Small for Gestational Age and the Metabolic Syndrome: Which Mechanism Is Suggested by Epidemiological and Clinical Studies?

Abstract

The metabolic and cardiovascular complications associated with in-utero undernutrition have been identified during the past 10 years. Reduced fetal growth is independently associated with an increased risk of development of cardiovascular diseases, the insulin-resistance syndrome or one of its components (i.e., hypertension, dyslipidaemia, impaired glucose tolerance and type 2 diabetes). Insulin resistance appears to be a key component underlying these metabolic complications. Although the mechanism remains unclear, several pieces of evidence support an active role of adipose tissue in the emergence of insulin resistance (an abnormal growth pattern and repartition, hypersensitivity to catecholamines, regulation of leptin and adiponectin secretion and modulation of peroxisome proliferator-activated receptor γ). Among individuals born SGA, those who are more at risk of gaining excess adiposity are those who are thin at birth following a period of fetal growth restriction. This period of undernutrition is followed by a neonatal period of catch-up growth and renutrition. This pattern induces important modifications in adipose tissue, with long-term consequences, among which is a high risk of early development of insulin resistance. Not all individuals born SGA will show such modifications in adipose tissue, meaning that not all of those born SGA are at risk of insulin resistance and diabetes. From a broader point of view, several hypotheses have been proposed over the past 10 years to explain this unexpected association between being born SGA and the later development of disease. Each of them points to a detrimental fetal environment, to a genetic susceptibility or to interactions between these two components playing a critical role in this context. Although not confirmed, the hypothesis suggesting that this association could be the consequence of genetic/environmental interactions remains the most attractive.

Macrophage migration inhibitory factor deficiency leads to age-dependent impairment of glucose homeostasis in mice

“…This has been observed in rat and mouse models with bilateral uterine artery ligation or isocalorie low protein nutrition during pregnancy (Simmons et al 2001, Song et al 2008, Cripps et al 2009, Hermann et al 2009). In addition, these data are also supported by human observations (Baker et al 1989, Levy-Marchal & Czernichow 2006. In our mouse model, we cannot fully rule out the impact of the low birth weight of the MIFK/K mice in their observed phenotype.…”

Adipose Tissue: A Metabolic Regulator. Potential Implications for the Metabolic Outcome of Subjects Born Small for Gestational Age (SGA)

“…Nonetheless, MartinezCordero et al found lower cord blood leptin levels in SGA than adequate for gestational age (AGA) infants [49]. Furthermore, in the Haguenau study, leptin levels were found to be decreased in young adults born SGA, even after correction for gender, BMI and hyperinsulinemia [31]. This could be due to a greater adiposity in adults born SGA.…”

“…The thrifty phenotype hypothesis [38] suggests that the fetus adapts to an adverse intrauterine environment by diverting limited nutrients to favor the survival and development of vital organs, such as the brain, at the expense of growth. Important metabolic pathways would be permanently programmed during fetal life, leading to metabolic disturbances in adulthood [31,39]. There is evidence suggesting that the degree of weight gain Finally, elevated plasma FFAs inhibit the insulin signal transduction system [24,113,114].…”

“…Subjects born small for gestational age (SGA) are prone to central redistribution of adipose tissue and are at high risk of developing insulin resistance, type 2 diabetes, metabolic syndrome and cardiovascular disease [31].…”

Bases biológicas e evidências epidemiológicas da contribuição do crescimento fetal e pós-natal na composição corporal: uma revisão

“…13 O fato de crianças nascidas a termo pequenas para a idade gestacional, apresentarem aceleração compensatória no ganho ponderal pós-natal e as grandes para a idade gestacional demonstrarem menor ritmo de crescimento, 13 corrobora com o pressuposto de que o risco para um ganho excessivo de gordura corporal pode derivar da interação entre as consequências da restrição do crescimento intraútero e os fatores genéticos e ambientais pós-natais. 19 A seguir, são apresentados alguns mecanismos envolvidos no favorecimento do aumento de peso e no acúmulo de tecido adiposo após o nascimento, decorrentes ou não da evidente restrição do crescimento fetal. ao aumento dos níveis circulantes de glicose após as refeições, 20 sendo um dos principais fatores de crescimento tanto intra quanto extraútero.…”