加强曾患妊娠糖尿病妇女的产后心脏代谢健康：药物和生活方式策略的下一步行

发布时间：2025-10-13 17:31

控制好血糖，避免妊娠糖尿病。 #生活常识# #养生常识# #孕妇保健#

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摘要

妊娠期糖尿病（GDM）影响全球14%的妊娠，其患病率呈上升趋势这一增长是由多种因素推动的：肥胖和超重率上升、产妇高龄、通过改进筛查方法和诊断标准加强检测、饮食、身体活动和生活方式的变化，以及种族和遗传影响。与血糖正常的妊娠相比，GDM与发生2型糖尿病（T2D）的风险增加10倍相关，特别是在分娩后的前5年内。胰岛素抵抗似乎是主要的机制既往患有GDM的女性患代谢综合征的风险增加2.4倍，患心血管疾病（CVD）的风险增加2倍针对有GDM病史的女性的长期心血管结局的研究表明，CVD的风险升高与发生T2D无关，且在妊娠后的前10年最为突出建议以减肥、饮食和运动为目标的生活方式改变，以降低产后T2D的风险然而，坚持改变生活方式的人很少。6,7因此，药物干预已被用于降低产后心脏代谢风险。研究人员对既往患有GDM的超重和肥胖女性的几种药物进行了研究，重点是预防T2D（二甲双胍、吡格列酮、曲格列酮）或对心脏代谢危险因素的影响（达格列净、利拉鲁肽），并显示了有希望的结果。在3个月至3年期间，与标准护理相比，二甲双胍、吡格列酮和曲格列酮可降低高达55%的T2D风险。然而，由于肝毒性，曲格列酮于2000年退出市场。与二甲双胍或达格列净单药治疗相比，达格列净和二甲双胍在降低空腹血糖和血糖漂移以及改善血脂方面更有效与单用二甲双胍相比，利拉鲁肽联合二甲双胍治疗84周后，体重、中枢性肥胖和胰岛素敏感性的降低幅度更大然而，利拉鲁肽和二甲双胍通常会引起胃肠道不适，恶心或呕吐，这可能导致依从性降低。此外，所研究的人口主要是白人，低社会经济阶层没有代表，表明这一差距需要在今后的研究中加以解决。目前还没有其他药物治疗方法在GDM8后预防T2D的研究，其长期效果尚不清楚。以肠促胰岛素为基础的治疗方法包括利拉鲁肽、西马鲁肽（GLP-1受体激动剂）和替西帕肽（GLP-1/GIP激动剂）已被批准用于治疗t2dm和肥胖，同时改变生活方式。这些药物的减肥效果是通过中枢介导的食欲下降和胃排空延迟来实现的在没有糖尿病的肥胖患者中，与安慰剂相比，利拉鲁肽在56周内的平均体重减轻5.6 kg，西马鲁肽在68个月内的平均体重减轻18.12.7 kg，替西帕肽在72周内的平均体重减轻16.1-23.6 kg。因此，在英国，利拉鲁肽和西马鲁肽已被批准用于治疗无糖尿病的肥胖，而国家健康与护理卓越研究所的技术评估预计将在2024年底完成。尽管胰高血糖素样肽-1 （GLP-1）治疗在降低体重和脂肪量方面有效，但会导致瘦体重减少25%-39%，这是不良健康结果的独立预测因子，并强调需要同时进行饮食和运动干预以防止肌肉损失这些疗法对心脏代谢健康具有多种有利的多效性作用，其作用超出了降糖和降体重的范围，21这些疗法可能对先前患有GDM的超重和肥胖妇女有益，以减少解释性体重增加，或实现理想的体重减轻，并为随后的妊娠进行代谢优化，从而降低未来GDM和T2D的风险。然而，这些疗法是否可以用于产后还不确定。开始药物治疗的最佳时机以及产后生活方式的改变以及这些干预措施的持续时间以达到最佳的心脏代谢结果尚不清楚。在这一人群中，药物治疗预防T2D和CVD以及降低中间危险因素（血脂异常、高血压、前驱糖尿病）的长期疗效和安全性尚不清楚，需要更大规模的以肠促胰岛素为基础的治疗和其他治疗的试验来建立证据基础，并支持临床指导，考虑到他们的年轻和未来可能怀孕的母婴结局。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Enhancing postpartum cardiometabolic health for women with previous gestational diabetes: Next steps and unanswered questions for pharmacological and lifestyle strategies

Gestational diabetes mellitus (GDM) affects 14% of pregnancies worldwide, and its prevalence is on the rise.1 This increase is driven by multiple factors: the growing rates of obesity and overweight, advanced maternal age, enhanced detection through improved screening methods and diagnostic criteria, shifts in diet, physical activity and lifestyle, as well as ethnic and genetic influences. GDM is associated with a 10-fold increased risk of developing type 2 diabetes (T2D) compared with a normoglycaemic pregnancy, particularly within the first 5 years after childbirth. Insulin resistance appears to be the predominant mechanism.2 Women with previous GDM are also at a 2.4-fold increased risk of metabolic syndrome3 and twofold increased risk of cardiovascular disease (CVD).4 Studies focusing on long-term cardiovascular outcomes in women with a history of GDM demonstrated that the elevated risk of CVD is independent of developing T2D and is most prominent in the first 10 years after pregnancy.4 Lifestyle modifications targeting weight loss, diet and exercise have been recommended to reduce the risk of T2D postpartum.5 However, adherence to lifestyle modification is low.6, 7 Therefore, pharmacologic interventions have been explored for reducing cardiometabolic risk postpartum.

Several pharmacologic agents8 were investigated in overweight and obese women with past GDM focusing on preventing T2D (metformin, pioglitazone, troglitazone) or on the effects on cardiometabolic risk factors (dapagliflozin, liraglutide) and showed promising results. Metformin,9 pioglitazone10 and troglitazone11 demonstrated up to 55% reduction in the risk of T2D compared with the standard of care over the period of 3 months to 3 years. However, troglitazone was withdrawn from the market in 2000 due to hepatotoxicity. Dapagliflozin and metformin were more effective in reducing fasting plasma glucose and glucose excursions and improving lipid profile versus metformin or dapagliflozin monotherapy after 24 weeks of treatment.12 Liraglutide and metformin combined resulted in a greater reduction in weight, central adiposity and improvement in insulin sensitivity versus metformin alone after 84 weeks of treatment.13 However, liraglutide and metformin commonly cause gastrointestinal discomfort, nausea or vomiting, which may lead to reduced adherence. Furthermore, the populations studied were predominantly White and low socio-economic strata were not represented, indicating that this gap needs to be addressed in future research. No other pharmacotherapies have been studied in the context of preventing T2D after GDM8 and long-term effects are unknown.

Incretin-based therapies including liraglutide, semaglutide (GLP-1 receptor agonists) and tirzepatide (GLP-1/GIP agonist) have been licensed for managing T2D and obesity without diabetes alongside lifestyle modification.14-16 Weight lowering effects of these medications are achieved via a centrally mediated decrease in appetite and by delaying gastric emptying.17 In people living with obesity and without diabetes, mean weight loss associated with these therapies versus placebo was 5.6 kg over 56 weeks for liraglutide,18 12.7 kg over 68 months for semaglutide19 and 16.1–23.6 kg over 72 weeks for tirzepatide. Therefore, in the United Kingdom, liraglutide and semaglutide have been approved for treating obesity without diabetes while the technology appraisal from National Institute for Health and Care Excellence is expected by the end of 2024. Although effective in reducing body weight and fat mass, glucagon-like-peptide-1 (GLP-1) based treatments cause a reduction in lean body mass by 25%–39%, which is an independent predictor of poor health outcomes and emphasizes the need for concurrent dietary and exercise interventions to prevent muscle loss.20 With multiple favourable pleiotropic effects on cardiometabolic health, which go beyond glucose and weight lowering,21 these therapies may be beneficial for overweight and obese women with previous GDM to reduce interpregnancy weight gain, or achieve desirable weight loss and metabolically optimize them for the following pregnancy, thus decreasing the risk of future GDM and T2D. However, there is uncertainty as to whether these therapies can be used in the postpartum period. The optimal timing of initiating pharmacotherapy in combination with lifestyle modification postpartum and duration of such interventions to achieve the best cardiometabolic outcomes is unknown. Long-term efficacy and safety of pharmacotherapies to prevent T2D and CVD and reduce intermediate risk factors (dyslipidaemia, hypertension, prediabetes) in this population are not known and larger trials of incretin-based and other therapies are needed to build the evidence base and support clinical guidance considering their young age and maternal and foetal outcomes of possible future pregnancies.

Pharmacological interventions for diabetes prevention should always be combined with lifestyle modifications. The efficacy of lifestyle interventions to prevent or delay T2D in high-risk groups has been demonstrated in clinical trials.22-25 Diabetes Prevention Program showed that in people with elevated fasting plasma glucose or in those with impaired glucose tolerance 150 min/week of physical activity reduced the incidence of T2D by 58% versus placebo and metformin reduced this risk by 31% versus placebo during 2.8 years.22 Da Quing Study demonstrated that in people with impaired glucose tolerance, lifestyle interventions over 6 years can prevent or delay T2D by up to 14 years after the active intervention versus control.23 Finnish Diabetes Prevention Study reported that in people with impaired glucose tolerance, lifestyle intervention (diet and exercise) reduced T2D risk by 58% versus control over 3.2 years.24 The National Health Service Diabetes Prevention Programme (NHSDPP) is an interventional programme implemented at scale in England aiming to prevent T2D in adults at risk (HbA1c 42–47 mmol/mol or fasting plasma glucose 5.5–6.9 mmol/L) through behaviour change achieved via health coaching and group support.26 NHSDPP has been more effective than usual care in reducing T2D risk with evidence of cost-effectiveness, but the uptake was ~50%.26 Main strategies proposed to implement and scale interventions while ensuring fidelity (i.e. the extent to which the intervention is implemented as intended) include providing a theoretical underpinning of the programme (logic model), involving professionals trained in behavioural change techniques, using clear criteria to evaluate intervention providers, robust quality assurance and investigating whether particular parts of the intervention or formats of delivery are better received by specific populations.27 While strategies to prevent T2D targeting at-risk groups and whole populations have been cost-effective or cost-saving,28 a systematic review of cost-effectiveness of interventions to improve cardiometabolic outcomes in women with previous GDM found no randomized controlled trials reporting cost-effectiveness of lifestyle or pharmacologic interventions and concluded that rigorously designed large-scale trials are needed to address this gap.29

Additional unanswered questions concern the impact of combined interventions on foetal outcomes in subsequent pregnancies as well as on psychological well-being, quality of life, breastfeeding outcomes and maternal–infant bonding. There is a lack of evidence of the role of digital health technology in enhancing the effectiveness of and adherence to combined pharmacotherapy and lifestyle interventions in women with previous GDM calling for more research in this area. Little is known about the influence of genetic factors on the effectiveness of combined pharmacotherapy and lifestyle interventions in women with a history of GDM.

Future studies must address lack of diversity by including non-White women from low socio-economic backgrounds. They should also explore strategies to overcome the barriers to implement behaviour change with or without pharmacotherapy across various healthcare settings including those with limited resources and examine how cultural beliefs and practices influence the acceptance of and adherence to these interventions in diverse populations. These studies should adopt a multi-disciplinary approach integrating expertise in women's health, diabetes and cardiometabolic disorders and behaviour change. Finally, current guidelines are limited by a one-size-fits-all approach, offering annual HbA1c monitoring and generic advice on lifestyle modifications aimed at weight control, diet and exercise without providing specific/personalized guidance.5

In summary, future studies involving women with past GDM should prioritize addressing the unresolved questions regarding the efficacy, safety (short- and long-term) and cost-effectiveness of postpartum interventions that combine pharmacotherapies with lifestyle modification, compared with lifestyle modification alone in relation to cardiometabolic health. Future research in women with a history of GDM should focus on generating evidence to support personalized postpartum advice on diet, exercise and other components of lifestyle (sleep, stress management) with or without pharmacotherapy tailored to each woman's cardiometabolic risk and potential benefit of each intervention component.

All authors declare no conflict of interest.

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加强曾患妊娠糖尿病妇女的产后心脏代谢健康：药物和生活方式策略的下一步行

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