Naoshi Hashimoto

The relationship between fatty liver and hyperinsulinemia in obese Japanese children

BACKGROUND Previous reports have revealed that fatty liver involving obesity is closely related to insulin resistance or hyperinsulinemia in adulthood. This study investigates the importance of hyperinsulinemia in obese children with fatty liver. METHODS The subjects were 228 obese children 6 to 15 years old in Niigata Prefecture, Japan. The serum level of glutamic pyruvic transaminase (GPT) was evaluated as an indicator of fatty liver. The effects of their percent obesity (percent over ideal body weight), Rohrer index (g/cm3), skinfold thickness, percent body fat measured by bioelectrical impedance analysis, total cholesterol (TC), high-density lipoprotein cholesterol, triglyceride (TG), blood glucose, and immuno-reactive insulin (IRI) on GPT were evaluated using regression analyses. RESULTS The incidence of fatty liver (GPT over 35 IU/I) was 24.1% in this study. In simple regression analyses, percent obesity, Rohrer index, skinfold thickness, TC, TG, blood glucose, and IRI correlated positively with GPT (p < 0.05). In stepwise regression analysis including these seven variables, the predictive equation for GPT as a function of IRI alone accounted for 24.2% of the total variance of GPT. The addition of TC alone, and TC and percent obesity together increased the coefficients of determination to 28.4% and 29.9%, respectively. Rohrer index, skinfold thickness, Tg, and blood glucose were not taken as related variables with GPT. CONCLUSION Hyperinsulinemia is an important contributor to the development of fatty liver, apparently more than anthropometric data, blood glucose, or serum lipids in childhood obesity.

Association of serum low‐density lipoprotein metabolism with oestrogen receptor gene polymorphisms in healthy children

The aim of this study was to reveal the association of serum lipid and apolipoprotein levels with oestrogen receptor (ER) Xba I and Pvu II polymorphisms in 102 healthy Japanese school children (56M, 46F) aged 10–15 y. Each genotype of the genomic DNA extracted from peripheral leukocytes was determined using polymerase chain reaction and digestion with Xba I or Pvu II. The genotypes were coded as either X1 or X2 (Xba I) and P1 or P2 (Pvu II), when X1, P1 signified the absence of and X2, P2 the presence of restriction sites. The fasting serum total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein (LDL) cholesterol, triglyceride and apolipoproteins A1, B and E were measured. In the Xba I polymorphism, LDL cholesterol, apolipoprotein B levels of the X1/X1 genotype were significantly higher than those of the others. The other lipid and apolipoprotein levels were not significantly different among the three genotypes. In the Pvu II polymorphism, there were no significant differences in serum lipids and lipoproteins among the three genotypes. This study reveals that Xba I polymorphisms are related to LDL metabolism. These findings support previous reports that the LDL‐lowering effects of oestrogen occur through the ER (α) pathway. The Xba I polymorphism may be one of the genetic factors in the control of LDL metabolism.

Plasma levels of carboxy terminal propeptide of type I procollagen and pyridinoline cross-linked telopeptide of type I collagen in healthy school children

The aim of this study was to reveal the relationship of the plasma levels of the carboxy terminal propeptide of type I procollagen (PICP) and the pyridinoline cross‐linked carboxyterminal telopeptide domains of type I collagen (ICTP) to age and height velocity (HV), and to compare PICP and ICTP levels in those who have not reached their final height with those who have. PICP and ICTP levels were measured by RIA in 271 healthy children (161M, 110F) aged from 10 to 15 y. The HV was calculated from their health check‐up cards. The subjects were divided into two groups in this study: the final height (FH) group whose HV was < 1.0 cm/y, and the non‐final height (NFH) group whose HV in the last year was ≥ 1.0 cm/y. PICP and ICTP levels almost paralleled the values of age‐related changes of HV. Furthermore PICP and ICTP levels significantly correlated with HV. PICP and ICTP levels of the FH group were higher than those of adults previously reported. The values will be useful as reference for healthy children and growth disorder. Before reaching final height, PICP and ICTP can be useful makers of not only bone turnover but also of linear growth. Bone turnover rate is still increasingly active just after linear growth has been completed, and then it become similar to the levels of adults.

SERUM LEVEL AND GENE POLYMORPHISM OF ANGIOTENSIN I CONVERTING ENZYME IN JAPANESE CHILDREN

The aim of the present study was to determine the distribution of the insertion/deletion polymorphism of angiotensin I converting enzyme (ACE) gene in Japanese children. In addition, the relationship between this polymorphism and serum ACE levels in the same population were analyzed. Insertion/deletion polymorphism located in intron 16 of the ACE gene was examined by polymerase chain reaction in Japanese children aged 10–15 years. Allele frequencies were 0.64 for the insertion allele and 0.36 for the deletion allele in 122 subjects. No association was found between genotypes in this polymorphism and the level of systolic or diastolic blood pressure. A significant relationship between this polymorphism and serum ACE activity was observed. These results suggest that interindividual variability of serum ACE level is strongly influenced by the ACE genotype as early as in childhood.

Criteria of normal blood pressure and hypertension in Japanese preschool children.

The blood pressure (BP) of 5332 Japanese preschool children from 2 to 6 years of age was measured using an automated BP recorder (Dinamap Model 8104). The third reading of the consecutive measurement of BP was used for analysis. This study adopted a definition of hypertension developed by The Task Force conducted in the United States in 1987, which showed the 95th percentiles of systolic and diastolic BP for age and sex. Stepwise regression analysis revealed that body height, weight and heart rate had significant effects on both systolic and diastolic BP, whereas age had an effect on diastolic BP only, while sex and area where the subjects lived did not affect either BP. The 95th percentiles of systolic/diastolic BP at 2, 3, 4, 5, and 6 years of age were 115/69, 113/68, 114/65, 118/67 and 116/69 mm Hg in boys, and 121/70, 114/69, 115/67, 118/68 and 120/69 mm Hg in girls, respectively. The BP of Japanese preschool children can be evaluated using the data shown in this study.

The usefulness of measuring body fat deposition for detecting obesity and atherogenesity in Japanese school children.

Body fat deposition was measured in overweight and non‐overweight children using a bioelectrical impedance method, and its relationship with serum lipids and apolipoproteins was investigated in 90 overweight children (over 120% of their ideal weight) and 241 non‐overweight children aged 10–15 years in Niigata Prefecture. The results were as follows. Overweight boys had significantly higher levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), atherogenic index (AI), RLP‐cholesterol (RLP‐C), apoA1, apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to apoAl than non‐overweight boys. Overweight girls had significantly higher levels of TC, LDL‐C, AI, remnant‐like lopoprotein cholesterol (RLP‐C), apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to apoA1 than non‐overweight girls. It has been reported that of all children studied 2.1% had higher levels of RLP‐C than its upper limit known for adults (12 mg/dL). Of the overweight children in the present study, 4.4% had a high level of RLP‐C whereas only 1.2% of non‐overweight children had a high RLP‐C level. No difference in the lipoprotein levels was found between overweight and non‐overweight children. In both boys and girls, relative weight, body fat, skinfold thickness and body mass index (BMI) were correlated with the lipoprotein levels. Non‐overweight boys whose body fat was over 20% had significantly higher levels of TC, LDL‐C, apoA2, apoB, apoC2, apoE and apoB/A1 than those whose body fat was less than 20%. It was concluded that the measurement of body fat deposition, together with relative weight, was useful for detecting obesity and atherogenesity in Japanese school children.

Analysis of Met235 to Thr variant of the angiotensinogen gene in relation to the blood pressure and family history of essential hypertension in Japanese children

A recent study reported a significant relationship between a T704→C (Met235→Thr) variant in exon 2 of the angiotensinogen gene in adults and essential hypertension. In the present study, this variant was detected in 131 Japanese children using a polymerase chain reaction. The allele frequency of the variant was 0.76. The genotype frequency of the homozygote for the allele was 0.59, and children who were homozygous had higher systolic blood pressure than those with the other two genotypes. No relationship was found between childrens polymorphism and a family history of essential hypertension. These findings suggest that this molecular variant of the angiotensinogen gene may play some role in the regulation of blood pressure in Japanese children.