Insulin sensitivity in children born small for gestational age (SGA)

In the past decade, several epidemiological studies have shown a relationship between intrauterine growth retardation and insulin resistance, type 2 diabetes and cardiovascular disease in adulthood. Although the biological mechanisms underlying this association are still largely unknown, different explanatory hypotheses have been proposed. It seems likely that the various pathways may interact with each other, all contributing at different degrees to the development of the metabolic disturbances.     

Pubertal course of persistently short children born small for gestational age (SGA) compared with idiopathic short children born appropriate for gestational age (AGA)

OBJECTIVE: Few data are available on the pubertal development of children born small for gestational age (SGA) who fail to show catch-up growth. DESIGN: A longitudinal analysis compared the pubertal course of persistently short children born SGA compared to children with idiopathic short stature who were appropriate for gestational age (AGA). One hundred and twenty-eight short children (height SDS<-1.7), including 76 (31 boys) born SGA and 52 (22 boys) born AGA, were regularly followed from early childhood to completion of puberty. RESULTS: Puberty was attained at normal age (10.5-14 Years in boys, 9.5-13 Years in girls) for most children in both the SGA and AGA groups (boys, 80% and 77%; girls, 76% and 78% respectively). The duration of puberty was similar in the SGA and AGA groups. Menarche occurred at normal age range but was significantly earlier in the SGA girls (P<0.01 by ANOVA). Despite the similar total pubertal growth, the patterns of growth differed significantly: SGA group - accelerated growth and bone maturation rates from onset of puberty with peak height velocity at Tanner stages 2-3, followed by a decelerated growth rate and earlier fusion of the epiphyses; AGA group - steady progression of bone elongation and maturation throughout puberty (pubertal growth, P<0.05 in both sexes; bone maturation, P<0.001 in both sexes). Final height in the SGA group was compromised compared with their target height (P<0.001). CONCLUSION: Children born SGA have a normal pubertal course with a distinct pubertal growth pattern. This pattern may represent an altered regulation of their growth modalities.     

The insulin-like growth factor-I (IGF-I) gene in individuals born small for gestational age (SGA)

OBJECTIVE: To investigate the association of genetic variation of the insulin-like growth factor-I (IGF-I) gene with birth size small for gestational age (SGA). SUBJECTS: We have studied a cohort of 120 SGA patients and 147 appropriate for gestational age (AGA) controls from Haguenau, France. METHODS: PCR-SSCP analysis was performed to detect sequence variation in the coding region of the IGF-I gene. Microsatellite markers near the IGF-I gene (intronic and D12S78) were selected and amplified to perform further analysis by association studies. RESULTS: A novel polymorphism in intron 2 was discovered, but allele-specific PCR analysis in the 120 SGA patients and 147 AGA controls found no association between this polymorphism and birth size SGA. Chi squared (chi2) analysis found no statistically significant association between the allele distribution of the microsatellite markers in the SGA subjects and the AGA controls. Power calculations estimate that the D12S78 marker has an 80% chance of detecting a 10-15% difference. CONCLUSIONS: These studies suggest that genetic variation of IGF-I alone does not result in birth size small for gestational age in this population. Thus, if this gene influences fetal size, it plays only a minor role in a multifactorial disorder which involves other genetic and environmental factors.     

Cortisol-cortisone ratios in small for gestational age (SGA) children without postnatal catch-up growth

OBJECTIVE: Low birthweight is a risk factor for metabolic and cardiovascular disorders in later adult life. Changes in the activity of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and the consequent disequilibrium between cortisol (F) and cortisone (E) are thought to be a key mechanism for these effects. We investigated whether prenatal programming leads to alterations in F/E ratios on a systemic level. DESIGN, PATIENTS AND METHODS: In a cross-sectional, retrospective study we analysed sera of 132 children born small for gestational age (SGA) (aged 2-13 years) with persistent short stature [< -2 standard deviation score (SDS)] and of 25 children born appropriate for gestational age (AGA) (aged 4-11 years) with normal body height. Thirty-one per cent of the SGA and 44% of the AGA children were born preterm. Serum E and F concentrations were measured using tandem mass spectrometry. To exclude species-specific effects, we studied the 11beta-HSD system by measuring the ratio of corticosterone (B) to dehydrocorticosterone (11OH-B) in rats that were born SGA after protein restriction of the female dams during pregnancy. RESULTS: F, E and the F/E ratio in serum did not differ in these children when comparing SGA to children who were born AGA and had normal height. The concentrations were independent of weight and length SDS at birth as well as gestational age. In rats born SGA, the B/11OH-B ratio was not different to that in normal control animals at 6, 11 and 15 weeks of life. CONCLUSION: We found no alterations in systemic cortisol-cortisone conversion either in short children born SGA or in SGA rats. However, local modifications of the 11beta-HSD system may be possible.     

Polymorphism in the IGF-I gene: clinical relevance for short children born small for gestational age (SGA)

Low birth weight is associated with an increased risk in adult life of type 2 diabetes, hypertension and cardiovascular disease (CVD). The fetal insulin hypothesis postulates that genes involving insulin resistance could effect birth weight and disease in later life (Hattersley, 1999). Besides insulin, there is extensive evidence that insulin-like growth factor-I and -II (IGF-I, IGF-II) play an important role in fetal growth. We hypothesized that minor genetic variation in the IGF-I gene could influence pre- and postnatal growth. Three microsatellite markers located in the IGF-I gene in 124 short children (height < -1.88 SDS) who were born small for gestational age (SGA) and their parents were studied. SGA was defined as both a birth weight and birth length below -1.88 SDS for gestational age. Two polymorphic markers showed transmission disequilibrium. Allele 191 of the IGF1.PCR1 marker was transmitted more frequently from parent to child (chi(2) = 4.8 and p = 0.02) and allele 198 of the 737/738 marker was transmitted less frequently from parent to child (chi(2)= 4.5 and p = 0.03). Children carrying the 191-allele had significantly lower IGF-1 levels than children not carrying this allele (-1.1 SDS vs. -0.05 SDS; p = 0.03). Also, head circumference SDS remained smaller in children with allele 191 compared to children without allele 191 (-2.1 SDS vs. -0.9 SDS; p = 0.003). Our results show that genetically determined low IGF-I levels may lead to a reduction in birth weight, length and head circumference and to persistent short stature and small head circumference in later life (proportionate small). Since low IGF-I levels are associated with type 2 diabetes and CVD, we propose that the IGF-I gene may provide a link between low birth weight and such diseases in later life.     

Adiposity in children born small for gestational age

Epidemiological studies indicate that children born small for gestational age (SGA) have an increased risk of metabolic and cardiovascular disorders as adults. This suggests that foetal undernutrition leads to permanent metabolic alterations, which predispose to metabolic abnormalities upon exposure to environmental factors such as low physical activity and/or high-energy intake in later life (thrifty phenotype hypothesis). However, this relationship is not restricted to foetal undernutrition or intrauterine growth retardation, but is also found for children born premature, or for high birth weight children. Furthermore, early post-natal nutrition, and more specifically catch-up growth, appear to modulate cardiovascular risk as well. Intrauterine growth retardation can be induced in animal models by energy/protein restriction, or ligation of uterine arteries. In such models, altered glucose homeostasis, including low beta-cell mass, low insulin secretion and insulin resistance is observed after a few weeks of age. In humans, several studies have confirmed that children born SGA have insulin resistance as adolescents and young adults. Alterations of glucose homeostasis and increased lipid oxidation can indeed be observed already in non-diabetic children born SGA at early pubertal stages. These children also have alterations of stature and changes in body composition (increased fat mass), which may contribute to the pathogenesis of insulin resistance. Permanent metabolic changes induced by foetal/early neonatal nutrition (metabolic inprinting) may involve modulation of gene expression through DNA methylation, or alterations of organ structure. It is also possible that events occurring during foetal/neonatal development lead to long-lasting alterations of the hypothalamo-pituitary-adrenal axis or the hypothalamo-pituitary-insulin-like growth factor-1 axis.     

Children born with intra-uterine growth retardation (IUGR) or small for gestational age (SGA): long term growth and metabolic consequences

Intra Uterine Growth Retardation (IUGR) refers to insufficient fetal growth diagnosed either by two direct intrauterine growth assessment (ultra-sonography) or when the fetus or newborn length (height) is less than two standard deviations (or third percentile) below the mean for gestational age (NIKLASSON et. al. 1991; DE ZEGLER 1997). When the fetus or newborn body size (wight or length) is insufficient for gestational age, that is less than 2 standard deviations below the mean (or third percentile) for gestation during the situation is referred to as Small for Gestational Age (SGA). Since both fetal weight and length (height) gains are closely related, there is much overlap between SGA and IUGR. The proportion of newborn with normal birth weight and overlap between SGA and IUGR, isolated low birth weight, isolate low birth length and combined low birth weight and length is presented in Tab. 1, according to the most recent series reported nb NIKLASSON (1991). SGA/IUGR is a public health problem, since 2.5-3.0 % of newborns are affected by definition, and 8-10 % of them do not catch up postnatally, presenting with a persistent severe height deficiency, developmental difficulties and poor outcome (UNDERWOOD 1991; SIEGEL et al. 1991; Albertson-WICKLAND et. al. 1993; LAKEMAN et al. 1994).     

MRI findings of the pituitary gland in short children born small for gestational age (SGA) in comparison with growth hormone-deficient (GHD) children and children with normal stature

BACKGROUND: Disturbances in the GH/IGF-I axis are reported in 25-60% of short children born small for gestational age (SGA). We hypothesized that these abnormalities might be related to abnormalities in the pituitary region. Therefore, the results of magnetic resonance imaging (MRI) of short SGA children were compared to MRI results of other groups of short children and to normal controls. PATIENTS AND METHODS: MRI was performed in four groups of short children: SGA children without GH deficiency (SGA group; n = 17), SGA children with isolated GH deficiency (SGA + IGHD group; n = 10), non-SGA children with isolated GH deficiency (IGHD group; n = 24) and non-SGA children with multiple pituitary hormone deficiencies (MPHD group; n = 15). MRI was also performed in children with normal stature (control group; n = 13). Pituitary height (PH) and thickness of the pituitary stalk (PS) were measured and their relationship with the maximum GH peak during a GH stimulation test, serum IGF-I and IGFBP-3 levels was evaluated. RESULTS: Short SGA children either with or without IGHD did not show major anatomical abnormalities in the hypothalamic-pituitary region in contrast to 58% of the non-SGA IGHD children and 87% of the MPHD children who had anatomical abnormalities. PH in SGA children without GHD was normal whereas it was significantly lower in SGA children with IGHD. The lowest PHs were measured in non-SGA children with MPHD. A moderate decrease in PH was associated with significantly lower maximum serum GH peaks and lower serum IGF-I and IGFBP-3 levels. CONCLUSION: Measuring PHs in children with less severe GHD, who underwent MRI as part of the diagnostic process, might support the diagnosis of GHD even in the absence of anatomical abnormalities. Our study demonstrates that there is no indication to perform MRI of the pituitary region in short children born SGA without GHD.     

Blood glucose concentrations are reduced in children born small for gestational age (SGA), and thyroid-stimulating hormone levels are increased in SGA with blunted postnatal catch-up growth

Fetal growth restriction is associated with an increased risk of developing insulin resistance and type 2 diabetes in adulthood. In addition, 10-20% of children born small for gestational age (SGA) do not achieve a normal final height. The purpose of this study was to investigate insulin sensitivity and endocrine status in SGA children, compared with that in children born appropriate for gestational age (AGA). Furthermore, within the SGA group, we aimed to relate postnatal growth to anthropometric, biochemical, and endocrine parameters. Eighty-two SGA children (with a mean age of 8.6 +/- 3.5 yr) and 53 short-AGA children (with a mean age of 9.3 +/- 3.3 yr) were studied. A case-control study was carried out in 26 SGA and 26 short-AGA subjects. For each SGA subject, we selected a short-AGA child matched for sex, age (within 1 yr), pubertal status, body mass index (within 0.5 kg/m(2)), and height (within 0.25 z-score). Children's statures were corrected for their midparental height, and SGA children were subdivided into 2 groups: catch-up growth (CG) group (children with corrected height with at least 0 z-score); and non-CG (NCG) group (subjects with corrected height with less than 0 z-score). Comparing SGA with short-AGA subjects, no significant differences in fasting insulin, fasting glucose/insulin ratio, homeostasis assessment model for insulin resistance, and homeostasis assessment model-beta-cell values were observed. SGA children showed significantly reduced levels of glucose (4.4 +/- 0.6 vs. 4.9 +/- 0.6 mM, P < 0.0001), total cholesterol (160.1 +/- 28.8 vs. 171.8 +/- 28.5 mg/dl, P = 0.02), and high-density-lipoprotein cholesterol (53.3 +/- 12.1 vs. 58 +/- 11.4 mg/dl, P = 0.02). The analysis of the subjects selected for the case-control study confirmed that SGA children did not have significant differences in the indices of insulin sensitivity but showed significantly lower glucose levels (4.4 +/- 0.7 vs. 4.9 +/- 0.4 mM, P < 0.005). Subdividing the SGA group into CG (n = 25) and NCG (n = 57) children, we found that NCG children showed significantly higher levels of TSH (2.5 +/- 1.3 vs. 1.9 +/- 0.6 mU/liter, P = 0.002). Our data indicate that SGA children do not have altered insulin sensitivity when compared with auxologically identical AGA subjects but show a significant reduction of glucose concentrations. Whether the lower glucose levels are attributable to an early phase of augmented insulin sensitivity, as previously reported in animal models, has to be established. The finding of higher TSH concentrations in SGA children with blunted CG suggests that intrauterine reprogramming might involve thyroid function, which, in turn, might affect postnatal growth and cholesterol metabolism, eventually increasing the risk of cardiovascular disease.     

Risk factors for diabetes mellitus type 2 and metabolic syndrome are comparable for previously growth hormone-treated young adults born small for gestational age (sga) and untreated short SGA controls

CONTEXT: Low birth weight might increase risk of diabetes mellitus type 2 and metabolic syndrome (MS). GH has insulin-antagonistic properties. Therefore, long-term follow-up of GH-treated children born small for gestational age (SGA) is important. OBJECTIVE AND PATIENTS: The objective of the study was to evaluate insulin sensitivity (Si) and disposition index (DI), all components of the MS and IGF-I and IGF binding protein (IGFBP)-3 levels in 37 previously GH-treated young SGA adults in comparison with 25 untreated short SGA controls. RESULTS: GH-treated subjects were 22.3 (1.7) yr old. Mean duration of GH treatment had been 7.3 (1.3) yr. Mean period after discontinuation was 6.5 (1.4) yr. Si and DI were comparable for GH-treated and untreated SGA subjects. Fasting glucose and insulin levels increased during GH treatment but recovered after discontinuation. Body mass index, waist circumference, high-density lipoprotein cholesterol levels, and triglycerides were equivalent. Systolic and diastolic blood pressure and cholesterol were significantly lower in GH-treated subjects. Thirty-two percent of untreated controls vs. none of the GH-treated subjects had an increased blood pressure. GH-induced rises in IGF-I and IGFBP-3 levels had completely recovered after GH stop. CONCLUSION: At 6.5 yr after discontinuation of long-term GH treatment, Si, DI, fasting levels of glucose and insulin, body mass index, waist circumference, and IGF-I and IGFBP-3 levels were equivalent for GH-treated and untreated young SGA adults. Systolic and diastolic blood pressure and serum cholesterol were even lower in GH-treated subjects. These data are reassuring because they suggest that long-term GH treatment does not increase the risk for diabetes mellitus type 2 and MS in young adults.     

Functional hypersomatotropism in small for gestational age (SGA) newborn infants

Basal plasma GH levels and the GH responses to an injection of 1 microgram/kg 1-44(NH2) GHRH were determined on day 3 postnatally in 5 small gestational age (SGA) twin newborns and their appropriate gestational age (AGA) co-twins, and in 10 SGA singleton newborns and 6 AGA singleton newborns. The mean basal plasma GH level was higher in the SGA than in the AGA infants but the difference was significant only for singleton newborns (p less than 0.01). The mean peak plasma GH level was markedly increased in SGA compared to AGA infants (p less than 0.05 for twins, p less than 0.01 for singletons). Twelve SGA infants re-tested at 1 month had lower basal and peak plasma GH levels (p less than 0.001 and p less than 0.01). In 21 SGA and 17 AGA infants, serum IGF-I, measured by RIA between 12 and 96 hours after birth, was significantly higher in SGA than in AGA (p less than 0.001). These results suggest that, whatever the mechanism, functional hypersomatotropism is present at day 3 in SGA infants. This hypersomatotropism may participate in the early catch-up growth process.     

Reduced insulin sensitivity and the presence of cardiovascular risk factors in short prepubertal children born small for gestational age (SGA)

BACKGROUND: Epidemiological studies have shown that the metabolic syndrome, a combination of type 2 diabetes mellitus, hypertension, dyslipidaemia and a high body mass index (BMI), occurs more frequently among adults who were born with a low birth weight. Because insulin is thought to play a key role in the pathogenesis of this syndrome we investigated insulin sensitivity and risk factors for cardiovascular disease in short prepubertal children born small for gestational age (SGA). PATIENTS AND METHODS: Frequently sampled intravenous glucose tolerance tests (FSIGT) were performed in 28 short prepubertal children born SGA. Short stature was defined as a height < -2SD. SGA was defined as a birth length and/or a birth weight for gestational age < -2SD. Twelve short children born appropriate for gestational age (AGA) were used as controls for the FSIGT's results only. AGA was defined as a birth weight and/or birth length for gestational age > -2SD. In short SGA children, blood pressure (BP), fasting levels of serum free fatty acids (FFA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) were measured and compared to reference values. RESULTS: Mean insulin sensitivity (Si) level in short SGA children was significantly reduced to 38% of the mean Si level measured in short AGA controls (P = 0.004). Mean acute insulin response (AIR) was significantly higher in SGA children compared to short AGA controls (P < 0.001). Differences in Si and AIR between the two groups remained significant after adjusting for age and BMI (P < 0.001 and P = 0.003, respectively). The mean (SD) systolic BP SDS was 1.3 (1,1), being significantly higher than zero. Mean fasting serum levels of FFA, TC, TG, HDL and LDL were all within the normal range. However, 6 of the 28 SGA children had serum FFA levels above the normal range. Cardiovascular risk factors could statistically be represented in two clusters. Both clusters played a significant role in the development of insulin insensitivity (1/Si). CONCLUSION: Although the metabolic syndrome has been described in adulthood, our study showed that risk factors for the development of type 2 diabetes mellitus and cardiovascular disease are already present during childhood in short prepubertal children born SGA, suggesting a pretype 2 diabetes mellitus phenotype.     

Altered cardiovascular rhythmicity in children born small for gestational age

Low birth weight is frequently associated with a disproportionately high incidence of cardiovascular disease, diabetes mellitus, and kidney disease in adulthood. Epidemiological studies have identified an inverse association between low birth weight or being small for gestational age and hypertension in adulthood. We hypothesized that children born with low birth weight might have altered circadian and ultradian cardiovascular rhythmicity independent of the prevailing blood pressure level. Twenty-four-hour ambulatory blood pressure and heart rate rhythmicity was prospectively evaluated by Fourier analysis in a cohort of healthy children born with low birth weight and compared with normative pediatric data. Seventy-five children born small for gestational age (mean age, 8.1±2.2 years) and 139 controls matched for age and sex were investigated. In addition to increased 24-hour, daytime, and especially nighttime blood pressure levels (P<0.05), children born small for gestational age exhibited blunted circadian (24-hour) and ultradian (12-, 8-, and 6-hour) blood pressure rhythmicity (P<0.05). In a multivariate analysis including children born with low birth weight and controls, being born with low birth weight independently influenced ultradian blood pressure rhythmicity, whereas in a multivariate analysis including children born with low birth weight only, circadian and ultradian rhythms were independently influenced by catch-up growth, gestational age, and blood pressure level. This study demonstrates blunted circadian and ultradian cardiovascular rhythmicity in prepubertal children born small for gestational age, independent from the presence of arterial hypertension. Circadian and ultradian rhythms may be sensitive indicators for detecting subtle early abnormalities of cardiovascular regulation.     

Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA)

Context  Several studies showed a decrease in height velocity during GnRH analogue (GnRHa) treatment. No information is available on GH levels during GnRHa treatment in short SGA girls.
Objective  To study overnight GH profiles and IGF-I and IGFBP-3 levels in girls with Tanner stage 2 and stage 3, before and after 3 months of GnRHa treatment, and to compare levels with those found in prepubertal short SGA girls.
Patients  Twenty-four pubertal and 16 prepubertal short SGA girls.
Intervention  After baseline overnight GH profiles, pubertal girls received leuprorelide acetate depots of 3·75 mg subcutaneously every 4 weeks.
Outcome measures  GH, IGF-I and IGFBP-3 levels.
Results  At baseline, GH levels were comparable to levels found in prepubertal short SGA girls and IGF-I and IGFBP-3 SDS were significantly below the population mean. After 3 months of GnRHa treatment, AUC₀ ( P  = 0·02), mean ( P  = 0·02) and maximum GH levels ( P  = 0·008) had significantly decreased. Mean GH levels were significantly lower than in prepubertal short SGA girls ( P  = 0·03). Eight girls with more than 40% decrease in mean GH levels also had a significantly greater decrease in IGF-I and IGFBP-3 levels. Mean and maximum GH levels at baseline correlated significantly with those after 3 months of GnRHa treatment.
Conclusion  Short SGA girls lack the normal increase in GH levels seen in puberty and have reduced IGF-I and IGFBP-3 levels, which might explain their reduced pubertal growth spurt. GnRHa treatment led to a significant reduction in GH levels. Therefore, combining GnRHa treatment with GH treatment might improve adult height of short SGA girls.     

Increased oxidative stress in prepubertal children born small for gestational age

CONTEXT: Low birth weight is associated with an increased risk of metabolic and cardiovascular diseases in adulthood. The development of insulin resistance (IR) seems to play a pivotal role; no data on the oxidant-antioxidant status are available in this risk group. OBJECTIVE: This study is an assessment of oxidant-antioxidant status in prepubertal children born small for gestational age (SGA) in comparison to healthy controls and the relationship to IR. DESIGN: This cross-sectional study compares indexes of IR and oxidant-antioxidant status in three different groups (SGA+, SGA-, controls), with analysis by post hoc and Pearson correlation. SETTING: The study was conducted in the Academic Department of Pediatrics. PARTICIPANTS: A total of 19 SGA+ and 16 SGA- children were compared with 13 controls. INTERVENTION: No intervention was used. MAIN OUTCOME MEASURES: Indexes of IR (glucose to insulin ratio, homeostasis model assessment of IR) were evaluated, and markers of oxidative stress (lag phase, malonildialdehyde, vitamin E) were measured. RESULTS: Homeostasis model assessment of IR was significantly higher in SGA+ than SGA- children (1.32+/-0.9 vs. 0.69+/-0.47; P=0.03) and controls (0.71+/-0.37; P=0.04). Glucose to insulin ratio was significantly lower in SGA+ than SGA- children (12.41+/-5.01 vs. 26.54+/-17.18; P=0.02) and controls (26.96+/-20.70; P=0.04). Lag phase was significantly shorter in SGA+ than SGA- children (24.3+/-4.38 vs. 35.59+/-11.29 min; P=0.003) and controls (45.28+/-7.69 min; P=0.0001) and in SGA- than controls (P=0.01). Malonildialdehyde was significantly higher in SGA+ than SGA- children (0.79+/-0.3 vs. 0.6+/-0.1 nmol/mg; P=0.03) and controls (0.36+/-0.04 nmol/mg; P=0.0001) and in SGA- children than controls (P=0.02). Vitamin E was significantly reduced in SGA+ children than controls (27.54+/-7.9 vs. 43.23+/-11.32 micromol/liter; P=0.002). CONCLUSION: Oxidative stress is present in both SGA+ and SGA- children, with a continuous alteration in relation to IR. Therefore, catch-up growth might exert the greatest influence in the development of future diseases.     

Visceral adiposity without overweight in children born small for gestational age

CONTEXT: Children born small for gestational age (SGA) tend to develop catch-up growth in infancy and become overweight by the age of 6 yr. Weight control is advocated as a preventive measure, but it is unknown whether such control suffices to prevent visceral fat excess and hypoadiponectinemia. SETTING: The study was performed at a university hospital. STUDY POPULATION AND DESIGN: A total of 64 children (32 matched pairs) aged 6 yr, of whom 32 were born appropriate for gestational age and 32 were born SGA, and had subsequently developed spontaneous catch-up growth were included in the study; matching was performed for gender, height, weight, and, thus, body mass index. MAIN OUTCOMES: Fasting insulin, IGF-I, high molecular weight adiponectin, leptin, visfatin, and lean and fat mass were calculated by absorptiometry, and abdominally sc and visceral fat by magnetic resonance imaging. RESULTS: After strict matching, SGA children had a total lean mass, total fat mass, leptinemia, and visfatinemia comparable to those in the appropriate for gestational age children, but they still had higher fasting insulin and IGF-I levels (P < 0.01), much lower high molecular weight adiponectin levels (P < 0.0001), and a striking shift from abdominally sc to visceral fat (P < 0.0001). Fasting insulin (r = 0.52; P < 0.00001) was a major determinant of visceral fat in boys and girls, explaining 28% of its variance. CONCLUSIONS: SGA children tend to be viscerally adipose and hypo-adiponectinemic, even if they are not overweight. Therefore, measures beyond weight control seem to be needed to allow most SGA children to normalize their body composition and endocrine-metabolic homeostasis.     

Growth hormone therapy for short children born small for gestational age

Approximately 10% of all children born small for gestational age (SGA) fail to achieve sufficient catch-up growth and remain with short stature throughout childhood and adult life. Abnormalities of the GH/IGF-1 axis are not always identified. Several studies have demonstrated that GH is an effective and well-tolerated therapy and most children will reach a normal adult height. In this review, it can be seen the encouraging results of GH treatment in growth-retarded children born SGA highlighting the benefits of early treatment.