Lactation and Incidence of Diabetes Mellitus in CARDIA Women

描述（由申请方提供）：哺乳对断奶后持续存在的心脏代谢风险因素水平具有有利影响，并可预防女性在中年至晚年发生2型糖尿病（DM）。然而，在同一研究中没有数据可以直接将哺乳与心脏代谢风险因素的持续变化联系起来（即，血浆脂质、葡萄糖、胰岛素、总体和中心性肥胖）或胰岛素抵抗的生物标志物以及随后的糖尿病发病率。我们假设较长的哺乳期对心脏代谢危险因素、胰岛素抵抗的生物标志物（即，脂肪因子、内皮功能和炎症）和内脏脂肪水平，这导致中年妇女新发糖尿病的风险降低，并且哺乳期糖尿病相关性不因妊娠期糖尿病（GDM）病史而不同。我们建议对年轻人冠状动脉风险发展（CARDIA）研究进行一项辅助研究，该研究是一项正在进行的、以美国人群为基础的纵向研究，纳入了5，115名年龄在18-30岁（1985-1986年）的黑人和白色女性和男性，由国家心肺血液研究所（NHLBI）资助。CARDIA记录了2 787名妇女的生育自然史，其中1 239人自基线（1986- 2006年）以来生育了2 147个孩子。进入第25个年头，CARDIA将测量心脏代谢风险因素（空腹血糖、胰岛素、血脂、BMI、腰围、血压）自基线以来最多8次（1986-2011），并在1995-1996或2005-2006年对不知道是糖尿病的个体进行口服葡萄糖耐量试验（OGTT），并将在2010-2011年再次举办。本研究的目的是前瞻性检查25年期间（1986-2011）的哺乳期持续时间和DM发病率，并评估哺乳是否对女性糖尿病发作前的心血管代谢风险因素以及胰岛素抵抗和肥胖的生物标志物（脂联素、IL-6、CRP、sICAM-1、瘦素、sOB-R、TNF-1）具有持久影响。我们建议从1987-1988年（第2年），1995-1996年（第10年），2000-2001年（第15年）和2005-2006年（第20年）收集的储存血清中检测生物标志物，并利用其他可用的生化和生物标志物数据来检查从怀孕前到怀孕后的变化，并评估其与中年期随后发生的DM的关系。我们还将通过计算机断层扫描检查哺乳期和中年（25岁，2010-2011年）的内脏脂肪。最后，在哺乳期事件的DM协会，我们将检查GDM的历史作为一个影响因素，和危险因素和生物标志物（怀孕前断奶后）的变化作为介质的协会。这项研究将是第一个检查“介质”的哺乳期糖尿病协会利用纵向生化数据，以保持时间的曝光（哺乳期）有关的生化变化以及疾病发作。这项研究可能会产生新的见解和假设哺乳对妇女糖尿病代谢途径的影响。母乳喂养是一种可改变的健康行为，可转化为预防DM的公共卫生干预措施，包括有GDM病史的妇女。 公共卫生相关性：母乳喂养可以降低血糖水平，防止妇女在怀孕数年后患糖尿病。目前，没有直接证据表明母乳喂养对预测女性以后患2型糖尿病的风险因素有持久的有益影响。这项拟议的研究将研究是否更长的母乳喂养时间可以保护妇女免受糖尿病的影响，并提供有关母乳喂养如何提供这种保护的新见解。

DESCRIPTION (provided by applicant): Lactation has favorable effects on cardiometabolic risk factor levels that persist after weaning, and may prevent the onset of type 2 diabetes mellitus (DM) in women in mid to late life. However, data are not available within the same study to directly link lactation to persistent changes in cardiometabolic risk factors (i.e., plasma lipids, glucose, insulin, overall and central adiposity) or biomarkers of insulin resistance as well as subsequent incidence of diabetes. We hypothesize that longer duration of lactation has lasting favorable effects on cardio- metabolic risk factors, biomarkers of insulin resistance (i.e., adipokines, endothelial function and inflammation) and visceral fat levels which lead to lower the risk of new onset diabetes in women during midlife, and the lactation-diabetes association does not differ by history of gestational diabetes mellitus (GDM). We propose an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) study, an ongoing, U.S. population-based, longitudinal study of 5,115 black and white women and men aged 18-30 yrs at enrollment (1985-1986) funded by the National Heart, Lung and Blood Institute (NHLBI). CARDIA recorded the natural history of child-bearing among 2,787 women, of whom 1,239 delivered 2,147 births since baseline (1986- 2006). Entering its 25th year, CARDIA will have measured cardiometabolic risk factors (fasting glucose, insulin, lipids, BMI, waist girth, blood pressure) up to 8 times since baseline (1986-2011), and performed oral glucose tolerance tests (OGTT) on individuals not known to be diabetic in 1995-1996 or 2005-2006, and is performing them again in 2010-2011. The goals of this study are to prospectively examine lactation duration and incidence of DM during a 25-year period (1986-2011), and assess whether lactation has lasting effects on cardio- metabolic risk factors, and biomarkers of insulin resistance and adiposity (adiponectin, IL-6, CRP, sICAM-1, leptin, sOB-R, TNF-1) that precede the onset of diabetes in women. We propose to assay biomarkers from stored sera collected in 1987-1988 (Year 2), 1995-1996 (Year 10), 2000-2001 (Year 15) and 2005-2006 (Year 20), and utilize other available biochemical and biomarker data to examine the changes from before to after pregnancy, and assess their relationship to subsequent incident DM in mid-life. We will also examine lactation duration and visceral fat in mid-life (Year 25, 2010-2011) via computed tomography. Finally, within the lactation-incident DM association we will examine history of GDM as an effect modifier, and changes in risk factors and biomarkers (prepregnancy to post-weaning) as mediators of the association. This study will be the first to examine "mediators" of the lactation-DM association by utilizing longitudinal biochemical data to preserve the temporality of the exposure (lactation) in relation to both biochemical changes as well as disease onset. The study may generate new insights and hypotheses for lactation's effects on metabolic pathways of diabetogenesis in women. Breastfeeding is a modifiable health behavior that may be translated into public health interventions for prevention of DM, including women with a history of GDM. PUBLIC HEALTH RELEVANCE: Breastfeeding may lower blood sugar levels and prevent women from developing diabetes years after pregnancy. Currently, there is no direct evidence that breastfeeding a child has lasting beneficial effects on risk factors that predict type 2 diabetes in women later in life. The proposed study will examine whether greater duration of breastfeeding protects women from developing diabetes and offer new insights on how breastfeeding may confer this protection.