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

描述（由申请人提供）：肥胖和2型糖尿病（T2D）在非裔美国女性中不成比例地发生。神经内分泌系统，特别是下丘脑-垂体-肾上腺（HPA）轴，通过调节能量摄入和消耗，在体重的稳态中起着关键作用。围产期事件可能导致瘦素和胰岛素水平的改变，从而改变下丘脑的发育，并对体重调节和葡萄糖稳态产生持久影响。慢性应激源可引起下丘脑轴和交感肾上腺髓质轴的失调，增加发生代谢性疾病如肥胖和糖尿病的风险。与美国白人女性相比，嗜酒者的女性更易受到影响神经内分泌系统功能的因素的影响。具体来说，嗜酒者协会的女性不太可能接受母乳喂养，更有可能早产和出生体重过低，更有可能遭受暴力侵害、种族主义、抑郁和睡眠剥夺。由于FTO基因在中枢神经系统和下丘脑中高度表达，并参与食物摄入调节，因此FTO基因的遗传变异可能是在影响神经内分泌功能的情况下更容易患肥胖或T2D的个体的特征。FTO基因是与AA和欧洲血统人群中脂肪量和肥胖最密切相关的基因。我们建议前瞻性评估上述因素是否与AA女性体重增加和T2D发病率相关，以及FTO基因的遗传变异是否改变了这些关联。我们的研究将以黑人妇女健康研究（BWHS）为基础，这是一项正在进行的队列研究，共有59000名黑人妇女参与，其中有大量前瞻性收集的数据和存储的DNA样本。自1995年基线以来，BWHS每两年在随访期间收集有关体重的信息，到2009年发生了6,000多例T2D事件。我们已经发表了关于体重指数、饮食因素和体育活动与T2D风险的关系的文章，也报道了种族主义和低社会经济地位与体重增加的正相关。这项拟议的研究将为AA女性和其他人群中肥胖和T2D流行的因素提供新的数据。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: African American (AA) women are disproportionately affected by obesity and type 2 diabetes (T2D), with a heavy burden of associated health problems. The proposed study will provide data on whether psychosocial stressors and other factors that unfavorably alter the neuroendocrine system, which is involved in regulation of body weight, contribute to increased weight gain and T2D incidence in AA women.