ReviewFetal origins of insulin resistance and the metabolic syndrome: A key role for adipose tissue?Contribution de l’environnement intra-utérin au développement de l’insulinorésistance et du syndrome métabolique à l’âge adulte : rôle clé du tissu adipeux ?
Introduction
The idea that fetal and early life events result in permanent alterations or developmental “programming” was first proposed by Barker et al. and Barker [1], [2], following a series of epidemiological observations. In humans, the link between fetal undernutrition per se and long-term abnormalities in glucose regulation has been clearly demonstrated in the follow-up of individuals born during the Dutch famine of World War II [3]. Young adults, exposed in utero to the famine, demonstrated higher 2-h plasma glucose values after oral glucose challenge than did controls born either before, or conceived after, the famine. Furthermore, exposure to famine during the late gestational period was associated with the highest 2-h plasma glucose levels. Barker et al. [1] found a relationship between the environmental influences that impair growth and development in early infancy, and the risk of ischaemic heart disease. To test this hypothesis, 5654 men born between 1911 and 1930 in six districts of Hertfordshire, England, were traced, and their weight during infancy recorded. Those with the lowest weights at birth and at age of 1 year had the highest death rates due to ischaemic heart disease. Similarly, Hales et al. [4] found a relationship between a reduction in birth-weight and either glucose intolerance or type 2 diabetes. Using a definition of the metabolic syndrome based on the occurrence of glucose intolerance, hypertension and hypertriglyceridaemia, the prevalence of the syndrome—also called “syndrome X”—was six times higher in men aged 65 years who weighed 2.5 kg or less at birth compared with those who weighed 4.5 kg or more [5]. For several years now, many studies in different populations have confirmed these initial findings. Moreover, these studies have confirmed a strong association between low-birth-weight, and insulin resistance and other metabolic disorders.
Section snippets
Definition of “small for gestational age” (SGA)
To study the relationship between birth-weight and the development of metabolic disorders later in life, published reports have either considered birth-weight as a continuum or defined SGA as the consequence of a restrictive fetal environment. Traditionally, the term has been used to describe a neonate whose weight and/or crown–heel length at birth is at least two standard deviations (SD) below the mean for gestational age, based on data derived from an appropriate reference population. Some
Birth-weight and cardiovascular mortality
The suggestion that coronary heart disease might have its origins during fetal development arose from the similarity of the geographical pattern of death rates among babies in Britain during the early 1900s [6] and the pattern of today's death rates from coronary heart disease. The usual certified cause of death in newborn babies at that time was low-birth-weight. Early epidemiological studies pointed to the possible importance of “programming” for coronary heart disease based on the
Birth-weight and impaired glucose tolerance or type 2 diabetes
The association between birth-weight, impaired glucose tolerance and type 2 diabetes was first reported in Hertfordshire [4], [11]. The prevalence of type 2 diabetes and impaired glucose tolerance was increased sixfold in individuals with a birth-weight less than 2.5 kg at birth compared with those whose birth-weight was greater than 4.5 kg [4]. Again, these associations with small size at birth were independent of social class, cigarette-smoking and alcohol consumption.
As insulin plays a central
Association between birth-weight and hypertension
Associations between low-birth-weight and raised blood pressure in childhood and adult life have been demonstrated in studies carried out around the world. Law and Shiell published a systematic review of studies [34] describing the association between birth-weight and blood pressure, based on 28 studies that included more than 15,000 people of all ages and from many countries. In almost all the studies, an increase in birth-weight was associated with a decrease in blood pressure. Differences in
Association between birth-weight and dyslipidaemia
Data from the literature are conflicting, and fail to demonstrate a robust association between birth-weight and serum lipid profiles. However, the information available is sparse and difficult to compare because of the wide differences in study populations in terms of age, gender and ethnic or genetic background. A meta-analysis by Lauren et al. [46] failed to strongly support a link between small size at birth and blood lipid levels in later life. In their review, the authors included
Association between the metabolic syndrome and birth-weight
The metabolic syndrome refers to a constellation of hypertension, dyslipidaemia (high serum triglyceride and low HDL-cholesterol concentrations), elevated blood pressure and abdominal obesity. Since the first observations by Barker et al. [5], other investigators studying various different populations have similarly reported an association between low-birth-weight and increased risk of the metabolic syndrome as adults. In the Haguenau cohort, at 22 years of age, 2.3% of individuals born SGA
Adipose tissue development and body composition in SGA individuals
It is well established that adipose tissue plays a key role in the development and worsening of insulin resistance and other metabolic disorders. Reduced fetal growth severely alters the perinatal development of adipose tissue (Fig. 1). SGA newborns show dramatically reduced body fat mass at birth, while the vast majority of low-birth-weight infants go on to show postnatal catch-up growth, mostly during the first 6–12 months of life. This particular growth pattern, rather than the previous
Conclusion
Many studies worldwide have shown that low-birth-weight confers an increased risk for metabolic or cardiovascular disorders later in life. However, it appears that not all individuals with a low-birth-weight are at the same risk of developing such complications. It may be that those at particular risk had fetal growth restriction followed by postnatal catch-up growth. However, other data suggest that influences in adult life, in addition to the effects of the intrauterine environment, are also
Conflict of interest
The author declares no conflict of interest in connection with this report.
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2023, Avery's Diseases of the NewbornGlucose, Insulin, and Lipids in Cord Blood of Neonates and Their Association with Birthweight: Differential Metabolic Risk of Large for Gestational Age and Small for Gestational Age Babies
2020, Journal of PediatricsCitation Excerpt :Our findings suggest that there is an optimal intrauterine environment driven by physiological insulin concentrations which result in AGA babies who have a lower cardiometabolic risk compared with both SGA and LGA babies. Although the exact mechanisms require further investigation, parents of SGA and LGA babies, especially those infants who experienced IUGR or who were born preterm, should be provided with tailored professional advice on optimal feeding and weight development of their babies as early as possible to prevent rapid postnatal growth and the risk of obesity in later life.40,43 In light of the critical impact of maternal BMI and nutritional conditions during pregnancy on neonatal growth, early efforts on maternal weight management and dietary control (eg, avoiding a high-carbohydrate diet) before and during pregnancy for optimizing fetal body composition should also be taken into consideration.44,45
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2018, Mechanisms of Ageing and Development11 beta-hydroxysteroid dehydrogenase 2 promoter methylation is associated with placental protein expression in small for gestational age newborns
2017, SteroidsCitation Excerpt :Being born small for gestational age (SGA) increases the risk of fetal, neonatal or infant death, and leads to impaired postnatal growth, immune and neuronal development alterations [2]. Low birth weight has also been related to several diseases in postnatal life and adulthood, such as glucose intolerance [6], metabolic syndrome [7], obesity [8], type 2 diabetes [7,9], cardiovascular disease, and chronic renal disease [10]. Hyperandrogenism and polycystic ovary syndrome in females [11], excessive adrenarch, precocious puberty, and infertility in males [5] have been associated with SGA as well.
Maternal dietary intake during pregnancy and offspring body composition: The Healthy Start Study
2016, American Journal of Obstetrics and GynecologyChanges in plasma adipokines in prepubertal children with a history of extrauterine growth restriction
2013, NutritionCitation Excerpt :However, this study demonstrates that prepubertal children with a history of EUGR exhibit changes in their adipokine profile, probably due to their neonatal malnutrition, which might be associated with the development of metabolic diseases and an increased risk for CVD later in life. There is evidence that intrauterine and early postnatal life can induce changes in the adipose tissue and in metabolic programming [11]. In fact, nutritional changes in early fetal and postnatal life might alter metabolic programming [12] because malnutrition occurs during the critical window of organic development, where functional changes may become permanent and cause alterations in metabolic mechanisms and physiological systems.