Makoto Hiura

Usefulness of Serum Adiponectin Level as a Diagnostic Marker of Metabolic Syndrome in Obese Japanese Children

This study aimed 1) to investigate the relationship between serum adiponectin levels and metabolic disorders and 2) to clarify the usefulness of serum adiponectin level as a diagnostic marker of metabolic syndrome in obese Japanese children. One hundred obese boys aged 8 to 13 years were examined. Serum adiponectin levels were measured by radioimmunoassay using a commercial kit. Abdominal fat thickness (maximum preperitoneal fat thickness: Pmax; minimum subcutaneous fat thickness: Smin) was measured by ultrasonography. The relationships between adiponectin and clinical characteristics were analyzed by simple regression. The relationships between anthropometric measurements and metabolic disorders were analyzed among three groups divided according to adiponectin percentile. The prevalence of metabolic syndrome was also analyzed, with metabolic syndrome defined as the presence of three or more complications of obesity. The criteria for metabolic syndrome by adiponectin were subjected to a receiver operating characteristic (ROC) analysis. Body weight, waist circumference, Pmax, alanine aminotransferase and fasting serum insulin were all inversely correlated with adiponectin. There were significant differences in the prevalence of severe obesity, the accumulation of visceral adipose tissue, hyperinsulinemia, high serum low density lipoprotein-cholesterol, the number of complications of obesity and the prevalence of metabolic syndrome among the three groups. The area under the ROC curve for adiponectin was 0.672±0.055 and the cut-off value was 6.65 μg/ml. Hypoadiponectinemia was associated with visceral fat accumulation and metabolic syndrome in obese Japanese boys. Evaluation of adiponectin might contribute to an early intervention for obese children with metabolic syndrome.

Obese Japanese children have low bone mineral density after puberty

The purpose of this study was to determine the relationship between BMD and childhood obesity. We examined 1070 obese children (722 boys and 348 girls) aged 7 to 15 years. Their mean relative weight, as a percentage of the standard weight for age, height, and sex, was 152.9 ± 14%. BMD was assessed, by a digital image processing method, in the second metacarpal bone of the left hand. We compared our results with those of healthy nonobese Japanese children based on both chronological and bone age. Mean BMD values for bone age in the obese children were significantly higher than those in control groups in boys aged 11 years and under and girls 9 years and under. On the other hand, in boys over 12 years old, BMD values for bone age were lower than those in the control groups. In girls over 11 years old, BMD values tended to be lower than those in the control groups. In conclusion, we studied the BMD of obese children from the point of view of advanced bone age. Our results showed that BMD was higher than in prepubertal obese children, but a low BMD value was found after puberty, due to poor gain of BMD during puberty. It is important to prevent obesity in childhood in order to prevent the low BMD after puberty.

Lower Birth Weight and Visceral Fat Accumulation Are Related to Hyperinsulinemia and Insulin Resistance in Obese Japanese Children

This study aimed to reveal the relation of birth weight (or the birth weight standard deviation score [BWSDS]) and visceral fat accumulation to hyperinsulinemia and insulin resistance. We examined obese Japanese children (650 boys and 317 girls) with a mean age of 10.3 years (range, 6–15 years). The mean percentage of overweight to the standard body weight of Japanese children was 52.1% in boys and 51.4% in girls. Abdominal fat thickness (maximum preperitoneal fat thickness; Pmax) was measured using ultrasonography. The fasting serum insulin and plasma glucose levels were measured, and the homeostasis model assessment-insulin resistance (HOMA-R) and quantitative insulin sensitivity check index (QUICKI) were calculated. We divided the subjects into four groups according to their birth weight or BWSDS, and compared anthropometric measurements, Pmax, blood pressure, serum insulin levels, HOMA-R and QUICKI among the quartiles. The relationships of both birth weight (or BWSDS) and Pmax to serum insulin levels (or HOMA-R, QUICKI) were examined with multiple regression analyses. The fasting serum insulin level and HOMA-R were highest in the quartile with the lowest birth weight or BWSDS. The birth weight and BWSDS were inversely related to the serum insulin levels and HOMA-R, positively related to QUICKI, and independent of Pmax. Our findings suggest that both lower birth weight and visceral fat accumulation may be independently related to hyperinsulinemia and insulin resistance in obese Japanese children.

Lower Birth Weight Associated with Current Overweight Status Is Related with the Metabolic Syndrome in Obese Japanese Children

The purpose of this study was to clarify the relationship between lower birth weight and current overweight status and to examine the involvement of these factors in the development of the metabolic syndrome (MS) in obese Japanese children. We examined 97 obese boys (mean age 11.3 years; mean percentage overweight [POW] 52.4%) and 29 obese girls (mean age 11.1 years; mean POW 58.3%). The anthropometric measurements, blood pressure, fasting serum insulin and blood glucose, liver enzymes, lipids and lipoproteins were measured. Birth weight and gestational weeks were also recorded. The subjects were divided into either an MS group or a Non-MS group using criteria proposed for Japanese children. We compared the weight parameters (birth weight, current weight and current weight–to−birth weight ratio [WBWR]) between the two groups and analyzed the relationships between the weight parameters and metabolic derangements. There were no significant differences in age or anthropometric measurements between the two groups. However, birth weight in the MS group was lower than that in the Non-MS group, while WBWR of the MS group was higher than that in the Non-MS group. Blood pressure and serum insulin correlated positively with WBWR. These findings suggested that lower birth weight with current overweight status was associated with the MS in obese Japanese children. We were unable to clarify whether subjects with lower birth weight who achieved proper weight gains had the same risk as subjects with appropriate birth weight. However, they should be assisted to grow adequately to prevent future metabolic derangements.

Two cases of pseudohypoparathyroidism type ia in duozygotic twins with different phenotypes.

Pseudohypoparathyroidism (PHP) type Ia is characterized by hypocalcemia due to PTH resistance and by features of Albrights hereditary osteodystrophy, including short stature, obesity, subcutaneous calcification and brachydactyly. A wide variety of clinical and biochemical manifestations have been reported. We report two cases of PHP type Ia in duozygotic twins with different phenotypes. The proband was a 10-yr-old girl. She showed subcutaneous ossification, shortening of the metacarpal bone, short stature, obesity and round face. She had normocalcemia (8.9 mg/dl), high-normal phosphate (5.0 mg/dl) and increased levels of serum intact PTH (152 pg/ml) and TSH (9.17 μIU/ml) levels. Her twin younger brother had atypical Albrights hereditary osteodystrophy with only mild obesity and subcutaneous calcifications, but he showed a low level of serum calcium (7.0 mg/dl) and high levels of serum phosphate (7.6 mg/dl), intact PTH (377 pg/ml) and TSH (6.9 μIU/ml). We diagnosed them as having PHP type Ia on the basis of clinical and biochemical findings, Ellsworth-Howard test and family history. There is considerable variability in clinical and biochemical features of PHP type Ia even among affected duozygotic twins. The differences of intrauterine environment and growth history cannot account for the variable phenotypes of PHP type Ia. Even if a patient shows no AHO features, examination of all family members should be undertaken.

The levels of serum low-density lipoprotein cholesterol using direct measurement in healthy Japanese school children.

This study aimed to investigate the levels of serum low-density lipoprotein cholesterol (LDLC) using direct measurement in healthy Japanese school children. The subjects were 621 children (325 boys and 296 girls) aged 9 to 10 in the 4th grade, and 688 children (334 boys and 354 girls) aged 12 to 13 in the 7th grade. The levels of serum LDLC and high-density lipoprotein cholesterol were measured by direct determination (Cholestest LDL and Cholestest NHDL; Daiichi Pure Chemicals Co., Ltd., Tokyo, Japan). In boys in the 4th grade, the mean, the 75th, the 90th and the 95th percentiles of LDLC levels (mg/dl) were 91.6, 104, 124 and 134, respectively. In girls in the 4th grade, they were 92.8, 108, 122 and 130. In boys in the 7th grade, they were 83.4, 96, 113 and 123. In girls in the 7th grade, they were 93.0, 106, 126 and 137. Serum LDLC levels in boys in the 7th grade were lower than those of other groups. The direct measurement of serum LDLC level is useful for evaluation of dyslipidemia in healthy school children, because the method is applicable to non-fasting serum.

A novel mutation in the human mineralocorticoid receptor gene in a Japanese family with autosomal-dominant pseudohypoaldosteronism type 1

Pseudohypoaldosteronism type 1 (PHA1) is a rare disease that manifests in infancy with hyponatremia, hyperkalemia, and metabolic acidosis, regardless of renin-angiotensin system (RAS) hyperactivity. PHA1 has autosomal recessive systemic and autosomal dominant renal forms. The systemic form of PHA1 is characterized by severe resistance to aldosterone in multiple organs, including the kidney, colon, sweat and salivary glands, and lung. Patients with renal PHA1 are treated with supplemental oral salt, and they typically show gradual clinical improvement with regard to renal salt loss during childhood. Usually, sodium supplementation becomes unnecessary at one to three years of age (1). Systemic PHA1 is caused by mutations in the amiloride-sensitive luminal sodium channel (ENaC) gene, the protein product of which is responsible for sodium reabsorption. In contrast, in the renal PHA1 form, aldosterone resistance is present only in the kidney. Renal PHA1 results in renal salt loss and failure to thrive during infancy. It is caused by mutations in NR3C2, which encodes the MR. NR3C2 consists of 10 exons; however, the first two (1α and 1β) are not translated. Translation starts from exon 2, which encodes the N-terminal domain (N-ter). Exons 3 and 4 encode the DNA-binding domain (DBD), whereas exons 5-9 encode the C-terminal ligand-binding domain (LBD). In 1998, Geller et al. identified four mutations in human NR3C2: two frameshift mutations and one nonsense mutation in exon 2, and one splicing mutation in intron 5 (2). To date, more than 100 mutations associated with PHA1 have been described (3–8), and several mutations have been identified in the LBD domain. Herein we report a novel mutation in NR3C2 in a Japanese family with renal PHA1. The results provide further information on the clinical consequences of NR3C2 mutations. Received: February 13, 2016 Accepted: July 1, 2016 Corresponding author: Dr. Keisuke Nagasaki, Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata city, Niigata 951-8510, Japan E-mail: nagasaki@med.niigata-u.ac.jp

The Relationship between Preheparin Lipoprotein Lipase and Metabolic Derangements in Obese Japanese Children

The aim of this study was to clarify the relationship between preheparin lipoprotein lipase (LPL) and derangements of metabolic status in obese Japanese children. We examined 102 obese children (55 boys and 47 girls; mean age 10.9 yr). Anthropometry, blood pressure and levels of liver transaminases, serum lipids and lipoproteins, uric acid, fasting blood glucose (FBG), serum insulin, LPL, leptin and adiponectin were measured. The subjects were divided into the metabolic syndrome (MS) and non-MS groups. The levels of LPL were compared between these groups. Statistical analysis showed that the LPL levels were significantly lower in the MS group compared with the non-MS group, with the levels decreasing progressively as the number of MS components increased. We conclude that LPL levels decrease also in obese Japanese children with a deteriorated metabolic status in the same way as in adults.