Kazushige Dobashi

Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017

Toray Industries, Inc., Tokyo, Japan Department of Diabetes, Metabolism and Endocrinology, Chiba University Graduate School of Medicine, Chiba, Japan National Center for Geriatrics and Gerontology, Aichi, Japan Department of Internal Medicine and Cardiology, Gifu Prefectural General Medical Center, Gifu, Japan Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University, Iwate, Japan Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, Japan Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima, Japan Egusa Genshi Clinic, Hiroshima, Japan Department of Cardiovascular Medicine, Juntendo University, Tokyo, Japan Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan Biomedical Informatics, Osaka University, Osaka, Japan Division of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan Department of Community Health Systems Nursing, Ehime University Graduate School of Medicine, Ehime, Japan Department of Vascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan Department of Vascular Surgery, Saitama Medical Center, Saitama, Japan Chief Health Management Department, Mitsui Chemicals Inc., Tokyo, Japan Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan Department of Neurology, Kita-Harima Medical Center, Hyogo, Japan Department of Internal Medicine, Mizonokuchi Hospital, Teikyo University School of Medicine, Kanagawa, Japan Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan Tsukasa Health Care Hospital, Kagoshima, Japan Faculty of Nutrition, Division of Clinical Nutrition, Kobe Gakuin University, Hyogo, Japan Department of Food and Nutrition, Faculty of Human Sciences and Design, Japan Women’s University, Tokyo, Japan 25 Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan Department of Medical Statistics, Toho University, Tokyo, Japan Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Department of Laboratory Medicine, Jikei University Kashiwa Hospital, Chiba, Japan Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka, Japan Department of Obstetrics and Gynecology, Aichi Medical University, Aichi, Japan 31 Department of Community Medicine, Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan Rinku General Medical Center, Osaka, Japan

Decreased plasma levels of brain-derived neurotrophic factor and its relationship with obesity and birth weight in obese Japanese children.

BACKGROUND Brain-derived neurotrophic factor (BDNF) plays important roles in the central regulation of food intake and body weight control. However, little is known about the role of BDNF in childhood obesity. OBJECTIVE To investigate the relationship between plasma levels of BDNF and anthropometric factors, metabolic derangements due to obesity, adipocytokine levels and birth weight in obese Japanese children. SUBJECTS AND METHODS Sixty-six obese Japanese children aged from 5 to 15 years old were enrolled. The age-matched control group consisted of 32 non-obese healthy children. The plasma levels of BDNF and adipocytokines (leptin and adiponectin) were assayed using ELISA techniques. RESULTS The mean BMI Z-scores were -0.67, +2.15 and +3.39 for the non-obese control children, obese (BMI ≥ 90th percentile, <99th percentile) and morbidly obese (BMI ≥ 99th percentile), respectively. The plasma levels of BDNF were significantly decreased in the morbidly obese children compared with the levels in the obese and non-obese control children (507 ± 33 pg/ml vs. 626 ± 46 pg/ml, 621 ± 35 pg/ml, p < 0.05). Univariate linear regression analysis showed that the plasma level of BDNF was positively correlated with birth weight (r = 0.264, p < 0.05) and inversely correlated with the BMI Z-score (r = -0.314, p < 0.05). Multivariate forward stepwise linear regression analysis revealed that the birth weight and BMI Z-score are independent predictors of the plasma BDNF level. CONCLUSION The plasma level of BDNF, which is decreased in morbidly obese children, is associated with birth weight and the BMI Z-score. Our results suggest that BDNF may play important roles in the development and pathophysiology of childhood obesity.

Evaluation of Obesity in School-Age Children

To prevent obesity in middle age, early precautions and interventions are required during childhood. Therefore, it is very important to accurately evaluate the degree of overweight in children. Body mass index (BMI) is widely used worldwide in adults, but not in children. Because standard BMI, which is calculated using the average height and weight for age, changes widely during growth, a constant cut-off point cannot be set for children. An international unified method defining childhood obesity has not been established. In many countries, BMI-for-age percentile (BMI%) value or Z (standard deviation) score is used, whereas in Japan, the percentage of overweight (POW), which is the modified weight-for-height method, is used. We compared BMI% values with POW values obtained using the anthropometric data of elementary and junior high school students based on the Japanese school survey conducted in 2000 and found that the values for the degree of overweight were significantly different between the two methods. It became clear that tall students were easily defined as being overweight, whereas short students tended to be evaluated as being underweight when using BMI%. POW method seemed to be more appropriate than BMI% for school-age children. Abdominal obesity, excess visceral adipose tissue (VAT), is highly associated with obesity-related complications. Waist circumference (WC) is now accepted as an appropriate guide to VAT accumulation. The cut-off value of WC defining excess VAT is 80 cm at the umbilical level in Japanese school-age children. It is not easy to decide the obesity criteria and optimum WC in school-age children. Childhood obesity should be discussed more internationally.

Accumulation of subcutaneous fat, but not visceral fat, is a predictor of adiponectin levels in preterm infants at term-equivalent age

BACKGROUND Preterm infants have altered fat tissue development, including a higher percentage of fat mass and increased volume of visceral fat. They also have altered adiponectin levels, including a lower ratio of high-molecular-weight adiponectin (HMW-Ad) to total adiponectin (T-Ad) at term-equivalent age, compared with term infants. AIMS The objective of this study was to investigate the association between adiponectin levels and fat tissue accumulation or distribution in preterm infants at term-equivalent age. STUDY DESIGN Cross-sectional clinical study. SUBJECTS Study subjects were 53 preterm infants born at ≤34weeks gestation with a mean birth weight of 1592g. OUTCOME MEASURES Serum levels of T-Ad and HMW-Ad were measured and a computed tomography (CT) scan was performed at the level of the umbilicus at term-equivalent age to analyze how fat tissue accumulation or distribution was correlated with adiponectin levels. RESULTS T-Ad (r=0.315, p=0.022) and HMW-Ad levels (r=0.338, p=0.013) were positively associated with subcutaneous fat area evaluated by performing CT scan at term-equivalent age, but were not associated with visceral fat area in simple regression analyses. In addition, T-Ad (β=0.487, p=0.003) and HMW-Ad levels (β=0.602, p<0.001) were positively associated with subcutaneous fat tissue area, but they were not associated with visceral fat area also in multiple regression analyses. CONCLUSION Subcutaneous fat accumulation contributes to increased levels of T-Ad and HMW-Ad, while visceral fat accumulation does not influence adiponectin levels in preterm infants at term-equivalent age.

Cord serum adiponectin is positively related to postnatal body mass index gain.

Background:  The roles of adiponectin and leptin in the early stages of life are poorly understood. We previously studied longitudinal changes in these adipocytokines from birth to 12 months of age. The aim of this investigation was to evaluate the correlation between cord serum adipocytokine levels and postnatal growth by 3 years of age.

Feeding choice has a gender-associated effect on infant growth

Appropriate nutrition during childhood is important for preventing future development of lifestyle‐related diseases. The effect of feeding choice on infant growth in Japan is not known.

Mosaic upd(7)mat in a patient with Silver–Russell syndrome

Mosaic upd(7)mat in a Patient With Silver–Russell Syndrome Tomoko Fuke-Sato, Kazuki Yamazawa, Kazuhiko Nakabayashi, Keiko Matsubara, Kentaro Matsuoka, Tomonobu Hasegawa, Kazushige Dobashi, and Tsutomu Ogata* Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan Division of Pathology, National Medical Center for Children and Mothers, Tokyo, Japan Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan

Guidance for Pediatric Familial Hypercholesterolemia 2017

This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH. FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started. Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥ 140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥ 10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be < 140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound. For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.

A novel de novo germline mutation Glu40Lys in AKT3 causes megalencephaly with growth hormone deficiency

Germline or somatic gain‐of‐function mutations in the v‐akt murine thymoma viral oncogene homolog 3 (AKT3) have been reported to cause syndromic megalencephaly. We describe a novel germline mutation, p.Glu40Lys, in AKT3. Phenotypically, the patient presented with megalencephaly with hypotonia, apparent connective tissue laxity, and growth hormone (GH) deficiency. To our knowledge, this is the first instance of a patient with megalencephaly with GH deficiency, harboring a germline de novo mutation in AKT3.

Evaluation of Hip/HeightP Ratio as an Index for Adiposity and Metabolic Complications in Obese Children: Comparison with Waist-related Indices

Aim: To investigate whether body adiposity index (BAI; hip/height1.5–18), pediatric BAI (BAIp; hip/height0.8–38), and other hip/heightP ratios are useful in obese children. Method: Ninety obese Japanese children, 55 boys and 35 girls, who visited our University Clinic, were enrolled. The age was 9.92 ± 2.6 (mean ± SD) years, and the percentage overweight (POW) was 51.6 ± 18.8%. We set the power value of the hip/heightP 0, 0.5, 0.8, 1, 1.5, and 2 and studied the association with overweight indices, biochemical data, and fat area measured by computed tomography. Waist, waist/height ratio, and waist/hip ratio were also evaluated. Results: Hip/height and hip/height0.8 (BAIp) were more closely correlated with POW, body mass index percentile, and percentage body fat than hip/height1.5 (BAI). The correlation coefficient of hip/height with POW (r = 0.855) was the highest among the studied hip/heightP indices. The approximate line to predict POW was 411 × hip/height−207. The waist/height was also highly correlated with POW (r = 0.879). Hip and hip/height0.5 were more closely correlated with visceral fat area than hip/height, BAIp, and hip/height1.5. Hip and hip/height0.5 were significantly correlated with insulin. Only hip was also significantly associated with dyslipidemia. All hip/heightP indices were not significantly correlated with alanine aminotransferase (ALT). Waist was significantly correlated with serum lipids, ALT, and insulin. Conclusion: Hip/height and BAIp are better markers for overweight (adiposity) in obese children than BAI. However, hip/height, BAIp, and BAI are not useful to predict metabolic complications. Waist appears to be the best index for obese children overall at this time.