Elsevier

Diabetes & Metabolism

Volume 36, Issue 1, February 2010, Pages 11-20
Diabetes & Metabolism

Review
Fetal 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 ?

https://doi.org/10.1016/j.diabet.2009.09.001Get rights and content

Abstract

For several years now, the epidemiological data have shown an inverse relationship between birth-weight and the development in later life of cardiovascular disease and metabolic disorders. The term “small for gestational age” (SGA) describes a neonate whose birth-weight is two standard deviations (SD) below the reference mean, corrected for gestational age and gender. SGA is associated with increased risks of developing hypertension, insulin resistance and type 2 diabetes. However, the association with an atherogenic lipid profile is less clear. Nevertheless, all of the components of the metabolic syndrome are present. Yet, in spite of the large body of data in the literature, the biological mechanisms underlying this association are still unclear. To explain the association, various hypotheses have been proposed, pointing to the role of a detrimental fetal environment or genetic susceptibility, or interaction between the two, and to the particular dynamic changes in adiposity that occur during catch-up growth. However, not only quantitative, but also qualitative, abnormalities of adipose tissue have been observed, suggesting a critical role of this organ in the development of metabolic complications.

Résumé

Une corrélation négative entre le poids de naissance et la mortalité cardiovasculaire a été mise en évidence pour la première fois voici bientôt 20 ans. Depuis, de nombreuses études sont venues confirmer ce résultat. Le petit poids de naissance est défini comme un poids et/ou une taille de naissance inférieur(e) à deux écart-types, rapporté pour l’âge gestationnel et selon la distribution de référence. Le petit poids de naissance pour l’âge gestationnel est aussi lié au développement d’une HTA, d’une obésité, d’une insulinorésistance, voire d’un diabète de type 2. L’effet sur le profil lipidique semble plus modeste. Ainsi, les différents composants du syndrome métabolique sont liés à l’antécédent de petit poids de naissance. Plusieurs mécanismes physiopathologiques ont été proposés pour expliquer les liens entre le petit poids de naissance et le développement, à l’âge adulte, de pathologies cardiovasculaires et métaboliques. Le rôle de l’environnement délétère intra-utérin ou celui des gênes de susceptibilité, voire l’association des deux, ont été évoqués. Le rattrapage pondéral, qui survient dans les premières années de la vie, semble largement contribuer à ces observations. Le lien avec l’index de masse corporelle (IMC) au moment de l’observation a été souligné. Le rôle de la croissance du tisse adipeux à la fois durant la période fœtale et postnatale semble déterminant pour le développement ultérieur de troubles métaboliques chez les sujets qui ont présenté un petit poids de naissance. L’adaptation de certains organes durant la vie fœtale pourraient devenir inappropriée une fois la période de restriction passée. Cependant, ces mécanismes restent pour le moment hypothétiques.

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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