Obese Japanese Subjects Research Articles

The integrated incretin effect is reduced by both glucose intolerance and obesity in Japanese subjects.

Incretin-based drugs are extensively utilized in the treatment of type 2 diabetes (T2D), with remarkable clinical efficacy. These drugs were developed based on findings that the incretin effect is reduced in T2D. The incretin effect in East Asians, whose pancreatic β-cell function is more vulnerable than that in Caucasians, however, has not been fully examined. In this study, we investigated the effects of incretin in Japanese subjects. A total of 28 Japanese subjects (14 with normal glucose tolerance [NGT], 6 with impaired glucose tolerance, and 8 with T2D) were enrolled. Isoglycemic oral (75 g glucose tolerance test) and intravenous glucose were administered. The numerical incretin effect and gastrointestinally-mediated glucose disposal (GIGD) were calculated by measuring the plasma glucose and entero-pancreatic hormone concentrations. The difference in the numerical incretin effect among the groups was relatively small. The numerical incretin effect significantly negatively correlated with the body mass index (BMI). GIGD was significantly lower in participants with T2D than in those with NGT, and significantly negatively correlated with the area under the curve (AUC)-glucose, BMI, and AUC-glucagon. Incretin concentrations did not differ significantly among the groups. We demonstrate that in Japanese subjects, obesity has a greater effect than glucose tolerance on the numerical incretin effect, whereas GIGD is diminished in individuals with both glucose intolerance and obesity. These findings indicate variances as well as commonalities between East Asians and Caucasians in the manifestation of incretin effects on pancreatic β-cell function and the integrated capacity to handle glucose.

Comparison of Weight Reduction, Change in Parameters and Safety of a Very Low Carbohydrate Diet in Comparison to a Low Carbohydrate Diet in Obese Japanese Subjects with Metabolic Disorders

Recently, low-carbohydrate diets (LCDs) have gained worldwide attention. LCDs are potentially effective for Japanese overweight and obese individuals with metabolic disorders. However, few randomized trials of LCDs have focused on the difference between LCDs and VLCDs. We conducted a randomized, prospective study of 42 Japanese, obese adults aged 28-65 years to evaluate the efficacy and safety of LCD and VLCD. To ensure the accuracy of the study, all test meals were provided, and compliance was checked using a smartphone app. Body composition measurements and blood tests were performed before and after the 2-month dietary intervention. The results showed that both methods significantly reduced body weight and fat, and also improved lipid abnormalities and liver function. In the current study, the reductions in weight and fat were comparable. The results of a questionnaire at the end of the study indicated that the LCD was easier to carry out than the VLCD, suggesting that the LCD was sustainable. The present study was unique in that it was a randomized, prospective study of Japanese subjects and that accurate data were obtained by providing meals.

Effects of paramylon-rich Euglena gracilisEOD-1 powder on visceral fat obesity in moderately obese Japanese adults: A randomized, double-blind, placebo-controlled, parallel-group trial.

To investigate whether supplementation of paramylon (PM)-rich Euglena gracilis EOD-1 powder (EOD-1) reduces visceral fat obesity in moderately obese Japanese subjects. A randomized, double-blind, placebo-controlled intervention study was conducted involving 36 Japanese adults with a body mass index (BMI) ≥25 and <30 kg/m2. Subjects were randomly assigned into two groups to consume EOD-1 capsules (EOD-1 group, 2.6g PM/day) or cellulose capsules (placebo group) for a 12-week period. Anthropometric measurements including visceral fat area (VFA) and blood samples were measured at baseline and throughout the trial. There was no significant difference in VFA between the two groups, although subgroup analysis by gender showed a significant decrease in VFA in the male EOD-1 group compared with the placebo group. Serum adiponectin levels in all subjects from the EOD-1 group were significantly higher than in the placebo group. By comparison with the placebo group, the subjects in the EOD-1 group showed a significant reduction in serum HbA1c levels. EOD-1 intake led to a significant reduction in VFA in male subjects with moderate obesity (BMI 25-30 kg/m2). PM in EOD-1 may contribute to preventing visceral fat obesity in male Japanese subjects. Moreover, PM may also contribute to improving glucose homeostasis in moderately obese Japanese adults.

Safety and Tolerability Study of Cotadutide in Japanese Obese Subjects With Type 2 Diabetes Melitus

Safety and Tolerability Study of Cotadutide in Japanese Obese Subjects With Type 2 Diabetes Melitus

There is a Close Association Between the Recovery of Liver Injury and Glycemic Control after SGLT2 Inhibitor Treatment in Japanese Subjects with Type 2 Diabetes: A Retrospective Clinical Study.

IntroductionSodium-glucose co-transporter 2 (SGLT2) inhibitors function not only to reduce hyperglycemia but also to ameliorate liver injury and reduce body weight. The aim of this study was to examine in which subjects SGLT2 inhibitors are more effective for glycemic control, liver injury, and obesity in Japanese subjects with type 2 diabetes mellitus.MethodsWe enrolled a total of 156 subjects with type 2 diabetes who initiated SGLT2 inhibitor treatment after September 1, 2014 in Kawasaki Medical School (Protocol No. 2375). We evaluated the alteration of glycemic control, liver injury, body mass composition, and various clinical parameters.ResultsSGLT2 inhibitors significantly ameliorated glycemic control and improved liver injury in Japanese subjects with type 2 diabetes. SGLT2 inhibitors were more effective for liver injury when glycemic control was improved with SGLT2 inhibitors. In multivariate analyses, the amelioration of glycemic control was an independent determinant factor for the improvement of liver damage in Japanese subjects with type 2 diabetes. The reverse was also correct; the improvement of liver damage was an independent determinant factor for the amelioration of glycemic control.ConclusionRecovery of liver injury with SGLT2 inhibitor treatment was closely associated with their effects on glycemic control in Japanese subjects with type 2 diabetes.

Effects of Whole Grain Wheat Bread on Visceral Fat Obesity in Japanese Subjects: A Randomized Double-Blind Study.

Metabolic syndrome is a risk factor for cardiovascular diseases and has become increasingly common in Japan. Epidemiological studies show inverse associations between intake of whole wheat grains and metabolic syndrome, but few dietary intervention trials have investigated the effect of whole wheat grain consumption. It was investigated whether a diet in which refined wheat bread (RW diet) was substituted by whole grain wheat bread (WW diet) would reduce visceral fat obesity in Japanese subjects. A randomized double-blind placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥ 23kg/m2. Subjects were randomly assigned WW (WW group) or RW diets (RW group) for 12weeks. Blood samples and computed tomography scans were obtained every 6th week. The WW group showed decrease (-4 cm2) in visceral fat area (VFA) (p< 0.05), whereas the RW group showed no significant changes. These time-dependent changes were significantly different between the groups. WW diet led to significant and safe reductions in VFA in subjects with BMI ≥ 23kg/m2. WW diet may contribute to preventing visceral fat obesity.

Lactic-fermented egg white improves visceral fat obesity in Japanese subjects\u2014double-blind, placebo-controlled study

BackgroundIt was reported that egg white protein (EWP) reduced body fat in rats. We developed a lactic-fermented egg white (LE) that facilitates the consumption of egg whites by fermenting them with lactobacillus, and were able to study their intake in humans. In this double-blind, placebo-controlled design, we evaluated the effect of LE on visceral fat area (VFA).MethodsParticipants included 37 adult males and females aged ≥40 years (VFA at navel ≥100 cm2). They were divided into two groups: the control group and the LE group. The control and LE groups consumed drinks containing whey and LE, respectively, for 12 weeks (providing 8 g protein/day). VFA was measured at baseline and at week 12 of intake. Abdominal girth was measured at baseline and at weeks 6 and 12.ResultsLE intake decreased VFA significantly compared with baseline (−8.89 cm2, p < 0.05), and VFA was significantly lower than that in the control group (+1.71 cm2, p < 0.05). The LE group showed significant improvement in the ratio of visceral to subcutaneous fat area compared with baseline and the control group (p < 0.05).ConclusionsThe results demonstrated that LE reduces VFA and improves the ratio of visceral to subcutaneous fat area. As other measurement items were not influenced, we concluded that LE improves visceral fat obesity.Trial registrationThis clinical trial was retrospectively registered with the University hospital Medical Information Network (UMIN) Center, (UMIN000026949; registered on 11/04/2017; http://www.umin.ac.jp/).

Seaweed Fucoxanthin Supplementation Improves Obesity Parameters in Mild Obese Japanese Subjects

Background: Fucoxanthin is a seaweed xanthophyll that has demonstrated an anti-obesity effect in rodents. However, clinical investigations of its influence on mildly obese subjects has not been performed. We conducted a clinical trial of fucoxanthin supplementation in Japanese obese subjects. Methods: We examined the effect of fucoxanthin (1 or 3 mg daily) in a double-blind placebo-controlled study. Capsules containing fucoxanthin or placebo capsules were administered for 4 weeks to male and female Japanese adults with a body mass index (BMI) of more than 25 kg/m2. Before and after treatment, the body weight, body composition, abdominal fat area, and the circumferences of the neck, arm, and thigh were evaluated.Results: There was significant reduction of the relative (ratio versus before treatment) body weight, BMI, and visceral fat area in the 3 mg/day fucoxanthin group compared to the placebo group. Relative values of total fat mass, subcutaneous fat area, waist circumference, and right thigh circumference were also significantly lower in the 1 mg/day fucoxanthin group than the placebo group. A significant decrease of the absolute right thigh circumference was noted in the 1 mg/day fucoxanthin group compared to the placebo group. In the subjects ingesting fucoxanthin, there were no abnormalities of the blood pressure, pulse rate, blood parameters, and urinalysis parameters, which thereby suggests adverse effects. Conclusions: Fucoxanthin reduced body weight, BMI, and abdominal fat by acting on both visceral and subcutaneous fat. Consequently, Fucoxanthin may be able to improve a moderate overweight state in both men and women. Keywords: Randomized, double-blind, placebo-controlled crossover trial; fucoxanthin; body mass index; body weight; subcutaneous fat; adipose tissue

Abstract 17026: Serum Adropin Level is Associated With Exercise Training-induced Improvement of Arterial Stiffness in Obese Adults

Introduction: Obesity-induced deterioration of arterial stiffness is reduced by habitual exercise, and increased production of nitric oxide (NO) participates in this effect. Adropin is a regulator of endothelial NO synthase and NO release, and circulating adropin level decreases in obese patients. However, the association between exercise-training effects of arterial stiffness and circulating adropin level in obese subjects remains unclear. Hypothesis: This study aimed to determine the serum adropin level related to exercise-training effects of arterial stiffness in obese subjects. Methods: Eighteen Japanese obese subjects (age: 65.7 ± 1.6 years, % body fat: 34.8 ± 1.6 %) and nine Japanese non-obese subjects (age: 69.1 ± 1.0 years, % body fat: 19.9 ± 2.4 %) participated in this study. Obese subjects completed 8-week of aerobic exercise training (60-70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). Before and after the intervention, we evaluated plasma nitrite/nitrate (NOx) and serum adropin concentrations, carotid beta-stiffness as an indicator of arterial stiffness, and VO2peak as an index of cardiorespiratory fitness. VO2peak was measured using an incremental cycle exercise test on a cycle ergometer. Results: Serum adropin level in the obese subjects was lower than that in the non-obese subjects. After the 8-week intervention, VO2peak was significantly increased and carotid beta-stiffness was significantly decreased (P &lt; 0.05). Moreover, plasma NOx level and serum adropin level was significantly increased after the 8-week intervention (P &lt; 0.05). Additionally, the exercise training-induced reduction in beta-stiffness was negatively correlated with the training-induced changes in serum adropin (r = -0.481, P &lt; 0.05) and plasma NOx levels (r = -0.668, P &lt; 0.01). Furthermore, a significant correlation was observed between the training-induced changes in serum adropin and plasma NOx levels (r = 0.677, P &lt; 0.01). Conclusions: These results suggest that the plasma adropin level is increased by aerobic exercise training intervention and is associated with exercise training-induced alternation of arterial stiffness in obese subjects. Thus, the increase in adropin may participate in the exercise-induced reduction of arterial stiffness.

Atheroma Progression in Obese Early-stage Diabetic Japanese Patients in Response to Glycemic Control: Sub-analysis from the DIANA Study.

Diabetes is accompanied by abdominal obesity, which produces various metabolic abnormalities. While metabolic factors have been considered to promote the development of coronary atherosclerosis in the early-stage of diabetes, it remains unknown whether the presence of obesity in early-stage diabetics affects the natural history of coronary atherosclerosis. We herein investigated the characteristics of the disease substrate in obese early-stage diabetics. The DIANA (DIAbetes and diffuse coronary NArrowing) study was a serial evaluation of angiographic disease progression in early-stage diabetics with coronary artery disease. A total of 252 study subjects were stratified into non-obese (n=168) and obese groups (n=84). Obesity in Japanese subjects was defined as a body mass index ≥25 kg/m(2) according to the statement about Japanese obesity from the Japan Society for the Study of Obesity. Coronary atherosclerotic changes were evaluated by a quantitative computed analysis. The total lesion length (TLL=total length of all atherosclerotic lesions) was compared between the groups. The obese patients were younger (p=0.0002) and had higher levels of fasting (p=0.002) and postprandial insulin (p=0.01), and higher triglyceride levels (p=0.02). On serial angiographic evaluations, obese patients had greater disease progression, reflected by a larger percent change in the TLL (24.7±13.7 vs. 7.4±10.0%, p=0.04). However, the improvement of abnormal glucose tolerance was associated with a slowing of disease progression in both non-obese (-0.9±10.7 vs. ＋15.0±11.2%, p=0.04) and obese (＋4.2±22.8 vs. ＋55.5±26.5%, p=0.005) patients. Obese patients with early-stage diabetes exhibit profound disease progression. Glycemic control attenuated the progression of their coronary atherosclerosis. Our findings indicate progressive but modifiable disease in obese early-stage diabetics under optimal glycemic management.

Relative Contribution of Insulin Secretion and Sensitivity at Different Stages of Glucose Tolerance: Non-obese versus Obese Japanese Subjects

We examined the relative contribution of insulin secretion and insulin sensitivity at different stages of glucose tolerance in non-obese and obese Japanese subjects. A total of 641 subjects who underwent 75-g glucose tolerance testing were divided into two groups: 436 non-obese subjects (body mass index: BMI <25) and 205 obese subjects (BMI ≥25). The subjects were further divided into four groups: those with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. We compared insulin secretion and sensitivity indices, such as the insulinogenic index (IGI), homeostatic model insulin resistance (HOMA-IR), homeostatic model assessment of β-cell (HOMA-β) and insulin sensitivity index (ISI). In a univariate analysis, the obese subjects had higher levels of HOMA-IR, HOMA-β and IGI associated with lower ISI values in comparison with that observed in the non-obese subjects at different stages of glucose tolerance. A multiple logistic regression analysis showed that the HOMA-IR was a significant independent factor between the non-obese and obese subjects; the odds ratio (OR) (95% confidential interval: CI) was 3.78 (2.04-7.01; p<0.01) in the NGT group, 4.91 (2.06-11.72; p<0.01) in the IGT group and 2.02 (1.22-3.34; p<0.01) in the diabetes group. Although a similar trend was also observed in the IFG group (OR=15.83), the difference did not reach a level of statistical significance (p=0.066). These data suggest that obese subjects are characterized by increased insulin resistance rather than reduced insulin secretion at all stages of glucose tolerance. Therefore, non-obese subjects and obese subjects are distinct entities at all stages of glucose tolerance.

Lower physical activity is a risk factor for a clustering of metabolic risk factors in non-obese and obese Japanese subjects: The Takahata study

In several countries including Japan, people without obesity but with a clustering of metabolic risk factors (MetRFs) were not considered to have the metabolic syndrome (MetS). Here, we examined whether lifestyle characteristics differed between non-obese and obese subjects with or without a clustering of MetRFs. From a population-based cross-sectional study of Japanese subjects aged ≥ 40 years, 1,601 subjects (age: 61.9 ± 10.3 years; 710/891 men/women) were recruited. Physical activity status and daily nutritional intake were estimated using questionnaires. A clustering of MetRFs was defined based on the presence of at least two non-essential risk factors for the diagnosis of the MetS in Japan. Energy intake was not higher in subjects with a clustering of MetRFs compared with those without. Among men, energy expenditure at work was significantly lower in non-obese (9.0 ± 8.2 vs. 11.3 ± 9.3 metabolic equivalents (METs), P = 0.025) and obese (9.0 ± 7.9 vs. 11.6 ± 9.4 METs, P = 0.017) subjects with a clustering of MetRFs than in those without. Multiple logistic regression analysis showed that energy expenditure at work was significantly associated with a clustering of MetRFs after adjusting for possible confounding factors including total energy intake. The ORs (per 1 METs) were 0.970 (95% CI, 0.944-0.997; P = 0.032) in non-obese men and 0.962 (0.926- 0.999; P = 0.043) in obese men. Similar associations were not observed in women. In Japanese males, lower physical activity, but not excessive energy intake, is a risk factor for a clustering of MetRFs independent of their obesity status.

Pancreatic beta cell function in lean and obese Japanese with various degrees of glucose tolerance

The aim of the current study was to investigate whether obese subjects have different insulin secretory capacity compared to lean subjects with the same glucose tolerance in a Japanese population. We included a total of 1749 Japanese employees who underwent 75-g oral glucose tolerance test (OGTT). The study population was divided into deciles of 120-min glucose levels and the indices of insulin secretion and insulin sensitivity in each decile were compared between the subjects with and without obesity (body mass index ≥ 25 kg/m2). The indices used in the current study were Matsuda index, insulinogenic index, and disposition index. Obese subjects had significantly lower values of Matsuda index and significantly higher value of insulinogenic index than non-obese subjects in every decile (all p < 0.05). On the other hand, disposition index was not significantly different between non-obese and obese subjects in any decile of 120-min glucose level (all p > 0.05). Similar findings were observed when the study population was classified by waist circumference. In conclusion, disposition index derived from the data of 75-g OGTT was similarly decreased in obese Japanese subjects compared to non-obese Japanese subjects with the same post-load glucose levels. Future studies will be needed to confirm whether the development of glucose intolerance in obese Japanese subjects is accompanied by the same degree of pancreatic beta cell dysfunction as non-obese Japanese subjects.

&lt;i&gt;NUDT3&lt;/i&gt; rs206936 is associated with body mass index in obese Japanese women

The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference, waist-hip ratio measurements and visceral fat area (VFA); the latter can be accurately measured by performing computed tomography (CT). In addition to environmental factors, genetic factors play an important role in obesity and fat distribution. New genetic loci associated with body mass index (BMI) and adiposity have been identified by genome-wide association studies (GWASs). This study utilized CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to higher BMI are associated with VFA, subcutaneous fat area (SFA), and the ratio of VFA to SFA (V/S ratio). We measured the VFA and SFA of 1424 obese Japanese subjects (BMI ≥ 25 kg/m(2), 635 men and 789 women) who were genotyped for 13 single nucleotide polymorphisms (SNPs) reported by recent GWASs, namely, TNNI3K rs1514175, PTBP2 rs1555543, ADCY3 rs713586, IRS1 rs2943650, POC5 rs2112347, NUDT3 rs206936, LINGO2 rs10968576, STK33 rs4929949, MTIF3 rs4771122, SPRY2 rs534870, MAP2K5 rs2241423, QPCTL rs2287019, and ZC3H4 rs3810291. The G-allele of NUDT3 rs206936 was significantly associated with increased BMI (P = 5.3 × 10(-5)) and SFA (P = 0.00039) in the obese Japanese women. After adjustment with BMI, the association between rs206936 and SFA was not observed. This significant association was not observed in the men. The other SNPs analyzed were not significantly associated with BMI, VFA, SFA, or V/S ratio. Our results suggest that NUDT3 rs206936 is associated with BMI in Japanese women.

Plasma amino acid profile is associated with visceral fat accumulation in obese Japanese subjects.

What is already known about this subject • Asians with metabolic complications associated with obesity, a low body mass index and a low waist circumference have a greater proportion of visceral adipose tissue for a given amount of total body fat compared with Europeans. • Apparent obese humans and obese animal models show an elevation of branched-chain amino acid levels in plasma. • A multivariate logistic regression model of plasma free amino acids has been used to screen for several types of cancers in clinical settings. What this study adds • A specific formula incorporating six amino acid values (Ala, Gly, Glu, Trp, Tyr and branched-chain amino acid) was developed for discrimination of subjects with high visceral fat area by multivariate logistic regression analyses. • The generated amino acid formula was strongly correlated with visceral fat area in both apparent and non-apparent obese subjects. • Measuring plasma free amino acids can be used to distinguish the non-apparent visceral obesity in clinical settings in Asian populations. Metabolic complications associated with obesity are becoming more common among Japanese subjects. However, visceral fat accumulation is not always apparent by measuring body mass index (BMI) or waist circumference in Asian populations because of the physiological characteristics particular to those ethnicities. Excess visceral fat accumulation raises the odds ratio for developing cardiovascular disease. Thus, high-throughput determination of the amount of abdominal adipose tissue is necessary. We hypothesized that accumulating visceral fat alters the peripheral amino acid profile and that a multivariate logistic regression model of plasma free amino acids can distinguish visceral obesity. A total of 1449 Japanese subjects (985 males and 464 females) who had undergone a comprehensive health screening were enrolled in this study. The visceral fat area was determined using computed tomography imaging, and a plasma free amino acid index to identify high visceral fat areas (≥100 cm(2) ) was developed. The sensitivity and specificity values of the generated amino acid index were 80% and 65%, respectively. In particular, the sensitivity of the generated index to identify subjects with non-apparent visceral obesity (BMI < 25 kg m(-2) ; visceral fat area ≥ 100 cm(2) ) was much greater than that of the waist circumference (73% vs. 46%, respectively). This index's high sensitivity and specificity may be the result of specific alterations in the patients' amino acid profiles, which were specifically correlated with the visceral fat areas and not with subcutaneous fat areas. This profile can be used as a predictor of elevated visceral obesity and a risk assessment tool for metabolic complications in Asian populations.

Effects of body weight reduction on cardio-ankle vascular index (CAVI)

Obesity is associated with type 2 diabetes, dyslipidemia and hypertension, contributing to atherogenesis. Weight reduction is the fundamental therapy for obesity. Recently, a novel arterial stiffness parameter called cardio-ankle vascular index (CAVI) has been developed. We hypothesized that CAVI may be a candidate marker of increased vascular stiffness in obese patients. The aim of this study is to investigate the effect of weight reduction on CAVI. Using CAVI as an indicator, we assessed the changes in arterial stiffness in 47 obese Japanese subjects (aged 46 ± 13 years) who underwent a 12-week weight reduction program consisting of a calorie restriction diet (20-25 kcal/day) and exercise therapy. Visceral fat area (VFA) was evaluated by CT. At baseline, CAVI correlated positively with age (r = 0.70), blood pressure (r = 0.23), VFA (r = 0.26) and HbA1c (r = 0.39). After 12 weeks of weight reduction, mean BMI decreased from 33.3 ± 7.5 to 30.7 ± 6.4 kg/m(2) (p < 0.0001), and mean CAVI decreased from 8.3 to 7.9 (p < 0.01). The change in VFA correlated positively with change in CAVI in subjects with decrease in CAVI (r = 0.47). Furthermore, change in VFA was a significant independent predictor for change in CAVI. No significant correlation was observed between change in CAVI and clinical variables such as BMI, HbA1c and lipids. This study demonstrated that CAVI decreased after weight reduction, and was associated with a decrease in VFA. CAVI reduction maybe a marker of improved vascular stiffness after weight reduction in subjects with visceral adiposity.

High prevalence of periodontitis in non-elderly obese Japanese adults

Several recent reports have indicated a high prevalence of periodontitis in obese subjects, but the results have not been consistent. This study was performed to investigate the prevalence of periodontitis in non-elderly obese Japanese adults and to explore the relationship between obesity and periodontitis. Ninety-five obese subjects (BMI ≥ 25; males: 44, females: 51) and 102 subjects with normal weight (BMI 18.5-25; males: 66, females: 36) were enrolled from April 1997 to March 1999 in the study. All subjects were aged 25-40 years old. The status of periodontitis was evaluated based on the intraoral community periodontal index (CPI) codes of the WHO, and the numbers of present teeth, untreated decayed teeth, missing teeth, and filled teeth were also examined. The prevalence of periodontitis was significantly higher in obese subjects, and particularly in females, compared to controls, whereas the numbers of present teeth, decayed teeth, missing teeth and filled teeth did not differ significantly between the obese subjects and the controls for both males and females. Multiple logistic regression analysis revealed that obesity was significantly related to periodontitis. A high prevalence of periodontitis was found in non-elderly Japanese obese subjects, and particularly in obese female adults. Correlation analysis also suggested that obesity carries a high risk for development of periodontitis.

Gender-Dependent Penetrance of Small Heterodimer Partner (SHP) Gene Deficiency in Overweight/Obese Chinese Pedigrees

Mutations of the small heterodimer partner (SHP) gene have been associated with mild obesity in Japanese subjects. This study was designed to investigate whether there was a similar association in 772 Chinese adults. A total of 272 subjects were normal weight, 423 were overweight and 77 were obese. Four non-synonymous mutations (R34X, H53fsdel10, G171A, G189E) were identified in 10 out of the 500 overweight/obese subjects, but were not seen in the normal weight controls (prevalence 2.00% versus 0.00%, respectively). The relatives of proband carriers, including 25 carriers and 33 non-carriers from three generations, were also screened for 10 multigenerational non-consanguineous pedigrees. A gender-dependent penetrance effect was observed in the pedigrees. Furthermore, the frequency of SHP gene mutations was significantly higher in those with type 2 diabetes compared with the non-diabetics (61.5% versus 28.1%, respectively). These data provide evidence of a gender-dependent effect on penetrance for SHP deficiency and suggest that SHP mutations increase susceptibility to type 2 diabetes.

Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population

There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2 (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1 (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15). To investigate the relationship between obesity and these genes in the Japanese population, we genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese subjects (n=1129, body mass index (BMI) > or =30 kg m(-2)) and normal-weight control subjects (n=1736, BMI <25 kg m(-2)). The SNP rs10913469 in SEC16B (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the TMEM18 gene (P=0.00015), all of which were in almost absolute linkage disequilibrium, were significantly associated with obesity in the Japanese population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.

Highly purified eicosapentaenoic acid reduces cardio-ankle vascular index in association with decreased serum amyloid A-LDL in metabolic syndrome

A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, reduces the incidence of cardiovascular diseases. However, the detailed mechanism underlying the anti-atherogenic effect of EPA is still poorly understood. In this study, we examined the effect of EPA on cardio-ankle vascular index (CAVI), a new index of arterial stiffness that is less influenced by blood pressure (BP), as well as on serum amyloid A-low-density lipoprotein (SAA-LDL), an oxidized LDL (oxLDL), in the metabolic syndrome. Ninety-two obese Japanese subjects with metabolic syndromes were randomly divided into two groups (n=46): the EPA-treated group (1.8 g administered daily for 3 months) and the control group. Measurements were taken to assess the changes in glucose-lipid metabolism, SAA-LDL, C-reactive protein (CRP), leptin, adiponectin and pulse wave velocity (PWV), and CAVI. EPA treatment significantly reduced the levels of immunoreactive insulin, triglycerides, SAA-LDL, CRP, PWV and CAVI and increased the levels of adiponectin relative to the control group for 3 months (P<0.05). Stepwise multivariate linear regression analysis revealed that the only significant determinant for a decrease in CAVI by EPA is a reduction in SAA-LDL (P<0.05). Moreover, the EPA-induced reduction of SAA-LDL was only significantly correlated with a decrease in total cholesterol and an increase in adiponectin (P<0.05). This study is the first demonstration that EPA improves arterial stiffness and is less influenced by BP, possibly through the suppression of SAA-LDL, thereby leading to a reduction in the frequency of cardiovascular disease development in metabolic syndrome.