Diabetes & Women's Health Study: long term health implications of GDM

糖尿病

• 批准号: 10684578
• 负责人: Edwina Yeung
• 金额: $ 0.35万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684578
• 关键词: Adult; Alcohol consumption; American; Behavior; Beta Cell; Biochemical Markers; Biological; Birth; Blood; Cardiometabolic Disease; Cardiovascular Diseases; Caring; Cell physiology; Clinical; Clinical Nutrition; Collaborations; Complications of Diabetes Mellitus; Consumption; Data; Data Collection; Deterioration; Development; Diabetes Mellitus; Diet; Diet Modification; Dietary Factors; Early identification; Enrollment; Environmental Risk Factor; Etiology; Fatty Liver; Fatty acid glycerol esters; Genetic; Genetic Markers; Genetic Risk; Gestational Diabetes; Goals; Health; Hybrids; Individual; Intake; Joints; Journals; Lactation; Life Style; Liver; Longitudinal Studies; Measures; Non-Insulin-Dependent Diabetes Mellitus; Nurses' Health Study; Nutrient; Outcome; Participant; Pathway interactions; Personal Satisfaction; Physical activity; Population; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Prevention; Process; Prolonged Lactations; Publishing; Recording of previous events; Renal function; Research; Risk; Risk Factors; Saliva; Structure of nail of toe; Suggestion; Thyroid Function Tests; Thyroid Hormones; Update; Urine; Woman; Women' s Health; Work; base; cardiometabolic risk; cardiometabolism; clinically relevant; cohort; comorbidity; design; diabetes risk; dietary; glucose metabolism; high risk; impaired glucose tolerance; improved; indexing; innovation; kidney dysfunction; member; modifiable risk; novel; offspring; prospective; public health intervention; sugar; sweetened beverage

The Diabetes & Womens Health Study, based on an innovative hybrid design combining new prospective data collection with historical data, aims to understand pathways and determinants underlying the progression from gestational diabetes (GDM) to type 2 diabetes (T2DM) and complications such as cardiovascular diseases. GDM is a common pregnancy complication. Women who develop impaired glucose tolerance and/or GDM in pregnancy are at substantially increased risk for T2DM in the years following pregnancy. Determinants underlying the transition from GDM to T2DM are not well studied and available studies are limited. There is limited information about the genetic and environmental factors that impact this transition in particular. Further, there is limited research aimed at following women with GDM long term through later adulthood for the development of T2DM and co-morbidities. These critical data gaps serve as the impetus for this study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health intervention in relation to the transition of GDM to T2DM. A secondary goal of the study is to evaluate feasibility of investigating the long-term impact of GDM and other intrauterine factors on the health and wellbeing of offspring. Data collection for this study builds upon two large existing cohorts: the Nurses' Health Study II (NHS-II) and the Danish National Birth Cohort (DNBC). The overall design of the study was published in 2014 (Zhang et al. Acta Obstetricia et Gynecologica Scandinavica). The DWH Study data collection was completed in 2016 and initial work focused on long-term comorbidities of GDM and potentially modifiable pathways. We recently published the cohort profile for the study which describes the study, the main findings, and opportunities for collaboration (Zhang BMJ Open 2019). Using data from the two independent populations within the DWH Study, the NHS-II and DNBC, we identified eight novel GDM SNPs (Ding et al. Diabetologia, 2018). These findings offer the potential to improve our understanding of the etiology of GDM, and particularly of biological mechanisms related to beta cell function. Further we have identified that in independent populations of white women with a history of GDM within the DWH study, a higher genetic risk score (GRS) for type 2 diabetes was significantly associated with a higher risk of T2D. The findings were largely consistent between the two populations. We also found suggestive evidence that the GRS association may be stronger among women with poorer dietary quality after the index pregnancy than among women with a better dietary quality. Using data from the DWH Study, we have demonstrated that GDM may be an early indicator of subsequent subclinical renal dysfunction (Rawal et al. Diabetes Care, 2018). Our findings suggest that in women with a history of GDM, deterioration of renal function may potentially precede the development of overt diabetes, although clinically relevant outcomes such as elevated UACR may manifest only after progression to diabetes. We have also shown that women with GDM during pregnancy were at an increased risk for fatty liver 9-16 years postpartum (Donnelly 2019 Journal of Diabetes). GDM may serve as another risk indicator for early identification and prevention of liver fat accumulation. We also examined for potentially modifiable risk-factors associated with long-term health among women with a history of GDM. In Danish women with a history of GDM, our findings suggest a positive association between a longer duration of lactation and higher levels of thyroid hormone 916 years postpartum, even among women with a single lifetime pregnancy (Panuganti et al. Nutrients, 2018). We identified lactation as a novel potential modifiable factor for thyroid function, and with replication, these findings may add thyroid function to the wide-array of long-term cardiometabolic outcomes associated with increased lactation duration. In addition, we demonstrated that prolonged lactation duration was related to lower risk of type 2 diabetes (Ley et al. Diabetes Care, 2020) and improved cardio-metabolic risk profiles (Ley et al. BMJ Diabetes Research and Care, 2020) among women with a history of GDM. We also investigated modifiable dietary factors among women with GDM. We found that that among Danish women with a history of GDM, a population at high risk for cardiometabolic diseases, artificially sweetened beverage intake was not associated with either improvements or determents in cardiometabolic complications (Hinkle et al. American Journal of Clinical Nutrition 2019). Although high-risk individuals are recommended to consume artificially sweetened beverage instead of sugar sweetened beverages as a means of reducing sugar intake and risk for cardio-metabolic diseases, we did not observe significant improvements or determinants in cardiometabolic health with higher artificially sweetened beverage intake in this population. in addition, we observed moderate alcohol consumption among U.S. women with a history of GDM was related to lower risk of type 2 diabetes (Hinkle et al. JAMA Network Open, 2021). Taken all these together, findings from the study suggested that the greater long-term risk for type 2 diabetes and comorbidity may be mitigated through modification of diet, lifestyle and behavior factors. The study team is in the process of examining the joint impacts of modifiable risk factors and genetic factors on long-term risk of type 2 diabetes and cardiovascular diseases among women following pregnancies complicated by GDM.

糖尿病与女性健康研究基于创新的混合设计，将新的前瞻性数据收集与历史数据相结合，旨在了解从妊娠期糖尿病（GDM）发展为2型糖尿病（T2 DM）和心血管疾病等并发症的途径和决定因素。 GDM是一种常见的妊娠并发症。妊娠期发生糖耐量受损和/或GDM的女性在妊娠后数年内发生T2 DM的风险显著增加。从GDM转变为T2 DM的决定因素尚未得到充分研究，现有研究有限。特别是关于影响这种转变的遗传和环境因素的信息有限。此外，有有限的研究旨在跟踪GDM女性长期到成年后期的T2 DM和合并症的发展。这些关键数据缺口是本研究的动力，其总体目标是研究遗传因素及其与GDM向T2 DM转变相关的临床或公共卫生干预风险因素的相互作用。本研究的第二个目的是评估研究GDM和其他宫内因素对后代健康和福祉的长期影响的可行性。 这项研究的数据收集建立在两个大型现有队列基础上：护士健康研究II（NHS-II）和丹麦国家出生队列（DNBC）。研究的总体设计于2014年发表（Zhang et al. Acta Obstetricia et Gynecologica Scandinavica）。DWH研究数据收集于2016年完成，初步工作集中在GDM的长期合并症和潜在的可改变途径。我们最近发表了这项研究的队列资料，其中描述了这项研究，主要发现和合作机会（Zhang BMJ Open 2019）。 使用DWH研究中两个独立人群（NHS-II和DNBC）的数据，我们确定了8种新的GDM SNP（Ding et al. Diabetologia，2018）。这些发现提供了提高我们对GDM病因学的理解的潜力，特别是与β细胞功能相关的生物学机制。此外，我们还发现，在DWH研究中，在有GDM病史的白色女性独立人群中，2型糖尿病遗传风险评分（GRS）较高与T2 D风险较高显著相关。这两个群体的研究结果基本一致。我们还发现了提示性证据，即在指数妊娠后饮食质量较差的女性中，GRS的相关性可能比饮食质量较好的女性更强。 使用DWH研究的数据，我们证明GDM可能是后续亚临床肾功能不全的早期指标（Rawal et al. Diabetes Care，2018）。我们的研究结果表明，在有GDM病史的女性中，肾功能恶化可能先于显性糖尿病的发展，尽管临床相关的结局（如UACR升高）可能仅在进展为糖尿病后才表现出来。我们还表明，妊娠期GDM女性产后9-16年患脂肪肝的风险增加（Donnelly 2019 Journal of Diabetes）。妊娠期糖尿病可作为早期识别和预防肝脏脂肪堆积的另一个风险指标。 我们还检查了与有GDM病史的女性长期健康相关的潜在可改变的风险因素。在有GDM病史的丹麦女性中，我们的研究结果表明，哺乳期较长与产后916年甲状腺激素水平较高之间存在正相关性，即使在一生中只有一次妊娠的女性中也是如此（Panuganti et al. Nutrients，2018）。我们确定哺乳是甲状腺功能的一个新的潜在可改变因素，并且通过复制，这些发现可能会将甲状腺功能添加到与哺乳时间增加相关的长期心脏代谢结果中。此外，我们证明了哺乳期延长与有GDM病史的女性中2型糖尿病风险降低（Ley et al. Diabetes Care，2020）和心脏代谢风险改善（Ley et al. BMJ Diabetes Research and Care，2020）相关。我们还调查了GDM妇女中可改变的饮食因素。我们发现，在有GDM病史的丹麦女性中，心脏代谢疾病的高风险人群，人工甜味饮料摄入与心脏代谢并发症的改善或抑制无关（Hinkle et al. American Journal of Clinical Nutrition 2019）。尽管建议高风险人群饮用人工加糖饮料而不是加糖饮料，作为减少糖摄入量和心脏代谢疾病风险的一种手段，但我们没有观察到该人群中人工加糖饮料摄入量较高时心脏代谢健康的显着改善或决定因素。此外，我们观察到有GDM病史的美国女性适度饮酒与2型糖尿病风险降低有关（Hinkle et al. JAMA Network Open，2021）。综上所述，研究结果表明，通过改变饮食、生活方式和行为因素，可以减轻2型糖尿病和合并症的长期风险。该研究小组正在研究可改变的风险因素和遗传因素对妊娠合并GDM的妇女患2型糖尿病和心血管疾病的长期风险的联合影响。

项目成果

Prevalence of Gestational Diabetes and Risk of Progression to Type 2 Diabetes: a Global Perspective.

• DOI: 10.1007/s11892-015-0699-x
• 发表时间: 2016-01
• 期刊: Current diabetes reports
• 影响因子: 4.2
• 作者: Zhu Y;Zhang C
• 通讯作者: Zhang C

Maternal dietary intakes of refined grains during pregnancy and growth through the first 7 y of life among children born to women with gestational diabetes.

• DOI: 10.3945/ajcn.116.136291
• 发表时间: 2017-07
• 期刊: The American journal of clinical nutrition
• 作者: Yeyi Zhu;S. Olsen;P. Mendola;T. Halldorsson;E. Yeung;C. Granström;A. Bjerregaard;Jing Wu;Shristi Rawal;J. Chavarro;F. Hu;Cuilin Zhang