The prevalence of obesity, sarcopenia and osteoporosis is rising and there is increasing interest in determinants operating in early life. Fetal programming is the phenomenon whereby alterations in fetal growth and development in response to the prenatal environment have long term or permanent effects. Evidence for fetal programming of body composition and musculoskeletal development comes from epidemiological studies, investigation of the role of early undernutrition and preliminary findings on underlying mechanisms. Low birth weight and poor prenatal nutrition are associated with changes in adult body composition including altered fat distribution, reduced muscle mass and strength, and low bone mineral content. The mechanisms include a direct effect on cell number, altered stem cell function and resetting of regulatory hormonal axes. The next stage is translation of these findings into testable preventive strategies to maintain optimum body composition and minimize the risk of obesity, sarcopenia and osteoporosis in later life.
"The developmental period that differs most dramatically between the VLBW and term-borns occurs after VLBW birth, during the period that would normally be the third trimester of pregnancy. This period is important for the development and adjustment of endocrine and metabolic systems, probably through metabolic programming, even if the exact mechanisms are unknown , , . This time is also crucial for fetal bone mineralization as up to 80% of the body calcium of a term newborn is being accrued during the last trimester . "
[Show abstract][Hide abstract] ABSTRACT: Osteocalcin (OC), a bone-derived protein, has been implicated in the regulation of glucose and energy metabolism. Young adults born with very low birth weight (VLBW) have altered glucose regulation and lower bone mineral density (BMD) compared with those born at term. The aim of this study was to explore the association between bone and glucose metabolism in healthy young adults born prematurely or at term.
The cohort of this cross-sectional study comprised 332 non-diabetic young adults (age 18 to 27 years) born either preterm with VLBW (n = 163) or at term (n = 169). OC, carboxylated osteocalcin (cOC) and markers of glucose metabolism were measured at fasting and after a 75-g oral glucose tolerance test (OGTT).
VLBW adults were shorter, had lower BMD (p<0.001) and higher fasting OC (p = 0.027) and cOC (p = 0.005) than term-born subjects. They also had higher 2-hour insulin (p = 0.001) and glucose (p = 0.037) concentrations. OGTT induced a significant reduction in OC (p<0.001), similar in both groups. OC reduction was not associated with OGTT-induced increases in insulin (p = 0.54). However, fasting total OC and cOC correlated negatively with fasting insulin after adjustment for age, gender, BMD and VLBW status (r = -0.182, p = 0.009 and r = -0.283, p<0.001, respectively).
Adults born with VLBW have higher OC and cOC than their peers born at term. This may in part reflect the mechanisms that underlie their lower BMD and decreased insulin sensitivity. Serum OC appears to be negatively associated with long-term glucose regulation whereas acute changes during OGTT may be mediated via other mechanisms.
PLoS ONE 05/2013; 8(5):e63036. DOI:10.1371/journal.pone.0063036 · 3.23 Impact Factor
"As well as alterations in fat mass, low-birth-weight individuals attain a lower lean muscle mass and strength and reduced bone density (Gale et al. 2001; Sayer & Cooper, 2005). Given that muscle is the primary tissue involved in the uptake of glucose, a reduction in the amount of muscle mass would also predict a reduced glucose tolerance, leading to a more rapid or severe decline in metabolic control. "
[Show abstract][Hide abstract] ABSTRACT: The increasing prevalence of the metabolic syndrome in numerous populations throughout the world is currently of major concern, and presents a huge global health problem. The link between low birth weight and the subsequent development of obesity, disrupted glucose homeostasis and hypertension is now well established, and there is extensive evidence supporting these associations in both epidemiological and experimental studies. Alterations in the secretion of, and responses to, the circulating hormones insulin and leptin are likely candidates in terms of disease development. The aim of current research is to define how the central and peripheral pathways in which these signals exert their effects may be disrupted following poor early growth, and how this disruption contributes to the development of metabolic disease. The present review aims to outline the existing evidence whereby alterations in early growth may programme an individual to be at increased risk of the metabolic syndrome. The development of central appetite and expenditure circuits and of peripheral metabolic tissues, are likely to play a key role in the long-term regulation of energy balance.
Proceedings of The Nutrition Society 06/2007; 66(2):198-206. DOI:10.1017/S0029665107005447 · 5.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Biomedical science has little considered the relevance of life history theory and evolutionary and ecological developmental biology to clinical medicine. However, the observations that early life influences can alter later disease risk--the "developmental origins of health and disease" (DOHaD) paradigm--have led to a recognition that these perspectives can inform our understanding of human biology. We propose that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course. Such adaptive processes allow genotypic variation to be preserved through transient environmental changes. Cues for plasticity operate particularly during early development; they may affect a single organ or system, but generally they induce integrated adjustments in the mature phenotype, a process underpinned by epigenetic mechanisms and influenced by prediction of the mature environment. In mammals, an adverse intrauterine environment results in an integrated suite of responses, suggesting the involvement of a few key regulatory genes, that resets the developmental trajectory in expectation of poor postnatal conditions. Mismatch between the anticipated and the actual mature environment exposes the organism to risk of adverse consequences-the greater the mismatch, the greater the risk. For humans, prediction is inaccurate for many individuals because of changes in the postnatal environment toward energy-dense nutrition and low energy expenditure, contributing to the epidemic of chronic noncommunicable disease. This view of human disease from the perspectives of life history biology and evolutionary theory offers new approaches to prevention, diagnosis and intervention.
American Journal of Human Biology 01/2007; 19(1):1-19. DOI:10.1002/ajhb.20590 · 1.70 Impact Factor
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