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Hiuge-Shimizu A.,Osaka University | Kishida K.,Osaka University | Funahashi T.,Osaka University | Ishizaka Y.,Center for Multiphasic Health Testing and Services | And 13 more authors.
Annals of Medicine | Year: 2012

Background. The management of cardiovascular risk factors is important for prevention of atherosclerotic cardiovascular diseases (ACVD). Visceral fat accumulation plays an important role in the clustering of cardiovascular risk factors, leading to ACVD. The present study investigated the gender-and age-specific relationship between obesity-related cardiovascular risk factor accumulation and computed tomography (CT)-measured fat distribution in a large-scale Japanese general population. Methods and results. Fat distribution was measured on CT scans in 12,443 subjects (males/females = 10,080/2,363), who underwent medical health check-up at 9 centers in Japan. The investigated obesity-related cardiovascular risk factors were hyperglycemia, dyslipidemia, and elevated blood pressure. Visceral fat area (VFA) for all males and old females showed almost symmetric distribution, while that of young females showed skewed distribution with a marked left shift. Only a small proportion of young females had large visceral fat and cardiovascular risk accumulation. The mean number of risk factors exceeded 1.0 at around 100 cm 2 for VFA in all groups, irrespective of gender, age (cut-off age 55), and BMI (cut-off BMI 25 kg/m 2). Conclusions. In this large-scale Japan-wide general population study, an absolute VFA value of about 100 cm 2 equated with obesity-related cardiovascular risk factor accumulation, irrespective of gender, age, and BMI. © 2012 Informa UK, Ltd. Source

Oka R.,Hokuriku Central Hospital | Aizawa T.,Diabetes Center | Yagi K.,Kanazawa University | Hayashi K.,Kanazawa University | And 2 more authors.
Diabetic Medicine | Year: 2014

Aims: To investigate whether the elevation of liver enzymes is associated with the progression from normal to impaired glucose tolerance. Methods: A historical cohort study was conducted in 594 male workers at public schools, who had normal glucose tolerance at baseline. The progression to impaired glucose tolerance and impaired fasting glycaemia during a mean follow-up of 3.1 years was measured using an oral glucose tolerance test. Results: Overall, 141 (23.7%) subjects developed impaired glucose tolerance and 68 (11.4%) subjects developed impaired fasting glycaemia, 23 of whom had combined impaired fasting glycaemia/impaired glucose tolerance. The incidence of impaired glucose tolerance increased significantly with increasing quartiles of serum aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase (P for trend <0.01). In Cox proportional hazards regression analysis, after adjusting for comprehensive risk factors, including plasma glucose levels, BMI and homeostatic model assessment of insulin resistance, the risk of progression to impaired glucose tolerance was significantly higher in the highest quartile of alanine aminotransferase than in the lowest quartile (hazard ratio 2.5; 95% CI 1.1-5.7). A significant association between alanine aminotransferase and the progression to impaired glucose tolerance was found after further adjustments for other liver enzymes or after the sample was limited to those with BMI < 25.0 kg/m2 or with fasting plasma glucose < 5.5 mmol/l. Conclusions: A higher level of alanine aminotransferase was independently associated with progression from normal to impaired glucose tolerance in Japanese men. The elevation of alanine aminotransferase may be a change that occurs early in the evolution of diabetes. © 2013 Diabetes UK. Source

Oka R.,Hokuriku Central Hospital | Yagi K.,Kanazawa University | Nakanishi C.,Kanazawa University | Konno T.,Kanazawa University | And 5 more authors.
Journal of Atherosclerosis and Thrombosis | Year: 2014

Aim: The commonly observed relationship between increased visceral adiposity and metabolic abnormalities may be partly mediated by a concomitant increase in liver fat content. We evaluated the independent association between the level of alanine aminotransferase (ALT) as a surrogate marker of the liver fat content and the incidence of metabolic abnormalities after adjusting for the amount of visceral adipose tissue (AT). Methods: The subjects included 1,118 Japanese individuals (44% women) who underwent computed tomography to assess the amount of visceral AT on medical checkups. Cross-sectional associations between the serum ALT, visceral AT and metabolic risk factors were examined. Results: The ALT level and visceral AT were found to show a significant correlation (r =0.41 in men and r =0.36 in women, p<0.001). In a multivariable linear regression analysis, the ALT level and visceral AT were found to be independently associated with blood pressure in men and triglycerides and 2-hour post-challenge glucose in both genders (p<0.01), whereas only visceral AT was found to be associated with HDL-cholesterol (p<0.01). When the participants were classified into four subgroups based on the 75th percentiles of ALT and visceral AT, the low-ALT/high-visceral AT group, but not the high-ALT/low-visceral AT group, had a significantly higher odds ratio for low HDL-cholesterol among both genders (p<0.05) and for hypertriglyceridemia in men only (p<0.05). Meanwhile, the high-ALT/low-visceral AT group, but not the low-ALT/high-visceral AT group, had a significantly higher odds ratio for IGT among women (p<0.05). Conclusions: Although the ALT level and visceral AT were found to be independently associated with most metabolic risk factors, visceral AT had a dominant association with dyslipidemia in both genders, while the ALT level appeared to have a closer association with IGT in women. Source

Oka R.,Hokuriku Central Hospital | Yagi K.,Kanazawa University | Hayashi K.,Kanazawa University | Kawashiri M.-A.,Kanazawa University | And 5 more authors.
Endocrine Journal | Year: 2014

The risk factors for impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have yet to be established. Our aim was to elucidate the predisposing factors for IFG and IGT in Japanese subjects with normal glucose tolerance (NGT). Using a 75 g oral glucose tolerance test (OGTT), we analyzed 604 adults with the ADA-defined NGT. Follow-up glucose tolerance status was determined by 75 g OGTT performed 3.7 yrs later. Glucose-stimulated insulin secretion (GSIS), whole body insulin sensitivity (SI) and beta cell function (BCF) were estimated by Stumvoll indices, ISIMatsuda, and a product of Stumvoll 1st and ISIMatsuda, respectively, and hepatic SI by quantitative insulin sensitivity check index. Logistic regression analysis revealed that attenuated BCF due to low GSIS was an independent risk factor for IFG. Low whole body SI was an additional risk for IGT. Male gender and high BMI were independently related to the progression to both IFG and IGT, whereas a positive diabetes family history was independently related to IGT. The worsening of glucose tolerance at large was predicted with 66% sensitivity by risk engine with GSIS, whole body SI, gender, BMI and glucose. This finding may help when implementing early intervention strategies for diabetes. © The Japan Endocrine Society. Source

Mabuchi H.,Kanazawa University | Nohara A.,Kanazawa University | Noguchi T.,Kanazawa University | Kobayashi J.,Kanazawa University | And 12 more authors.
Atherosclerosis | Year: 2014

Backgrounds: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by hypercholesterolemia, tendon xanthomas, and premature coronary heart disease. FH is caused by mutations of "FH genes," which include the LDL-receptor (LDLR), apolipoprotein B-100 (APOB) or proprotein convertase subtilisin/kexin type 9 (PCSK9). We evaluated the usefulness of FH gene analysis for diagnosing homozygous FH (homo-FH), particularly in cases caused by gain-of-function (g-o-f) mutations in PCSK9 (PCSK9 E32K). Objectives: To evaluate the frequency of homo-FH caused by PCSK9 E32K compared with FH due to other genetic causes and to report the phenotypic features of homo-FH caused by PCSK9 E32K. Methods: Genomic DNA was prepared from white blood cells, and LDLR and PCSK9 mutations were identified using the Invader assay method. Results: Of the 1055 hetero-FH patients, 62 patients (5.9%) carried the PCSK9 E32K mutation, while in the 82 alleles of 41 homo-FH patients, 13 (15.9%) had double mutations of LDLR allele and PCSK9 E32K mutation. Mean plasma total cholesterol (TC) (9.93±2.95mmol/L, mean±SD) in true homo-FH cases with PCSK9 E32K or double hetero-FH cases with PCSK9 E32K and LDLR mutations were significantly lower than those in true homo-FH (18.06±4.96mmol/L) and compound heterozygous cases with LDLR mutations (14.84±1.62mmol/L). Mean plasma TC concentrations in the 59 hetero-FH cases with PCSK9 E32K (7.21±1.55mmol/L) were significantly lower than those (8.94±1.53mmol/L) in the hetero-FH by LDLR mutations. Conclusions: FH caused by PCSK9 g-o-f mutations is relatively common in Japan and causes a mild type of homo- and hetero-FH compared with FH caused by LDLR mutations. © 2014 Elsevier Ireland Ltd. Source

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