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(Abstracted from N Engl J Med 2023;388(23):2132-2144) Gestational diabetes mellitus is a common pregnancy complication. It is associated with adverse outcomes, including preeclampsia, obstetrical intervention, large-for-gestational-age neonates, shoulder dystocia, birth trauma, and neonatal hypoglycemia. Cohort studies have found that women with hyperglycemia before 20 weeks of gestation are more likely to experience accelerated fetal growth by 24 to 28 weeks than those diagnosed with GDM later in pregnancy.

Aims: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. Methods: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012–2014). In women with a BMI ≥29 kg/m 2, insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. Results: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50–7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20–4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. Conclusions: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

Aims: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. Methods: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012–2014). In women with a BMI ≥29 kg/m2, insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. Results: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50–7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20–4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. Conclusions: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

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 o

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, I

Background: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity. Objectives: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed. Methods: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest. Results: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower me

Objective Whether HMG-CoA-reductase inhibition, the main mechanism of statins, plays a role in the pathogenesis of osteoporosis, is not entirely known so far. Consequently, this study was set out to investigate the relationship of different kinds and dosages of statins with osteoporosis, hypothesising that the inhibition of the synthesis of cholesterol could influence sex-hormones and therefore the diagnosis of osteoporosis. Methods Medical claims data of all Austrians from 2006 to 2007 was used to identify all patients treated with statins to compute their daily defined dose averages of six different types of statins. We applied multiple logistic regression to analyse the dose-dependent risks of being diagnosed with osteoporosis for each statin individually. Results In the general study population, statin treatment was associated with an overrepresentation of diagnosed osteoporosis compared with controls (OR: 3.62, 95% CI 3.55 to 3.69, p<0.01). There was a highly non-trivial dependence of statin dosage with the ORs of osteoporosis. Osteoporosis was underrepresented in low-dose statin treatment (0–10 mg per day), including lovastatin (OR: 0.39, CI 0.18 to 0.84, p<0.05), pravastatin (OR: 0.68, 95% CI 0.52 to 0.89, p<0.01), simvastatin (OR: 0.70, 95% CI 0.56 to 0.86, p<0.01) and rosuvastatin (OR: 0.69, 95% CI 0.55 to 0.87, p<0.01). However, the exceeding of the 40 mg threshold for simvastatin (OR: 1.64, 95% CI 1.31 to 2.07, p<0.01), and the exceeding of a 20 mg threshold for atorvastatin (OR: 1.78, 95% CI 1.41 to 2.23, p<0.01) and for rosuvastatin (OR: 2.04, 95% CI 1.31 to 3.18, p<0.01) was related to an overrepresentation of osteoporosis. Conclusion Our results show that the diagnosis of osteoporosis in statin-treated patients is dose-dependent. Thus, osteoporosis is underrepresented in low-dose and overrepresented in high-dose statin treatment, demonstrating the importance of future studies’ taking dose-dependency into account when investigating the relationship bet

__Background:__ Gestational diabetes mellitus (GDM) is associated with perinatal health risks to both mother and offspring, and represents a large economic burden. The DALI study is a multicenter randomized controlled trial, undertaken to add to the knowledge base on the effectiveness of interventions for pregnant women at increased risk for GDM. The purpose of this study was to evaluate the cost-effectiveness of the healthy eating and/or physical activity promotion intervention compared to usual care among pregnant women at increased risk of GDM from a societal perspective. __Methods:__ An economic evaluation was performed alongside a European multicenter-randomized controlled trial. A total of 435 pregnant women at increased risk of GDM in primary and secondary care settings in nine European countries, were recruited and randomly allocated to a healthy eating and physical activity promotion intervention (HE + PA intervention), a healthy eating promotion intervention (HE intervention), or a physical activity promotion intervention (PA intervention). Main outcome measures were gestational weight gain, fasting glucose, insulin resistance (HOMA-IR), quality adjusted life years (QALYs), and societal costs. __Results:__ Between-group total cost and effect differences were not significant, besides significantly less gestational weight gain in the HE + PA group compared with the usual care group at 35-37 weeks ( 2.3;95%CI:-3.7;-0.9). Cost-effectiveness acceptability curves indicated that the HE + PA intervention was the preferred intervention strategy. At 35-37 weeks, it depends on the decision-makers' willingness to pay per kilogram reduction in gestational weight gain whether the HE + PA intervention is cost-effective for gestational weight gain, whereas it was not cost-effective for fasting glucose and HOMA-IR. After delivery, the HE + PA intervention was cost-effective for QALYs, which was predominantly caused by a

BACKGROUND: The influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB. METHODS: In this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed using 1H-magnetic resonance spectroscopy (1H-MRS). RESULTS: RYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ± 1.1% vs. 0.1 ± 0.2% in the OB and vs. 0.8 ± 0.6% in the NW groups, p < 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ± 5.22% vs.5.68 ± 4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group. CONCLUSION: GLP-1 is mainly involved in the regulation of postprandial glucose metabo

_Context:_ Lifestyle approaches for preventing gestational diabetes mellitus (GDM) have produced mixed results. _Objective:_ The aim of the present study was to compare the effectiveness of 3 lifestyle interventions [healthy eating (HE), physical activity (PA), and both HE and PA (HE+PA)] with usual care (UC) in reducing GDM risk. _Design:_ The present study was a multicenter randomized controlled trial conducted from 2012 to 2014 [the DALI (vitamin D and lifestyle intervention for GDM prevention) lifestyle study]. _Setting:_ The study occurred at antenatal clinics across 11 centers in 9 European countries. _Patients:_ Consecutive pregnant women at <20 weeks of gestation with a body mass index (BMI) of ≥29 kg/m2 and without GDM using the International Association of Diabetes and Pregnancy Study Group criteria (n = 436). For the intervention, women were randomized, stratified by site, to UC, HE, PA, or HE+PA. The women received 5 face-to-face and ≤4 telephone coaching sessions using the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. The coaches received standardized training and an intervention toolkit tailored to their culture and language. _Main Outcome Measures:_ The endpoints were the GWG at 35 to 37 weeks and the fasting glucose and insulin sensitivity [homeostasis model assessment insulin resistance (HOMA-IR)] at 24 to 28 weeks. _Results:_ We randomized 108 women to HE+PA, 113 to HE, 110 to PA, and 105 to UC. In the HE+PA group, but not HE or PA alone, women achieved substantially less GWG than did the controls (UC) by 35 to 37 weeks (−2.02; 95% confidence interval, −3.58 to −0.46 kg). Despite this reduction, no improvements were seen in fasting or postload glucose levels, insulin concentrations, or HOMA-IR. The birthweights and large and small for gestational age rates were similar. _Conclusions:_ The combined HE+PA intervention was able to limit GWG but did not reduce fasting glycemia. Thus, lifestyle changes alon

Aims/hypothesis: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. Methods: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnanc

Background: Depression during pregnancy is associated with higher maternal morbidity and mortality, and subsequent possible adverse effects on the cognitive, emotional and behavioral development of the child. The aim of the study was to identify maternal characteristics associated with poor mental health, in a group of overweight/obese pregnant women in nine European countries, and thus, to contribute to better recognition and intervention for maternal depression. Methods: In this cross-sectional observational study, baseline data from early pregnancy (< 20 weeks) of the DALI (Vitamin D and Lifestyle Intervention for gestational diabetes mellitus prevention) study were analyzed. Maternal mental health was assessed with the World Health Organization Well-Being Index (WHO-5). Women were classified as having a low (WHO-5 ≤ 50) or high wellbeing. Results.: A total of 735 pregnant women were included. The prevalence of having a low wellbeing was 27.2%, 95% CI [24.0, 30.4]. Multivariate analysis showed independent associations between low wellbeing and European ethnicity, OR = .44, 95% CI [.25,.77], shift work, OR = 1.81, 95% CI [1.11, 2.93], insufficient sleep, OR = 3.30, 95% CI [1.96, 5.55], self-efficacy, OR = .95, 95% CI [.92,.98], social support, OR = .94, 95% CI [.90,.99], and pregnancy-related worries (socioeconomic: OR = 1.08, 95% CI [1.02, 1.15]; health: OR = 1.06, 95% CI [1.01, 1.11]; relationship: OR = 1.17, 95% CI [1.05, 1.31]). Conclusions: Mental health problems are common in European overweight/obese pregnant women. The identified correlates might help in early recognition and subsequent treatment of poor mental health problems during pregnancy. This is important to reduce the unfavorable effects of poor mental health on pregnancy outcomes. Trial registration:ISRCTN70595832 , 02.12.2011.

BACKGROUND: Depression during pregnancy is associated with higher maternal morbidity and mortality, and subsequent possible adverse effects on the cognitive, emotional and behavioral development of the child. The aim of the study was to identify maternal characteristics associated with poor mental health, in a group of overweight/obese pregnant women in nine European countries, and thus, to contribute to better recognition and intervention for maternal depression. METHODS: In this cross-sectional observational study, baseline data from early pregnancy (< 20 weeks) of the DALI (Vitamin D and Lifestyle Intervention for gestational diabetes mellitus prevention) study were analyzed. Maternal mental health was assessed with the World Health Organization Well-Being Index (WHO-5). Women were classified as having a low (WHO-5 ≤ 50) or high wellbeing. RESULTS: A total of 735 pregnant women were included. The prevalence of having a low wellbeing was 27.2%, 95% CI [24.0, 30.4]. Multivariate analysis showed independent associations between low wellbeing and European ethnicity, OR = .44, 95% CI [.25, .77], shift work, OR = 1.81, 95% CI [1.11, 2.93], insufficient sleep, OR = 3.30, 95% CI [1.96, 5.55], self-efficacy, OR = .95, 95% CI [.92, .98], social support, OR = .94, 95% CI [.90, .99], and pregnancy-related worries (socioeconomic: OR = 1.08, 95% CI [1.02, 1.15]; health: OR = 1.06, 95% CI [1.01, 1.11]; relationship: OR = 1.17, 95% CI [1.05, 1.31]). CONCLUSIONS: Mental health problems are common in European overweight/obese pregnant women. The identified correlates might help in early recognition and subsequent treatment of poor mental health problems during pregnancy. This is important to reduce the unfavorable effects of poor mental health on pregnancy outcomes. TRIAL REGISTRATION: ISRCTN70595832 , 02.12.2011.

BACKGROUND: Gestational diabetes mellitus (GDM) is an increasing problem world-wide. Lifestyle interventions and/or vitamin D supplementation might help prevent GDM in some women. METHODS/DESIGN: Pregnant women at risk of GDM (BMI ≥ 29 (kg/m(2))) from 9 European countries will be invited to participate and consent obtained before 19+6 weeks of gestation. After giving informed consent, women without GDM will be included (based on IADPSG criteria: fasting glucose<5.1 mmol; 1 hour glucose <10.0 mmol; 2 hour glucose <8.5 mmol) and randomized to one of the 8 intervention arms using a 2 × (2 × 2) factorial design: (1) healthy eating (HE), 2) physical activity (PA), 3) HE+PA, 4) control, 5) HE+PA+vitamin D, 6) HE+PA+placebo, 7) vitamin D alone, 8) placebo alone), pre-stratified for each site. In total, 880 women will be included with 110 women allocated to each arm. Between entry and 35 weeks of gestation, women allocated to a lifestyle intervention will receive 5 face-to-face, and 4 telephone coaching sessions, based on the principles of motivational interviewing. The lifestyle intervention includes a discussion about the risks of GDM, a weight gain target <5 kg and either 7 healthy eating 'messages' and/or 5 physical activity 'messages' depending on randomization. Fidelity is monitored by the use of a personal digital assistance (PDA) system. Participants randomized to the vitamin D intervention receive either 1600 IU vitamin D or placebo for daily intake until delivery. Data is collected at baseline measurement, at 24-28 weeks, 35-37 weeks of gestation and after delivery. Primary outcome measures are gestational weight gain, fasting glucose and insulin sensitivity, with a range of obstetric secondary outcome measures including birth weight. DISCUSSION: DALI is a unique Europe-wide randomised controlled trial, which will gain insight into preventive measures against the development of GDM in overweight and obese women. TRIAL REGISTRATION: ISRCTN70595832.

Background: Gestational diabetes mellitus is a potentially serious condition that affects many pregnancies and its prevalence is increasing. Evidence suggests early detection and treatment improves outcomes, but this is hampered by continued disagreement and inconsistency regarding many aspects of its diagnosis. Methods: The Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) research programme aims to promote pan-European standards in the detection and diagnosis of gestational diabetes and to develop effective preventive interventions. To provide an overview of the context within which the programme will be conducted and its findings interpreted, systematic searching and narrative synthesis have been used to identify and review the best available European evidence relating to the prevalence of gestational diabetes, current screening practices and barriers to screening. Results: Prevalence is most often reported as 2-6% of pregnancies. Prevalence may be lower towards the Northern Atlantic seaboard of Europe and higher in the Southern Mediterranean seaboard. Screening practice and policy is inconsistent across Europe, hampered by lack of consensus on testing methods, diagnostic glycaemic thresholds and the value of routine screening. Poor clinician awareness of gestational diabetes, its diagnosis and local clinical guidelines further undermine detection of gestational diabetes. Conclusions: Europe-wide agreement on screening approaches and diagnostic standards for gestational diabetes could lead to better detection and treatment, improved outcomes for women and children and a strengthened evidence base. There is an urgent need for well-designed research that can inform decisions on best practice in gestational diabetes mellitus screening and diagnosis. © 2011 The Authors. Diabetic Medicine© 2011 Diabetes UK.