Pathobiology and Reversibility of Prediabetes in a Biracial Cohort

糖尿病前期的双相队列研究(PROP-ABC)的病理生物学和可逆性 建议研究一个现有的队列，其中包括大约400名血糖正常的非裔美国人和 患有2型糖尿病的父母的高加索后代再多活5年。受试者是 在2006至2009年间注册，并一直跟踪到2012年，在此期间，11人 患糖尿病的有100人，糖尿病前期有100人，没有种族差异的证据。这个 这项建议的目的是为了更全面地了解自然历史和 通过评估种族在早期血糖异常中的作用，预测早期血糖异常的代谢指标 第二波血糖进展，以及糖尿病前期可逆性的时间依赖性。 这项研究检验了4个假设：1)在患有2型糖尿病的父母的子女中，早期 从正常到受损的血糖调节进展(在5年内)发生在高危人群中。 受试者不受种族影响，而晚期(5-10岁)表现出种族差异， 由生理、生化和行为标志物预测；2)早期微血管 并发症、外周血管疾病(PVD)和内皮功能障碍在 从正常到血糖调节受损的转变，表现出种族差异，以及 由血糖和非血糖因子预测；3)“代谢健康”的胰岛素敏感型 肥胖(ISO)表型与心脏代谢风险的相关性存在种族差异 非裔美国人和高加索人父母子女血糖异常的相关因素和发病情况 2型糖尿病；以及4)糖尿病前期状态的持续时间是糖尿病前期的主要决定因素 与生活方式干预诱导糖尿病前期患者消退的效果成反比 正常血糖调节的表型和恢复。100名糖尿病前期患者 将接受强化生活方式干预(ILI)，以逆转糖尿病前期并恢复 血糖正常。维持正常血糖状态的~260名参与者将继续 随访5年；糖尿病前期患者将立即接受ILI。 了解脱离正常血糖的预测因素，种族的作用，以及 新发糖尿病前期的可逆性至关重要，因为发现 逆转糖尿病前期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。另外5年的跟踪调查将提供有关10年利率和 糖尿病前期发病的预测因素，第二波进展中的种族模式，以及， 糖尿病前期随时间变化的可逆性。关注糖尿病前期具有极大的公众性 这对健康具有重要意义，因为它的成功逆转可以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.