Obese Japanese Children Research Articles

Association of Type 2 Deiodinase Thr92Ala Polymorphism with Pediatric Obesity in Japanese Children: A Case-Control Study.

sGenetic factors play critical roles in the onset and progression of obesity. Brown adipose tissue (BAT) activity is also critical for adiposity. The objective of this study was to evaluate the prevalence and effects of BAT gene polymorphisms in pediatric obesity. This case-control study included 270 non-obese and 86 obese children. All participants underwent genotyping for type 2 deiodinase (DIO2) Thr92Ala (rs225014). The prevalence of the homozygous Ala/Ala allele of the DIO2 gene in the obese group was 15.1% versus 6.3% in the non-obese group, resulting in an odds ratio (OR) of 3.393 (p = 0.003). The results of this study indicate that the homozygous Ala/Ala allele of the DIO2 gene is associated with an increased risk of pediatric obesity and suggest that pediatric obesity might be suitable for assessing the association with gene polymorphisms related to BAT, especially DIO2 Thr92Ala.

Adiponectin, ALT and family history as critical markers for the development of type 2 diabetes in obese Japanese children.

Aims/IntroductionAn association between the pathogenesis of type 2 diabetes mellitus (T2D) and that of metabolic syndrome (MS) in obese children has been suggested. We clarified the critical markers for the development of T2D in obese Japanese children.MethodsOne hundred and seven obese children who visited our outpatient clinic were enrolled in this study. The obese subjects were divided into 3 groups: Group A, T2D (n = 19); Group B, MS but not T2D (n = 19); and Group C: non‐T2D, non‐MS (n = 69). In all the subjects, a biochemical examination was performed and the serum adiponectin and leptin levels were measured. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured using computed tomography images.ResultsGroup A tended to have higher VAT values and VAT/SAT ratios and lower leptin and adiponectin levels, compared with Groups B and C. In Group A, the alanine aminotransferase (ALT) level was significantly higher and the aspartate aminotransferase (AST)/ALT ratio was significantly lower than in Group C. A receiver operating characteristic (ROC) analysis showed that the optimal cut‐off point for adiponectin was 6.4 μg/mL (AUC = 0.859). The cut‐off points for ALT, the AST/ALT ratio and VAT were 35 IU/L (AUC = 0.821), 0.85 (AUC = 0.794) and 78 cm2 (AUC = 0.713), respectively. Group A had a significantly higher frequency of a family history of T2D than Group B.ConclusionsOur study revealed that the adiponectin level, ALT level, AST/ALT ratio, VAT value and a family history of T2D may be critical characteristic markers for T2D among obese Japanese children.

Day length may make geographical difference in body size and proportions: An ecological analysis of Japanese children and adolescents.

There is a north-south gradient in the body heights of Japanese children. A hypothesis had previously been proposed that differences in thyroid hormone activity induced by geographical differences in effective day length (duration of photoperiod exceeding a predetermined light intensity) might cause the differences in height. If thyroid hormone is involved, the effect should extend to body weight. This study examined whether geographical differences in body height and weight can be explained in terms of thyroid hormone activity induced by geographical differences in the photoperiodic environment using prefecture-level anatomical data and Japanese Mesh Climatic Data. Multiple regression analysis demonstrated that the combination of effective day length and weight was statistically significant as a predictor of height. Controlling for body weight revealed that effective day length was inversely correlated with height. Multiple regression analysis revealed that a combination of effective day length and height was statistically significant as a predictor of weight. Controlling for height demonstrated that effective day length was positively correlated with weight. Assuming an inverse correlation between effective day length and thyroid hormone activity, these results appear to show that short day-length will increase the activity of thyroid hormone and contribute to increasing height, but will inhibit weight gain; in contrast, long day-length will decrease the activity of thyroid hormone and contribute to increasing weight but will inhibit height gain. Geographical differences in height, and weight, and part of the prevalence of obesity in Japanese children and early adolescents may be explained by geographical differences in effective day length.

Efficacy and Safety of Globin Digest as a Functional Beverage for the Treatment of Childhood Obesity

<b>Background and aims</b>: Childhood obesity is a serious health concern in many countries in the world. In addition to lifestyle education, functional foods or beverages may be useful for preventing and treating obesity. Here we evaluated the effectiveness and safety of a globin digest (GD) functional beverage for the treatment of childhood obesity. <b>Methods</b>: Twenty-eight obese Japanese children (median age, 12.4 years; range, 6.0–17.3 years; 18 males) were randomly assigned to receive orally either placebo beverage (n = 14) or GD beverage containing 6 mg of the amino acid residue Val-Val-Tyr-Pro (n = 14) within 1 h of eating dinner daily for 3 months. Changes in body weight, body mass index percentile, and percentage overweight were based on Japanese age-, sex-, and height-specific body-weight standards. The prevalence of adverse events was also evaluated. <b>Results</b>: The changes in body weight, body mass index percentile, or percentage overweight were not significantly different between the two groups at 3 months or at 6 months after the start of GD intake. No adverse events were reported in any of the subjects. <b>Conclusions</b>: Although the effectiveness of GD beverages for the treatment of childhood obesity needs further evaluation, the GD beverage used in the present study was safe and had good compliance in obese Japanese children.

Seasonal changes in objectively measured sedentary behavior and physical activity in Japanese primary school children.

BackgroundThe recent prevalence of obesity in Japanese children is much higher compared to 1980. The present study compared daily sedentary behavior (SB) and physical activity (PA) between the school year and summer vacation in Japanese primary school children.MethodsParticipants were 98 Japanese boys (8.9 ± 1.8 years at baseline) and 111 girls (9.1 ± 1.8 years). SB and PA were measured in May (school term) and July/August (summer vacation), 2011. SB and PA were assessed using a triaxial accelerometer (Active style Pro HJA-350IT, Omron Healthcare) for 7 consecutive days. The average number of minutes spent in SB (no more than 1.5 metabolic equivalents (METs)), light intensity activity (LPA; more than 1.5 to less than 3.0 METs) and moderate-to-vigorous physical activity (MVPA; 3.0 METs or more), and step counts were calculated for each individual. Moreover, the determinants/moderators of changes in SB and PA were examined.ResultsDaily SB was significantly higher in the summer vacation than in the school year for both boys and girls (p < 0.05). Ambulatory and total LPA and MVPA, non-ambulatory LPA and step counts were lower in summer vacation in both genders (p < 0.001). Moreover, non-ambulatory MVPA was significantly lower in the summer vacation than in the school year for girls (p < 0.001). The decrease in non-ambulatory MVPA in boys and increase in SB in girls were significantly lower in those who participated in sports compared to those who did not (p < 0.040 or p < 0.033). The change in SB for boys was significantly associated with having a TV in the bedroom (p < 0.022).ConclusionsThese findings show that primary school children in Japan are less active in the summer vacation, as indicated by both higher SB and lower LPA and ambulatory MVPA in both genders. Moreover, the seasonal change in non-ambulatory MVPA for Japanese children was affected by gender. This study also suggests that sports participation and bedroom TV ownership may moderate seasonal changes in PA and SB. The results emphasize the need to take summer vacation into account when planning interventions aimed at decreasing SB or increasing PA in Japanese children.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3633-5) contains supplementary material, which is available to authorized users.

Transient Elastography-Based Liver Profiles in a Hospital-Based Pediatric Population in Japan.

Background & AimsThe utility of transient elastography (FibroScan) is well studied in adults but not in children. We sought to assess the feasibility of performing FibroScans and the characteristics of FibroScan-based liver profiles in Japanese obese and non-obese children.MethodsFibroScan examinations were performed in pediatric patients (age, 1–18 yr) who visited Osaka City University Hospital. Liver steatosis measured by controlled attenuation parameter (CAP), and hepatic fibrosis evaluated as the liver stiffness measurement (LSM), were compared among obese subjects (BMI percentile ≥90%), non-obese healthy controls, and non-obese patients with liver disease.ResultsAmong 214 children examined, FibroScans were performed successfully in 201 children (93.9%; median, 11.5 yr; range, 1.3–17.6 yr; 115 male). CAP values (mean±SD) were higher in the obese group (n = 52, 285±60 dB/m) compared with the liver disease (n = 40, 202±62, P<0.001) and the control (n = 107, 179±41, P<0.001) group. LSM values were significantly higher in the obese group (5.5±2.3 kPa) than in the control (3.9±0.9, P<0.001), but there were no significant differences in LSM between the liver disease group (5.4±4.2) and either the obese or control group. LSM was highly correlated with CAP in the obese group (ρ = 0.511) but not in the control (ρ = 0.129) or liver disease (ρ = 0.170) groups.ConclusionsChildhood obesity carries a high risk of hepatic steatosis associated with increased liver stiffness. FibroScan methodology provides simultaneous determination of CAP and LSM, is feasible in children of any age, and is a non-invasive and effective screening method for hepatic steatosis and liver fibrosis in Japanese obese children.

Association of thyroid hormones with obesity and metabolic syndrome in Japanese children.

Obesity is associated with health consequences, and thyroid dysfunction may be an adaption to the increased energy expenditure in obesity. With the rising prevalence of obesity in childhood, the prevalence of metabolic syndrome may also increase. In the current study, we have shown gender differences in the association of thyroid hormones with obesity, and attempted to elucidate the relationship between thyroid hormones and anthropometric parameters and biochemical data in obese Japanese children. We analyzed anthropometric measurements, blood pressure, body composition, thyroid hormones, and lipid profiles in 283 obese children. The association between thyroid hormones and several parameters differed by gender. The free T3 to free T4 ratio (fT3/fT4) in boys was negatively associated with the quantitative insulin sensitivity check index, whereas in girls, thyroid-stimulating hormone levels were positively correlated with levels of glucose, diastolic blood pressure, and non-high density lipoprotein-cholesterol, and fT3/fT4 was positively correlated with uric acid levels. FT3/fT4 in boys with metabolic syndrome was relatively higher than in those without metabolic syndrome. The cause of gender differences is unknown. Therefore, further studies with larger sample sizes and a long-term follow-up period are needed to address the influence of thyroid hormones on various parameters.

Socio-demographic and lifestyle factors for child's physical growth and adiposity rebound of Japanese children: a longitudinal study of the 21st century longitudinal survey in newborns.

BackgroundIt is unknown whether childhood physical development in Asian populations differs from western populations, since no longitudinal analysis has been performed in Asian countries yet. Utilizing the 21st Century Longitudinal Survey in Newborns, we studied the timing of adiposity rebound (AR) among Japanese children and determined whether AR occurs earlier in obese children compared to nonobese children. Furthermore, we identified important demographic, social, and lifestyle factors that affect their physical development.MethodsWe used data from the annual surveillance of Japanese children born in 2001, with 45,392 eligible subjects. We applied survival analysis to evaluate the AR and a trajectory method for the BMI transition across 5 ½ years. Time-dependent and time-independent factors affecting BMI changes were investigated using longitudinal analysis. Accounting for the known difference in prevalence between Japanese and Western children, we adopted a 95th percentile of BMI as criterion for obesity.ResultsMean BMI at birth and at ages 1 ½, 2 ½, 3 ½, 4 ½, and 5 ½ years for all subjects were 12.6, 16.3, 16.1, 15.8, 15.5, and 15.4, respectively, showing a progressive reduction after 1 ½ years. However, among obese children at 5 ½ years, 39.6% had experienced AR as early as at age 4 ½ years. Controlling for sex, Cox’s proportional hazards model showed that obese children had a 48.5% higher hazard to experience AR than nonobese children. The difference in BMI transition between obese and non-obese children was also captured by a trajectory method. In longitudinal analysis, BMI was lower for children who had a longer gestational period whereas children who received parental care from non-family members gained higher BMI values.ConclusionsWith the 95th percentile cutoff for children obesity, obese Japanese children developed AR earlier than nonobese Japanese children, similar to those in Western countries reported in the literature. Primary caretakers and length of gestational period were the most important socio-demographic factors affecting physical development.

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

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. 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. 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. 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. 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.

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.

Relation between Delayed Superfluous Insulin Secretion during An Oral Glucose Tolerance Test and Metabolic Disorders in Obese Japanese Children

The aim of this study was to clarify the relation between postprandial hyperinsulinemia and metabolic disorders in obese children. Twenty-eight obese Japanese children (8.8–16.2 yr) were divided into four groups: without impaired liver function and dyslipidemia (Group A), with impaired liver function (Group B), with dyslipidemia (Group C), and with impaired liver function and dyslipidemia (Group D). The levels of PG, serum immunoreactive insulin (IRI) and serum C-peptide (CPR) were measured during an oral glucose tolerance test (OGTT). The subjects had delayed superfluous insulin and CPR secretion during the OGTT compared with healthy references. In regard to the insulin secretion pattern, Group A’s response peaked at 60 min and then decreased gradually until 120 min, Group B’s response peaked at 60 min, remained at the peak until 120 min and then decreased gradually until 180 min, Group C’s response peaked at 120 min and then decreased gradually until 180 min, and Group D’s response peaked at 120 min and remained at the peak until 180 min. These results suggest that delayed superfluous insulin secretion during an OGTT is related to metabolic disorders in obese Japanese children and that these patients will experience a vicious cycle of postprandial hyperinsulinemia and metabolic disorders. It is important to prevent healthy children from becoming obese and to improve management of childhood obesity.

Impact of leptin and leptin‐receptor gene polymorphisms on serum lipids in Japanese obese children

Leptin is one of the factors affecting serum lipid profile. We investigated the association between serum lipids and leptin/leptin receptor (LEPR) gene polymorphisms in obese Japanese children. One hundred and thirty-six obese children (99 males and 37 females, relative weight over than 20%) from 5 to 17 years of age were recruited from 10 institutes. Four known polymorphisms in leptin gene [(+19)A G, (-2548)G A, (-188)C A, (-633)C T] and four known polymorphisms in LEPR gene [Lys109Arg, Gln223Arg, Pro(G)1019Pro(A), Ser(T)343Ser(C)] were determined using polymerase chain reaction-restriction fragment length polymorphism-based analyses. No associations were found between leptin gene polymorphisms and serum lipid profile. On the other hand, Lys109Arg and Ser343Ser polymorphism in LEPR gene, but not Gln223Arg or Pro1019Pro, had significant relationships with serum lipid profile; lower total and low-density lipoprotein cholesterol levels in Arg109Arg homozygotes, and lower TG levels in Ser343Ser(C/C) homozygotes. In addition, LEPR gene also associated with relative weight; Arg109Arg homozygotes had higher relative weight and Ser343Ser(C/C) homozygotes had lower one. These results suggest that LEPR gene polymorphisms may partly contribute to serum lipid profile in obese children.

Hyperuricemia in Obese Children and Adolescents: The Relationship with Metabolic Syndrome

The prevalence of hyperuricemia in obese children and adolescents and its association with metabolic syndrome are largely unknown. The objective of our study was to characterize hyperuricemia in relation to metabolic syndrome in Japanese children and adolescents with obesity. Between 2005 and 2008, we performed a cross-sectional study of 1,027 obese children and adolescents aged 6–14 years. Based on the reference value of serum uric acid we had established previously, hyperuricemia was defined as one standard deviation over the mean value at each age. The diagnosis of metabolic syndrome was made based on the Japanese criteria for children. A total of 213 children and adolescents (20.7%) was found to have hyperuricemia. The prevalence of hyperuricemia was significantly higher in the male gender and older age group. Sixty-five out of 213 subjects with hyperuricemia (30.5%) had metabolic syndrome, whereas 111 out of 814 subjects without hyperuricemia (13.6%) had metabolic syndrome. The most common abnormal component of metabolic syndrome was triglyceride, followed by diastolic blood pressure, systolic blood pressure, fasting blood glucose, and HDL-cholesterol. Such a tendency was almost identical between the two groups. We concluded that considering the association between hyperuricemia and metabolic syndrome in obese Japanese children and adolescents, the role of hyperuricemia in metabolic syndrome should receive more attention, beginning in early childhood.

Increased plasma isoprostane is associated with visceral fat, high molecular weight adiponectin, and metabolic complications in obese children

Oxidative stress is considered to be increased in obese subjects. However, the association of oxidative stress with visceral adiposity and adiponectin level is not fully understood in children. Forty-four obese Japanese children and adolescents, 28 boys and 16 girls, with median age of 9.9 years [5.2-13.8 years], and the 28 age-matched non-obese healthy controls, 15 boys and 13 girls, were enrolled in this study. The median BMI Z scores were +2.21 [1.31-4.38] for the obese subjects and -0.72 [-2.11-1.31] for the control. Plasma concentrations of 8-epi-prostaglandin F₂α (isoprostane), a marker of oxidative stress, and adiponectin fractions were assayed using ELISA. 8-epi-PGF₂α levels were significantly higher in the obese group (37.1 [4.7-112.7], median and the range) than in the control (11.5 [4.5-27.3]). In a univariate analysis, concentrations of 8-epi-PGF₂α positively correlated with visceral adipose tissue area measured by computed tomography, waist circumference, serum triglycerides, alanine aminotransferase, insulin levels, and the homeostasis of minimal assessment of insulin resistance and inversely correlated with high-density-lipoprotein cholesterol and high-molecular weight (HMW) adiponectin. Total-, medium-, or low-molecular weight adiponectin fraction did not show a significant correlation with 8-epi-PGF₂α Forty of 44 obese children had one or more metabolic complications. The 8-epi-PGF[Formula: see text] levels also elevated with increasing numbers of obesity-related complications. These results suggest that oxidative stress is enhanced in relation to visceral fat accumulation and decreasing HMW adiponectin level in childhood obesity. Oxidative stress may be associated with the development of obesity-related complications.

Effect of Diet and Exercise Treatment for Obese Japanese Children on Abdominal Fat Distribution

The purpose of this study was to investigate the combined effect of dietary treatment and exercise treatment on abdominal fat distribution and the risk factors for chronic disease in obese Japanese children. The subjects were 33 obese children. The areas of subcutaneous and visceral fat were measured using CT images at the level of the umbilicus. Blood samples were taken to measure risk factors for chronic disease such as triglycerides (TG), total cholesterol (T-Cho), high-density lipoprotein cholesterol (HDL-C), insulin, asparate amino-transferase (AST), alanine aminotransferase (ALT) and uric acid (UA). Supervised exercise treatment at 50% Vo2max for about 60 min/day was performed 5 or 7 days/week for 3 months. The dietary treatment was varied with daily calorie intake between 1400 and 1900 kcal depending on the degree of obesity. After dietary treatment combined with exercise treatment, the areas of subcutaneous and visceral fat decreased significantly, and such risk factors as TG, T-Cho, insulin, AST, ALT, and UA were noticeably reduced. These data suggest that dietary treatment combined with exercise treatment in obese children normalizes the distribution of abdominal fat and reduces the risk factors for chronic disease.

Tracking overweight and obesity in Japanese children; a six years longitudinal study

Childhood overweight/obesity is growing steeply, globally. It is usually regarded as a risk factor for severe obesity over life-time course. Here, we investigated temporal course of overweight/obesity development in Japanese school children. A six-year longitudinal study was performed on 16,245 Japanese primary school children (8,427 boys and 7,818 girls) comprising three cohorts of 1(st) approximately 3(rd) grade. A baseline survey was conducted at 2001, followed by annual baseline studies from 2002 approximately 2007 to determine the prevalence and track overweight/obesity. Our results showed that the prevalence of overweight was 15 approximately 23% in boys and 15 approximately 18% in girls, however, for obesity it ranged between 4 approximately 7% in boys; and 2 approximately 4% in girls. As regards for tracking status, 60 approximately 80% of overweight and 35 approximately 70% of obese Japanese primary school boys track into overweight or obese junior high school adolescents. However, these percentages are lower among primary school girls, where only 50 approximately 70% overweight and 30 approximately 60% obese primary school girls track into overweight and obese adolescents, respectively. We conclude that Japanese boys are fatter than girls; and approximately 80% of overweight/obese Japanese primary school children track into junior high school overweight/obese adolescents.

BMI centile curves for Japanese children aged 5–17 years in 2000–2005

To examine changes in the age-specific prevalence of overweight and obesity in Japanese children between 2000 and 2005 and compare Japanese centile curves with international ones. A large, Japanese, representative cross-sectional growth study. Japan. Japanese children aged 5-17 years, including 669,986 subjects in 2000, 670,143 in 2001, 668,760 in 2002, 670,785 in 2003, 669,120 in 2004 and 668,234 in 2005. BMI (weight/height2). The prevalence of overweight and obesity in children aged 5-17 years decreased from 2000 to 2005 in both males and females, according to the definitions of the Centers for Disease Control and Prevention and the International Obesity Taskforce. For each year, the centile curves were drawn so that at age 17 years they passed through respectively 24.46 kg/m2 and 24.70 kg/m2 for males, and 29.41 kg/m2 and 29.69 kg/m2 for females, which are the BMI values at age 17 years from the international reference curves. The study results indicate that centile curves can change according to the time of observation, thus suggesting that international reference curves therefore need to be regularly revised while including more data from a larger range of countries.

Usefulness of GPT for Diagnosis of Metabolic Syndrome in Obese Japanese Children

The aim of this study was to evaluate the usefulness of glutamate pyruvate transaminase (GPT) levels in the diagnosis of metabolic syndrome (MS) in obese Japanese children. We examined 193 obese boys (mean age: 12.1 yrs; mean percent overweight [POW]: 53.9%) and 37 obese girls (mean age: 11.4 yrs; mean POW: 57.2%). Anthropometric measurements, blood pressure and levels of liver transaminases, serum lipids and lipoproteins, fasting blood glucose (FBG), serum insulin and adiponectin were measured. The subjects were divided into either an MS or a non-MS group according to the MS definition criteria for Japanese children. The level of GPT was significantly higher in the MS group in both genders. Correlation analysis revealed positive correlations between GPT and waist circumference, blood pressure, maximum preperitoneal fat thickness, serum insulin and homeostasis model assessment-insulin resistance (HOMA-R), but no correlation between GPT and FBG. ANOVA showed a significant difference in GPT levels between MS and non-MS subgroups, whereas there was no difference in FBG between the two groups. Receiver operating characteristic curves demonstrated that GPT was clearly superior to FBG as a diagnostic marker of MS. We conclude that an elevation in GPT in obese children most likely reflects insulin resistance and that GPT is superior to FBG as a marker of MS.

Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients

Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated. Direct sequencing of two exons and flanking sequences of SHP in 805 diabetic patients and 752 non-diabetic controls identified 15 different mutations in 44 subjects, including 6 novel mutations. Functional analyses of the mutant proteins revealed significantly reduced activity of nine of the mutations. Mutations with reduced activity were found in 19 patients (2.4%) in the diabetic group and in 6 subjects (0.8%) in the control group. The frequency difference between DM and control subjects adjusted for sex and age was statistically significant (P=0.029, odds ratio 2.67, 95% CI 1.05-6.81, 1-beta=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese.

Plasma Visfatin Concentration as a Surrogate Marker for Visceral Fat Accumulation in Obese Children

This study was designed to elucidate whether the plasma visfatin level reflects visceral or subcutaneous fat accumulation and metabolic derangement in obese children. Fifty-six obese Japanese children, including 37 boys and 19 girls were enrolled in the study. The age of the subjects ranged from 5 to 15 (10.2 +/- 0.3; mean +/- s.e.m.) years. The age-matched control group for measuring visfatin consisted of 20 non-obese children. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured by computed tomography. The plasma concentrations for visfatin and leptin were assayed by enzyme-linked immunosorbent assay kits. The plasma visfatin level was higher in the obese (14.7 +/- 0.9 ng/ml) than in the control children (8.6 +/- 0.6 ng/ml). In a univariate analysis, the visfatin correlated significantly with age, height, body weight, waist circumference, VAT and SAT area, triglyceride (TG), insulin, and the homeostasis model assessment for insulin resistance (HOMA-R). After being adjusted for age and sex, only the VAT area retained significant partial correlation with visfatin, and in contrast the body weight, BMI-s.d., and SAT area with leptin. The plasma visfatin concentration was not correlated with leptin. The plasma visfatin levels in the control, non-metabolic syndrome (MS) (n = 49), and MS groups (n = 7) were significantly different from each other. These results suggest that plasma visfatin level is a specific marker for visceral fat accumulation in obese children. As a good surrogate marker, plasma visfatin level can predict the VAT area in obese children.