The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have We Learned from the DALI Studies?

Purpose of Review: The DALI (vitamin D and lifestyle intervention in the prevention of gestational diabetes mellitus (GDM)) study aimed to prevent GDM with lifestyle interventions or Vitamin D supplementation (1600 IU/day). This review summarizes the learnings from the DALI studies among pregnant women with a BMI ≥ 29 kg/m2. Recent Findings: Women diagnosed with GDM earlier in pregnancy had a worse metabolic profile than those diagnosed later. A combined physical activity (PA) and healthy eating (HE) lifestyle intervention improved both behaviours, limited gestational weight gain (GWG) and was cost-effective. Although GDM risk was unchanged, neonatal adiposity was reduced due to less sedentary time. Neither PA nor HE alone limited GWG or GDM risk. Fasting glucose was higher with HE only intervention, and lower with Vitamin D supplementation. Summary: Our combined intervention did not prevent GDM, but was cost-effective, limited GWG and reduced neonatal adiposity

Correction to: The Effects of Lifestyle and/or Vitamin D Supplementation Interventions on Pregnancy Outcomes: What Have we Learned from the DALI Studies? (Current Diabetes Reports, (2019), 19, 12, (162), 10.1007/s11892-019-1282-7)

The original version of this review article unfortunately contained a mistake

Beliefs, barriers and preferences of European overweight women to adopt a healthier lifestyle in pregnancy to minimize risk of developing gestational diabetes mellitus: an explorative study

Introduction: Overweight and obese women are at high risk of developing gestational diabetes mellitus (GDM). Lifestyle programs might help curb the GDM risk. We explored beliefs, perceived barriers and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future high quality lifestyle interventions. Methods: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI≥25kg/m2). In three European countries (Belgium, Netherlands, United Kingdom) interviews were conducted, followed by questionnaires in six other European countries (Austria, Denmark, Ireland, Italy, Poland, Spain). Content analysis, descriptive and chi square statistics were applied (p<0.05). Results: Women preferred to obtain detailed information about their personal risk. The health of their baby was major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. Conclusions: Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women

Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe

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 pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. Results: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24–28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35–37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. Conclusions/interpretation: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies

Mediators of lifestyle behaviour changes in obese pregnant women. Secondary analyses from the DALI lifestyle randomised controlled trial

Altres ajuts: The project described has received funding from the European Community's 7th Framework Programme (FP7/2007-2013) under grant agreement no. 242187. In the Netherlands, additional funding was provided by the Netherlands Organization for Health Research and Development (ZonMw) (grant no. 200310013). In Poland, additional funding was obtained from Polish Ministry of Science (grant no. 2203/7. PR/2011/2). In Denmark, additional funding was provided by the Odense University Free Research Fund. In the United Kingdom, the DALI team acknowledge the support received from the NIHR Clinical Research Network: Eastern, especially the local diabetes clinical and research teams based in Cambridge. In Spain, additional funding was provided by CAIBER 1527-B-226. The funders had no role in any aspect of the study beyond funding.A better understanding of what drives behaviour change in obese pregnant overweight women is needed to improve the effectiveness of lifestyle interventions in this group at risk for gestational diabetes (GDM). Therefore, we assessed which factors mediated behaviour change in the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) Lifestyle Study. A total of 436 women, with pre-pregnancy body mass index ≥29 kg/m , ≤19 + 6 weeks of gestation and without GDM, were randomised for counselling based on motivational interviewing (MI) on healthy eating and physical activity, healthy eating alone, physical activity alone, or to a usual care group. Lifestyle was measured at baseline, and at 24-28 and 35-37 weeks of gestation. Outcome expectancy, risk perception, task self-efficacy and social support were measured at those same time points and considered as possible mediators of intervention effects on lifestyle. All three interventions resulted in increased positive outcome expectancy for GDM reduction, perceived risk to the baby and increased task self-efficacy. The latter mediated intervention effects on physical activity and reduced sugared drink consumption. In conclusion, our MI intervention was successful in increasing task self-efficacy, which was related to improved health behaviours

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 65 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

Altres ajuts: In Spain, additional funding was provided by CAIBER 1527-B-226.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. 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/m 2, 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. 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). 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

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

Altres ajuts: Netherlands Organization for Health Research and Development (ZonMw, 200310013); Polish Ministry of Science (2203/7, PR/2011/2); Odense University Free Research Fund; NIHR Clinical Research Network: Eastern; In Spain (CAIBER 1527-B-226); Spanish Diabetes Society (SED) XI Grant for clinical research projects in diabetes.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/m 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 β coefficient (β) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24-28 weeks (β 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, β 0.127, p = 0.027) at 35-37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-β) at <20 and 24-28 weeks (β −0.124, p = 0.045 and β −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, β 0.149, p = 0.048) at 24-28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24-28 and 35-37 weeks (β 0.168, p = 0.030, β 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

A reduction in sedentary behaviour in obese women during pregnancy reduces neonatal adiposity : the DALI randomised controlled trial

Altres ajuts: Funding The project described has received funding from the European Community's 7th Framework Programme (FP7/2007-2013) under grant agreement no. 242187. In the Netherlands, additional funding was provided by the Netherlands Organisation for Health Research and Development (ZonMw) (grant no. 200310013). In Poland, additional funding was obtained from the Polish Ministry of Science (grant no. 2203/7, PR/2011/2). In Denmark, additional funding was provided by Odense University Free Research Fund. In the UK, the DALI team acknowledges the support received from the National Institute for Health Research Clinical Research Network Eastern, especially the local diabetes clinical and research teams based in Cambridge. In Spain, additional funding was provided by CAIBER (Consorcio de Apoyo a la Investigación Biomédica en Red; 1527-B-226). The funders had no role in any aspect of the study beyond funding.Aims/hypothesis: Offspring of obese women are at increased risk of features of the metabolic syndrome, including obesity and diabetes. Lifestyle intervention in pregnancy might reduce adverse effects of maternal obesity on neonatal adiposity. Methods: In the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention (DALI) lifestyle trial, 436 women with a BMI ≥29 kg/m were randomly assigned to counselling on healthy eating (HE), physical activity (PA) or HE&PA, or to usual care (UC). In secondary analyses of the lifestyle trial, intervention effects on neonatal outcomes (head, abdominal, arm and leg circumferences and skinfold thicknesses, estimated fat mass, fat percentage, fat-free mass and cord blood leptin) were assessed using multilevel regression analyses. Mediation of intervention effects by lifestyle and gestational weight gain was assessed. Results: Outcomes were available from 334 neonates. A reduction in sum of skinfolds (−1.8 mm; 95% CI −3.5, −0.2; p = 0.03), fat mass (−63 g; 95% CI −124, −2; p = 0.04), fat percentage (−1.2%; 95% CI −2.4%, −0.04%; p = 0.04) and leptin (−3.80 μg/l; 95% CI −7.15, −0.45; p = 0.03) was found in the HE&PA group, and reduced leptin in female neonates in the PA group (−5.79 μg/l; 95% CI −11.43, −0.14; p = 0.05) compared with UC. Reduced sedentary time, but not gestational weight gain, mediated intervention effects on leptin in both the HE&PA and PA groups. Conclusions/interpretation: The HE&PA intervention resulted in reduced adiposity in neonates. Reduced sedentary time seemed to drive the intervention effect on cord blood leptin. Implications for future adiposity and diabetes risk of the offspring need to be elucidated. Trial registration: ISRCTN70595832

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