A Biobehavioral Model of Diabetes Risk in Chinese Immigrants

 描述（由申请人提供）：华裔美国人是亚裔美国人中最大的一个亚群，超过76%的华裔美国人是在国外出生的。现在有充分的证据表明，移民到美国会导致各种慢性疾病的风险增加。例如，亚裔美国人的2型糖尿病发病率上升至接近甚至超过美国白色人群的发病率，因为华裔美国人的糖尿病患病率（约12-13%）高于美国白人的4-7%，尽管他们的肥胖患病率相对较低。在中国移民中观察到的糖尿病风险增加主要归因于移民后饮食和体重增加的变化，但这些变化只能部分解释疾病风险的差异。移民健康模型表明，适应新国家生活的压力对身体健康有相当大的影响。然而，很少有研究考虑到移民对健康和疾病风险生物标志物的心理社会影响。中国移民经历了相当大的文化适应压力，社会孤立（例如，由于语言障碍，与家人分离），移民后的种族歧视，这些因素可能通过激活连接免疫系统和新陈代谢的信号通路导致亚裔美国人整体健康状况较差。这些途径部分由中性粒细胞驱动，特别是中性粒细胞弹性蛋白酶（NE）的分泌，这会损害胰岛素信号传导并增强胰岛素抵抗。目前，这些途径在人群中还没有得到很好的表征，但更广泛地了解炎症过程，特别是NE，可能会导致新的治疗方法，用于预防中国移民（相对非肥胖人群）的糖尿病。因此，在移民健康的综合生物行为模型的指导下，我们建议对美国华人移民男性和女性进行纵向研究，以解决以下具体目标：目标1：检查心理社会因素（例如，随着时间的推移，文化适应性压力、社会隔离、歧视）与2型糖尿病风险标志物相关;目的2：检查心理社会因素和糖尿病风险标志物之间的关联是否由炎症途径（包括NE分泌）介导;以及目的3：确定关键变量（即性别，美国居住时间），可能会缓和心理社会因素和炎症之间的关联，在这个移民群体。总之，该项目提供了第一个系统的机会，以评估独立的和协同作用的贡献，心理社会和行为因素对新的生物学途径潜在的糖尿病风险在美国华人。研究结果将增加我们对美国移民中观察到的健康轨迹的复杂途径的理解，并提供前所未有的机会，以确定在移民后经历重大健康转变的未充分研究的人群中进行早期干预或预防的新途径。

 DESCRIPTION (provided by applicant): Chinese Americans represent the largest subgroup of Asian Americans, and over 76% of Chinese Americans are foreign-born. It is now well-documented that immigration to the US leads to increased risk for various chronic diseases. For example, rates of type 2 diabetes in Asian Americans rise to converge with, or even exceed, rates in the US white population, as the prevalence of diabetes in Chinese Americans (~12-13%) is higher than the rates of 4-7% observed in US whites, despite their relatively low prevalence of obesity. The increased diabetes risk observed among Chinese immigrants has been primarily attributed to changes in diet and weight gain following immigration, but these changes can only partially explain disparities in disease risk. Models of immigrant health suggest that the stress of adapting to life in a new country has a considerable impact on physical health. However, few studies have considered the psychosocial impact of immigration upon biomarkers of health and disease risk. Chinese immigrants experience considerable acculturative stress, social isolation (e.g., due to language barriers, separation from family), an racial discrimination following immigration, factors that may contribute to poorer overall health among Asian Americans via activation of signaling pathways that link the immune system and metabolism. These pathways are driven in part by neutrophils and, in particular, the secretion of neutrophil elastase (NE), which can impair insulin signaling and boost insulin resistance. At present, these pathways are not well-characterized in human populations, but a greater understanding of inflammatory processes more broadly, and of NE specifically, could lead to new therapeutic approaches for preventing diabetes in Chinese immigrants, a relatively non-obese population. Therefore, guided by a comprehensive biobehavioral model of immigrant health, we propose to conduct a longitudinal study of US Chinese immigrant men and women to address the following specific aims: Aim 1: To examine whether psychosocial factors (e.g., acculturative stress, social isolation, discrimination) are associated with markers of type 2 diabetes risk over time; Aim 2: To examine whether the association between psychosocial factors and diabetes risk markers is mediated by inflammatory pathways, including NE secretion; and Aim 3: To identify key variables (i.e. gender, length of US residence) that may moderate the association between psychosocial factors and inflammation in this immigrant population. In sum, the proposed project offers one of the first systematic opportunities to assess the independent and synergistic contributions of psychosocial and behavioral factors on novel biologic pathways underlying diabetes risk in US Chinese. Study findings will increase our understanding of the complex pathways underlying the health trajectories observed among US immigrants and provide an unprecedented opportunity to identify new pathways for early intervention or prevention in this understudied population that experiences significant health transition upon migration.