Nobuhiko Nagano

Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat

The concept of the developmental origins of health and disease is based on studies by Barker et al. They proposed a hypothesis that undernutrition in utero permanently changes the body’s structure, function, and metabolism in ways that lead to atherosclerosis and insulin resistance in later life. In addition, profound effects on the extent of body fatness and insulin sensitivity are demonstrated, if there is a “mismatch” between prenatal and postnatal environments. In previous studies, undernutrition in utero has been evaluated simply by birth weight itself or birth weight for gestational age, and the degree of mismatch has been estimated by postnatal rapid weight gain. Recently, we investigated subcutaneous fat accumulation in small-for-gestational-age infants and found that a rapid catch-up in skinfold thickness developed prior to the body weight catch-up. Furthermore, insulin-like growth factor-I and lipoprotein lipase mass concentrations also demonstrate rapid increase during the neonatal period with fat accumulation. Investigating the precise mechanisms of developmental origins of health and disease including mediating metabolic and hormonal factors may provide a new approach to prevent atherosclerosis and insulin resistance. Better management of undernutrition during gestation and neonatal growth during the early postnatal period is an important theme for future health.

Residual blood volume in the umbilical cord of extremely premature infants.

The aim of this study was to investigate residual blood volume in the umbilical cord of extremely premature infants.

Early postnatal changes of lipoprotein subclass profile in late preterm infants

BACKGROUND Late preterm infants (LPIs; 34-37 gestational weeks at birth) have higher risk for several morbidities than do term infants (TIs). It has been suggested that a cholesterol and fatty acid supply may improve their outcomes. We investigated the lipoprotein subclass profile in LPIs to evaluate their early postnatal lipid metabolism. METHODS Eighty-one infants (25 LPIs, 56 TIs) were included. Cholesterol and triglyceride (TG) concentrations in 12 lipoprotein subclasses were measured at birth and at 1 month using HPLC. RESULTS In LPIs, the cord blood exhibited higher cholesterol concentrations in medium and large subclasses of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) compared to the values in TIs. During the first month of life, LPIs had greater increases in cholesterol concentrations of medium and large subclasses of VLDL than TIs, whereas postnatal increases in cholesterol concentrations of medium and large subclasses of LDL and HDL were smaller. TG concentrations were not different in each VLDL subclass at birth and at 1 month. CONCLUSIONS In LPIs, cord blood lipoprotein subclass profiles and the early postnatal change exhibited different, especially in cholesterol concentrations.

Insulin resistance at diagnosis in Japanese children with type 2 diabetes mellitus

Background:  Insulin resistance at diagnosis was investigated in Japanese children with type 2 diabetes mellitus (T2DM).

Influence of plasma glucagon levels on glycemic control in children with type 1 diabetes.

Objective:  The aim of this study was to investigate the association between plasma glucose (PG), HbA1c and plasma glucagons levels in children with type 1 diabetes to determine the influence of plasma glucagon on their glycemic control.

Diabetes caused by Kir6.2 mutation: Successful treatment with oral glibenclamide switched from continuous subcutaneous insulin infusion in the early phase of the disease

Neonatal diabetes mellitus (NDM) is very rare, with an estimated incidence of one in 500 000 neonates. Its etiology and long-term clinical course are not well known. In most cases, blood glucose levels during the neonatal and infantile periods are controlled by insulin treatment. Diabetes mellitus (DM) diagnosed before 6 months of age, classified as NDM, frequently results from mutations of the KCNJ11 gene that encodes the Kir6.2 subunit of the adenosine triphosphate (ATP)-sensitive potassium channel (KATP channel). These are activating mutations, resulting in hyperpolarization of the cell membrane, and, in the case of the pancreatic b-cells, inhibition of insulin secretion. Notably, it has been reported that in these patients, treatment with a sulfonylurea (SU), which binds to the sulfonylurea receptor 1 (SUR1) subunit and closes the KATP channel, can stimulate insulin secretion and improve blood glucose control. We report a case of NDM caused by the Kir6.2 mutation (R201C) in a young infant, in whom treatment initiated with continuous subcutaneous insulin infusion (CSII) could subsequently be switched successfully to oral sulfonylurea treatment with glibenclamide.

Retinopathy of prematurity after sildenafil treatment

1 Aquil B, Merrit BY, Elghetany MT, Kamdar KY, Lu XY, Curry CV. Childhood nodal marginal zone lymphoma with unusual clinicopathologic and cytogenetic features for the pediatric variant: a case report. Pediatr. Dev. Pathol. 2015; 18: 167–71. 2 Rizzo KA, Streubel B, Pittaluga S et al. Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR. Mod. Pathol. 2010; 23: 866–73. 3 Taddesse-Heath L, Pittaluga S, Sorbara L, Bussey M, Raffeld M, Jaffe ES. Marginal zone B-cell lymphoma in children and young adults. Am. J. Surg. Pathol. 2003; 27: 522–31. 4 Gitelson E, Al-Saleem T, Robu V, Millenson MM, Smith MR. “Pediatric” nodal marginal zone lymphoma in adults. Leuk. Lymphoma 2010; 51: 89–94.

Genetic ablation of Bach1 gene enhances recovery from hyperoxic lung injury in newborn mice via transient upregulation of inflammatory genes

Background:BTB and CNC homology 1 (Bach1) is a transcriptional repressor of heme oxygenase (HO)-1. The effects of Bach1 disruption on hyperoxic lung injury in newborn mice have not been determined. We aimed to investigate the role of Bach1 in the newborns exposed to hyperoxia.Methods:Bach1−/− and WT newborn mice were exposed to 21% or 95% oxygen for 4 d and were then allowed to recover in room air. Lung histology was assessed and lung Bach1, HO-1, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 mRNA levels were evaluated using RT-PCR. Lung inflammatory cytokine levels were determined using cytometric bead arrays.Results:After 10 d recovery from neonatal hyperoxia, Bach1−/− mice showed improved lung alveolarization compared with WT. HO-1, IL-6, and MCP-1 mRNA levels and IL-6 and MCP-1 protein levels were significantly increased in the Bach1−/− lungs exposed to neonatal hyperoxia. Although an increase in apoptosis was observed in the Bach1−/− and WT lungs after neonatal hyperoxia, there were no differences in apoptosis between these groups.Conclusion:Bach1−/− newborn mice were well-recovered from hyperoxia-induced lung injury. This effect is likely achieved by the antioxidant/anti-inflammatory activity of HO-1 or by the transient overexpression of proinflammatory cytokines.

Apolipoprotein A-V concentration in preterm infants

BACKGROUND Fetal organs require much lipid for growth, but the cord blood had low TG concentrations, compared to adult serum. We investigated the association between the concentration of apolipoprotein A-V (apoA-V) and lipid profile in cord blood and neonatal serum. OBJECTIVE ApoA-V was identified as an important determinant of plasma triglyceride concentrations. We sought to determine the association between serum apoA-V concentrations and lipoprotein profile in preterm infants and its early postnatal change. METHODS Sixty-three neonates (35 males and 28 females; 15 term and 48 preterm) were included. Serum lipoprotein profile and apoA-V concentrations were determined at birth and 1 month. RESULTS Cord blood apoA-V concentrations in appropriate-for-gestational age infants were extremely low (13.1 ± 3.4 ng/mL in term infants, 4.4 ± 0.9 ng/mL in preterm infants) compared with adult values, and those of small-for-gestational age infants were further low (6.4 ± 4.2 ng/mL, 2.2 ± 1.3 ng/mL, respectively). During the first month, serum apoA-V concentration markedly increased, and the concentration of preterm appropriate-for-gestational age infants caught up, whereas that of preterm small-for-gestational age infants did not. At birth, apoA-V concentration positively correlated with gestational age (r = 0.354, P = .0069) but not with birth weight Z-score. ApoA-V concentration had a positive association with very low-density lipoprotein triglyceride concentrations (r = 0.646, P < .0001), and the relationships still remained at 1 month (r = 0.283, P = .0348). CONCLUSIONS ApoA-V in neonates was unique in its serum concentration and in the association with lipoprotein profile.

Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.