Lactation and Incidence of Diabetes Mellitus in CARDIA Women

描述(申请人提供)：哺乳对断奶后持续存在的心脏代谢危险因素水平有良好的影响，并可能防止女性在中老年发生2型糖尿病(DM)。然而，在同一项研究中，没有数据直接将哺乳与心脏代谢风险因素(即血脂、血糖、胰岛素、总体和中心性肥胖)或胰岛素抵抗的生物标记物以及随后的糖尿病发病率的持续变化联系起来。我们假设，较长的哺乳时间对心脏代谢风险因素、胰岛素抵抗的生物标记物(即脂肪因子、内皮功能和炎症)和内脏脂肪水平具有持久的有利影响，从而降低女性中年新发糖尿病的风险，并且哺乳与糖尿病的相关性不因妊娠期糖尿病(GDM)病史而异。我们建议对青年成人冠状动脉风险发展(CARDIA)研究进行一项辅助研究，这是一项正在进行的、基于美国人群的纵向研究，由美国国家心肺血液研究所(NHLBI)资助，研究对象为5,115名18-30岁的黑人和白人女性和男性(1985-1986)。CARDIA记录了2,787名妇女的生育自然历史，其中1,239名妇女自基线(1986-2006年)以来分娩了2,147名婴儿。进入第25个年头以来，CARDIA将自基线(1986-2011年)以来8次测量心脏代谢风险因素(空腹血糖、胰岛素、血脂、BMI、腰围、血压)，并在1995-1996年或2005-2006年对未知糖尿病患者进行口服葡萄糖耐量测试(OGTT)，并将在2010-2011年再次进行这些测试。这项研究的目标是前瞻性地检查25年(1986-2011年)期间的哺乳期和糖尿病发病率，并评估哺乳期是否对女性糖尿病发病前的心脏代谢危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、肿瘤坏死因子-1)具有持久的影响。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怀孕前到怀孕后的变化，并评估它们与中年DM后续发生的关系。我们还将通过计算机断层扫描检查中年(25年，2010-2011年)的哺乳期和内脏脂肪。最后，在哺乳-糖尿病关联中，我们将检查妊娠期糖尿病的病史作为影响因素，以及风险因素和生物标记物(孕前到断奶后)的变化作为关联的中介。这项研究将首次通过利用纵向生化数据来保存暴露(哺乳)与生化变化以及疾病发病的关系的时间性，来检查哺乳期-糖尿病相关性的“中介”。这项研究可能会对哺乳期对女性糖尿病发生的代谢途径的影响产生新的见解和假设。母乳喂养是一种可改变的健康行为，可转化为预防糖尿病的公共卫生干预措施，包括有妊娠期糖尿病病史的妇女。

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.