Serum adiponectin levels were investigated in 28 small-forgestational-age (SGA) and 34 appropriate-for-gestational-age (AGA) term neonates to examine how fetal growth correlates with adiponectin levels. A blood sample for determination of adiponectin was obtained during the first 24 h of life. The levels of serum adiponectin were significantly higher in all newborn infants than in healthy children (28.7 Ϯ 17.0 versus 9.3 Ϯ 6.1 g/mL; p Ͻ 0.01). There was a significant difference in adiponectin levels between SGA and AGA infants (23.2 Ϯ 14.8 versus 33.2 Ϯ 17.5 g/mL; p ϭ 0.02). For all of the newborn groups, serum adiponectin levels correlated positively with birth weight (r ϭ 0.27, p Ͻ 0.05) and head circumference (r ϭ 0.30, p Ͻ 0.05). There was no relationship between serum adiponectin levels and gestational age, birth length, blood glucose levels, or blood sampling time after birth. There was no gender difference in adiponectin levels in the entire newborn group (30.0 Ϯ 19.7 versus 28.0 Ϯ 15.5 g/mL, in male and female infants). Our results suggest that hyperadiponectinemia and a positive relationship between the serum levels of adiponectin and birth weight in newborns cannot be explained by the low percentage of body fat alone. Lower adiponectin levels in SGA infants than in AGA infants are unlikely to suggest insulin resistance in intrauterine growth-retarded infants in early postnatal life but may be a predisposing factor in the future development of insulin resistance or type 2 diabetes. Adiponectin is a protein derived from adipose tissue in humans, and serum adiponectin levels are paradoxically reduced in obese individuals (1). Decreased concentrations of adiponectin are also seen in patients with insulin resistance or type 2 diabetes (2). Insulin-sensitizing agents such as thiazolidinediones increase adiponectin concentrations in humans (3) and in animals (4), whereas administration of adiponectin increases insulin sensitivity in animals (4). However, intrauterine growth retardation is associated with an increased risk of developing type 2 diabetes and cardiovascular disease (5,6). To explain this association, the concept of "reprogramming" was introduced (7): fetal adaptation to an adverse intrauterine environment determines an altered programming of endocrine pathways, leading to permanent metabolic changes, including insulin resistance. The present study was undertaken to examine how different intrauterine growth patterns relate to adiponectin secretion in early neonatal life. METHODS Infants.Thirty-four newborns (20 boys and 14 girls) with appropriate-for-gestational-age (AGA) birth weight (relative birth weight below ϩ2 or above Ϫ2 SD) and 28 (16 boys and 12 girls) with small-for-gestational-age (SGA) birth weight (relative birth weight, Ϫ2 or less SD) were included in the study (Table 1). All neonates had no asphyxia at birth and were found to be well on physical examination performed at the time of blood sampling. All infants in both groups were breast-fed, with similar frequencies ranging from 3 to...

A 3-year-old girl with phenotypic and cytogenetic manifestations of the ICF syndrome and DNA hypomethylation but without DNMT3B gene mutation is described. At age 3 months, she had an apneic spell that left her with spastic paraplegia and severe mental retardation. At age 8 months, she suffered meningococcal meningitis and sepsis. When seen by us at age 3 years with virilization, she had a cleft plate, macroglossia, and an atrial septal defect. An adenoma was surgically removed from the right adrenal cortex. Her serum immunoglobulin levels were normal except IgA at the low normal border. Her lymphocytes showed paracentromeric stretching of chromosomes 1 and 16 in 7% of metaphases, and multiradial figures involving these chromosomes in 1% of cells. Hypomethylation of classical satellite 2 DNA was observed with BstBI digestion, but in a lesser degree than those in the individuals with proven DNMT3B mutations. No mutation was found in the coding and promoter regions of the gene. Several alternative interpretations were considered to explain the low frequencies of chromosomal instabilities and the lower degree of DNA hypomethylation, and undetected DNA3B mutations. A mutation may be present in the gene but undetected, present in other DNA methyltransferases (DNMT) genes or in a DNMT-associated protein gene.

The present study showed for the first time that the fasting IGFBP-1 level was suppressed in prepubertal obese children with fasting normoinsulinaemia. We speculate that the hyperinsulinaemia which cannot be detected in the fasting state may have suppressed hepatic production of IGFBP-1. Alternatively, the reduced IGFBP-1 is likely to be a compensatory response to impaired insulin sensitivity. Thus, the IGFBP-1 level may be a useful predictor for the early identification in the development of insulin resistance in prepubertal obese children.

Background: Adiponectin, one of the adipocytokines, is postulated to play a key role in fetal growth, probably enhancing the growth-promoting effect of insulin through insulin-sensitizing action. Objectives and Methods: To examine how different intrauterine or postnatal growth patterns relate to adiponectin secretion, we measured serum adiponectin concentrations in 30 appropriate-for-gestational-age (AGA) and 19 small-for-gestational-age (SGA) preterm infants on the first day of life and at term-equivalent age. Results: The serum levels of adiponectin increased significantly in all preterm infants from birth to term-equivalent age. The adiponectin levels at term-equivalent age were significantly higher in the AGA than in the SGA group [mean (SD) 40.4 (12.3) vs. 28.4 (10.4) µg/ml; p < 0.01] after adjustment for gestational age or term-equivalent body weight. The increase in adiponectin levels from birth to term-equivalent age was significantly higher in the AGA than in the SGA group, and was positively correlated with the weight gain rate (g/kg/day) in the combined groups (r = 0.37, p < 0.01). A multiple regression analysis with the adiponectin increase from birth to term-equivalent age as the dependent variable for all the subjects revealed that only weight gain rate was independently associated with the adiponectin increase. Conclusions: Our results suggest that the change in serum adiponectin levels may reflect postnatal growth from birth to term-equivalent age in preterm infants.

Background/Aim: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro. Methods: We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis. Results: The thyroid hormone levels of the patients were normal in early infancy, although their serum levels of TSH were mildly elevated. After supplemental treatment with levothyroxine sodium (L-T4) was started, we had to increase the dose to maintain the level of TSH within the normal range in all patients. Thyroid dysfunction became obvious in one patient at reexamination during adolescence when L-T4 treatment was stopped for 1 month. Four patients were examined for intelligence quotient and their scores were normal. Conclusions: Thyroid hormone replacement therapy should be considered based on biological data in patients with hyperthyrotropinemia who have a homozygous R450H mutation of the TSHR gene even if they do not exhibit obvious hypothyroidism in infancy.

These novel inactivating mutations contribute to understanding of the structure-function relationship of the TSH receptor. To date, all of the patients with TSH resistance resulting from TSH receptor mutations identified in Japan possessed the R450H mutation at least in one allele. These observations suggest that the R450H mutation is a commonly observed TSH receptor mutation in patients with TSH resistance in Japan.

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