Teratology Information Service, Department of Emergency Medicine and Services, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
Diabetologia. 2022 Aug;65(8):1291-1301. doi: 10.1007/s00125-022-05712-7. Epub 2022 Apr 30.
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.
The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m 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.
Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA) 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.
ClinicalTrials.gov identifier: NCT01698385.
目的/假设：本研究旨在评估遗传风险与生活方式干预对妊娠糖尿病（GDM）和产后糖尿病发生的相互作用。
RADIEL 研究是一项 RCT，旨在通过生活方式干预预防 GDM 和产后糖尿病。BMI≥30kg/m2 和/或既往有 GDM 的参与者在妊娠前或孕早期被分配到干预组和对照组。研究访视在妊娠前每 3 个月进行一次，在每个孕早期、孕中期和产后 6 周及 6 和 12 个月进行一次。我们根据 50 个 2 型糖尿病风险变异体计算了多基因风险评分（PRS）。
共有 516 名参与者提供了遗传和 GDM 数据。PRS 与妊娠中、晚期和产后 12 个月时的血糖水平（空腹血糖和/或 HbA）和胰岛素分泌指数较低以及产后 12 个月时 GDM 和血糖异常的发生率较高相关（n=356）。在分析妊娠期间第一次研究访视时没有 GDM 的参与者（n=386）时，PRS 与生活方式干预之间存在交互作用（妊娠时 p=0.016，产后 p=0.024）。当根据 PRS 将女性分为三分位时，仅在遗传风险最高的组中，干预措施才有效降低了年龄校正后的 GDM 发生率（OR 0.37；95%CI 0.17,0.82）。在调整 BMI、产次、吸烟和教育因素后，同一组女性产后 12 个月时血糖异常的风险降低（OR 0.35；95%CI 0.13,0.97）。
结论/解释：糖尿病遗传易感性改变了生活方式干预预防 GDM 和产后糖尿病的反应。这表明，根据遗传风险调整生活方式干预可能会受益。
ClinicalTrials.gov 标识符：NCT01698385。
