Early-Life Nutrition Supplementation Was Associated with Attenuated Postprandial Glycemia in Adulthood

Abstract

Abstract Objectives Populations who were malnourished in early life are susceptible to cardiometabolic disturbances. Metabolic flexibility, the adaptive response to environmental signals such as food ingestion, is integral to cardiometabolic health. We hypothesized that participants exposed to improved nutrition in early life, compared with those unexposed, have better metabolic flexibility. Methods In 1969–77, Guatemalan participants were randomized at the village level to receive either a protein and energy supplement or a low-calorie control. In 2015–17, we collected plasma samples before and 2 h after a mixed-component meal challenge. We characterized metabolic flexibility through meal-induced lipid, glycemic, and pro- and anti-inflammatory responses. Using linear regression for single-marker responses and multivariate analysis of variance (MANOVA) for domain-specific responses, we compared metabolic flexibility between participants exposed to the nutrition supplement from conception to 2y (the “first 1000 days”) versus others. Using structural equation modelling (SEM), we investigated the relationships among postprandial biomarker responses. Results Among 1027 participants (aged 44.0 ± 4.2 y, 59.4% women) who completed the meal challenge, 22.9% were exposed to the supplement in the full first 1000 days. At the single-marker level, insulin increased the most (>2x), whereas non-esterified fatty acids (NEFA) decreased the most (by half) post meal, regardless of early-life nutritional exposure status (P > 0.05 for insulin and NEFA, respectively). Glucose increased by 11.4% in the exposed group, compared with 15.7% in the unexposed group (P < 0.05). SEM identified three latent variables (LV) for postprandial biomarker changes. LV1 and 3 were lipid response-dominant; LV2 was glycemic response-dominant (comparative fit index 0.89, root mean square error of approximation 0.10). MANOVA results showed that the glycemic domain differed by early-life nutritional exposure (P = 0.03). No difference was observed in other domains. Conclusions Early-life exposure to improved nutrition was associated with more favorable glycemic response in this population but not with significant differences in lipid or inflammatory responses. Funding Sources National Institutes of Health Grant No. HD075784.