Rationale, design, and baseline characteristics of the Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Authors: JENSEN, ELIZABETH - Wake Forest School Of Medicine; BERTONI, ALAIN - Wake Forest School Of Medicine; CRAGO, OSA - Wake Forest School Of Medicine; HOFFMAN, KRISTI - Baylor College Of Medicine; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); ARZUMANYAN, ZORAYR - Harbor-Ucla Medical Center; LAM, LOK - Harbor-Ucla Medical Center; ROLL, KATHRYN - Harbor-Ucla Medical Center; SANDOW, KEVIN - Harbor-Ucla Medical Center; WU, MARTIN - University Of Virginia; RICH, STEPHEN - University Of Virginia; ROTTER, JEROME - Harbor-Ucla Medical Center; CHEN, YII - Harbor-Ucla Medical Center; PETROSINO, JOSEPH - Baylor College Of Medicine; GOODARZI, MARK - Cedars-Sinai Medical Center

Submitted to: Diabetes Obesity and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/16/2020
Publication Date: 7/20/2020
Citation: Jensen, E.T., Bertoni, A.G., Crago, O.L., Hoffman, K.L., Wood, A.C., Arzumanyan, Z., Lam, L.S., Roll, K., Sandow, K., Wu, M., Rich, S.S., Rotter, J.I., Chen, Y.D., Petrosino, J.F., Goodarzi, M.O. 2020. Rationale, design, and baseline characteristics of the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Diabetes Obesity and Metabolism. https://doi.org/10.1111/dom.14145.
DOI: https://doi.org/10.1111/dom.14145

Interpretive Summary: We know that diet can both increase the risk of type 2 diabetes (T2D), and also convey protection from developing T2D. How the diet alters T2D risk, i.e. knowing the specific biological pathways that are activated and their effects on health, offers promise for designing new T2D prevention/intervention strategies, tailoring dietary advice to individuals' underlying predisposition, and for improving dietary guidelines at a global level. However, the pathways between dietary intake and T2D risk are not well understood. The gut microbiome consists of the bacteria in people's stomach and digestive tract, as well as the genetic make-up of these bacteria. The gut microbiome is the major factor involved in the digestion of the diet and its metabolism into to active biological factors. Therefore, the gut microbiome is a lead candidate for understanding how the diet conveys risk or protection from T2D, and since the make-up of the gut microbiome differs between individuals, for helping us understand why the same diet can have different effects of risk of T2D in different people. However, to date, the interplay between the diet and composition of the gut microbiome has not been well described. To address this, we have initiated a longitudinal study of 500 older US adults, in which we measure glucose tolerance (a measure of T2D risk), the diet, and the gut microbiome at several time points in order to look at how the interplay between diet and gut bacteria influence the development of T2D. The Microbiome Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic White participants aged 40-80 years without diabetes, with three planned study visits (at baseline, 15 months, and 30 months), and here we report on our initial recruitment efforts, as well as the baseline characteristics of the MILES population. After screening 875 individuals, 129 African American and 224 non-Hispanic White participants (N=353) 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 to the non-Hispanic White participants. On average, African American participants are less insulin sensitive and have higher acute insulin secretion and lower insulin clearance. Data collection for subsequent visits is ongoing. 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. It is hoped that the results of MILES will improve our ability to discern causal relationships between the gut microbiome and dietary intake in the development of T2D. The goals of MILES are to help us improve dietary advice for preventing T2D, and to set the stage for future microbiome-directed therapies to prevent and treat T2D.

Technical Abstract: The Microbiome Insulin Longitudinal Evaluation Study (MILES) was initiated to investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion, insulin clearance) whose dysfunction leads to type 2 diabetes (T2D). The study focuses on African American and non-Hispanic White participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 months, 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 to 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.