Interaction between rs10830963 polymorphism in MTNR1B and lifestyle intervention on occurrence of gestational diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the interaction between melatonin receptor 1B gene (MTNR1B) rs10830963 polymorphism and lifestyle intervention during pregnancy on occurrence of gestational diabetes mellitus (GDM) in high-risk women. METHODS: This is a secondary analysis of the randomised controlled gestational diabetes prevention trial 'RADIEL', conducted between 2008 and 2014 in four maternity hospitals in southern Finland. A total of 226 women with a history of GDM and/or a pre-pregnancy BMI ≥ 30 kg/m(2) were enrolled at <20 weeks of gestation (mean 13 weeks) and randomised into an intervention group receiving counselling on diet, physical activity and weight control and a control group receiving standard antenatal care. The main outcome was incidence of GDM, defined as one or more pathological glucose values in a standard 75 g 2-h OGTT. The MTNR1B rs10830963 was genotyped for further analyses. RESULTS: No significant differences were found in the genotype distribution between the intervention and the control group. A significant interaction was observed between the rs10830963 genotypes and the lifestyle intervention on age-adjusted occurrence of gestational diabetes (p = 0.038). Among women homozygous for the C allele of rs10830963, the OR for GDM was significantly lower in the intervention group than in the control group (OR 0.16 [95% CI 0.03, 0.85], p = 0.014). This difference was not seen in women heterozygous (OR 0.88 [95% CI 0.32, 2.41], p = 0.798) or homozygous (OR 2.25 [95% CI 0.34, 14.69], p = 0.384) for the risk allele G. CONCLUSIONS/INTERPRETATION: In women at high risk of GDM, only those not carrying the risk allele G benefited from the lifestyle intervention. Our results indicate that certain genetic risk variants may modify the effectiveness of lifestyle interventions. This may provide important information when planning GDM prevention studies in the future.

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.

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.

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.