背景：孕妇妊娠期高血压疾病（HDP）已被认为有助于后代心血管疾病的发展，但经验证据仍然不一致。这项研究旨在评估从儿童到成年早期，母亲整体和特定类型的HDP与后代糖尿病的关系。
方法：使用丹麦国家健康登记册，这项研究共纳入了1978年至2018年在丹麦出生的2,448,753人.孕产妇HDP包括慢性高血压，妊娠期高血压,和先兆子痫.感兴趣的结果是后代的糖尿病（包括1型，2型和妊娠期糖尿病）。后代的随访始于出生，并在首次诊断为糖尿病时结束，从丹麦移民，死亡,或时间于2018年12月31日结束，以先到者为准。Cox比例风险回归用于评估从出生到年轻成年（长达41岁）的后代中母体HDP与糖尿病（包括1型，2型和妊娠期糖尿病）之间的关联的风险比（HRs）和95％置信区间（CI）。以后代的年龄为时间尺度。
结果：在长达41年（中位数：19.3年）的随访中，患有HDP的母亲所生的1247个后代和没有HDP的母亲所生的23,645个后代被诊断患有糖尿病。与没有HDP的母亲所生的后代相比，患有HDP的母亲所生的人患整体糖尿病的风险增加（HR=1.27，95％CI=1.20-1.34），以及2型糖尿病（HR=1.57，95％CI=1.38-1.78）和妊娠糖尿病（HR=1.37，95％CI=1.25-1.49）。我们没有观察到1型糖尿病的风险明显增加（HR=1.08，95％CI=0.98-1.18）。妊娠期高血压（HR=1.37，95％CI=1.00-1.88）或先兆子痫（HR=1.62，95％CI=1.41-1.87）的母亲的后代患2型糖尿病的风险更高。重度先兆子痫的相关性最强，2型糖尿病风险为2倍（HR=2.00，95%CI=1.42-2.82）。孕妇HDP与1型糖尿病之间的关联没有达到统计学意义。妊娠高血压除外(HR=1.41，95CI=1.17-1.71)。此外,我们发现，有任何亚型母亲HDP的母亲所生的后代患妊娠期糖尿病的风险更高，和相应的慢性高血压的HR（95CIs），妊娠期高血压,子痫前期为1.60（1.06-2.41），1.29(1.04-1.59),和1.38（1.24-1.53），分别。我们还观察到，患有HDP和共病糖尿病的母亲的后代之间的关联比单独患有HDP或糖尿病的母亲的后代更强（HR=4.64，95CI=3.85-5.60）。
结论：患有HDP的母亲的后代，尤其是患有糖尿病的母亲，在他们生命后期患糖尿病的风险增加。我们的研究结果表明，应将及时有效地预防育龄妇女的HDP作为几代人的糖尿病预防和控制策略。
Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood.
Using Danish national health
registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring\'s age as the time scale.
During a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20-1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38-1.78) and gestational diabetes (HR=1.37, 95% CI=1.25-1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98-1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00-1.88) or preeclampsia (HR=1.62, 95% CI=1.41-1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42-2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17-1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06-2.41), 1.29 (1.04-1.59), and 1.38 (1.24-1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85-5.60) than offspring of mothers with HDP or diabetes alone.
Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.
