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.

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.

Motivation for Behavior Change among Women with Recent Gestational Diabetes and Their Partners-A Qualitative Investigation among Participants in the Face-It Intervention.

Promoting diet and physical activity is important for women with recent gestational diabetes mellitus (GDM) and their partners to reduce the risk of future type 2 diabetes (T2D). The study aimed to understand how motivation for changing diet and physical activity behaviors among women with recent GDM and their partners was experienced after participation in the Danish Face-it intervention. Fourteen couples' interviews were conducted. Data analysis followed a reflexive thematic analysis. Guided by self-determination theory and interdependence theory, we identified four themes affecting couples' motivation for health behavior change: (1) The need to feel understood after delivery; (2) adjusting health expectations; (3) individual and mutual preferences for health behaviors; and (4) the health threat of future T2D as a cue to action. We found that couples in general perceived the Face-it intervention as useful and motivating. Using couple interviews increased our understanding of how the women and partners influenced each other's perspectives after a GDM-affected pregnancy and thus how targeting couples as opposed to women alone may motivate health behavior change.

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.

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.

Validation of Danish registry-cases of type 1 diabetes in women giving live birth using a clinical cohort as gold standard.

INTRODUCTION: The aim of this study was to validate type 1 diabetes in women giving live birth in the Danish national registries against a clinical cohort of confirmed cases (the Danish Diabetes Birth Registry [DDBR] cohort). METHODS: National registries including diagnosis codes, redeemed prescriptions and background data were combined. Three main algorithms were constructed to define type 1 diabetes in women giving live birth: (1) Any diabetes diagnosis registered before delivery and before age of 30, (2) a specific type 1 diabetes diagnosis registered before delivery regardless of maternal age and (3) a 'preexisting type 1 diabetes in pregnancy' diagnosis registered before delivery. In additional sub-algorithms, we added information on anti-diabetic medicine and gestational diabetes diagnosis. We calculated positive predictive value (PPV) and completeness using the DDBR cohort as gold standard. Since DDBR included between 75 and 93% of women with confirmed type 1 diabetes giving live birth, we used quantitative bias analysis to assess the potential impact of missing data on PPV and completeness. RESULTS: Main algorithm 2 had the highest PPV (77.4%) and shared the highest completeness (92.4%) with main algorithm 1. Information on anti-diabetic medicine and gestational diabetes increased PPV, on expense of completeness. All algorithms varied with PPV between 65.7 and 87.6% and completeness between 73.6 and 92.4%. The quantitative bias analysis indicated that PPV was underestimated, and completeness overestimated for all algorithms. For algorithm 2, corrected PPV was between 82.1 and 94.6% and corrected completeness between 84.7 and 91.2%. CONCLUSIONS: The Danish national registries can identify type 1 diabetes in women giving live birth with a reasonably high accuracy. The registries are a valuable source for future comparative outcome studies and may also be suitable for monitoring prevalence and incidence of type 1 diabetes in women giving live birth.

The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity: An Exploratory Sub-Analysis of the DALI Study.

Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria: <20 weeks gestation, body mass index ≥29 kg/m2 and information on exposure and outcome variables at baseline. Measurements: A 75 g OGTT at <20, 24−28 and 35−37 weeks gestation (except if previous diabetes diagnosis). Exposure variables: 25OHD2, 25OHD3 and C3-epimer. Outcome variables: fasting and post-challenge insulin sensitivity and secretion indices, corresponding disposition indices (DI), plasma glucose at fasting and 1 and 2 h, hyperglycemia in pregnancy (HiP). Statistics: Multivariate regression analyses with adjustment. Results: Baseline VitD sufficiency was 66.3%. Overall, VitD compounds did not show strong associations with any glucose homeostasis measures. 25OHD3 showed direct significant associations with: FPG at <20 and 24−28 weeks (standardized ß coefficient (ß) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24−28 weeks (ß 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, ß 0.127, p = 0.027) at 35−37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-ß) at <20 and 24−28 weeks (ß −0.124, p = 0.045 and ß −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, ß 0.149, p = 0.048) at 24−28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24−28 and 35−37 weeks (ß 0.168, p = 0.030, ß 0.239, p = 0.006). No significant association with C3-epimer was observed at any time period. Conclusions: In these women with average baseline VitD in sufficiency range, VitD compounds did not show clear beneficial associations with glucose homeostasis measures.

Long-Term Metabolic Outcomes after Gestational Diabetes Mellitus (GDM): Results from the Odense GDM Follow-Up Study (OGFUS).

Aims: To compare metabolic profiles and the long-term risk of metabolic dysfunction between women with previous gestational diabetes mellitus (pGDM) and women without pGDM (non-GDM) matched on age, prepregnancy body mass index (BMI), and parity. Methods: In total, 128 women with pGDM (median follow-up: 7.8 years) and 70 non-GDM controls (median follow-up: 10.0 years) completed a 2 h oral glucose tolerance test (OGTT) with assessment of glucose, C-peptide, insulin, and other metabolic measures. Additionally, anthropometrics, fat mass, and blood pressure were assessed and indices of insulin sensitivity and beta cell function were calculated. Results: The prevalence of type 2 diabetes mellitus (T2DM) was significantly higher in the pGDM group compared to the non-GDM group (26% vs. 0%). For women with pGDM, the prevalence of prediabetes (38%) and the metabolic syndrome (MetS) (59%) were approximately 3-fold higher than in non-GDM women (p's < 0.001). Both insulin sensitivity and beta cell function were significantly reduced in pGDM women compared to non-GDM women. Conclusion: Despite similar BMI, women with pGDM had a substantially higher risk of developing T2DM, prediabetes, and the MetS compared to controls. Both beta cell dysfunction and reduced insulin sensitivity seem to contribute to this increased risk.

Home Blood Pressure for the Prediction of Preeclampsia in Women With Preexisting Diabetes.

CONTEXT: Outside of pregnancy, home blood pressure (BP) has been shown to be superior to office BP for predicting cardiovascular outcomes. OBJECTIVE: This work aimed to evaluate home BP as a predictor of preeclampsia in comparison with office BP in pregnant women with preexisting diabetes. METHODS: A prospective cohort study was conducted of 404 pregnant women with preexisting diabetes; home BP and office BP were measured in early (9 weeks) and late pregnancy (35 weeks). Discriminative performance of home BP and office BP for prediction of preeclampsia was assessed by area under the receiver operating characteristic curves (AUC). RESULTS: In total 12% (n = 49/404) developed preeclampsia. Both home BP and office BP in early pregnancy were positively associated with the development of preeclampsia (adjusted odds ratio (95% CI) per 5 mm Hg, systolic/diastolic): home BP 1.43 (1.21-1.70)/1.74 (1.34-2.25) and office BP 1.22 (1.06-1.40)/1.52 (1.23-1.87). The discriminative performance for prediction of preeclampsia was similar for early-pregnancy home BP and office BP (systolic, AUC 69.3 [61.3-77.2] vs 64.1 [55.5-72.8]; P = .21 and diastolic, AUC 68.6 [60.2-77.0] vs 66.6 [58.2-75.1]; P = .64). Similar results were seen when comparing AUCs in late pregnancy (n = 304). In early and late pregnancy home BP was lower than office BP (early pregnancy P < .0001 and late pregnancy P < .01 for both systolic and diastolic BP), and the difference was greater with increasing office BP. CONCLUSION: In women with preexisting diabetes, home BP and office BP were positively associated with the development of preeclampsia, and for the prediction of preeclampsia home BP and office BP were comparable.

Twins in Guinea-Bissau have a 'thin-fat' body composition compared to singletons.

The 'thrifty phenotype' hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.Anthropometric data were available on 7-34 year-old twins (n = 209, 97 males) and singletons (n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, -0.21, p = 0.055), weight (WAZ -0.73, p = 0.024) and BMI (BAZ -0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.

The Temporal Profile of Circulating miRNAs during Gestation in Overweight and Obese Women with or without Gestational Diabetes Mellitus.

Circulating non-coding microRNAs (miRNAs) are important for placentation, but their expression profiles across gestation in pregnancies, which are complicated by gestational diabetes mellitus (GDM), have not been fully established. Investigating a single time point is insufficient, as pregnancy is dynamic, involving several processes, including placenta development, trophoblast proliferation and differentiation and oxygen sensing. Thus, the aim of this study was to compare the temporal expression of serum miRNAs in pregnant women with and without GDM. This is a nested case-control study of longitudinal data obtained from a multicentric European study (the 'DALI' study). All women (n = 82) were overweight/obese (BMI ≥ 29 kg/m2) and were normal glucose tolerant (NGT) at baseline (before 20 weeks of gestation). We selected women (n = 41) who were diagnosed with GDM at 24-28 weeks, according to the IADPSG/WHO2013 criteria. They were matched with 41 women who remained NGT in their pregnancy. miRNA (miR-16-5p, -29a-3p, -103-3p, -134-5p, -122-5p, -223-3p, -330-3p and miR-433-3p) were selected based on their suggested importance for placentation, and measurements were performed at baseline and at 24-28 and 35-37 weeks of gestation. Women with GDM presented with overall miRNA levels above those observed for women remaining NGT. In both groups, levels of miR-29a-3p and miR-134-5p increased consistently with progressing gestation. The change over time only differed for miR-29a-3p when comparing women with GDM with those remaining NGT (p = 0.044). Our findings indicate that among overweight/obese women who later develop GDM, miRNA levels are already elevated early in pregnancy and remain above those of women who remain NGT during their pregnancy. Maternal circulating miRNAs may provide further insight into placentation and the cross talk between the maternal and fetal compartments.

Systematically developing a family-based health promotion intervention for women with prior gestational diabetes based on evidence, theory and co-production: the Face-it study.

BACKGROUND: Women with prior gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes; however, this risk can be reduced by engaging in positive health behaviours e.g. healthy diet and regular physical activity. As such behaviours are difficult to obtain and maintain there is a need to develop sustainable behavioural interventions following GDM. We aimed to report the process of systematically developing a health promotion intervention to increase quality of life and reduce diabetes risk among women with prior GDM and their families. We distil general lessons about developing complex interventions through co-production and discuss our extensions to intervention development frameworks. METHODS: The development process draws on the Medical Research Council UK Development of complex interventions in primary care framework and an adaptation of a three-stage framework proposed by Hawkins et al. From May 2017 to May 2019, we iteratively developed the Face-it intervention in four stages: 1) Evidence review, qualitative research and stakeholder consultations; 2) Co-production of the intervention content; 3) Prototyping, feasibility- and pilot-testing and 4) Core outcome development. In all stages, we involved stakeholders from three study sites. RESULTS: During stage 1, we identified the target areas for health promotion in families where the mother had prior GDM, including applying a broad understanding of health and a multilevel and multi-determinant approach. We pinpointed municipal health visitors as deliverers and the potential of using digital technology. In stage 2, we tested intervention content and delivery methods. A health pedagogic dialogue tool and a digital health app were co-adapted as the main intervention components. In stage 3, the intervention content and delivery were further adapted in the local context of the three study sites. Suggestions for intervention manuals were refined to optimise flexibility, delivery, sequencing of activities and from this, specific training manuals were developed. Finally, at stage 4, all stakeholders were involved in developing realistic and relevant evaluation outcomes. CONCLUSIONS: This comprehensive description of the development of the Face-it intervention provides an example of how to co-produce and prototype a complex intervention balancing evidence and local conditions. The thorough, four-stage development is expected to create ownership and feasibility among intervention participants, deliverers and local stakeholders. TRIAL REGISTRATION: ClinicalTrials.gov NCT03997773 , registered retrospectively on 25 June 2019.

The effects of dietary and lifestyle interventions among pregnant women with overweight or obesity on early childhood outcomes: an individual participant data meta-analysis from randomised trials.

BACKGROUND: The impact of maternal obesity extends beyond birth, being independently associated with an increased risk of child obesity. Current evidence demonstrates that women provided with a dietary intervention during pregnancy improve their dietary quality and have a modest reduction in gestational weight gain. However, the effect of this on longer-term childhood obesity-related outcomes is unknown. METHODS: We conducted an individual participant data meta-analysis from RCTs in which women with a singleton, live gestation between 10+0 and 20+0 weeks and body mass index (BMI) ≥ 25 kg/m2 in early pregnancy were randomised to a diet and/or lifestyle intervention or continued standard antenatal care and in which longer-term maternal and child follow-up at 3-5 years of age had been undertaken. The primary childhood outcome was BMI z-score above the 90th percentile. Secondary childhood outcomes included skinfold thickness measurements and body circumferences, fat-free mass, dietary and physical activity patterns, blood pressure, and neurodevelopment. RESULTS: Seven primary trials where follow-up of participants occurred were identified by a systematic literature search within the International Weight Management in Pregnancy (i-WIP) Collaborative Group collaboration, with six providing individual participant data. No additional studies were identified after a systematic literature search. A total of 2529 children and 2383 women contributed data. Approximately 30% of all child participants had a BMI z-score above the 90th percentile, with no significant difference between the intervention and control groups (aRR 0.97; 95% CI 0.87, 1.08; p=0.610). There were no statistically significant differences identified for any of the secondary outcome measures. CONCLUSIONS: In overweight and obese pregnant women, we found no evidence that maternal dietary and/or lifestyle intervention during pregnancy modifies the risk of early childhood obesity. Future research may need to target the pre-conception period in women and early childhood interventions. TRIAL REGISTRATION: PROSPERO, CRD42016047165.

Adapting fasting plasma glucose threshold for GDM diagnosis according to the population distribution - An approach to the Danish paradox.

AIMS: To examine third trimester fasting venous plasma glucose (FVPG) according to the distribution of a Danish population of pregnant women and identify potential local FVPG thresholds for GDM diagnosis related to risks of adverse pregnancy outcomes. METHODS: In the observational Odense Child Cohort (OCC) study, 1516 women had FVPG measured at 27-28 weeks' gestation and were considered normal by Danish criteria and remained untreated. Maternal FVPG from OCC were standardized according to the local FVPG mean and standard deviation calibrated to data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Associations between maternal FVPG and clinical and anthropometric outcomes were analysed. Potential FVPG cut points were identified. RESULTS: Unadjusted areas under the ROC curve for FVPG to discriminate for large for gestational age (LGA) and hypertensive disorders of pregnancy were 0.61 (95% CI 0.56, 0.67) and 0.57 (95% CI 0.52, 0.63), respectively. The Youden FVPG cut point for LGA was 5.5 mmol/L and 5.0 mmol/L for hypertensive disorders of pregnancy. CONCLUSIONS: This study identified a potential locally appropriate third trimester FVPG cut point between 5.5 and 5.7 mmol/L based on LGA risk in pregnancy. This cut point should be validated prospectively in other Danish cohorts.

The Predictive Value of miR-16, -29a and -134 for Early Identification of Gestational Diabetes: A Nested Analysis of the DALI Cohort.

Early identification of gestational diabetes mellitus (GDM) aims to reduce the risk of adverse maternal and perinatal outcomes. Currently, no circulating biomarker has proven clinically useful for accurate prediction of GDM. In this study, we tested if a panel of small non-coding circulating RNAs could improve early prediction of GDM. We performed a nested case-control study of participants from the European multicenter 'Vitamin D and lifestyle intervention for GDM prevention (DALI)' trial using serum samples from obese pregnant women (BMI ≥ 29 kg/m2) entailing 82 GDM cases (early- and late- GDM), and 41 age- and BMI-matched women with normal glucose tolerance (NGT) throughout pregnancy (controls). Anthropometric, clinical and biochemical characteristics were obtained at baseline (<20 weeks of gestation) and throughout gestation. Baseline serum microRNAs (miRNAs) were measured using quantitative real time PCR (qPCR). Elevated miR-16-5p, -29a-3p, and -134-5p levels were observed in women, who were NGT at baseline and later developed GDM, compared with controls who remained NGT. A combination of the three miRNAs could distinguish later GDM from NGT cases (AUC 0.717, p = 0.001, compared with fasting plasma glucose (AUC 0.687, p = 0.004)) as evaluated by area under the curves (AUCs) using Receiver Operator Characteristics (ROC) analysis. Elevated levels of individual miRNAs or a combination hereof were associated with higher odds ratios of GDM. Conclusively, circulating miRNAs early in pregnancy could serve as valuable predictive biomarkers of GDM.

Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women-a secondary analysis of the DALI study.

BACKGROUND/OBJECTIVES: Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women. SUBJECTS/METHODS: In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness. RESULTS: 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011). CONCLUSIONS: As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.

Diabetes in urban Guinea-Bissau; patient characteristics, mortality and prevalence of undiagnosed dysglycemia.

BACKGROUND: The burden of diabetes mellitus in Sub-Saharan Africa is growing rapidly, and yet the prevalence and patient characteristics are still largely unknown. OBJECTIVES: We analyzed clinical and demographic characteristics of Type 2 diabetes (T2DM) patients attending a diabetes clinic in Guinea-Bissau from February 2008 to April 2014, and estimated the prevalence and risk factors of unknown-impaired fasting plasma glucose (FPG) and diabetes, as well as excess mortality associated with T2DM. METHODS: We characterized T2DM patients attending the national diabetes clinic in Bissau. Diabetes was diagnosed based on FPG. We matched T2DM patients 1:1 with non-diabetes community controls on age and sex to determine relevant risk factors for T2DM using logistic regression. Furthermore, we matched patients 1:6 with community controls to assess long-term survival (until February 2019) in a Cox regression using calendar time as the underlying timescale. Verbal autopsies determined the cause of death among T2DM patients and controls. RESULTS: The mean age among T2DM was 50.6 (SD 11.1), and the mean FPG at first consultation was high (13.2 mmol/L (SD 5.1)). Ethnicity, family history of diabetes, hypertension, and anthropometrics differed among T2DM patients, community controls with impaired FPG, and healthy controls. Family history of diabetes (OR = 5.65, 95% CI: 3.10-10.3) and elevated waist circumference (2.33, 1.26-4.29) were significant risk factors for T2DM. 20.4% (59/289) of community controls had abnormal FPG. T2DM patients had an excess mortality hazard ratio of 3.53 (95%CI: 1.92-6.52). Deaths caused by bacterial infections, including foot ulcers, were more common among T2DM patients, compared with community controls (54% (7/13) vs. 19% (5/27) (P = 0.02)). CONCLUSION: Several risk factors including were associated with T2DM in Guinea-Bissau. We found a high prevalence of elevated FPG among randomly selected community controls. In combination with higher mortality among T2DM patients, an urgent need for better treatment options and increased awareness.

Live-born children after assisted reproduction in women with type 1 diabetes and type 2 diabetes: a nationwide cohort study.

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes are among the most prevalent chronic diseases in women in the fertile years and women with diabetes may experience several reproductive issues. We aimed to examine the chance of biochemical pregnancy, clinical pregnancy and live birth after assisted reproductive technology (ART) treatment in women with type 1 and type 2 diabetes and whether obesity per se influenced the results. METHODS: This nationwide register-based cohort study is based on the Danish ART Registry comprising 594 women with either type 1 diabetes or type 2 diabetes from 2006 to 2017. RESULTS: Relative to women without diabetes, the adjusted OR (95% CI) of a live birth per embryo transfer was 0.50 (0.36, 0.71) in women with type 2 diabetes and 1.10 (0.86, 1.41) in women with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our data on the efficacy of ART treatment in women with type 1 and type 2 diabetes is the first in this field. When compared with women without diabetes, women with type 1 diabetes had an equivalent chance of a live birth per embryo transfer whereas women with type 2 diabetes had a reduced chance. The findings in women with type 2 diabetes did not seem to be driven by obesity per se as the same pattern was seen in both normal-weight and obese women. Graphical abstract.

Protocol for a randomised controlled trial of a co-produced, complex, health promotion intervention for women with prior gestational diabetes and their families: the Face-it study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with an increased risk of future diabetes in both mother, father and offspring. More knowledge is needed about how to effectively reduce the risk of diabetes through sustained behavioural interventions in these families. The Face-it intervention is a complex health promotion intervention embedded in multi-level supportive environments. The aim of the intervention is to reduce type 2 diabetes risk and increase quality of life among families in the first year following a GDM-affected pregnancy by promoting physical activity, healthy dietary behaviours and breastfeeding through a focus on social support, motivation, self-efficacy, risk perception and health literacy. METHODS: This national multicentre study is a two-arm randomised controlled trial including 460 women with GDM in a ratio of 2 (intervention):1 (usual care). The Face-it intervention consists of three main components: 1) additional visits from municipal health visitors, 2) digital health coaching tailored to family needs and 3) a structured cross-sectoral communication system in the health care system. The intervention runs from 3 to 12 months after delivery. The primary outcome is maternal body mass index at 12 months after delivery as a proxy for diabetes risk. The women will be examined at baseline and at follow-up, and this examination will include blood tests, oral glucose tolerance test (OGTT), anthropometrics, blood pressure, self-reported diet and physical activity, breastfeeding, quality of life, health literacy, physical and mental health status, risk perception and social support. Aside from those data collected for OGTT and breastfeeding and offspring parameters, the same data will be collected for partners. Data on offspring anthropometry will also be collected. Information on pregnancy- and birth-related outcomes will be derived from the medical records of the woman and child. DISCUSSION: This randomised controlled trial seeks to demonstrate whether the Face-it intervention, addressing the individual, family and health care system levels, is superior to usual care in reducing diabetes risk for mothers and their families. Coupled with a process evaluation and an economic analysis, the study will provide evidence for policymakers and health services about health promotion among families affected by GDM and the potential for reducing risk of type 2 diabetes and associated conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03997773. Registered June 25, 2019 - Retrospectively registered.

Physical activity, sedentary behavior and development of preeclampsia in women with preexisting diabetes.

AIMS: To explore the association between physical activity in early pregnancy and development of preeclampsia in women with preexisting diabetes. METHODS: In a prospective cohort study of 189 women with preexisting diabetes (110 type 1 and 79 type 2 diabetes), physical activity during pregnancy including sedentary behavior was evaluated with the Pregnancy Physical Activity Questionnaire. Primary outcome was preeclampsia. Secondary outcomes were preterm delivery, large and small for gestational age infants. RESULTS: Women developing preeclampsia (n = 23) had higher diastolic blood pressure in early pregnancy (mean 82 ± 9 SD vs. 77 ± 8, p = 0.004) and were more often nulliparous (91 vs. 52%, p < 0.001) compared with the remaining women (n = 166). Total physical activity in early pregnancy was similar between the groups (median 148 metabolic equivalent of task hours per week (MET-h/week) (interquartile range 118-227) versus 153 (121-205), p = 0.97). In early pregnancy, women developing preeclampsia reported a higher level of sedentary behavior (15 MET-h/week (7-18) versus 7 (4-15); p = 0.04); however, when adjusting for parity, diastolic blood pressure and smoking, the association attenuated (p = 0.13). Total physical activity and sedentary behavior in early pregnancy were not associated with preterm delivery, large or small for gestational age infants. CONCLUSIONS: Among women with diabetes, sedentary behavior was reported higher in early pregnancy in women developing preeclampsia compared with the remaining women, while total physical activity was similar. Sedentary behavior was a predictor of preeclampsia in the univariate analysis, but not in the multiple regression analysis, and larger studies are needed to evaluate this possible modifiable risk factor. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT02890836).