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

体重增加、2型糖尿病以及影响神经内分泌功能的因素

• 批准号: 8280039
• 负责人: Edward Antonio Ruiz-Narvaez
• 金额: $ 31.17万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8280039
• 关键词: Adolescent; Adrenal Glands; Affect; African American; Alleles; Birth; Body Weight; Body mass index; Breast Feeding; Childhood; Chronic; Cohort Studies; DNA; Data; Data Collection; Development; Diagnosis; Dietary Factors; Energy Intake; Energy Metabolism; Enrollment; Epidemic; European; Event; Exposure to; Fatty acid glycerol esters; Food Intake Regulation; Gene-Modified; Genes; Geographic Locations; Health; High Prevalence; Homeostasis; Hypothalamic structure; Incidence; Individual; Insulin; Lead; Leptin; Low Birth Weight Infant; Mediating; Mental Depression; Metabolic Diseases; Nested Case-Control Study; Neuraxis; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Perinatal; Persons; Physical activity; Play; Population; Population Group; Premature Birth; Psychosocial Factor; Publishing; Regulation; Relative (related person); Reporting; Research Design; Resources; Risk; Sampling; Sleep; Sleep Deprivation; Variant; Victimization; Violence; Weight; Weight Gain; Woman; Women' s Health; base; blood glucose regulation; depressive symptoms; experience; follow-up; genetic analysis; genetic variant; high risk; hypothalamic-pituitary-adrenal axis; low socioeconomic status; novel; psychosocial; racial discrimination; racism; shift work; stressor

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.

描述（由申请人提供）：肥胖和2型糖尿病（T2 D）在非洲裔美国人（AA）女性中发生不成比例。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，在体重的体内平衡中起着关键作用。围产期事件可能会导致瘦素和胰岛素水平的变化，从而改变下丘脑发育，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HPA轴和交感肾上腺髓质轴的失调，增加发展代谢疾病如肥胖和T2 D的风险。相对于美国白色女性，AA女性更容易暴露于可能不利地改变神经内分泌系统功能的因素。具体而言，AA妇女不太可能接受母乳喂养，更有可能早产和出生体重低，更有可能经历暴力受害，种族主义，抑郁症和睡眠剥夺。因为FTO基因，与AA以及欧洲血统人群中的脂肪量和肥胖最密切相关的基因，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，FTO基因的遗传变异可能表征在影响神经内分泌功能的条件下更容易患肥胖症或T2 D的个体。我们建议前瞻性评估上述因素是否与AA女性的体重增加和T2 D发病率相关，以及FTO基因中的遗传变异是否改变了这些相关性。我们的研究将基于黑人妇女健康研究（BWHS），这是一项对59，000名AA妇女进行的队列研究，具有丰富的前瞻性收集数据和存储的DNA样本。自1995年基线以来，BWHS每两年在随访期间收集一次体重信息，截至2009年，已发生6，000多例T2 D事件。我们已经发表了关于体重指数，饮食因素和身体活动与T2 D风险的关系，并且还报告了种族主义和低社会经济地位与BWHS体重增加的正相关性。拟议的研究将提供有关可能导致AA女性和其他人群中肥胖和T2 D流行的因素的新数据。 公共卫生相关性：非裔美国人（AA）妇女不成比例地受到肥胖和2型糖尿病（T2 D）的影响，伴随着相关健康问题的沉重负担。拟议的研究将提供数据，说明心理社会压力源和其他对参与体重调节的神经内分泌系统产生不利影响的因素是否会导致AA女性体重增加和T2 D发病率增加。