Lactation and Incidence of Diabetes Mellitus in CARDIA Women

描述（由申请人提供）：哺乳对断奶后持续存在的心脏代谢危险因素水平有有利影响，并可能预防中老年妇女发生2型糖尿病（DM）。然而，在同一项研究中，没有数据可以直接将哺乳与心脏代谢危险因素（即血浆脂质、葡萄糖、胰岛素、整体和中心肥胖）或胰岛素抵抗的生物标志物以及随后的糖尿病发病率的持续变化联系起来。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）和内脏脂肪水平有持久的有利影响，从而降低中年妇女新发糖尿病的风险，并且哺乳期与糖尿病的关联并不因妊娠糖尿病（GDM）史而异。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，CARDIA研究是一项正在进行的、基于美国人群的纵向研究，由国家心肺血液研究所（NHLBI）资助，在入组时（1985-1986）对5115名年龄在18-30岁的黑人和白人女性和男性进行研究。CARDIA记录了2,787名妇女的自然生育史，其中1,239人自基线（1986- 2006年）以来生产了2,147个孩子。进入第25个年头，CARDIA将自基线（1986-2011）以来测量心脏代谢危险因素（空腹血糖、胰岛素、血脂、BMI、腰围、血压）多达8次，并在1995-1996年或2005-2006年对未患糖尿病的个体进行口服葡萄糖耐量试验（OGTT），并在2010-2011年再次进行这些试验。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和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）有持久影响。我们建议检测1987-1988年（第2年级）、1995-1996年（第10年级）、2000-2001年（第15年级）和2005-2006年（第20年级）收集的血清中的生物标志物，并利用其他可用的生化和生物标志物数据来检查怀孕前后的变化，并评估它们与中年糖尿病后续事件的关系。我们还将通过计算机断层扫描检查中年（2010-2011年25岁）的哺乳时间和内脏脂肪。最后，在哺乳期发生的糖尿病关联中，我们将研究GDM的历史作为影响调节因素，以及危险因素和生物标志物（妊娠前至断奶后）的变化作为关联的中介。这项研究将是第一个通过纵向生化数据来检验泌乳-糖尿病关联的“介质”，以保持暴露（泌乳）的时间性与生化变化和疾病发作的关系。该研究可能为哺乳对女性糖尿病发生代谢途径的影响提供新的见解和假设。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，包括有糖尿病史的妇女。

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.