Early ascending growth is associated with maternal lipoprotein profile during mid and late pregnancy and in cord blood.

INTRODUCTION: Intrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth. METHODS: The RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings' first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm). RESULTS: From the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002). CONCLUSION: Ascending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, http://www. CLINICALTRIALS: com , NCT01698385.

Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. METHODS: The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m2 and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. RESULTS: Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). CONCLUSIONS/INTERPRETATION: Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01698385.

Ideal Cardiovascular Health and Vascular Phenotype Associations in Mothers with Obesity and Their Six-Year-Old Children.

BACKGROUND: Heredity and family-shared lifestyle contribute to cardiovascular risk, but the magnitude of their influence on arterial structure and function in early childhood is unknown. We aimed to assess associations between child and maternal ideal cardiovascular health, maternal subclinical atherosclerosis, and child arterial phenotype. METHODS: Cross-sectional analysis of 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL) longitudinal cohort was done at child age 6.1 ± 0.5 years with assessments of ideal cardiovascular health (BMI, blood pressure, fasting glucose, total cholesterol, diet quality, physical activity, smoking), body composition, very-high frequency ultrasound of carotid arteries (25 and 35 MHz), and pulse wave velocity. RESULTS: We found no association between child and maternal ideal cardiovascular health but report evidence of particular metrics correlations: total cholesterol (r=0.24, P=0.003), BMI (r=0.17, P=0.02), diastolic blood pressure (r=0.15, P=0.03), and diet quality (r=0.22, P=0.002). Child arterial phenotype was not associated with child or maternal ideal cardiovascular health. In the multivariable regression explanatory model adjusted for child sex, age, systolic blood pressure, lean body mass, and body fat percentage, child carotid intima-media thickness was independently associated only with maternal carotid intima-media thickness (0.1 mm increase [95% CI 0.05, 0.21, P=0.001] for each 1 mm increase in maternal carotid intima-media thickness). Children of mothers with subclinical atherosclerosis had decreased carotid artery distensibility (1.1 ± 0.2 vs 1.2 ± 0.2%/10 mmHg, P=0.01) and trend toward increased carotid intima-media thickness (0.37 ± 0.04 vs 0.35 ± 0.04 mm, P=0.06). CONCLUSION: Ideal Cardiovascular Health metrics are heterogeneously associated in mother-child pairs in early childhood. We found no evidence of child or maternal Ideal Cardiovascular Health effect on child arterial phenotype. Maternal carotid intima-media thickness predicts child carotid intima-media thickness, but the underlying mechanisms remain unclear. Maternal subclinical atherosclerosis is associated with local carotid arterial stiffness in early childhood.

No effect of gestational diabetes or pre-gestational obesity on 6-year offspring left ventricular function-RADIEL study follow-up.

AIMS: We aimed to investigate associations between pre-pregnancy obesity, gestational diabetes (GDM), offspring body composition, and left ventricular diastolic and systolic function in early childhood. METHODS: This is an observational study, including 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL; 96 with GDM, 128 with pre-pregnancy obesity) with follow-up from gestation to 6-year postpartum. Follow-up included dyads anthropometrics, body composition, blood pressure, and child left ventricular function with comprehensive echocardiography (conventional and strain imaging). RESULTS: Offspring left ventricular diastolic and systolic function was not associated with gestational glucose concentrations, GDM, or pregravida obesity. Child body fat percentage correlated with maternal pre-pregnancy BMI in the setting of maternal obesity (r = 0.23, P = 0.009). After adjusting for child lean body mass, age, sex, systolic BP, resting HR, maternal lean body mass, pre-gestational BMI, and GDM status, child left atrial volume increased by 0.3 ml (95% CI 0.1, 0.5) for each 1% increase in child body fat percentage. CONCLUSIONS: No evidence of foetal cardiac programming related to GDM or maternal pre-pregnancy obesity was observed in early childhood. Maternal pre-pregnancy obesity is associated with early weight gain. Child adiposity in early childhood is independently associated with increased left atrial volume, but its implications for long-term left ventricle diastolic function and cardiovascular health remain unknown.

Bone health in women with a history of gestational diabetes or obesity.

INTRODUCTION: Type 2 diabetes is associated with an increased risk of bone fractures. However, bone health of women with a history of gestational diabetes (GDM) has received little attention. This cross-sectional study compares bone health between premenopausal women with and without a history of GDM, and examines factors associated with bone health in women with a history of GDM or obesity. MATERIAL AND METHODS: We measured areal bone mineral density for total hip, lumbar spine and whole body, and total body fat percentage (fat%) with dual-energy X-ray absorptiometry in 224 women. In addition, we measured bone characteristics of radius and tibia with peripheral quantitative computed tomography. RESULTS: When compared with women without a history of GDM (mean age 39 years [SD 5], body mass index [BMI] 35 kg/m2 [SD 6], fat% 48 [SD 7]), women with a history of GDM (age 41 years [SD 4], BMI 31 kg/m2 [SD 7], fat% 43 [SD 10]) had lower hip and whole body bone mineral densities, and inferior tibia outcomes. However, the differences in bone characteristics disappeared after controlling for age, height, BMI and fat%. After controlling for age, height, BMI and smoking, physical activity and healthier diet were positively associated with bone outcomes, whereas fat%, HbA1c and screen time were negatively associated with bone outcomes. Particularly, fat% showed independent negative associations with whole body bone mineral density and several tibia and radius characteristics. CONCLUSIONS: Fat% is associated with adverse bone health, independently of BMI, in women with a history of GDM or obesity. Promoting healthy lifestyle and reducing fat% in high-risk women could improve bone health and prevent future fractures.

Effect of lifestyle counselling on health-related quality of life in women at high risk for gestational diabetes.

BACKGROUND: The incidence of gestational diabetes (GDM) is increasing and interventions to curb the detrimental effects of GDM are needed. We have previously reported that a combined diet and physical activity intervention has the potential to reduce GDM among high-risk women. It is also important to know whether the intervention affects health-related quality of life (HRQoL). METHODS: A total of 378 women at high risk for GDM were randomized into an intervention (lifestyle counselling four times during pregnancy, n=192), or a control group (n=186) before 20 gestational weeks. HRQoL was assessed with the 15D-instrument six times: once during each trimester and at six weeks, six months and 12 months postpartum. RESULTS: In this study population, the cumulative incidence of GDM was similar in the intervention and the control group (45.7 vs. 44.5%). There was no difference between the 15D scores of the control and intervention groups at any of the time points. CONCLUSIONS: Combined diet and physical activity intervention did not provide HRQoL benefits in the study. A high prevalence of GDM in both study groups may have confounded the effect of the intervention.

Long-term effects of a preconception lifestyle intervention on cardiometabolic health of overweight and obese women.

BACKGROUND: The global prevalence of obesity in women keeps increasing. The preconception period may be a window of opportunity to improve lifestyle, reduce obesity and improve cardiometabolic health. This study assessed the effect of a preconception lifestyle intervention on long-term cardiometabolic health in two randomized controlled trials (RCTs). METHODS: Participants of the LIFEstyle and RADIEL preconception lifestyle intervention studies with a baseline body mass index (BMI) ≥29 kg/m2 were eligible for this follow-up study. Both studies randomized between a lifestyle intervention targeting physical activity, diet and behaviour modification or usual care. We assessed cardiometabolic health 6 years after randomization. RESULTS: In the LIFEstyle study (n = 111) and RADIEL study (n = 39), no statistically significant differences between the intervention and control groups were found for body composition, blood pressure, arterial stiffness, fasting glucose, homeostasis model assessment of insulin resistance, HbA1c, lipids and high sensitive C-reactive protein levels 6 years after randomization. Participants of the LIFEstyle study who successfully lost ≥5% bodyweight or reached a BMI <29 kg/m2 during the intervention (n = 22, [44%]) had lower weight (-8.1 kg; 99% CI [-16.6 to -0.9]), BMI (-3.3 kg/m2; [-6.5 to -0.8]), waist circumference (-8.2 cm; [-15.3 to -1.3]), fasting glucose (-0.5 mmol/L; [-1.1 to -0.0]), HbA1c (-4.1 mmol/mol; [-9.1 to -0.8]), and higher HDL-C (0.3 mmol/L; [0.1-0.5]) compared with controls. CONCLUSION: We found no evidence of improved cardiometabolic health 6 years after a preconception lifestyle intervention among overweight and obese women in two RCTs. Women who successfully lost weight during the intervention had better cardiometabolic health 6 years later, emphasizing the potential of successful preconception lifestyle improvement.

Effects of a Lifestyle Intervention During Pregnancy and First Postpartum Year: Findings From the RADIEL Study.

Context: Women with a history of gestational diabetes (GDM) have a sevenfold risk of developing type 2 diabetes. Objective: To assess the effects of a lifestyle intervention during pregnancy and first postpartum year on glucose regulation, weight retention, and metabolic characteristics among women at high GDM risk. Design: In the Finnish Gestational Diabetes Prevention study, trained study nurses provided lifestyle counseling in each trimester and 6 weeks, 6 months, and 12 months postpartum. Setting: Three maternity hospitals in the Helsinki area and one in Lappeenranta. Patients: In total, 269 women with previous GDM and/or a prepregnancy body mass index ≥30 kg/m2 were enrolled before 20 gestational weeks and allocated to either a control or an intervention group. This study includes the 200 participants who attended study visits 6 weeks and/or 12 months postpartum. Intervention: The lifestyle intervention followed Nordic diet recommendations and at least 150 minutes of moderate exercise was recommended weekly. Main Outcome Measure: The incidence of impaired glucose regulation (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) during the first postpartum year. Results: Impaired glucose regulation was present in 13.3% of the women in the control and in 2.7% in the intervention group [age-adjusted odds ratio, 0.18 (95% confidence interval, 0.05 to 0.65), P = 0.009] during the first postpartum year. There were no differences between the groups in weight retention, physical activity, or diet at 12 months postpartum. Conclusions: A lifestyle intervention during pregnancy and the first postpartum year successfully reduced the incidence of postpartum impairment in glucose regulation.

A randomized lifestyle intervention preventing gestational diabetes: effects on self-rated health from pregnancy to postpartum.

INTRODUCTION: The purpose was to examine the effects of a randomized lifestyle intervention on self-rated health from pregnancy to postpartum in participants at high risk for gestational diabetes mellitus. METHODS: We included 266 women with a history of gestational diabetes and/or prepregnancy BMI ≥30 kg/m2. The intervention group (n = 144) received individualized counseling on diet, physical activity, and weight management from trained nurses at six timepoints between the first trimester of pregnancy and 12 months postpartum, and met three times with a dietitian. The control group (n = 122) received standard antenatal care. We assessed self-rated health at the six timepoints by means of a single question with five response options ranging from good (1) to poor (5). Baseline-adjusted mean changes in self-rated health level were assessed with a mixed model for repeated measure methods. RESULTS: The mean (SD) for self-rated health at baseline was 1.8 (0.8) in the intervention group and 2.1 (0.9) in the control group (p = 0.006). Self-rated health varied over time (time effect p < 0.001) and was the poorest in the third trimester. The sample indicated that self-rated health improved in the intervention group and deteriorated in the control group from the first trimester to 12 months postpartum, but the difference between the groups did not reach statistical significance (group effect p = 0.064). DISCUSSION: The self-rated health level varied over time from the first trimester of pregnancy to 12 months postpartum in women at risk for gestational diabetes. Improving self-rated health among high-risk pregnant women through lifestyle intervention calls for further research.

Healthy Food Intake Index (HFII) - Validity and reproducibility in a gestational-diabetes-risk population.

BACKGROUND: The aim was to develop and validate a food-based diet quality index for measuring adherence to the Nordic Nutrition Recommendations (NNR) in a pregnant population with high risk of gestational diabetes (GDM). METHODS: This study is a part of the Finnish Gestational Diabetes Prevention Study (RADIEL), a lifestyle intervention conducted between 2008 and 2014. The 443 pregnant participants (61 % of those invited), were either obese or had a history of GDM. Food frequency questionnaires collected at 1st trimester served for composing the HFII; a sum of 11 food groups (available score range 0-17) with higher scores reflecting higher adherence to the NNR. RESULTS: The average HFII of the participants was 10.2 (SD 2.8, range 2-17). Factor analysis for the HFII component matrix revealed three factors that explained most of the distribution (59 %) of the HFII. As an evidence of the component relevance 9 out of 11 of the HFII components independently contributed to the total score (item-rest correlation coefficients <0.31). Saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, sucrose, and fiber intakes (among other nutrients) showed linearity across the HFII categories (P ≤ 0.030 for all nutrients tested); the higher the HFII, the closer the nutrient intake to the recommended intake level. Educational attainment (P = 0.0045), BMI (P = 0.0098), smoking (P = 0.007), and leisure time physical exercise (P = 0.038) showed linearity across the HFII categories. Intra-class correlation coefficient for the HFII was 0.85 (CI 0.79, 0.90). CONCLUSIONS: The HFII components reflect the food guidelines of the NNR, intakes of relevant nutrients, and characteristics known to vary with diet quality. It largely ignores energy intake, its components have independent contribution to the HFII, and it exhibits reproducibility. The main shortcomings are absence of red and processed meat component, and the validation in a selected study population. It is suitable for ranking participants according to the adherence to the NNR in pregnant women at high risk of GDM.

Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled Trial.

OBJECTIVE: To assess whether gestational diabetes mellitus (GDM) can be prevented by a moderate lifestyle intervention in pregnant women who are at high risk for the disease. RESEARCH DESIGN AND METHODS: Two hundred ninety-three women with a history of GDM and/or a prepregnancy BMI of ≥30 kg/m(2) were enrolled in the study at <20 weeks of gestation and were randomly allocated to the intervention group (n = 155) or the control group (n = 138). Each subject in the intervention group received individualized counseling on diet, physical activity, and weight control from trained study nurses, and had one group meeting with a dietitian. The control group received standard antenatal care. The diagnosis of GDM was based on a 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation. RESULTS: A total of 269 women were included in the analyses. The incidence of GDM was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40-0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM status, and the number of weeks of gestation). Gestational weight gain was lower in the intervention group (-0.58 kg [95% CI -1.12 to -0.04 kg]; adjusted P = 0.037). Women in the intervention group increased their leisure time physical activity more and improved their dietary quality compared with women in the control group. CONCLUSIONS: A moderate individualized lifestyle intervention reduced the incidence of GDM by 39% in high-risk pregnant women. These findings may have major health consequences for both the mother and the child.

Prevention of gestational diabetes through lifestyle intervention: study design and methods of a Finnish randomized controlled multicenter trial (RADIEL).

BACKGROUND: Maternal overweight, obesity and consequently the incidence of gestational diabetes are increasing rapidly worldwide. The objective of the study was to assess the efficacy and cost-effectiveness of a combined diet and physical activity intervention implemented before, during and after pregnancy in a primary health care setting for preventing gestational diabetes, later type 2 diabetes and other metabolic consequences. METHODS: RADIEL is a randomized controlled multi-center intervention trial in women at high risk for diabetes (a previous history of gestational diabetes or prepregnancy BMI ≥30 kg/m2). Participants planning pregnancy or in the first half of pregnancy were parallel-group randomized into an intervention arm which received lifestyle counseling and a control arm which received usual care given at their local antenatal clinics. All participants visited a study nurse every three months before and during pregnancy, and at 6 weeks, 6 and 12 months postpartum. Measurements and laboratory tests were performed on all participants with special focus on dietary and exercise habits and metabolic markers.Of the 728 women [mean age 32.5 years (SD 4.7); median parity 1 (range 0-9)] considered to be eligible for the study 235 were non-pregnant and 493 pregnant [mean gestational age 13 (range 6 to 18) weeks] at the time of enrollment. The proportion of nulliparous women was 29.8% (n = 217). Out of all participants, 79.6% of the non-pregnant and 40.4% of the pregnant women had previous gestational diabetes and 20.4% of the non-pregnant and 59.6% of the pregnant women were recruited because of a prepregnancy BMI ≥30 kg/m2. Mean BMI at first visit was 30.1 kg/m2 (SD 6.2) in the non-pregnant and 32.7 kg/m2 (SD 5.6) in the pregnant group. DISCUSSION: To our knowledge, this is the first randomized lifestyle intervention trial, which includes, besides the pregnancy period, both the prepregnancy and the postpartum period. This study design also provides an opportunity to focus upon the health of the next generation. The study is expected to produce novel information on the optimal timing and setting of interventions and for allocating resources to prevent obesity and diabetes in women of reproductive age.