Association of adipocytokines and adipocytokine ratios with cardiovascular risk factors in Japanese preadolescents.

OBJECTIVES: Asians are particularly susceptible to obesity-associated disorders and rapid progression of obesity from childhood to adulthood. Data on the association between adipocytokine parameters, particularly adipocytokine ratios, and cardiovascular risk factors in childhood remain limited. Herein, we assessed the association of resistin, adiponectin, and leptin levels and leptin/adiponectin and resistin/adiponectin ratios with selected cardiovascular risk factors and the influence of unhealthy weight on such associations in children aged 9-10 years. METHODS: We included 380 children aged 9-10 years from three public elementary schools in Japan. RESULTS: The body mass index (BMI) was significantly higher in male preadolescents than in female adolescents (median 16.5 kg/m2 vs. 16.2 kg/m2, p=0.032). No differences in height, weight, waist circumference (WC), waist/height ratio (W/Hr), total cholesterol and high-density lipoprotein cholesterol levels, or atherosclerosis index (AI) were observed between the sexes. Of the adipocytokine levels and ratios analyzed, only the leptin level and leptin/adiponectin ratio (L/Ar) were strongly and significantly positively correlated with the cardiovascular risk factors WC, W/Hr, and BMI (all p<0.05). The AI was not strongly correlated with any adipocytokine levels or ratios. Apart from the strong positive correlation between the L/Ar and W/Hr, no other significant associations were observed between any of the adipocytokine levels or ratios and the selected cardiovascular risk factors. CONCLUSIONS: Our findings confirmed the value of adipocytokine ratios in risk assessment in pediatric populations, with leptin levels and leptin/adiponectin ratios strongly correlating with risk factors in children aged 9-10 years.

Population-based cross-sectional study on insulin resistance and insulin-secretory capacity in Japanese school children.

AIMS/INTRODUCTION: Little information is available regarding the status of insulin resistance (IR) and insulin deficiency (ID), as well as their relationship with obesity in children using the homeostasis model assessment (HOMA) in a population-based setting. MATERIALS AND METHODS: The study included a total of 445 ninth-grade children participating in health check-up programs implemented in Tsunan Town, Niigata, Japan (boys/girls, 252/193 [participation rates: 98.1/95.5%]). HOMA of insulin resistance ≥2.5 was defined as IR, and HOMA of ß-cell function <40 defined as ID. RESULTS: The medians (25-75th percentiles) of HOMA of insulin resistance, HOMA of ß-cell function, Disposition Index and body mass index in boys were 1.2 (0.8-1.7), 64 (44-93), 52 (43-64) and 19.2 (18.0-20.7) kg/m2 , respectively, vs 1.5 (1.0-2.0), 86 (63-120), 60 (50-74) and 20.4 (18.9-22.0) kg/m2 , respectively, in girls. The HOMA of insulin resistance, HOMA of ß-cell function and Disposition Index values were significantly higher in the girls (P = 0.002, P < 0.001 and P < 0.001, respectively). Those with IR accounted for a significantly higher proportion of girls than boys (15.5/8.7%; P = 0.027); those with obesity accounted for 9.9/10.7% (boys/girls); and those with IR and obesity accounted for 2.4/4.7%. Those with ID accounted for a significantly higher proportion of boys than girls (20.6/8.8%; P = 0.001), whereas those with ID and obesity accounted for a very small proportion of either group (0.4/0.5%). CONCLUSIONS: The presence of IR was higher among the girls. In contrast, ID was more frequent among the boys. The infrequent presence of ID among children might support the presence of non-obese type 2 diabetes adults in Japan.

Changes in the Composition of Adiponectin Fractions over a 3-Year Period in Children: A Population-Based Cohort Study.

BACKGROUND: Little information is available regarding changes in adiponectin fractions. The objective of this study was to examine changes in the composition of differing adiponectin fractions using a population-based, prospective pediatric cohort. METHODS: A total of 358 fourth graders (9-10 years old) from Ina town in Saitama, Japan, were followed up for 3 years. BMI and total adiponectin (TAD), high-molecular weight adiponectin (HAD), medium-molecular weight adiponectin, and low-molecular weight adiponectin levels were measured in these subjects at baseline and at the end of the follow-up. RESULTS: Of the fourth graders participating in the study, 326 (172 boys and 154 girls; follow-up rate, 91.1%) became available for follow-up. No significant changes were observed in TAD values after 3 years. HAD values were significantly decreased in both the boys (2.4 to 2.2 µg/mL: p < 0.001) and girls (3.1 to 2.7 µg/mL: p = 0.005). All values in the parameters examined at baseline and after 3 years were significantly correlated. A negative correlation was found between the ratios of follow-up compared to baseline values for BMI and those for TAD (boys, r = -0.322, p < 0.001; girls, r = -0.433, p < 0.001) as well as those for HAD (boys, r = -0.353, p < 0.001; girls, r = -0.351, p < 0.001). CONCLUSIONS: HAD had the most robust correlation between its values at baseline and those after 3 years in both boys and girls. The changes in HAD also had the most robust correlation between the changes in BMI in 3 years.

Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study.

OBJECTIVE: The study examined changes in and relationship between body mass index (BMI), leptin and adiponectin levels over a 3-year period in a pediatric population-based cohort. STUDY DESIGN: A 3-year prospective cohort study of 268 boys and 251 girls aged 9-10 in Ina, Saitama, Japan. RESULTS: Median body mass index (BMI) significantly increased from baseline (age 9-10) to follow up (age 12-13) in boys from 17.1 to 18.3 kg/m2 (P < 0.001) and in girls from 16.5 to 18.5 kg/m2 (P < 0.001), respectively. Adiponectin values significantly decreased from baseline to follow up in boys (13.5 to 8.9 microg/ml, respectively) (P < 0.001) and in girls (12.4 to 9.5 microg/ml, respectively) (P < 0.001). Leptin values at follow up significantly decreased from baseline in boys (4.9 to 2.3 ng/dl, respectively) (P < 0.001) and also in girls (5.3 to 5.1 ng/dl, respectively) (P = 0.049). A relatively strong correlation was seen in BMI (Spearman's correlation coefficient, r = 0.864, P < 0.001 in boys; r = 0.873, P < 0.001 in girls), adiponectin (r = 0.705, P < 0.001 in boys; r = 0.695, P < 0.001 in girls), and leptin (r = 0.449, P < 0.001 in boys; r = 0.610, P < 0.001 in girls) before and after the three-year period. The ratio of follow up to baseline BMI was negatively correlated with that for adiponectin (r = -0.224, P < 0.001 in boys; r = -0.165, P = 0.001 in girls) and positively correlated with that for leptin (r = 0.518, P < 0.001 in boys; r = 0.609, P < 0.001 in girls). CONCLUSION: This study demonstrated that baseline adiponectin, leptin and BMI values measured at ages 9-10 correlated with those measured three years later. However, adiponectin values decreased and leptin values increased in those subjects whose BMI increased during over this period.

Low prevalence of metabolic syndrome and its components in rural Japan.

Tsunan, Niigata is a non-westernized rural Japanese town, known for heavy snowfalls and as a rice-producing area, whose inhabitants have a long life expectancy. We investigated the prevalence of obesity, metabolic syndrome (MetS) and its components in Tsunan. A total of 1,155 men and women, 40-69 years of age were recruited from participants in the 2005 public-health program in Tsunan. Obesity was defined as body-mass index (BMI) >or= 25 kg/m(2). MetS was defined as BMI >or= 25 kg/m(2) as well as at least two of the following three items: (1) high glycosylated hemoglobin (HbA1c >or= 5.5%); (2) high blood pressure (HBP: systolic blood pressure >or= 130 mmHg or diastolic blood pressure >or= 85 mmHg), and (3) low high-density lipoprotein cholesterol (HDL-C < 40 mg/dL). If an individual was diagnosed with diabetes, hypertension, or dyslipidemia, each item was recorded as a positive finding. The prevalence of MetS and its components among Tsunan inhabitants were compared to the results of the 2005 Japanese nationwide survey. The prevalence of MetS was 4.6% in males and 4.2% in females. The prevalence of obesity, high HbA1c, HBP, and low HDL-C were 22.1/22.2%, 13.4/16.4%, 46.6/40.0%, and 9.2/3.9% in males/females, respectively. All values were significantly lower than the national results, except for the rate of female obesity. The lower prevalence of MetS and its components in Tsunan may be due to the consumption of traditional Japanese food, which is still commonly eaten there, and the higher levels of regular physical activity of farmers.

The micronucleus test and erythropoiesis: effects of cyclic adenosine monophosphate (cAMP) on micronucleus formation.

The aim of this study was to determine the mechanism of the rodent bone marrow micronucleus test in relation to erythropoiesis. We have previously reported that an acceleration of erythropoiesis increases the frequency of micronucleated polychromatic erythrocytes (MPCE) induced by mutagens. The blood plasma erythropoietin level increased after the injection of N6-2-O-dibutyladenosine-3',5'-cyclic monophosphate into adenosine 3',5'-cyclic monophosphate (cAMP) at a dose of 500 mg/kg. A peak of erythropoietin induction was observed 3 h after the injection of cAMP. cAMP itself did not induce any micronuclei in erythroblasts of BALB/c mice. So, the frequency of MPCE did not increase after injection of cAMP. The highest frequency of MPCE and the dose-response relationship between the cAMP doses and micronucleus frequency were observed 30 h after injection of mitomycin C (MMC) in mice which had been administered cAMP 24 h previously. The highest effect of cAMP on the increase of MPCE was observed when cAMP was given 24 h before MMC injection, thus indicating that accelerating the multiplication of erythroblasts increases the frequency of MPCE induced by mutagens. The induction of MPCE in the bone marrow by three other chemicals (carboquone, 5-fluorouracil, and vincristine) also increased after pretreatment with cAMP. Our results suggest that the increase of MPCE induced by mutagens can be amplified following the acceleration of erythropoiesis by pretreatment with cAMP.

Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure.

BACKGROUND: The large clinical trials proved that Basal-Bolus (BB) insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy. METHODS: In PROBE (Prospective, Randomized, Open, Blinded-Endpoint) design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range) age: 64.5(56.8-71.0)years) with secondary failure of sulfonylurea (SU) were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group) or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group), and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT) of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups. RESULTS: After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1-11.3) --> 7.4(6.9-8.7)%, p < 0.01, vs BB;8.9(7.7-10.0) --> 6.9(6.2-7.3)%, p < 0.01), with no significant difference between the groups in percentage change in HbA1c (30 Mix; -14.7(-32.5- (-)7.5)% vs BB -17.8(-30.1- (-)11.1)%, p = 0.32). There was a significant decrease in daily glycemic profile at all points except dinner time in both groups compared to baseline. There was a significant increase in the amount of insulin used in the 30 Mix group after treatment compared to baseline (30 Mix;0.30(0.17-0.44) --> 0.39(0.31-0.42) IU/kg, p = 0.01). There was no significant difference in IMT, BMI, QOL or adiponectin levels in either group compared to baseline. CONCLUSION: Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure. TRIAL REGISTRATION: Current Controlled Trials number, NCT00348231.

Ratio of high-, medium-, and low-molecular weight serum adiponectin to the total adiponectin value in children.

In 760 children age 9 to 10 years, the serum adiponectin composition (high molecular weight [HMW], hexameric medium molecular weight [MMW], and trimeric low molecular weight [LMW]) was found to vary markedly depending on whether the total adiponectin value was high or low. A lower total adiponectin value was associated with a lower ratio of HMW adiponectin.

Gender differences in the relationship between percent body fat (%BF) and body mass index (BMI) in Japanese children.

The purpose of the present study was to examine whether gender differences exist in the relationship between percent body fat (%BF) and body mass index (BMI) in Japanese children using a population-based cohort. Subjects are comprised of 187 boys and 163 girls aged 9-10, and 137 boys and 155 girls aged 12-13. Percent BF was measured using a bipedal biometrical impedance analysis (BIA) device. The relationship between %BF and BMI was investigated as a function of age and gender with Pearson's correlation coefficient. Strong linear relationships existed between %BF and BMI, especially in girls (9-10-year-old boys: r=0.779, P<0.0001; 9-10-year-old girls: r=0.975, P<0.0001; 12-13-year-old boys: r=0.786, P<0.0001; 12-13-year-old girls: r=0.975, P<0.000l). These results indicate that %BF can be predicted from BMI in Japanese children aged 9-10 and 12-13 years. The correlations in boys were not as strong as those observed in girls, that is, less variability was explained for girls than for boys. Further study will be necessary to ascertain whether the strong correlation seen among girls will be observed in different age or ethnic groups, and to ascertain the mechanism that produces this gender difference.

Glycated albumin is low in obese, type 2 diabetic patients.

This study is to clarify whether obesity status affects glycated albumin (GA) and HbA1c levels in adults with type 2 diabetes. One hundred and seven individuals with type 2 diabetes without advanced complications participated in this study. The relationship between HbA1c, GA, hemoglobin (Hb), albumin (ALB), absolute value of GA (aGA) and Body Mass Index (BMI) were examined using Pearson's correlation coefficient. The comparison of each parameter was conducted using unpaired t-test between the obese (BMI> or =25) and the non-obese (BMI<25) group. Additionally the multiple regression analyses to find factors related with GA (i.e. BMI, HbA1c, age, ALB and the insulin therapy) were performed. HbA1c level and BMI showed very weak correlation (r=-0.04; p=0.65). However, GA, aGA and BMI showed a significant negative correlation (r=-0.28; p=0.004, r=-0.22; p=0.024). The GA and aGA values of the obese group were significant lower than those in the non-obese group. In multiple regression analysis, BMI (beta=-0.24; p=0.001) was negatively, and HbA1c (beta=3.65; p<0.001) was positively correlated with GA. In conclusion, the current analysis demonstrated a need of careful evaluation of GA values in obese diabetic patients in daily practice. Further researches are required to elucidate the underlying mechanisms.

Waist circumference estimation from BMI in Japanese children.

Waist circumference, not BMI, is one of the factors in the definition of metabolic syndrome in adults. In children, waist circumference is also a well known predictor of metabolic syndrome. However, waist circumference measurement is not as commonly recorded as weight and height measurements in physical examinations in schools. This means BMI data is available for every child, but waist circumference is not. Therefore, we investigated whether there is an alternative way to estimate waist circumference even in those children whose waist circumference measurement has not been taken. We evaluated the relationship between BMI and the waist circumference of schoolchildren using a relatively large-scale population-based cohort in Japan. There was a significant linear relationship between BMI and waist circumference noted in each age- and sex-divided group [9-10-year-old boys: waist=13.99+2.63BMI (r=0.940, p<0.001), 9-10-year-old girls: waist=15.09+2.61BMI (r=0.933, p<0.001), 12-13-year-old boys: waist=23.67+2.22BMI (r=0.880, p<0.001), 12-13-year-old girls: waist=23.83+2.15BMI (r=0.859, p<0.001)]. This means it is possible to estimate waist circumference from height and weight, at least among those age groups of children in Japan. This estimation could be an alternative way and useful in detecting childhood metabolic syndrome or obesity disease in which a waist circumference figure is necessary.

A case of prolactin deficiency with familial puerperal alactogenesis accompanying impaired ACTH secretion.

We report here the case of a 34-year-old female with puerperal alactogenesis. Her menstrual cycle was regular and breast development normal. She had delivered a healthy boy but could not breast-feed after parturition. Endocrinological studies disclosed that the cause was a prolactin (PRL) deficiency. In addition, she showed accompanying impaired ACTH secretion that was believed to be triggered by encephalitis, although her plasma levels of GH, TSH, LH and FSH remained intact. Pituitary MRI showed no specific findings and anti-pituitary antibody tests were negative. Interestingly, both her mother and grandmother also reported puerperal alactogenesis. The sequences of all five exons of the PRL gene, including promoter region and transcription initiation point, were surveyed in order to examine for certain genetic disorders, but no mutations were identified. Although it cannot be definitively concluded that this PRL deficiency was not a genomic DNA disorder, in our case at least, her PRL gene was normal and, therefore, was not directly responsible for the patient's impaired PRL secretion. This evidence suggests that familial puerperal alactogenesis and PRL deficiency can be induced by other causes such as via disorders of unknown transcription factors or molecules that contribute to translation of PRL gene.

Childhood obesity and its relation to serum adiponectin and leptin: a report from a population-based study.

This study examined the relationships between serum adiponectin (AD) and leptin (LP) levels, and obesity using a population-based cohort consisted of 315 (9-10 year olds: G1) and 308 (12-13 year olds: G2) school children. Serum AD, LP and other markers were compared according to the presence of obesity. The prevalence rates of obesity were 14.9% in G1 and 9.4% in G2. The medians of serum AD (microg/dl: non-obese/obese) were statistically lower in obese children (9.6/8.3 in G1, p<0.05; 8.9/6.6 in G2, p<0.05), and the medians of serum LP (ng/dl) were statistically higher in obese children (3.7/12.5 in G1, p<0.05; 2.9/8.4 in G2, p<0.05). The serum LP levels were significantly positively correlated with percent overweight (POW) irrespective of age and sex, and the serum AD levels were significantly negatively correlated with POW except for boys in G1. Multivariate regression analyses revealed that LP, LDL-cholesterol and gender in G1, and LP, AD, blood pressure and gender in G2 were significantly correlated with POW. A large-scale, population-based study revealed that AD was lower and LP higher in obese children, and that the obese status in G2 was related to a worse metabolic profile than the case in G1.

Glycated albumin is low in obese, non-diabetic children.

The current study evaluates the indices of glucose control for diabetics (i.e., glycated albumin (GA), hemoglobin A1c (HbA1c), plasma glucose (PG) and immuno-reactive insulin (IRI)) in non-diabetic children from a population-based cohort, and compares those values according to the presence of obesity to examine any differences in these indices. GA, HbA1c, casual PG and casual IRI in obese children (n = 209) were compared to those of non-obese children (n = 1060) in Ina town, Saitama Prefecture, in 2002-2003. In obese children, the levels of HbA1c, PG and IRI were statistically higher when compared to those of non-obese children. In contrast, the median and intra-quartile range (IQR) of GA of obese children (13.6%: 12.6-14.7) was statistically lower when compared to that of non-obese children (14.3%: 13.5-15.4, p < 0.001). The low GA (%) in obese children is mainly due to the low absolute value of GA (g/dl) rather than a higher albumin value (g/dl). This is the first report to reveal that GA levels are low in obese, non-diabetic children. Additional data collection and an experimental approach are necessary to reveal the reasons behind lower GA levels in obese children.