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.
    Full-text · Article · Oct 2014 · American Journal of Human Biology
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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.
    Full-text · Article · Jan 2014 · American Journal of Human Biology
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    ABSTRACT: Malnutrition below 5 years remains a global health issue. Severe acute malnutrition (SAM) presents in childhood as oedematous (kwashiorkor) or nonoedematous (marasmic) forms, with unknown long-term cardiovascular consequences. We hypothesized that cardiovascular structure and function would be poorer in SAM survivors than unexposed controls. We studied 116 adult SAM survivors, 54 after marasmus, 62 kwashiorkor, and 45 age/sex/body mass index-matched community controls who had standardized anthropometry, blood pressure, echocardiography, and arterial tonometry performed. Left ventricular indices and outflow tract diameter, carotid parameters, and pulse wave velocity were measured, with systemic vascular resistance calculated. All were expressed as SD scores. Mean (SD) age was 28.8±7.8 years (55% men). Adjusting for age, sex, height, and weight, SAM survivors had mean (SE) reductions for left ventricular outflow tract diameter of 0.67 (0.16; P<0.001), stroke volume 0.44 (0.17; P=0.009), cardiac output 0.5 (0.16; P=0.001), and pulse wave velocity 0.32 (0.15; P=0.03) compared with controls but higher diastolic blood pressures (by 4.3; 1.2-7.3 mm Hg; P=0.007). Systemic vascular resistance was higher in marasmus and kwashiorkor survivors (30.2 [1.2] and 30.8 [1.1], respectively) than controls 25.3 (0.8), overall difference 5.5 (95% confidence interval, 2.8-8.4 mm Hg min/L; P<0.0001). No evidence of large vessel or cardiac remodeling was found, except closer relationships between these indices in former marasmic survivors. Other parameters did not differ between SAM survivor groups. We conclude that adult SAM survivors had smaller outflow tracts and cardiac output when compared with controls, yet markedly elevated peripheral resistance. Malnutrition survivors are thus likely to develop excess hypertension in later life, especially when exposed to obesity.
    Full-text · Article · Dec 2012 · Artery Research
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