Pathobiology and Reversibility of Prediabetes in a Biracial Cohort

糖尿病前期的病理生物学和可逆性的一项双胎队列研究（PROP-ABC） 建议研究一个现存的队列，包括约400名血糖正常的非洲裔美国人和 父母患有2型糖尿病的白种人后代额外5年。受试者 在2006年至2009年期间入组，并随访至2012年，在此期间， 100人发展为糖尿病，100人发展为糖尿病前期，没有种族差异的证据。的 本提案的目的是更全面地了解自然历史， 早期血糖异常的代谢预测因子，通过评估种族在 血糖进展的第二波，以及糖尿病前期可逆性的时间依赖性。 该研究测试了4个假设：1）在父母患有2型糖尿病的后代中， 从正常进展到受损的葡萄糖调节（5年内）发生在最高风险 受试者与种族无关，而晚期进展（5-10年）显示种族差异， 并通过生理、生化和行为指标预测; 2）早期微血管 并发症，外周血管疾病（PVD）和内皮功能障碍表现在 从正常血糖调节转变为受损血糖调节，显示种族差异， 血糖和非血糖因素预测; 3）“代谢健康”的胰岛素敏感性 肥胖（ISO）表型在与心脏代谢风险相关性方面显示种族差异 非裔美国人和白种人父母的后代中的因素和事件性障碍 2型糖尿病;和4）糖尿病前期状态的持续时间是一个主要的决定因素， 与生活方式干预诱导糖尿病前期患者消退的疗效呈负相关。 表型和恢复正常的葡萄糖调节。100名糖尿病前期患者 将接受强化生活方式干预（ILI），以逆转糖尿病前期， 正常约260名维持正常血糖状态的受试者将继续 随访5年;发生前驱糖尿病的人将立即接受ILI。 了解摆脱血糖正常的预测因素、种族的作用以及 新发前驱糖尿病的可逆性是至关重要的，因为 逆转前驱糖尿病的干预措施也将有助于消除下游地区的种族差异。 糖尿病事件。额外的5年随访将提供10年率的数据， 糖尿病前期事件的预测因素，第二波进展期间的种族模式，以及， 糖尿病前期的时间依赖性可逆性。关注糖尿病前期是巨大的公众 健康意义，因为它的成功逆转预防糖尿病和相关并发症。

The Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study proposes to study an extant cohort, comprising ~400 normoglycemic African American and Caucasian offspring of parents with type 2 diabetes for an additional 5-year. The subjects were enrolled between 2006 and 2009 and have been followed up to 2012, during which 11 have developed diabetes and 100 developed prediabetes, without evidence of racial disparities. The objective of the present proposal is to gain a fuller understanding of the natural history and metabolic predictors of early glucose abnormalities, by assessing the role of race during the second wave of glycemic progression, and the time dependency of reversibility of prediabetes. The study tests 4 hypotheses: 1) Among offspring of parents with type 2 diabetes, early progression from normal to impaired glucose regulation (within 5 yr) occurs in the highest-risk subjects independently of race, whereas late progression (5-10 yr) displays racial disparities, and is predicted by physiological, biochemical and behavioral markers; 2) Early microvascular complications, peripheral vascular disease (PVD), and endothelial dysfunction manifest during transition from normal to impaired glucose regulation, display racial disparities, and are predicted by glycemic and nonglycemic factors; 3) The "metabolically healthy" insulin-sensitive obese (ISO) phenotype displays racial disparities in its association with cardiometabolic risk factors and incident dysglycemia among African-Americans and Caucasians offspring of parents with type 2 diabetes; and 4) Duration of the prediabetic state is a major determinant of, and is inversely related to, the efficacy of lifestyle intervention to induce regression of the prediabetic phenotype and restoration of normal glucose regulation. The 100 participants with prediabetes will receive Intensive Lifestyle intervention (ILI), to reverse prediabetes and restore normoglycemia. The ~260 participants who have maintained normal glucose status will continue follow-up for 5 years; persons who develop prediabetes will immediately receive ILI. Understanding the predictors of the escape from normoglycemia, the role of race, and the reversibility of new-onset prediabetes is of utmost importance, because the discovery of interventions for reversal of prediabetes will also help eliminate ethnic disparities in downstream diabetes events. The additional 5 years of follow-up will provide data on 10-yr rates and predictors of incident prediabetes, racial patterns during the second wave of progression, and, time-dependent reversibility of prediabetes. Focusing on prediabetes is of immense public health significance, as its successful reversal prevents diabetes and associated complications.