Growth and Cardiometabolic Profile in Young Adults Born LGA
Context The association between large for gestational age (LGA) phenotype, postnatal growth and cardiometabolic risk (CMR) in adult life remains unclear. The role of IGF1 genotype on LGA-related outcomes in adult life is unknown.
Aim To assess the postnatal growth, IGF-I levels, CMR and the influence of the 737.738 IGF1 in adults born LGA.
Subjects Case–control study (n = 515) nested in a population-based prospective cohort (n = 2063); 117 LGA and 398 gender-matched controls appropriate for gestational age (AGA) subjects.
Methods Anthropometry was evaluated at birth, at 9–10 and at 23–25 years old. At the age of 23–25 years, blood pressure (BP), glycaemia, insulinaemia, homeostasis model assessment – insulin resistance, lipids, fibrinogen, and plasma IGF-I and 737.738 IGF1 polymorphism were assessed.
Results Large for gestational age subjects remained heavier and taller than AGA at 9–10 and 23–25 years (P < 0·05); at 23–25 years, LGA had greater waist circumference (WC; P < 0·05) and higher BP (P < 0·05) than controls. Body proportionality at birth did not predict metabolic outcome. LGA subjects presenting catch-down of weight in childhood had lower body mass index (BMI; P = 0·001), lower WC (P < 0·05) and lower BP (P < 0·05) at 23–25 years. 737.738 IGF-I genotype differed between groups (P < 0·001). Homozygosis for polymorphic alleles was associated with increased odds of LGA (OR: 3·2; 95% CI: 1·5–6·9), higher IGF-I (56·9 ± 16·4 vs 37·7 ± 16·0 nm; P < 0·01) and lower BP (114/68 vs 121/73 mmHg; P < 0·05).
Conclusions Young adults born LGA presented higher BMI, WC and BP and appear to be at higher CMR risk than AGA subjects. The 737.738 IGF1 polymorphism appears to play a role on birth size and LGA-related metabolic outcomes.
Large for gestational age (LGA) infants are defined as having foetal or neonatal weight above the 90th percentile for an appropriate reference population for gestational age and sex. Children born LGA remained taller and heavier at the age of 83 months. They are prone to excessive fat accumulation in early childhood, thereby increasing the risk for subsequent overweight. The interest in the study of the LGA phenotype is growing because this condition has been associated with increased risk of obesity, insulin resistance and metabolic syndrome (MetS) in later life.
The association of LGA phenotype, in the presence or absence of maternal gestational diabetes (GD), with the later onset of obesity and type 2 diabetes (T2D) was initially observed in Pima Indians. In these subjects, this association was U shaped, with the highest prevalence of diabetes occurring in both high and low birth weight subjects. Later, the relationship between LGA phenotype and development of MetS and T2D was also described in American children and adolescents.
The mechanisms involved in being born LGA and its long-term consequences are less understood. Moreover, GD and maternal obesity, variations in genes related to the secretion and action of insulin, and insulin-like growth factors I (IGF-I) and II (IGF-II) may be implicated. IGF-I plays an essential role in growth and it has been implicated in the pathogenesis of T2D and cardiovascular disease. The 737.738 IGF1 polymorphism is a microsatellite comprising a variable number of dinucleotide cytosine–adenine (CA) repeats in the promoter of the IGF1 gene (OMIM* 147440, NM_000618.2). Studies have linked this polymorphism to variations in birth weight, IGF-I levels, increased risk for T2D and other cardiovascular risk factors. Most of these studies were cross-sectional and their results are conflicting.
In the present study, we compared body proportionality at birth, pattern of postnatal growth, plasma IGF-I levels and metabolic parameters in early adult life in a large cohort of subjects born LGA with those of a control population born appropriate for gestational age (AGA). As no previous studies have focused on the possible association of the IGF1 gene polymorphisms with LGA phenotype and its long-term consequences, we also evaluated whether variability in birth size and associated outcomes are related to the 737.738 IGF1 polymorphism.
Abstract and Introduction
Abstract
Context The association between large for gestational age (LGA) phenotype, postnatal growth and cardiometabolic risk (CMR) in adult life remains unclear. The role of IGF1 genotype on LGA-related outcomes in adult life is unknown.
Aim To assess the postnatal growth, IGF-I levels, CMR and the influence of the 737.738 IGF1 in adults born LGA.
Subjects Case–control study (n = 515) nested in a population-based prospective cohort (n = 2063); 117 LGA and 398 gender-matched controls appropriate for gestational age (AGA) subjects.
Methods Anthropometry was evaluated at birth, at 9–10 and at 23–25 years old. At the age of 23–25 years, blood pressure (BP), glycaemia, insulinaemia, homeostasis model assessment – insulin resistance, lipids, fibrinogen, and plasma IGF-I and 737.738 IGF1 polymorphism were assessed.
Results Large for gestational age subjects remained heavier and taller than AGA at 9–10 and 23–25 years (P < 0·05); at 23–25 years, LGA had greater waist circumference (WC; P < 0·05) and higher BP (P < 0·05) than controls. Body proportionality at birth did not predict metabolic outcome. LGA subjects presenting catch-down of weight in childhood had lower body mass index (BMI; P = 0·001), lower WC (P < 0·05) and lower BP (P < 0·05) at 23–25 years. 737.738 IGF-I genotype differed between groups (P < 0·001). Homozygosis for polymorphic alleles was associated with increased odds of LGA (OR: 3·2; 95% CI: 1·5–6·9), higher IGF-I (56·9 ± 16·4 vs 37·7 ± 16·0 nm; P < 0·01) and lower BP (114/68 vs 121/73 mmHg; P < 0·05).
Conclusions Young adults born LGA presented higher BMI, WC and BP and appear to be at higher CMR risk than AGA subjects. The 737.738 IGF1 polymorphism appears to play a role on birth size and LGA-related metabolic outcomes.
Introduction
Large for gestational age (LGA) infants are defined as having foetal or neonatal weight above the 90th percentile for an appropriate reference population for gestational age and sex. Children born LGA remained taller and heavier at the age of 83 months. They are prone to excessive fat accumulation in early childhood, thereby increasing the risk for subsequent overweight. The interest in the study of the LGA phenotype is growing because this condition has been associated with increased risk of obesity, insulin resistance and metabolic syndrome (MetS) in later life.
The association of LGA phenotype, in the presence or absence of maternal gestational diabetes (GD), with the later onset of obesity and type 2 diabetes (T2D) was initially observed in Pima Indians. In these subjects, this association was U shaped, with the highest prevalence of diabetes occurring in both high and low birth weight subjects. Later, the relationship between LGA phenotype and development of MetS and T2D was also described in American children and adolescents.
The mechanisms involved in being born LGA and its long-term consequences are less understood. Moreover, GD and maternal obesity, variations in genes related to the secretion and action of insulin, and insulin-like growth factors I (IGF-I) and II (IGF-II) may be implicated. IGF-I plays an essential role in growth and it has been implicated in the pathogenesis of T2D and cardiovascular disease. The 737.738 IGF1 polymorphism is a microsatellite comprising a variable number of dinucleotide cytosine–adenine (CA) repeats in the promoter of the IGF1 gene (OMIM* 147440, NM_000618.2). Studies have linked this polymorphism to variations in birth weight, IGF-I levels, increased risk for T2D and other cardiovascular risk factors. Most of these studies were cross-sectional and their results are conflicting.
In the present study, we compared body proportionality at birth, pattern of postnatal growth, plasma IGF-I levels and metabolic parameters in early adult life in a large cohort of subjects born LGA with those of a control population born appropriate for gestational age (AGA). As no previous studies have focused on the possible association of the IGF1 gene polymorphisms with LGA phenotype and its long-term consequences, we also evaluated whether variability in birth size and associated outcomes are related to the 737.738 IGF1 polymorphism.
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