Glucose Metabolism in Adult Survivors of Severe Acute Malnutrition

Francis-Emmanuel, Patrice; Thompson, Debbie; Barnett, Alan T; Osmond, Clive; Byrne, Christopher D.; Hanson, Mark A.; Gluckman, Peter D.; Forrester, Terrence; Boyne, Michael S.

doi:10.1210/jc.2013-3511

Cited by 47 publications

(46 citation statements)

References 31 publications

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“…Previously, in a larger group of adult survivors of SAM in this population, we described differences between marasmic and kwashiorkor survivors with marasmic survivors having worse glucose tolerance and beta cell function (Francis-Emmanuel et al, 2014). Also, both kwashiorkor and marasmus adult survivors had differences in cardiac structure and function, and blood pressure when compared with controls (Tennant et al, 2014).…”

Section: Discussionmentioning

confidence: 89%

“…Children who initially are successfully treated for kwashiorkor or marasmus maintain persistent phenotypic and pathophysiological differences into adulthood. As adults survivors of marasmus are shorter, have lower lean body mass, and are more glucose intolerant than their kwashiorkor counterparts (Forrester et al, 2012, Francis-Emmanuel et al, 2014). Both syndromes show persistent behavioral and cognitive deficits throughout childhood and adolescence, which carry through into adulthood when economic underperformance and psychiatric morbidities are added to the disease burden (Galler et al, 2012, Galler et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

Sheppard

Ngo

et al. 2017

EBioMedicine

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BackgroundSevere acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences.MethodsWe extracted genomic DNA from muscle biopsies obtained from adult survivors of kwashiorkor (n = 21) or marasmus (n = 23) and compared epigenetic profiles (CpG methylation) between the two groups using the Infinium® 450 K BeadChip array.FindingsWe found significant differences in methylation of CpG sites from 63 genes in skeletal muscle DNA. Gene ontology studies showed significant differential methylation of genes in immune, body composition, metabolic, musculoskeletal growth, neuronal function and cardiovascular pathways, pathways compatible with the differences in the pathophysiology of adult survivors of SAM.InterpretationThese findings suggest persistent developmental influences on adult physiology in survivors of SAM. Since children who develop marasmus have lower birth weights and after rehabilitation have different intermediary metabolism, these studies provide further support for persistent developmentally-induced phenomena mediated by epigenetic processes affecting both the infant response to acute malnutrition and later life consequences.FundingSupported by a Grant from the , Grand Challenge “Discover New Ways to Achieve Healthy Growth.”Evidence Before This StudyPrevious research has shown that infants who develop either kwashiorkor or marasmus in response to SAM differ in birth weight and subsequently have different metabolic patterns in both infancy and adulthood.Added Value of This StudyThis study demonstrates epigenetic differences in the skeletal muscle of adult survivors of marasmus versus kwashiorkor and these differences are in genes that may underlie the longer-term consequences.Implications of All the Available EvidenceThese data are compatible with the different clinical responses to SAM arising from developmentally-induced epigenetic changes laid down largely before birth and provide evidence for the predictive adaptive response model operating in human development.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

Sheppard

Ngo

et al. 2017

EBioMedicine

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“…Studies in adults from this cohort show the persistence of differences in metabolic control into adulthood, with those individuals who had formerly been marasmic showing both insulin resistance and glucose intolerance (Francis‐Emmanuel et al . ).…”

Section: Introductionmentioning

confidence: 97%

The biology of developmental plasticity and the Predictive Adaptive Response hypothesis

Bateson

Gluckman

Hanson

2014

The Journal of Physiology

402

345

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Many forms of developmental plasticity have been observed and these are usually beneficial to the organism. The Predictive Adaptive Response (PAR) hypothesis refers to a form of developmental plasticity in which cues received in early life influence the development of a phenotype that is normally adapted to the environmental conditions of later life. When the predicted and actual environments differ, the mismatch between the individual's phenotype and the conditions in which it finds itself can have adverse consequences for Darwinian fitness and, later, for health. Numerous examples exist of the long-term effects of cues indicating a threatening environment affecting the subsequent phenotype of the individual organism. Other examples consist of the long-term effects of variations in environment within a normal range, particularly in the individual's nutritional environment. In mammals the cues to developing offspring are often provided by the mother's plane of nutrition, her body composition or stress levels. This hypothetical effect in humans is thought to be important by some scientists and controversial by others. In resolving the conflict, distinctions should be drawn between PARs induced by normative variations in the developmental environment and the ill effects on development of extremes in environment such as a very poor or very rich nutritional environment. Tests to distinguish between different developmental processes impacting on adult characteristics are proposed. Many of the mechanisms underlying developmental plasticity involve molecular epigenetic processes, and their elucidation in the context of PARs and more widely has implications for the revision of classical evolutionary theory.

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“…1b in [1]). Now we know that this defect in insulin secretion persists into adult life [41] and is also seen in survivors of early fetal deprivation during the Dutch famine [42]. This then may link to our finding that there is much greater sensitivity to later adult diabetes in some countries, for example, Mexico [43] and other Latin American societies, many Asian countries [44], and those in the Middle East [45] and Africa.…”

Section: Combatting Diabetes and Obesity: The Importance Of A Lifelonmentioning

confidence: 65%

From Treating Childhood Malnutrition to Public Health Nutrition

James¹

2018

Ann Nutr Metab

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Background: This analysis sets out an overview of an IUNS presentation of a European clinician’s assessment of the challenges of coping with immediate critical clinical problems and how to use metabolic and a mechanistic understanding of disease when developing nutritional policies. Summary: Critically ill malnourished children prove very sensitive to both mineral and general nutritional overload, but after careful metabolic control they can cope with a high-quality, energy-rich diet provided their initial lactase deficiency and intestinal atrophy are taken into account. Detailed intestinal perfusion studies also showed that gastroenteritis can be combatted by multiple frequent glucose/saline feeds, which has saved millions of lives. However, persisting pancreatic islet cell damage may explain our findings of pandemic rates of adult diabetes in Asia, the Middle East and Mexico and perhaps elsewhere including Africa and Latin America. These handicaps together with the magnitude of epigenetic changes emphasized the importance of a whole life course approach to nutritional policy making. Whole body calorimetric analyses of energy requirements allowed a complete revision of estimates for world food needs and detailed clinical experience showed the value of redefining stunting and wasting in childhood and the value of BMI for classifying appropriate adult weights, underweight and obesity. Lithium tracer studies of dietary salt sources should also dictate priorities in population salt-reduction strategies. Metabolic and clinical studies combined with meticulous measures of population dietary intakes now suggest the need for far more radical steps to lower the dietary goals for both free sugars and total dietary fat unencumbered by flawed cohort studies that neglect not only dietary errors but also the intrinsic inter-individual differences in metabolic responses to most nutrients. Key Messages: Detailed clinical and metabolic analyses of physiological responses combined with rigorous dietary and preferably biomarker of mechanistic pathways should underpin a new approach not only to clinical care but also to the development of more radical nutritional policies.

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Glucose Metabolism in Adult Survivors of Severe Acute Malnutrition

Cited by 47 publications

References 31 publications

Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

Molecular Evidence for Differential Long-term Outcomes of Early Life Severe Acute Malnutrition

The biology of developmental plasticity and the Predictive Adaptive Response hypothesis

From Treating Childhood Malnutrition to Public Health Nutrition

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