Early childhood growth failure and the developmental origins of adult disease: Do enteric infections and malnutrition increase risk for the metabolic syndrome?

Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA Institute of Biomedicine, Federal University of Ceará, Fortaleza, Ceará, Brazil Division of Developmental & Behavioral Pediatrics, Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA, and the Center for Global Health, University of Virginia, Charlottesville, Virginia, USA Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA Division of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Nutrition Reviews (Impact Factor: 6.08). 11/2012; 70(11):642-653. DOI: 10.1111/j.1753-4887.2012.00543.x
Source: PubMed


Hypotheses regarding the developmental origins of health and disease postulate that developing fetuses - and potentially young children - undergo adaptive epigenetic changes that have longstanding effects on metabolism and other processes. Ongoing research explores whether these adaptations occur during early life following early childhood malnutrition. In the developing world, there remains a high degree of nutritional stunting, defined as linear growth failure caused by inadequate caloric intake, which may be exacerbated by inflammation from ongoing infections. In areas with poor sanitation, children experience vicious cycles of enteric infections and malnutrition, resulting in poor nutrient absorption as a result of changes in the intestinal mucosa, now termed "environmental enteropathy." Emerging evidence links early childhood diarrhea and/or growth failure with an increased occurrence of risk factors for cardiovascular disease in later life, including dyslipidemia, hypertension, and glucose intolerance. The mechanisms for these associations remain poorly understood and may relate to epigenetic responses to poor nutrition, increased inflammation, or both. Given the increased incidence of cardiovascular disease in developing areas of the world, associations between childhood malnutrition, early-life infections, and the increased occurrence of risk factors for cardiovascular disease underscore further reasons to improve nutrition and infection-related outcomes for young children worldwide.

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    • "American Journal of Human Biology b-cells, resulting in decreased insulin production. Alternatively , pro-inflammatory consequences (e.g., increase in tumor necrosis factor) of repeated infections and/or chronic stress during childhood might lead to insulin resistance and thereby increase risk for type 2 diabetes (DeBoer et al., 2012). The Dutch Famine Study demonstrated that even a short period of moderate or severe undernutrition during the postnatal period can increase risk for diabetes (van Abeelen et al., 2012). "
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    ABSTRACT: Objectives Studies from developed societies have shown that individuals with short legs relative to height have higher risk of type 2 diabetes. This has been much less explored in less developed populations where influences on relative leg length and diabetes may differ. The Brazilian Longitudinal Study of Adult Health (in Portuguese, ELSA-Brasil) allows us to test, in a cohort born (1934–1975) and raised when undernutrition was common, whether short legs relative to height is positively associated with diabetes, independent of early-life factors, including birth weight, age at menarche, and young-adult BMI.Methods We used baseline, cross-sectional data from 15,105 participants aged 35–74 years participating in ELSA-Brasil. We created age-and-sex-specific Z scores for leg length index (leg length/height × 100) according to an external reference. Diabetes was defined by self-reported physician diagnosis, medication use, fasting and 2-h post-75-g-load glucose, and A1C.ResultsA one-unit decrement in leg-length-index Z score was associated with 12% (8–17%) higher prevalence of diabetes in Brazilian adults, after adjustment through Poisson regression for confounders, including race, maternal education, and birth weight. This association persisted after further adjustment for menarche age, BMI (at age 20), buttocks circumference, and waist circumference. It was stronger among women with early menarche (P interaction = 0.02). Leg length index was also inversely associated with fasting glucose, fasting insulin, 2-h glucose, and A1C (P < 0.05).Conclusions In contemporary Brazilian adults, short legs relative to height is positively associated with diabetes independent of measures of intrauterine growth, pubertal timing, and young-adult adiposity. This association is stronger in women with early menarche. Am. J. Hum. Biol., 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.
    American Journal of Human Biology 10/2014; 27(2). DOI:10.1002/ajhb.22641 · 1.70 Impact Factor
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    • "We hypothesize that exposure to environmental pathogens, measured through household sanitation and individual illness history, will be associated with acute elevations in CRP. Further, we would expect to see this pattern more strongly in children and adolescents with higher exposures in rural areas, since children tend to be more vulnerable to environmental pathogens (DeBoer et al. 2012). Second, we hypothesize that moderate elevations in CRP will be associated with obesogenic exposures, such as high BMI and waist circumference, that are increasingly common among adults living in urban areas. "
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    ABSTRACT: Influenced by pathogen exposure and obesity, inflammation provides a critical biological pathway linking changing environments to the development of cardiometabolic disease. This study tests the relative contribution of obesogenic and pathogenic factors to moderate and acute CRP elevations in Chinese children, adolescents and adults. Data come from 8795 participants in the China Health and Nutrition Study. Age-stratified multinomial logistic models were used to test the association between illness history, pathogenic exposures, adiposity, health behaviors and moderate (1-10 mg/L in children and 3-10 mg/L in adults) and acute (>10mg/L) CRP elevations, controlling for age, sex and clustering by household. Backward model selection was used to assess which pathogenic and obesogenic predictors remained independently associated with moderate and acute CRP levels when accounting for simultaneous exposures. Overweight was the only significant independent risk factor for moderate inflammation in children (RRR 2.10, 95%CI 1.13-3.89). History of infectious (RRR 1.28, 95%CI 1.08-1.52) and non-communicable (RRR 1.37, 95%CI 1.12-1.69) disease, overweight (RRR 1.66, 95%CI 1.45-1.89) and high waist circumference (RRR 1.63, 95%CI 1.42-1.87) were independently associated with a greater likelihood of moderate inflammation in adults while history of infectious disease (RRR 1.87, 95%CI 1.35-2.56) and overweight (RRR 1.40, 95%CI 1.04-1.88) were independently associated with acute inflammation. Environmental pathogenicity was associated with a reduced likelihood of moderate inflammation, but a greater likelihood of acute inflammation in adults. These results highlight the importance of both obesogenic and pathogenic factors in shaping inflammation risk in societies undergoing nutritional and epidemiological transitions. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.
    American Journal of Human Biology 01/2014; 26(1). DOI:10.1002/ajhb.22462 · 1.70 Impact Factor
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    ABSTRACT: More than one-fifth of the world's population live in extreme poverty, where a lack of safe water and adequate sanitation enables high rates of enteric infections and diarrhoea to continue unabated. Although oral rehydration therapy has greatly reduced diarrhoea-associated mortality, enteric infections still persist, disrupting intestinal absorptive and barrier functions and resulting in up to 43% of stunted growth, affecting one-fifth of children worldwide and one-third of children in developing countries. Diarrhoea in children from impoverished areas during their first 2 years might cause, on average, an 8 cm growth shortfall and 10 IQ point decrement by the time they are 7-9 years old. A child's height at their second birthday is therefore the best predictor of cognitive development or 'human capital'. To this 'double burden' of diarrhoea and malnutrition, data now suggest that children with stunted growth and repeated gut infections are also at increased risk of developing obesity and its associated comorbidities, resulting in a 'triple burden' of the impoverished gut. Here, we Review the growing evidence for this triple burden and potential mechanisms and interventions that must be understood and applied to prevent the loss of human potential and unaffordable societal costs caused by these vicious cycles of poverty.
    Nature Reviews Gastroenterology &#38 Hepatology 12/2012; 10(4). DOI:10.1038/nrgastro.2012.239 · 12.61 Impact Factor
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