Weight gain, type 2 diabetes, and factors that affect neuroendocrine function

摘要 肥胖和2型糖尿病(T2D)在非裔美国人(AA)女性中发生的比例不成比例。这个 神经内分泌系统，尤其是下丘脑-垂体-肾上腺(HPA)轴在 通过调节能量摄入和消耗来维持体重的动态平衡。围产期事件可能会导致 瘦素和胰岛素水平的变化导致下丘脑发育改变和对身体的持久影响 体重调节和血糖稳态。慢性应激源可导致两个HPA轴的放松调节 和交感肾上腺髓质轴，增加了患代谢性疾病的风险，如 肥胖和T2D。相对于美国白人女性，AA女性对以下因素的暴露更高 不利地改变神经内分泌系统的功能。具体地说，再生障碍性贫血女性不太可能有 母乳喂养，更有可能早产，出生体重低，更有可能 经历暴力侵害、种族主义、抑郁和睡眠剥夺。因为FTO基因，这个基因 在AA和欧洲血统的人群中，与脂肪质量和肥胖密切相关的是 在中枢神经系统和下丘脑表达，并参与食物摄取调节，基因 FTO基因的变异可能是以下情况下更容易发生肥胖或T2D的个体的特征 影响神经内分泌功能的疾病。我们建议前瞻性地评估上述情况是否- 上述因素与AA女性的体重增加和T2D的发生率有关，以及是否遗传 FTO基因的变异改变了这些联系。我们的研究将基于黑人妇女的健康 研究(BWHS)，一项正在进行的队列研究，对59,000名再生障碍性贫血女性进行了研究，其中包括大量前瞻性收集的数据和 储存的DNA样本。BWHS在随访期间每两年收集一次体重信息 自1995年基线以来，截至2009年，共发生了6,000多起T2D事件。我们已经这么做了 发表了关于体重指数、饮食因素和体力活动与T2D风险的关系的文章，还 据报告，种族主义和低社会经济地位与BWHS的体重增加有积极关联。这个 拟议中的研究将为可能导致肥胖和T2D流行的因素提供新的数据 在再障妇女和其他人口群体中也是如此。

ABSTRACT Obesity and type 2 diabetes (T2D) occur disproportionately among African-American (AA) women. The neuroendocrine system, and in particular the hypothalamic-pituitary-adrenal (HPA) axis, plays a key role in the homeostasis of body weight through regulation of energy intake and expenditure. Perinatal events may cause changes in leptin and insulin levels that lead to altered hypothalamic development and lasting effects on body weight regulation and glucose homeostasis. Chronic stressors can cause deregulation of both the HPA axis and the sympathetic adrenal medullary axis, increasing the risk of developing metabolic diseases such as obesity and T2D. Relative to U.S. white women, AA women have a higher exposure to factors that can unfavorably alter functioning of the neuroendocrine system. Specifically, AA women are less likely to have been breastfed, more likely to have been born preterm and with a low birth weight, and more likely to experience violence victimization, racism, depression, and sleep deprivation. Because the FTO gene, the gene most strongly associated with fat mass and obesity in AA as well as European ancestry populations, is highly expressed in the central nervous system and hypothalamus and is involved in food intake regulation, genetic variants of the FTO gene may characterize individuals who are more susceptible to obesity or T2D under conditions that affect neuroendocrine functioning. We propose to prospectively assess whether the above- mentioned factors are associated with weight gain and incidence of T2D in AA women, and whether genetic variants in the FTO gene modify these associations. Our study will be based on the Black Women's Health Study (BWHS), an ongoing cohort study of 59,000 AA women with a wealth of prospectively collected data and with stored DNA samples. The BWHS has collected information on weight every two years during follow-up since baseline in 1995, and over 6,000 incident cases of T2D have occurred through 2009. We have already published on the relation of body mass index, dietary factors, and physical activity to risk of T2D and have also reported positive associations of racism and low socioeconomic status with weight gain in the BWHS. The proposed study will provide novel data on factors that may be contributing to the epidemic of obesity and T2D in AA women and in other population groups as well.