Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Department of Molecular Virology and Microbiology, Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA.
Diabetes Obes Metab. 2020 Nov;22(11):1976-1984. doi: 10.1111/dom.14145. Epub 2020 Aug 20.
To investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion and insulin clearance) whose dysfunction leads to type 2 diabetes (T2D).
The Microbiome and Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic white participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 and 30 months). Baseline measurements include assessment of the stool microbiome and administration of an oral glucose tolerance test, which will yield indexes of insulin sensitivity, insulin secretion and insulin clearance. The gut microbiome profile (composition and function) will be determined using whole metagenome shotgun sequencing along with analyses of plasma short chain fatty acids. Additional data collected include dietary history, sociodemographic factors, health habits, anthropometry, medical history, medications and family history. Most assessments are repeated 15 and 30 months following baseline.
After screening 875 individuals, 129 African American and 224 non-Hispanic white participants were enrolled. At baseline, African American participants have higher blood pressure, weight, body mass index, waist and hip circumferences but similar waist-hip ratio compared with the non-Hispanic white participants. On average, African American participants are less insulin-sensitive and have higher acute insulin secretion and lower insulin clearance.
The longitudinal design and robust characterization of potential mediators will allow for the assessment of glucose and insulin homeostasis and gut microbiota as they change over time, improving our ability to discern causal relationships between the microbiome and the insulin homeostasis traits whose deterioration determines T2D, setting the stage for future microbiome-directed therapies to prevent and treat T2D.
研究肠道微生物组在调节关键胰岛素稳态特征（胰岛素敏感性、胰岛素分泌和胰岛素清除）中的作用，这些特征的功能障碍导致 2 型糖尿病（T2D）。
肠道微生物组和胰岛素纵向评估研究（MILES）专注于年龄在 40-80 岁之间、没有糖尿病的非裔美国人和非西班牙裔白人参与者。计划进行三次研究访问（基线、15 和 30 个月）。基线测量包括粪便微生物组评估和口服葡萄糖耐量试验，该试验将产生胰岛素敏感性、胰岛素分泌和胰岛素清除的指标。肠道微生物组谱（组成和功能）将通过全宏基因组鸟枪法测序以及血浆短链脂肪酸分析来确定。收集的其他数据包括饮食史、社会人口统计学因素、健康习惯、人体测量学、病史、药物和家族史。大多数评估在基线后 15 和 30 个月重复进行。
在筛选了 875 个人后，招募了 129 名非裔美国人和 224 名非西班牙裔白人参与者。在基线时，非裔美国参与者的血压、体重、体重指数、腰围和臀围较高，但与非西班牙裔白人参与者的腰臀比相似。平均而言，非裔美国参与者的胰岛素敏感性较低，急性胰岛素分泌较高，胰岛素清除率较低。
纵向设计和对潜在介质的稳健表征将允许评估葡萄糖和胰岛素稳态以及肠道微生物组随时间的变化，从而提高我们辨别微生物组与决定 T2D 的胰岛素稳态特征之间因果关系的能力，为未来基于微生物组的治疗方法预防和治疗 T2D 奠定基础。
