identify and characterize groups of pregnant women with type 2 diabetes with distinct hemoglobin A1c (HbA1c) trajectories across gestation and to examine the association with adverse obstetric and perinatal outcomes. RESEARCH DESIGN AND METHODS: This was a retrospective Danish national cohort study including all singleton pregnancies in women with type 2 diabetes, giving birth to a liveborn infant, between 2004 and 2019. HbA1c trajectories were identified using latent class linear mixed-model analysis. Associations with adverse outcomes were examined with logistic regression models. RESULTS: A total of 1,129 pregnancies were included. Three HbA1c trajectory groups were identified and named according to the glycemic control in early pregnancy (good, 59%; moderate, 32%; and poor, 9%). According to the model, all groups attained an estimated HbA1c <6.5% (48 mmol/mol) during pregnancy, with no differences between groups in the 3rd trimester. Women with poor glycemic control in early pregnancy had lower odds of having an infant with large for gestational age (LGA) birth weight (adjusted odds ratio [aOR] 0.57, 95% CI 0.40-0.83), and higher odds of having an infant with small for gestational age (SGA) birth weight (aOR 2.49, 95% CI 2.00-3.10) and congenital malformation (CM) (aOR 4.60 95% CI 3.39-6.26) compared with women with good glycemic control. There was no evidence of a difference in odds of preeclampsia, preterm birth, and caesarean section between groups. CONCLUSIONS: Women with poor glycemic control in early pregnancy have lower odds of having an infant with LGA birth weight, but higher odds of having an infant with SGA birth weight and CM.

Do WHO criteria for gestational diabetes fit a rural population in Tanzania? - A follow-up study assessing mother and child health six years after a pregnancy diagnosed with gestational diabetes.

AIMS AND METHODS: In low- and middle- income countries (LMICs) consequences of gestational diabetes (GDM) is understudied. Using a prospective cohort of mothers (n = 197)and children (n = 251), from rural north-eastern Tanzania, we assessed prediabetes and type 2 diabetes (T2D) prevalence six years after a pregnancy with/without GDM. RESULTS: The prevalence of prediabetes (49.4 % vs. 46.4 %) orT2D (20.0 % vs. 16.1 %), p ≥ 0.36, based on fasting plasma glucose (FPG) or HbA1clevels (prediabetes: 16.9 % vs. 13.8 % and T2D 1.2 % vs. 0 %, p = 0.47), andcardio-metabolic health parameters,weresimilar between women with/without previous GDM. These results were supported by similar perinatal outcomes and child health at follow-up.The overall prevalence ofprediabetes/T2D was high, but no differences in other cardio-metabolic risk markers were observed in women with prediabetes/T2D compared to women with normal glucose tolerance. CONCLUSIONS: Despite high prevalence of GDM amongTanzanian women, the diagnosis was not associated with adverse pregnancy outcomes, nor with increased risk of prediabetes or T2D at follow-up. FPG and HbA1c may be poor markers for diabetes in this population, and further follow-up studies with longer time intervals are warranted to evaluate which GDM diagnostic criteria are most optimal for women in rural Tanzania and similar LMIC settings.

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Early-onset vs late-onset preeclampsia and risk of coronary atherosclerosis later in life: a clinical follow-up study.

BACKGROUND: Younger women with previous preeclampsia have an increased risk of coronary atherosclerosis. It is unknown if this risk is associated with the time of onset of preeclampsia. OBJECTIVE: This study aimed to investigate if women with early-onset preeclampsia have a higher risk of coronary atherosclerosis compared with women with late-onset preeclampsia, independent of other perinatal risk factors. STUDY DESIGN: A total of 911 women with previous preeclampsia aged 35 to 55 years participated in a clinical follow-up study, including clinical examination, comprehensive questionnaires, and cardiac computed tomography scan 13 years (range, 0-28) after index pregnancy. Early- and late-onset preeclampsia were defined as gestational age at delivery of <34+0 and ≥34+0 gestational weeks, respectively. The primary outcome of the study was the presence of coronary atherosclerosis on the cardiac computed tomography. A logistic regression analysis was performed to investigate the association between time of onset of preeclampsia, perinatal risk factors, and the primary outcome. RESULTS: Women with early-onset preeclampsia (N=139) were older (46.2±5.7 vs 44.4±5.5 years; P<.001), more likely to have hypertension (51.1% vs 35.1%; P≤.001), and had a higher body mass index (27.9±6.3 vs 26.9±5.5 kg/m2; P=.051) compared with women with late-onset preeclampsia (N=772) at follow-up. The prevalence of the primary outcome (coronary atherosclerosis) on the cardiac computed tomography among women with early- and late-onset preeclampsia was 28.8% vs 22.2%, respectively (P=.088; adjusted odds ratio, 1.74; 95% confidence interval, 1.01-3.01; P=.045 after adjustment for maternal age at index pregnancy, prepregnancy body mass index, parity, diabetes in pregnancy, smoking in pregnancy, offspring birthweight and sex, and follow-up length). CONCLUSION: Women with early-onset preeclampsia had a slightly higher risk of coronary atherosclerosis compared with women with late-onset preeclampsia. However, according to the current evidence, it does not seem indicated to limit screening, diagnostic, and preventive measures for cardiovascular disease only to women with early-onset preeclampsia.

Type 2 diabetes risk after gestational diabetes according to country/region of origin. A nationwide register-based study.

CONTEXT: The risk of gestational diabetes mellitus (GDM) differs between the Danish population and several migrant groups. However, it is unclear if the incidence and timing of type 2 diabetes mellitus (T2DM) following GDM vary similarly. OBJECTIVE: To investigate the incidence of T2DM according to migration background based on country/region of origin among women with a previous GDM diagnosis and explore the role of time since GDM diagnosis on the association. METHOD: Using nationwide registry data, we followed women diagnosed with GDM in Denmark during 2004-2018 to Dec 31, 2020. Poisson regression models were used to estimate incidence rates (IRs) of T2DM according to country/region of origin, adjusted for age, education, and body mass index. RESULTS: The study included 20,873 women with a GDM diagnosis, of whom 22.3% were of migrant background and 77.7% were Danish. The mean follow-up time was 7.3 years, and 10.9% were registered with T2DM during the study period. Generally, migrant women had higher IRs of T2DM compared to Danish women, with substantial variations in risk between migrant groups. Women from Pakistan and Sri Lanka had three-four times higher IRs compared to Danish women. The timing of T2DM onset also varied, with women from Sri Lanka and Pakistan having an earlier onset of T2DM compared to other migrant and Danish women. CONCLUSION: This study demonstrated that country/region of origin is an important risk factor for T2DM in women with GDM. These findings underscore the importance of prevention programs targeting women with GDM and a high-risk origin.

Pre-analytical diagnostic differences despite high adherence to guidelines for gestational diabetes mellitus.

Regional variations in the prevalence of gestational diabetes mellitus (GDM) have been found across Denmark. The objectives of this exploratory survey were to evaluate adherence to the national guideline for screening and diagnosing GDM and to identify variations in pre-analytical or analytical factors, which could potentially contribute to variations in GDM prevalence across regions. In a national interview-based survey, obstetric departments and laboratories throughout Denmark handling GDM screening or diagnostic testing were invited to participate. Survey questionnaires were completed through personal interviews. In total, 21 of 22 identified obstetric departments and 44 of 45 identified laboratories participated. Adherence to guideline among obstetric departments ranged 67-100% and uniformity in laboratory procedures was high. However, the gestational age at the time of late diagnostic testing with oral glucose tolerance test (OGTT) varied considerably, with 48% (10/21) of departments testing outside the recommended 24-28 weeks' gestation. Procedural heterogeneity was most pronounced for the parts not described in current guidelines, with choice of laboratory equipment being the most diverse factor ranging 3-39% nationally. In conclusion, the overall adherence to the national guidelines was high across regions, and obstetric departments and laboratories had high uniformity in the procedures for screening and diagnosing GDM. Uniformity was generally high for procedures included in the guideline and low if not included. However, a high proportion of GDM testing was performed outside the recommended gestational window in late pregnancy, which may be a pre-analytical contributor to regional differences in GDM prevalence.

Mean Glucose and Gestational Weight Gain as Predictors of Large-for-Gestational-Age Infants in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitoring.

Aims/hypothesis: To compare glycemic metrics during pregnancy between women with type 1 diabetes (T1D) delivering large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants, and to identify predictors of LGA infants. Materials and Methods: A cohort study including 111 women with T1D using intermittently scanned continuous glucose monitoring from conception until delivery. Average sensor-derived metrics: mean glucose, time in range in pregnancy (TIRp), time above range in pregnancy, time below range in pregnancy, and coefficient of variation throughout pregnancy and in pregnancy intervals of 0-10, 11-21, 22-33, and 34-37 weeks were compared between women delivering LGA and AGA infants. Predictors of LGA infants were sought for. Infant growth was followed until 3 months postdelivery. Results: In total, 53% (n = 59) delivered LGA infants. Mean glucose decreased during pregnancy in both groups, with women delivering LGA infants having a 0.4 mmol/L higher mean glucose from 11-33 weeks (P = 0.01) compared with women delivering AGA infants. Mean TIRp >70% was obtained from 34 weeks in women delivering LGA infants and from 22-33 weeks in women delivering AGA infants. Independent predictors for delivering LGA infants were mean glucose throughout pregnancy and gestational weight gain. At 3 months postdelivery, infant weight was higher in infants born LGA compared with infants born AGA (6360 g ± 784 and 5988 ± 894, P = 0.04). Conclusions/interpretations: Women with T1D delivering LGA infants achieved glycemic targets later than women delivering AGA infants. Mean glucose and gestational weight gain were independent predictors for delivering LGA infants. Infants born LGA remained larger postdelivery compared with infants born AGA.

Childhood adversity and the risk of gestational diabetes: A population-based cohort study of nulliparous pregnant women.

AIMS: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications, and though it may be linked to childhood adversity, the effect of different types of adversity remains unclear. Childhood adversity is linked to a younger maternal age, which may hide the overall impact of adversity on GDM risk. We therefore aimed to explore the association between different types of childhood adversity and GDM while accounting for the potential impact of maternal age. METHODS: We used Danish nation-wide register data, including 208,207 women giving birth for the first time from 2004 to 2018. Five adversity groups were used to examine the effect of childhood adversity on GDM risk: (1) low (referent group), (2) early life material deprivation, (3) persistent deprivation, (4) loss or threat of loss within the family and (5) high adversity. RESULTS: 5375 women were diagnosed with GDM in the study population (2.6% absolute risk). Compared to women who experienced low adversity, the other adversity groups had a higher GDM risk (absolute difference [%]) directly; early material deprivation (0.64% [95% CI 0.44; 0.84]), persistent deprivation (0.63% [0.41; 0.86]), loss or threat of loss (0.73% [0.42; 1.05]) and high adversity (0.80% [0.32; 1.27]). The indirect effect of maternal age attenuated the total effect of childhood adversity on GDM by an absolute difference of 0.25%-0.46%. CONCLUSIONS: Experiencing childhood adversity to any extent is associated with a higher risk of GDM. Interventions aimed at preventing childhood adversity may have a positive effect in reducing GDM burden and the associated health risks.

Liraglutide treatment for the prevention of glucose tolerance deterioration in women with prior gestational diabetes mellitus: A 52-week randomized controlled clinical trial.

AIM: We investigated the effect of 52-week treatment with liraglutide, a glucagon-like peptide 1 receptor agonist, on glucose tolerance and incretin effect in women with previous gestational diabetes mellitus (pGDM). MATERIALS AND METHODS: Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash-out. RESULTS: In total, 104 women [age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2 ] were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was -173 (95% confidence interval -250 to -97) mmol/L × min, p < .0001, but after wash-out the difference disappeared [ETD 58 (-30 to 146) mmol/L × min, p = .536]. Liraglutide reduced FPG [ETD -0.2 (-0.4 to -0.1) mmol/L, p = .018], HbA1c [-2.2 (-3.5 to -0.8) mmol/mol, p = .018] and bodyweight [-3.9 (-6.2 to -1.6) kg, p = .012]. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo [adjusted odds ratio 0.10 (0.03-0.32), p = .002]. CONCLUSIONS: Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1-week drug wash-out, the effect was lost.

Fetal Overgrowth and Preterm Delivery in Women With Type 1 Diabetes Using Insulin Pumps or Multiple Daily Injections: A Post Hoc Analysis of the EVOLVE Study Cohort.

OBJECTIVE: To compare the risk of fetal overgrowth and preterm delivery in pregnant women with type 1 diabetes (T1D) treated with insulin pumps versus multiple daily injections (MDI) and examine whether possible differences were mediated through improved glycemic control or gestational weight gain during pregnancy. RESEARCH DESIGN AND METHODS: The risk of pregnancy and perinatal outcomes were evaluated in a cohort of 2,003 pregnant women with T1D enrolled from 17 countries in a real-world setting during 2013-2018. RESULTS: In total, 723 women were treated with pumps and 1,280 with MDI. At inclusion (median gestational weeks 8.6 [interquartile range 7-10]), pump users had lower mean HbA1c (mean ± SD 50.6 ± 9.8 mmol/mol [6.8 ± 0.9%] vs. 53.6 ± 13.8 mmol/mol [7.1 ± 1.3%], P < 0.001), longer diabetes duration (18.4 ± 7.8 vs. 14.4 ± 8.2 years, P < 0.001), and higher prevalence of retinopathy (35.3% vs. 24.4%, P < 0.001). Proportions of large for gestational age (LGA) offspring and preterm delivery were 59.0% vs. 52.2% (adjusted odds ratio [OR] 1.36 [95% CI 1.09; 1.70], P = 0.007) and 39.6% vs. 32.1% (adjusted OR 1.46 (95% CI 1.17; 1.82), P < 0.001), respectively. The results did not change after adjustment for HbA1c or gestational weight gain. CONCLUSIONS: Insulin pump treatment in pregnant women with T1D, prior to the widespread use of continuous glucose monitoring or automated insulin delivery, was associated with a higher risk of LGA offspring and preterm delivery compared with MDI in crude and adjusted analyses. This association did not appear to be mediated by differences in glycemic control as represented by HbA1c or by gestational weight gain.

Faster-acting insulin aspart versus insulin aspart in the treatment of type 1 or type 2 diabetes during pregnancy and post-delivery (CopenFast): an open-label, single-centre, randomised controlled trial.

BACKGROUND: Faster-acting insulin aspart (faster aspart) is considered safe for use during pregnancy and breastfeeding but has not been evaluated in this population. We aimed to evaluate the effect of faster aspart versus insulin aspart on fetal growth, in women with type 1 or type 2 diabetes during pregnancy and post-delivery. METHODS: This open-label, single-centre, superiority trial was conducted at Rigshospitalet, Copenhagen, Denmark. Participants aged 18 years or older with type 1 or type 2 diabetes were stratified by diabetes type and insulin treatment modality (multiple daily injections or insulin pump), randomly assigned 1:1 to faster aspart or insulin aspart, from 8 weeks and 0 days (8+0) of gestation to 13+6 weeks of gestation, and followed up until 3 months post-delivery. Primary outcome was infant birthweight SD score. Secondary outcomes included HbA1c as well as maternal and fetal outcomes in all participants during the trial. This trial is registered with ClinicalTrials.gov, NCT03770767. FINDINGS: Between Nov 11, 2019 and May 10, 2022, 109 participants were included in the faster aspart group and 107 in the insulin aspart group. Primary outcome data were available in 203 (94%) of 216 participants, and no participants discontinued treatment during the trial. Mean birthweight SD score was 1·0 (SD 1·4) in the faster aspart group versus 1·2 (1·3) in the insulin aspart group; estimated treatment difference -0·22 [-0·58 to 0·14]; p=0·23. At 33 weeks of gestation, mean HbA1c was 42 mmol/mol (SD 6 mmol/mol; 6·0% [SD 0·9%]) versus 43 mmol/mol (SD 7 mmol/mol; 6·1% [SD 1·2%]); estimated treatment difference -1·01 (-2·86 to 0·83), p=0·28. No additional safety issues were observed with faster aspart compared with insulin aspart. INTERPRETATION: Treatment with faster aspart resulted in similar fetal growth and HbA1c, relative to insulin aspart, in women with type 1 or type 2 diabetes. Faster aspart can be used in women with type 1 or type 2 diabetes during pregnancy and post-delivery with no additional safety issues. FUNDING: Novo Nordisk. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Health promotion intervention among women with recent gestational diabetes mellitus: penetration, participation, and baseline findings from the Face-it randomized controlled trial.

INTRODUCTION: Face-it is a randomized controlled trial for women with recent gestational diabetes mellitus (GDM) and their families designed to evaluate the effect of a health promotion intervention on type 2 diabetes mellitus (T2DM) risk and quality of life. This study examined (1) the penetration and participation rates for the Face-it trial, (2) the characteristics of the participating women and the potential differences in characteristics according to partner participation status, and (3) representativity of the women at baseline. RESEARCH DESIGN AND METHODS: We identified women with GDM during pregnancy and invited them and their partners to a baseline examination 10-14 weeks after delivery. Representativity was assessed by comparing the baseline participants with non-participating women, the general population of women with GDM delivering in Denmark, and populations from other intervention trials. RESULTS: The penetration rate was 38.0% (867/2279) and the participation rate was 32.9% (285/867). The 285 women who attended baseline had a mean age of 32.7 (±4.8) years and body mass index (BMI) of 28.1 (±5.4) kg/m2, and 69.8% had a partner who participated. The women participating with a partner were more often primiparous, born in Denmark (82.8% vs 68.2%), were younger, and more often had a BMI ≤24.9 kg/m2 (35.7% vs 21.2%) compared with women without a partner. Compared with the general population of women with GDM in Denmark, these women broadly had similar degree of heterogeneity, but had higher rates of primiparity and singleton deliveries, and lower rates of preterm delivery and prepregnancy obesity. CONCLUSIONS: The penetration and participation rates were acceptable. We found a high rate of partner participation. Overall, women participating with a partner were comparable with those participating without a partner. Participating women were broadly similar to the general national GDM population, however with prepregnancy obesity, multiparity, preterm delivery, and multiple pregnancy being less represented. TRIAL REGISTRATION NUMBER: NCT03997773.

Prediction and prevention of preeclampsia in women with preexisting diabetes: the role of home blood pressure, physical activity, and aspirin.

Women with type 1 or type 2 (preexisting) diabetes are four times more likely to develop preeclampsia compared with women without diabetes. Preeclampsia affects 9%-20% of pregnant women with type 1 diabetes and 7%-14% of pregnant women with type 2 diabetes. The aim of this narrative review is to investigate the role of blood pressure (BP) monitoring, physical activity, and prophylactic aspirin to reduce the prevalence of preeclampsia and to improve pregnancy outcome in women with preexisting diabetes. Home BP and office BP in early pregnancy are positively associated with development of preeclampsia, and home BP and office BP are comparable for the prediction of preeclampsia in women with preexisting diabetes. However, home BP is lower than office BP, and the difference is greater with increasing office BP. Daily physical activity is recommended during pregnancy, and limiting sedentary behavior may be beneficial to prevent preeclampsia. White coat hypertension in early pregnancy is not a clinically benign condition but is associated with an elevated risk of developing preeclampsia. This renders the current strategy of leaving white coat hypertension untreated debatable. A beneficial preventive effect of initiating low-dose aspirin (150 mg/day) for all in early pregnancy has not been demonstrated in women with preexisting diabetes.

A qualitative investigation into the perceptions and experiences of the stigma attached to gestational diabetes mellitus among women in Denmark.

AIM: The aim of this study was to explore the perceptions of women with gestational diabetes mellitus (GDM) in Denmark, with a particular focus on GDM-specific stigma. METHOD: We conducted semi-structured interviews with 20 women with GDM from January to May 2022. All interviews were transcribed and analysed abductively using Braun and Clarke's framework for applied reflexive analysis. RESULTS: Five themes were identified, 1) victim-blaming narrative, 2) identity threat, 3) non-disclosure and anticipated stigma, 4) stigma in a clinical setting, and 5) stigma reduction in a clinical setting. Additionally, intersectionality was identified between GDM-specific stigma, notions of how to be a good mother, and stigma associated with having type 2 diabetes mellitus and overweight. Implications of GDM-specific stigma included suboptimal GDM care and management, i.e., not attending screening for GDM, and not wanting to disclose the diagnosis. CONCLUSION: The impact of GDM-specific stigma on the informants' lives included some informants not accepting all services provided by the healthcare system, and some not wanting to identify with the diagnosis. These findings may help inform both healthcare personnel and future health promotion interventions to minimize the reproduction of a victim-blaming narrative and thereby promote well-being among women with GDM.

Applying WHO2013 diagnostic criteria for gestational diabetes mellitus reveals currently untreated women at increased risk.

AIMS: To estimate the prevalence of gestational diabetes mellitus (GDM) in a Danish cohort comparing the current Danish versus the WHO2013 diagnostic criteria, and to evaluate adverse pregnancy outcomes among currently untreated women in the gap between the diagnostic thresholds. METHODS: Diagnostic testing was performed by a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation in a cohort of pregnant women. GDM diagnosis was based on the current Danish criterion (2-h glucose ≥ 9.0 mmol/L, GDMDK) and on the WHO2013 criteria (fasting ≥ 5.1, 1 h ≥ 10.0 or 2 h glucose ≥ 8.5 mmol/L, GDMWHO2013). Currently untreated women fulfilling the WHO2013 but not the Danish diagnostic criteria were defined as New-GDM-women (GDMWHO2013-positive and GDMDK-negative). Adverse outcomes risks were calculated using logistic regression. RESULTS: OGTT was completed by 465 women at a median of 25.7 weeks' gestation. GDMDK prevalence was 2.2% (N = 10) and GDMWHO2013 21.5% (N = 100). New-GDM was present in 19.4% (N = 90), of whom 90.0% had elevated fasting glucose. Pregnancies complicated by New-GDM had higher frequencies of pregnancy-induced hypertension (13.3% vs 4.1%, p = 0.002), large-for-gestational-age infants (22.2% vs 9.9%, p = 0.004), neonatal hypoglycaemia (8.9% vs 1.9%, p = 0.004) and neonatal intensive care unit admission (16.7% vs 5.8%, p = 0.002) compared to pregnancies without GDM. CONCLUSIONS: GDM prevalence increased tenfold when applying WHO2013 criteria in a Danish population, mainly driven by higher fasting glucose levels. Untreated GDM in the gap between the current Danish and the WHO2013 diagnostic criteria resulted in higher risks of adverse pregnancy outcomes.

Maturity-onset diabetes of the young and pregnancy.

Maturity-onset diabetes of the young (MODY) is a group of hereditary monogenetic forms of diabetes. MODY accounts for 1-3% of all persons with diabetes but is often undiagnosed or misdiagnosed as type 1 diabetes, type 2 diabetes, or gestational diabetes. Diagnosing MODY is essential, as the most optimal treatment both during and outside of pregnancy depends on the MODY type. This review focuses on the outcome and treatment of the three most common types of MODY during pregnancy.

The impact of inter-laboratory glucose bias on the diagnosis of gestational diabetes mellitus: Comparison of common automated central laboratory methods.

BACKGROUND AND AIMS: The diagnosis of gestational diabetes mellitus (GDM) is based exclusively on glucose measurements, which are highly influenced by pre-analytical and analytical factors. Therefore, poor agreement across laboratories may affect the prevalence of GDM. We aimed to determine the inter-laboratory bias of glucose measurements and the impact on GDM prevalence. MATERIAL AND METHODS: A prospective cohort study of women (n = 110) referred for second-trimester GDM diagnostics using a 75 g oral glucose tolerance test. Maternal glucose was assessed from venous plasma at fasting, 1 h and 2 h. Venous blood were collected in Fluoride Citrate tubes and frozen. Samples were analyzed at five central laboratories using four different automated glucose Hexokinase methods and GDM prevalence was evaluated according to WHO2013 diagnostic criteria. RESULTS: Maximum inter-laboratory bias was 0.19, 0.30 and 0.27 mmol/L in fasting, 1 h and 2 h samples, respectively. GDM prevalence ranged 30.0-41.1% across laboratories. CONCLUSION: Inter-laboratory bias for mean venous glucose was low and within desirable limits. Nonetheless, the impact on GDM prevalence was considerable, which may inappropriately affect clinical practice.

Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Body Mass Index Trajectories in Children Exposed to Gestational Diabetes in Utero: A Nationwide Register-based Study.

CONTEXT: Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing overweight and obesity, but their postnatal growth trajectories and risk profiles remain unclear. OBJECTIVE: We aimed to identify distinct body mass index (BMI) trajectories from birth to 10 years of age in children exposed to GDM and to explore their associations with infant and maternal characteristics. METHODS: This nationwide cohort study linked data from Danish registries on 15 509 children exposed to GDM in utero, born in Denmark from January 2008 to October 2019. We applied latent class trajectory modeling to identify distinct BMI trajectories. Associations of BMI trajectories with infant and maternal characteristics were analyzed using multiple linear regression. RESULTS: We identified 3 distinct BMI trajectories characterized by a "normal" (60%), a "late accelerating" (28%) and an "early accelerating" (12%) BMI trajectory, the 2 latter at risk of overweight and obesity, respectively, at age 10 years, relative to World Health Organization child growth standards. Children in the "late accelerating" BMI trajectory were more often born large for gestational age (P < .001). More children in the "early accelerating" BMI trajectory were boys, born small for gestational age, and had mothers with a higher pre-pregnancy BMI compared to the other groups (P < .001). CONCLUSION: Children exposed to GDM in utero differ widely in their BMI trajectory. The detection of risk profiles based on early BMI growth and infant and maternal characteristics provides an opportunity for future targeted care and prevention.