Genetic risk of type 2 diabetes modifies the association between lifestyle and glycemic health at 5 years postpartum among high-risk women.

INTRODUCTION: Lifestyle interventions are effective in preventing type 2 diabetes, but genetic background may influence the individual response. In the Finnish gestational diabetes prevention study, RADIEL, lifestyle intervention during pregnancy and first postpartum year was effective in preventing gestational diabetes (GDM) and postpartum glycemic abnormalities only among women at highest genetic risk of type 2 diabetes. This study aimed to assess whether still 5 years postpartum the genetic risk modifies the association between lifestyle and glycemic health. RESEARCH DESIGN AND METHODS: The RADIEL study (randomized controlled trial) aimed to prevent GDM with a lifestyle intervention among high-risk women (body mass index ≥30 kg/m2 and/or prior GDM). The follow-up study 5 years postpartum included anthropometric measurements, laboratory assessments, device-measured physical activity (PA), and questionnaires. A Healthy Lifestyle Score (HLS) indicated adherence to lifestyle goals (PA, diet, smoking) and a polygenic risk score (PRS) based on 50 type 2 diabetes risk alleles depicted the genetic risk. RESULTS: Altogether 314 women provided genetic and glycemic data 5 years postpartum. The PRS for type 2 diabetes was not associated with glycemic abnormalities, nor was HLS in the total study sample. There was, however, an interaction between HLS and type 2 diabetes PRS on glycemic abnormalities (p=0.03). When assessing the association between HLS and glycemic abnormalities in PRS tertiles, HLS was associated with reduced risk of glycemic abnormalities only among women at the highest genetic risk (p=0.008). CONCLUSIONS: These results extend our previous findings from pregnancy and first postpartum year demonstrating that still at 5 years postpartum, healthy lifestyle is associated with a lower risk of prediabetes/diabetes only among women at the highest genetic risk of type 2 diabetes.

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.

Metabolomic Profiles of Nonobese and Obese Women With Gestational Diabetes.

CONTEXT: In non-pregnant population, nonobese individuals with obesity-related metabolome have increased risk for type 2 diabetes and cardiovascular diseases. The risk of these diseases is also increased after gestational diabetes. OBJECTIVE: This work aimed to examine whether nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) women with gestational diabetes mellitus (GDM) and obese non-GDM women differ in metabolomic profiles from nonobese non-GDM controls. METHODS: Levels of 66 metabolic measures were assessed in early (median 13, IQR 12.4-13.7 gestation weeks), and across early, mid (20, 19.3-23.0), and late (28, 27.0-35.0) pregnancy blood samples in 755 pregnant women from the PREDO and RADIEL studies. The independent replication cohort comprised 490 pregnant women. RESULTS: Nonobese and obese GDM, and obese non-GDM women differed similarly from the controls across early, mid, and late pregnancy in 13 measures, including very low-density lipoprotein-related measures, and fatty acids. In 6 measures, including fatty acid (FA) ratios, glycolysis-related measures, valine, and 3-hydroxybutyrate, the differences between obese GDM women and controls were more pronounced than the differences between nonobese GDM or obese non-GDM women and controls. In 16 measures, including HDL-related measures, FA ratios, amino acids, and inflammation, differences between obese GDM or obese non-GDM women and controls were more pronounced than the differences between nonobese GDM women and controls. Most differences were evident in early pregnancy, and in the replication cohort were more often in the same direction than would be expected by chance alone. CONCLUSION: Differences between nonobese and obese GDM, or obese non-GDM women and controls in metabolomic profiles may allow detection of high-risk women for timely targeted preventive interventions.

Supporting lifestyle change in obese pregnant mothers through the wearable internet-of-things (SLIM) -intervention for overweight pregnant women: Study protocol for a quasi-experimental trial.

OBJECTIVES: To assess, in terms of self-efficacy in weight management, the effectiveness of the SLIM lifestyle intervention among overweight or obese women during pregnancy and after delivery, and further to exploit machine learning and event mining approaches to build personalized models. Additionally, the aim is to evaluate the implementation of the SLIM intervention. METHODS: This prospective trial, which is a non-randomized, quasi-experimental, pre-post intervention, includes an embedded mixed-method process evaluation. The SLIM Intervention is delivered by public health nurses (n = 9) working in maternity clinics. The public health nurses recruited overweight women (n = 54) at their first antenatal visit using convenience sampling. The core components of the intervention i.e. health technology, motivational interviewing, feedback, and goal setting, are utilized in antenatal visits in maternity clinics starting from gestational week 15 or less and continuing to 12 weeks after delivery. Mixed effect models are used to evaluate change over time in self-efficacy, weight management and weight change. Simple mediation models are used to assess calories consumed and moderate to vigorous physical activity (MVPA) as mediators between self-efficacy and weight change. Signal processing and machine learning techniques are exploited to extract events from the data collected via the Oura ring and smartphone-based questionnaires. DISCUSSION: The SLIM intervention was developed in collaboration with overweight women and public health nurses working in maternity clinics. This study evaluates the effectiveness of the intervention among overweight women in increasing self-efficacy and achieving a healthy weight; thus, impacting the healthy lifestyle and long-term health of the whole family. The long-term objective is to contribute to women's health by supporting weight-management through behavior change via interventions conducted in maternity clinics. TRIAL REGISTRATION: The trial was registered at the Clinicaltrials.gov register platform (ID NCT04826861) on 17 March 2021.

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.

Longitudinal Metabolic Profiling of Maternal Obesity, Gestational Diabetes, and Hypertensive Pregnancy Disorders.

CONTEXT: Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden. OBJECTIVE: To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders. DESIGN, SETTING AND PARTICIPANTS: A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women. MAIN OUTCOME MEASURES: We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation. RESULTS: Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders. CONCLUSIONS: This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.

Ascending Growth is Associated with Offspring Adiposity in Pregnancies Complicated with Obesity or Gestational Diabetes.

CONTEXT: Early growth is associated with childhood adiposity, but the influence of lifestyle remains unknown. OBJECTIVE: This work aimed to investigate the association of growth profiles from high-risk pregnancies with adiposity at age 5 years, taking into account lifestyle and several antenatal/postnatal exposures. METHODS: This prospective cohort study. INCLUDED: 609 children born during the Finnish Gestational Diabetes Prevention Study (RADIEL), recruiting women with body mass index (BMI) greater than or equal to 30 and/or prior gestational diabetes mellitus (GDM) (2008-2013). Altogether 332 children attended the 5-year follow-up (2014-2017). Main outcome measures included growth profiles based on ponderal index (PI = weight/height3), investigated using latent class mixed models. Adiposity was assessed with anthropometrics and body composition (InBody720). RESULTS: We identified 3 growth profiles: ascending (n = 82), intermediate (n = 351), and descending (n = 149). Children with ascending growth had a higher body fat percentage, ISO-BMI, and waist circumference (P < .05) at age 5 years. Ascending (ß 4.09; CI, 1.60-6.58) and intermediate (ß 2.27; CI, 0.50-4.03) profiles were associated with higher fat percentage, even after adjustment for age, sex, gestational age, diet, physical activity, education, and prepregnancy BMI. Similar associations existed with ISO-BMI. After adjusting for age and education, ascending growth was associated with prepregnancy BMI (odds ratio [OR] 1.06; CI, 1.01-1.12), primiparity (OR 3.07; CI, 1.68-5.62), cesarean delivery (OR 2.23; CI, 1.18-4.21), and lifestyle intervention (OR 2.56; CI, 1.44-4.57). However, meeting the intervention goals and exclusive breastfeeding for 3 months or more were associated with lower odds of ascending growth. CONCLUSION: Accelerated early growth was associated with higher adiposity in 5-year-old children from high-risk pregnancies, even when adjusted for lifestyle. Reducing cesarean deliveries and promoting breastfeeding may be beneficial for postnatal growth.

Macronutrient intake during pregnancy in women with a history of obesity or gestational diabetes and offspring adiposity at 5 years of age.

BACKGROUND/OBJECTIVES: The impact of maternal macronutrient intake during pregnancy on offspring childhood adiposity is unclear. We assessed the associations between maternal macronutrient intake during and after pregnancy with offspring adiposity at 5 years of age. Additionally, we investigated whether gestational diabetes (GDM), BMI, or breastfeeding modified these associations. SUBJECTS/METHODS: Altogether, 301 mother-child dyads with maternal prepregnancy BMI ≥ 30 and/or previous GDM participated in the Finnish Gestational Diabetes Prevention Study (RADIEL) and its 5 years follow-up. Macronutrient intakes (E%) were calculated from 3-day food records collected at 5-18 weeks' gestation, in the third trimester, and at 12 months and 5 years after pregnancy. Offspring body fat mass (BFM) and fat percentage (BF%) at 5 years were measured by bioimpedance. Statistical analyses were multivariate linear regression. RESULTS: Mean (SD) prepregnancy BMI was 33(4) kg/m2. GDM was diagnosed in 47%. In normoglycemic women, higher first half of pregnancy n-3 PUFA intake was associated with lower offspring BFM (g) (ß -0.90; 95% CI -1.62, -0.18) and BF% (ß -3.45; 95% CI -6.17, -0.72). In women with GDM, higher first half of pregnancy n-3 PUFA intake was associated with higher offspring BFM (ß 0.94; 95% CI 0.14, 1.75) and BF% (ß 3.21; 95% CI 0.43, 5.99). Higher SFA intake in the third trimester and cumulative intake across pregnancy (mean of the first half and late pregnancy) was associated with higher BFM and BF% (across pregnancy: ß 0.12; 95% CI 0.03, 0.20 and ß 0.44; 95% CI 0.15, 0.73, respectively). Higher carbohydrate intake across pregnancy was associated with lower BFM (ß -0.044; 95% CI -0.086, -0.003), and borderline associated with BF% (ß -0.15; 95% CI -0.31, 0.00). CONCLUSIONS: The macronutrient composition of maternal diet during pregnancy is associated with offspring BFM and BF% at 5 years. GDM modifies the association between prenatal n-3 PUFA intake and offspring anthropometrics.

Norethisterone and its acetate - what's so special about them?

INTRODUCTION: Progestogens (progestins) are widely used for contraception, in postmenopausal hormone therapy, and in treatment of abnormal uterine bleeding and endometriosis. Norethisterone (NET) and its acetate (NETA) differ from other progestogens by their partial conversion to ethinylestradiol (EE). We review their special characteristics and focus on the clinically relevant risk factors associated with estrogen action, such as migraine with aura and risk of thrombosis. METHODS: Narrative review based on a medical literature (OvidMedline and PubMed) search. RESULTS: NET converts to significant amounts of EE; 10-20 mg NET corresponds to 20-30 µg EE. The effects of NET on the endometrium are pronounced, making it a good choice for treating abnormal uterine bleeding, endometriosis, and endometrial hyperplasia. NET also has beneficial effects on bone mineral density and positive or neutral effects on cardiovascular health. Conversely, long-term use of NET is associated with a slightly increased breast cancer risk, and the risk of venous thromboembolism is moderately increased. This risk seems to be dose-dependent; contraceptive use carries no risk, but therapeutic doses might be associated with an increased risk. Studies suggest an association between combinations of EE and progestogens and ischaemic stroke, which in particular concerns women with migraine. No studies have, however, assessed this risk related to the therapeutic use of NET. CONCLUSIONS: NET is a potent progestogen, especially when considering the endometrium. Its partial conversion to EE, however, is important to remember. Clinical consideration is required with women at high risk for either breast cancer or thromboembolism, or experiencing migraine with aura.

Lifestyle and glycemic health 5 years postpartum in obese and non-obese high diabetes risk women.

AIM: Women with prior gestational diabetes (GDM) are at increased diabetes risk. This study aimed to assess whether lifestyle is associated with glycemic health of high-risk women 5 years postpartum, taking into account the pre-pregnancy BMI. METHODS: The RADIEL study enrolled before or in early pregnancy 720 women with pre-pregnancy BMI ≥ 30 kg/m2 and/or prior GDM. The follow-up visit 5 years postpartum included questionnaires and measurements of anthropometrics, blood pressure, and physical activity (PA) as well as analyses of glucose metabolism, lipids, and inflammatory markers. We measured body composition (Inbody) and calculated a Healthy Food Intake Index (HFII) from Food Frequency Questionnaires (FFQ). ArmBand measured PA, sedentary time, and sleep. To take into account the diverse risk groups of GDM, we divided the women based on pre-pregnancy BMI over/under 30 kg/m2. RESULTS: Altogether 348 women attended the follow-up. The obese and non-obese women showed similar prevalence of glycemic abnormalities, 13% and 19% (p = 0.139). PA levels were higher among the non-obese women (p < 0.05), except for step count, and their HFII was higher compared to the obese women (p = 0.033). After adjusting for age, education, and GDM history, PA and HFII were associated with glycemic health only among obese women. When both lifestyle factors were in the same model, only PA remained significant. PA associated with other markers of metabolic health also among the non-obese women, excluding HbA1c. CONCLUSION: Lifestyle 5 years postpartum was associated with better glycemic health only among the obese high-risk women. PA, however, is essential for the metabolic health of all high-risk women. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.com , NCT01698385.

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.

Oral Health in Women with a History of High Gestational Diabetes Risk.

We studied oral health in 115 women with and without a history of gestational diabetes (GDM), expecting poorer oral health in the GDM group. Full-mouth examinations were performed 5 years postpartum and the number of teeth, total dental index (TDI) and decayed, missing, filled teeth (DMFT) index were calculated. Bleeding on probing (BOP), probing depth (PD), visible plaque index (VPI), and clinical attachment level (CAL) were recorded. The periodontal inflammatory burden index (PIBI) was calculated. Panoramic radiographs were taken and signs of infections recorded. Oral health habits, symptoms and participants' own opinion of oral health were recorded with questionnaires. At the time of examination, 45% of the women had a history of GDM in the index pregnancy. Mild periodontitis (62%) and bleeding on probing (46%) were common. VPI (13% and 17%, p = 0.009) and PIBI (13.1 and 17.5, p = 0.041) were lower among women with a history of GDM compared with those with no history of GDM. There was no difference between groups in DMFT scores. All women reported good subjective oral health. Thus, contrary to our hypothesis, women with a history of GDM showed better oral health parameters than women without a history of GDM.

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.

Heterogeneity of gestational diabetes (GDM) and challenges in developing a GDM risk score.

AIMS: Gestational diabetes (GDM) affects a growing number of women and identification of individuals at risk, e.g., with risk prediction models, would be important. However, the performance of GDM risk scores has not been optimal. Here, we assess the impact of GDM heterogeneity on the performance of two top-rated GDM risk scores. METHODS: This is a substudy of the RADIEL trial-a lifestyle intervention study including women at high GDM risk. We assessed the GDM risk score by Teede and that developed by Van Leeuwen in our high-risk cohort of 510 women. To investigate the heterogeneity of GDM, we further divided the women according to GDM history, BMI, and parity. With the goal of identifying novel predictors of GDM, we further analyzed 319 women with normal glucose tolerance in the first trimester. RESULTS: Both risk scores underestimated GDM incidence in our high-risk cohort. Among women with a BMI ≥ 30 kg/m2 and/or previous GDM, 49.4% developed GDM and 37.4% received the diagnosis already in the first trimester. Van Leeuwen score estimated a 19% probability of GDM and Teede succeeded in risk identification in 61%. The lowest performance of the risk scores was seen among the non-obese women. Fasting plasma glucose, HbA1c, and family history of diabetes were predictors of GDM in the total study population. Analysis of subgroups did not provide any further information. CONCLUSIONS: Our findings suggest that the marked heterogeneity of GDM challenges the development of risk scores for detection of GDM.

Prevention of gestational diabetes with a prepregnancy lifestyle intervention - findings from a randomized controlled trial.

PURPOSE: Lifestyle intervention studies performed during pregnancy have shown inconsistent results in relation to prevention of gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the effect of an intervention initiated already before pregnancy in prevention of GDM in high-risk women. PATIENTS AND METHODS: A randomized controlled trial was conducted in four Finnish maternity hospitals between the years 2008 and 2014. Altogether 228 high-risk women planning pregnancy were randomized to an intervention (n=116) or a control group (n=112). The risk factors were body mass index ≥30 kg/m2 (n=46), prior GDM (n=120), or both (n=62), without manifest diabetes at study inclusion. Trained study nurses provided individualized lifestyle counseling every 3 months in addition to a group session with a dietician. The control group received standard antenatal care. GDM was defined as one or more pathological glucose values in a 75 g 2-hour oral glucose tolerance test, performed between 12 and 16 weeks of gestation and if normal repeated between 24 and 28 weeks of gestation. RESULTS: Within 12 months, 67% of the women (n=72) in the intervention group and 63% of the women (n=71) in the control group (p=0.84) became pregnant. The cumulative incidence of GDM among the women available for the final analyses was 60% (n=39/65) in the intervention group and 54% (n=34/63) in the control group (p=0.49). GDM was diagnosed already before 20 weeks of gestation in 60% (n=44/73) of the cases. CONCLUSION: The preconceptional lifestyle intervention applied in the present study did not reduce the incidence of GDM.

Effect of a lifestyle intervention during pregnancy-findings from the Finnish gestational diabetes prevention trial (RADIEL).

OBJECTIVE: To assess the effect of lifestyle counseling on perinatal outcomes among women at high risk for gestational diabetes. STUDY DESIGN: A total of 492 women with obesity and/or prior gestational diabetes were allocated to intervention (four sessions of lifestyle counseling, n = 249) or usual care (n = 243) before 20 weeks' gestation. RESULT: Lifestyle indicators, gestational weight gain, or obstetric and perinatal outcomes did not differ between the two groups. An oral glucose tolerance test in the first half of pregnancy was pathological in 37.7% (n = 87/144) of intervention and 36.5% (n = 72/197) of control group women (p = 0.81). The total incidence of gestational diabetes diagnosed in the first or second half of pregnancy was 44.8% (107/239) in the intervention and 48.1% (111/231) in the control group (p = 0.48). CONCLUSIONS: The high prevalence of impaired glucose metabolism was observed already in early pregnancy, which may have contributed to the lack of effect of the intervention.

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.

Heterogeneity of gestational diabetes (GDM) and long-term risk of diabetes and metabolic syndrome: findings from the RADIEL study follow-up.

AIMS: To assess the metabolic health of obese and non-obese women at high GDM risk 5 years postpartum. METHODS: This is a secondary analysis of the 5-year follow-up of the RADIEL GDM prevention study including 333 women at high GDM risk (BMI ≥ 30 kg/m2 and/or previous GDM). Five years postpartum metabolic health was assessed including anthropometric measurements, oral glucose tolerance test, lipid metabolism, and body composition as well as medical history questionnaires. For the analysis, we divided the women into four groups based on parity, BMI, and previous history of GDM. RESULTS: Five years postpartum impaired glucose regulation (IFG, IGT, or diabetes) was diagnosed in 15% of the women; 3.6% had type 2 diabetes. The highest prevalence was observed among obese women with a history of GDM (26%), and the lowest prevalence (8%) among primiparous obese women (p = 0.021). At follow-up 25-39% of the obese women fulfilled the diagnostic criteria for the metabolic syndrome, in the non-obese group 11% (p < 0.001). This was associated with body fat percentage. The non-obese group, however, faced metabolic disturbances (IFG, IGT, diabetes, or metabolic syndrome) at a significantly lower BMI (p < 0.001). Among women who were non-obese before pregnancy, 5 years postpartum, the obesity prevalence based on BMI was 14% and based on body fat percentage 58%. CONCLUSIONS: The prevalence of impaired glucose regulation and metabolic syndrome is high 5 years postpartum among women at high risk of GDM. There are high-risk women also among the non-obese, who develop metabolic derangements already at a lower BMI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.com , NCT01698385.

Heterogeneity of maternal characteristics and impact on gestational diabetes (GDM) risk-Implications for universal GDM screening?

OBJECTIVE: To study the incidence of gestational diabetes mellitus (GDM) in relation to phenotypic characteristics and gestational weight gain (GWG) among women at high risk for GDM. MATERIALS AND METHODS: This is a secondary analysis of a GDM prevention study (RADIEL), a randomized controlled trial conducted in Finland. 269 women with a history of GDM and/or a pre-pregnancy body mass index (BMI) ≥ 30 kg/m(2) were enrolled before 20 weeks of gestation and divided into four groups according to parity, BMI and previous history of GDM. The main outcome was incidence of GDM. RESULTS: There was a significant difference in incidence of GDM between the groups (p < 0.001). Women with a history of GDM and BMI <30 kg/m(2) showed the highest incidence (35.9%). At baseline they had fewer metabolic risk factors and by the second trimester they gained more weight. There was no interaction between GWG and GDM outcome and no significant difference in the prevalence of diabetes-associated antibodies. CONCLUSION: Despite a healthier metabolic profile at baseline the non-obese women with a history of GDM displayed a markedly higher cumulative incidence of GDM. GWG and the presence of diabetes-associated antibodies were not associated with GDM occurrence among these high-risk women. Key message Despite a healthier metabolic profile at baseline the non-obese women with previous gestational diabetes mellitus display a markedly higher cumulative incidence of gestational diabetes mellitus.