Nutrition and infection are key determinants of child growth and survival. Chronic inflammation, which results in part from an increased lifetime burden of infectious disease, is an underlying determinant of adult cardiometabolic disease. The modifiability of this risk by improving nutrition in early life is unknown. Our principal objective is to determine whether improvements in early-life nutrition can attenuate the development of cardiometabolic risk. We will collect new data from the INCAP (Guatemala) Nutrition Supplementation Trial cohort. From 1969-77, 2392 children received atole, a high protein and calorie supplement, or fresco, a low calorie drink, for up to 8 y. Children who received atole in the first 3 y of life grew better in childhood and recovered more quickly from diarrheal illness episodes than did children who received fresco. We have followed this cohort prospectively. We propose to re-contact the surviving members of the cohort. The cohort will be 38-53 y old, an ideal age to assess cardiometabolic risk. We will conduct clinical examinations, including (for the first time in this cohort) collection of biomarkers of cardiometabolic risk. We will assay the samples for established and novel biomarkers, including highly innovative metabolomic profiling. We will update and enhance the extensive life-course data that we collected in previous surveys. We will link the new data to our existing rich database to address critical questions regarding the long-term effects on cardiometabolic health of both chronic under-nutrition and an effective intervention to combat under-nutrition, in the context of a community-randomized trial that controls for otherwise intractable questions of endogeneity. The study will be unique in its ability to address unanswered questions relating to early life determinants of adult health. This prospectively-studied cohort has reached an age where the prevalence of cardiometabolic risk is non-negligible. The highly productive research team has extensive experience with survey work among this cohort, demonstrated capacity to link data across study waves, and extensive experience with the appropriate field methods, laboratory methods, and statistical approaches to data analysis. The resulting extensive repository of data and samples will enhance the value of the cohort for future research. Taken together, these elements ensure that the study will be well positioned to successfully address critical understudied questions in human health and development.
Non-communicable diseases, especially cardiometabolic diseases and cancer, are a large and rapidly growing proportion of the global burden of disease. Early-life factors, including undernutrition, have been implicated in the etiology of this epidemic Our study will address the critical question of whether improvements in early life nutrition can modify adult health and socioeconomic development by examining the cascade of events from early life nutrition and infections through chronic inflammation to cardiometabolic risk in a cohor who participated as children in a nutrition supplementation trial.
|Rao, Anuradha; Kosters, Astrid; Mells, Jamie E et al. (2016) Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice. Sci Transl Med 8:357ra122|