Osamu Arisaka

Adiposity Rebound and the Development of Metabolic Syndrome

OBJECTIVE: The age of adiposity rebound (AR) is defined as the time at which BMI starts to rise after infancy and is thought to be a marker of later obesity. To determine whether this age is related to future occurrence of metabolic syndrome, we investigated the relationship of the timing of AR with metabolic consequences at 12 years of age. METHODS: A total of 271 children (147 boys and 124 girls) born in 1995 and 1996 were enrolled in the study. Serial measurements of BMI were conducted at the ages of 4 and 8 months and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 years, based on which age of AR was calculated. Plasma lipids and blood pressure were measured at 12 years of age. RESULTS: An earlier AR (<4 years of age) was associated with a higher BMI (≥20) and a lipoprotein phenotype representative of insulin resistance. This phenotype consists of elevated triglycerides, apolipoprotein B, and atherogenic index and decreased high-density lipoprotein cholesterol in boys and elevated apolipoprotein B in girls at 12 years of age. The earlier AR was also related to elevated blood pressure in boys. CONCLUSIONS: This longitudinal population-based study indicates that children who exhibit AR at a younger age are predisposed to future development of metabolic syndrome. Therefore, monitoring of AR may be an effective method for the early identification of children at risk for metabolic syndrome.

Association between Timing of Adiposity Rebound and Body Weight Gain during Infancy

OBJECTIVE To investigate whether increments of weight gain in early infancy are related to the timing of adiposity rebound (AR). STUDY DESIGN A total of 271 children (147 boys and 124 girls) in 1 community were enrolled in the study. Serial measurements of body mass index were carried out at the ages of 4, 8, and 12 months and 1.5, 2, 3, 4, 5, 6, 7, 8, 9, and 10 years, based on which the age of AR was determined. We also calculated body weight increments in 3 separate periods: birth to 4 months, 4-8 months, and 8-12 months. RESULTS There was no significant relationship between weight gain in any period of infancy and the age of AR. Weight gain between birth and 4 months was positively correlated only with body mass index at 7 years of age. CONCLUSIONS We could not find an association between body weight gain during infancy and the timing of AR. This suggests that infantile weight gain is not related to childhood obesity through AR.

Early Adiposity Rebound and Small Dense Low-Density Lipoprotein in Childhood Obesity

Aim: The adiposity rebound (AR) corresponds to the second rise in the body mass index (BMI) curve that occurs between ages 5 and 7 years. The goal of this study was to determine whether age at AR is related to the presence at 12 years old of small dense low-density lipoprotein (SDLDL), an atherogenic lipoprotein produced as a metabolic consequence of AR. Methods: A longitudinal population-based prospective study was performed in 215 children. Serial measurements of BMI were conducted at ages 1, 1.5, 2 and yearly thereafter until 12, based on which age at AR was calculated. The subjects were divided into 5 groups according to age at AR of ≤4, 5, 6, 7 and ≥8 years. Plasma lipids and SDLDL were measured at 12 years of age. SDLDL (LDL particle size <25.5 nm) was determined by nondenaturing 2-16% gradient gel electrophoresis. Results: The prevalences of SDLDL were 15.0% in children with age at AR ≤4 y, 8.1% in those with age at AR 5 y, and 0% in all other groups (AR at ≥6 years). An earlier AR was significantly associated with higher BMI, increased plasma triglyceride (p < 0.05), increased atherogenic index (p < 0.05), and decreased HDL-cholesterol (p < 0.05) at 12 years of age. Conclusion: Children with AR before 4 years old showed a high prevalence of atherogenic SDLDL, indicating a predisposition for future cardiovascular disease.

Estimation of LDL Particle Size Using Lipid Indices: A Population-Based Study of 1578 Schoolchildren

BACKGROUND Low-density lipoprotein (LDL) is atherogenic and LDL particles are reduced in diameter in the presence of insulin resistance, forming small, dense LDL. This study was conducted to assess the relationship between commonly used lipid indices and LDL particle size and furthermore to clarify the best surrogate lipid markers that could conveniently be used to estimate LDL particle size in children. METHODS We determined LDL particle diameter by gradient gel electrophoresis in 1578 children aged 10-12 years. At the fasting state, the relationships between measured LDL particle size and lipid variables [total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), atherogenic index [(TC-HDL-C)/HDL-C, TG/HDL-C, LDL-C/HDL-C, and LDL-C/apolipoprotein B (Apo B) and non-HDL-C (TC-HDL-C)] were analyzed. RESULTS The LDL particle diameter was 26.64 (mean) ± 0.48 (SD) nm in boys (n = 820) and 26.66 ± 0.49 nm in girls (n = 758); there was not a statistically significant difference. There were statistically significant correlations between LDL particle size and TG or HDL-C concentrations (r = 0.28∼0.37), but the correlations with LDL-C and ApoB were very weak. The combined lipid measures, such as atherogenic index, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C showed moderate correlations (r = 0.33∼0.38) with LDL particle size; however, the correlation of non-HDL-C with LDL particle size was weak (r = 0.18∼0.19). Simple HDL-C measure appeared to be of comparable value to combined lipid measures. CONCLUSIONS Our data indicate that various lipid indices are not superior to HDL-C levels alone as a clinical tool for estimating LDL particle size. Non-HDL-C was less valuable in this aspect.

Factors affecting the timing of adiposity rebound

Background The age of adiposity rebound (AR), when body mass index (BMI) starts to rise after infancy, is thought to be an origin of obesity in later life. We have already reported that children who exhibited an earlier AR were associated with the higher BMI value and atherogenic metabolic status at 12 years of age. We investigated which factors influenced on an earlier AR, birth weight, initial feeding, family history, meals or exercise.

Transient ischaemic attack in a case of a morbidly obese girl associated with metabolic syndrome.

Sir, It is well known that transient ischaemic attack (TIA) associated with hypertension occurs in the elderly, but there is scant information available on the incidence of such a condition in children (1). We recently encountered a morbidly obese girl who developed sudden onset of hemiparesis, transient symptoms with no neurological sequelae, and was diagnosed with TIA. Transiently worsened hypertension with a background of metabolic syndrome associated with increased insulin resistance was considered to contribute to the underlying pathogenesis that caused the TIA in the present patient. A 12-year-old girl, who had been suffering from simple obesity since entering elementary school, fell down outside at her home in the morning hours of June, when she was intending to go to school. On that occasion, she felt sudden weakness in her left upper and lower leg, followed by a temporal blackout (several seconds). Her blood pressure was immediately measured by automated sphygmomanometer by her mother, who worked as occupational health nurse, and was unexpectedly elevated to 160 ⁄102 mmHg. The patient was unable to communicate smoothly, but she could complain of mild sensory disturbance on the left side of her body. However, all of these symptoms subsided rapidly (the duration of the symptoms was within 10 min), when she was brought to the emergency visit from the hospital. Upon her arrival at the hospital, her consciousness was clear, and the systolic blood pressure was 150 ⁄ 95mm Hg. Her height was 162 cm (+1.8 SD above the average Japanese girls height for age), and body weight, 75 kg (+3.8 SD). Her BMI (body mass index) was 28.3 (>97th percentile). Her growth chart is shown in the Figure 1. By further detailed questioning, it was confirmed that she had not lost any memory of the entire course of events except for the loss of several seconds. No abnormal neurological signs including the optic fundus were observed except for decreased left grip strength of 12 kg (right grip was not measured). In the family history taken by her parents, antihypertensive medications were indicated for essential hypertension. Ambulatory blood pressure monitoring of the patient during her daily life revealed that the average systolic and diastolic blood pressures were 145 and 85 mmHg, respectively, indicating the persistently elevated blood pressure. As the cause of TIA, brain computed tomography, magnetic resonance (MR) imaging and MR angiography revealed normal parenchymal and vascular imaging: no findings of arteriopathies, including moyamoya disease, vasculitis or dissection, were evident. Laboratory examinations of plasma renin activity, plasma concentrations of electrolytes, ACTH, cortisol, thyroid hormones and catecholamines were all within the normal range. Thus, endocrine diseases responsible for secondary hypertension were ruled out. In the evaluation of the patient’s obesity, increased waist circumference (82.6 cm), associated with elevated serum triglyceride concentration (140 mg ⁄ dL) and elevated blood pressure, met the criteria of metabolic syndrome in Japanese children (2). Serum total cholesterol and high-density lipoprotein– cholesterol (156 and 50 mg ⁄ dL, respectively) levels were normal. The abdominal CT scan showed remarkable fatty changes of the liver and increased visceral fat accumulation [the proportion of visceral fat to subcutaneous fat was notably increased to 23.14%