Project Summary / Abstract Cardiometabolic diseases are largely preventable but have remained the leading cause death worldwide for over 15 years. Low and Middle Income Countries (LMIC) shoulder an increasing majority of this burden. Though often overlooked, rural, remote LMIC regions, such as the Amazon rainforest, are of particular interest as they are undergoing massive anthropogenic changes (i.e. resource extraction, infrastructure development and rapid ur- banization) and as a result, have increasing availability of, and access to, the Western Diet. Addressing diet- related health risks associated with the demographic and nutritional transitions in these LMIC regions is crucial, but has been limited by the lack of quantitative biomarkers to measure dietary intake. Two promising non- invasive biomarkers for this application are carbon and nitrogen stable isotope ratios (CIR and NIR). The CIR is elevated in key components (corn, sugar cane) of the Western, but not the traditional Amazonian (cassava, potatoes) diet. In contrast, the NIR is elevated in fish, a key traditional protein, but is not in animal-based foods characteristic of Westernization (e.g. farmed chicken, beef). Thus, CIR and NIR, which are potentially more sensitive and less biased than diet surveys, can provide objective enculturation proxies. While CIR and NIR have demonstrated associations with cardiometabolic risks in upper income countries, the associations in LMIC have yet to be investigated. The central hypothesis of this study is that CIR and NIR reflect the changing epidemio- logical profiles associated with urbanization and infrastructure development in a nutritionally transitioning popu- lations. The objective of this proposal is to evaluate changes in adult dietary patterns and cardiometabolic dis- ease risk profiles (hbA1C, HDL-C, LDL-C, height, weight, waist-hip ratio, blood pressure, and triglycerides) as- sociated with the construction of the Interoceanic Highway (IOH) through Peru's Southern Amazon by measuring these biomarkers of the nutrition transition and complementary dietary survey data. This study leverages two related studies that draw from the same population (combined cohort n=1958) with well-suited highway-adjacent and riverine comparison groups in varying stages of nutrition transition. Aim 1 tests the association between highway exposure and household level western diet adoption using stored samples from 2014. Aim 2 and Aim 3 follow the cohort forward in 2021 to test whether CIR and NIR are associated with cardiometabolic risks factors in the Amazon (Aim 2) and whether large-scale anthropogenic change modifies the diet-disease relationship (Aim 3) using stratified random effects models to account for household and community clustering. The expected contribution of this research is improved understanding of the specific changes in the dietary drivers of cardi- ometabolic disease risks associated with infrastructure development in remote LMIC regions by using novel unbiased dietary assessment tools. This work substantially adds to the limited body of evidence on novel bi- omarkers of the nutrition and transition. It and could apply to other areas undergoing infrastructure development and contribute to effective disease prevention strategies.

Project Narrative The proposed research is relevant to public health because it is the first study to apply the use of unbiased, objective biomarkers of the western diet pattern to study cardiometabolic disease risks following large-scale anthropogenic development in an LMIC. This project is relevant to the mission of the Fogarty International Center (FIC) to support the next generation of scientists trained to think and work across multiple disciplines to address global health needs. It speaks to the FIC strategic plan goal to improve the understanding of complex ecosystems in which non communicable disease risk factors, including rapid urbanization, lifestyle changes, nutrition and others interact to contribute to the epidemic of non-communicable diseases in low and middle income countries.