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

摘要 肥胖和2型糖尿病（T2 D）在非洲裔美国人（AA）女性中不成比例地发生。的 神经内分泌系统，特别是下丘脑-垂体-肾上腺（HPA）轴，在神经内分泌系统中起着关键作用。 通过调节能量摄入和消耗来保持体重的平衡。围产期事件可能导致 瘦素和胰岛素水平的变化，导致下丘脑发育的改变和对身体的持久影响 体重调节和葡萄糖稳态。慢性应激源可导致HPA轴和HPA轴的失调， 和交感肾上腺髓质轴，增加患代谢疾病的风险， 肥胖和T2 D。相对于美国白色女性，AA女性有更高的暴露因素， 不利地改变神经内分泌系统的功能。具体来说，AA女性不太可能有 母乳喂养，更有可能早产和低出生体重，更有可能 经历暴力受害、种族歧视、抑郁和睡眠剥夺。因为FTO基因 在AA以及欧洲血统人群中，与脂肪量和肥胖最密切相关的是高度 在中枢神经系统和下丘脑中表达，并参与食物摄入调节、遗传 FTO基因的变体可能表征在以下情况下更易患肥胖症或T2 D的个体： 影响神经内分泌功能的病症。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T2 D发病率相关， FTO基因的变异改变了这些关联。我们的研究将基于黑人妇女的健康 研究（BWHS）是一项正在进行的队列研究，纳入了59，000名AA女性，前瞻性收集了大量数据， 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，2009年发生了6，000多例T2 D事件。我们已经 发表了关于体重指数、饮食因素和体力活动与T2 D风险的关系的研究， 据报道，种族主义和低社会经济地位与体重增加的BWHS的积极协会。的 拟议的研究将提供有关可能导致肥胖和T2 D流行的因素的新数据 在AA妇女和其他人群中也是如此。

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.