BackgroundAbdominal visceral obesity has been reported to be associated with cardiovascular risks than body mass index, waist circumference, and abdominal subcutaneous fat. On the other hand, there is evidence that subcutaneous fat has a beneficial role against cardio-metabolic risks such as diabetes or dyslipidemia. However, little is known regarding the association between high visceral fat with low subcutaneous fat accumulation and the risk for atherosclerosis.MethodsThis study was designed to elucidate whether high visceral fat with low subcutaneous fat accumulation enhances the risk for atherosclerosis in patients with type 2 diabetes. This is a cross-sectional study of 148 patients with type 2 diabetes (mean age 65 ± 12 years; 44.5 % female). Visceral fat area (VFA, cm2) and subcutaneous fat area (SFA, cm2) were assessed by abdominal computed tomography. Carotid intima media thickness (CIMT, mm) measured by ultrasonography was used for the assessment of atherosclerosis. Patients were divided into four groups: SFA < 100 cm2 and VFA < 100 cm2 [S(−)V(−)], SFA ≥ 100 cm2 and VFA < 100 cm2 [S(+)V(−)], SFA < 100 cm2 and VFA ≥ 100 cm2 [S(−)V(+)], and SFA ≥ 100 cm2 and VFA ≥ 100 cm2 [S(+)V(+)]. Linear regression analysis with a stepwise procedure was used for the statistical analyses.ResultsAmong the patients examined, 16.3 % were S(−)V(+). Mean (95 % confidence interval) of CIMT adjusting for age and gender were 0.80 (0.69–0.91), 0.86 (0.72–1.01), 1.28 (1.11–1.44) and 0.83 (0.77–0.88) in patients with S(−)V(−), S(+)V(−), S(−)V(+) and S(+)V(+), respectively (p < 0.001). The S(−)V(+) patients exhibited significantly older than S(−)V(−) patients and those with S(+)V(+) and had a highest VFA-SFA ratio (V/S ratio) among the four groups. S(−)V(+) patients were male predominant (100 % male), and S(+)V(−) patients showed female predominance (82 % female). In multivariate linear regression analysis (Adjusted R2 = 0.549), S(−)V(+) was significantly associated with CIMT (Standardized β 0.423, p < 0.001). Notably, S(+)V(+) was inversely associated with CIMT in the multivariate model.ConclusionsThis study provides evidence that high visceral fat with low subcutaneous fat accumulation is an important determinant of carotid atherosclerosis and high subcutaneous fat could be protective against atherosclerosis in patients with type 2 diabetes.

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ObjectiveNormal-weight abdominal obesity has been reported to be associated with poor mortality. We aimed to investigate the impact of increased visceral adiposity with normal weight (OB(−)VA(+)) on the progression of arterial stiffness in patients with type 2 diabetes.MethodsThis was a cross-sectional study of 414 patients with type 2 diabetes (mean age 64±12 years; 40.3% female). Visceral fat area (VFA, cm2) was measured by a dual bioelectrical impedance analyzer. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV, cm/s). Patients were divided into four groups by VFA and body mass index (BMI, kg/m2) as the following: BMI<25 kg/m2 and VFA<100 cm2 (obesity (OB)(−)visceral adiposity (VA)(−)), BMI≥25 kg/m2 and VFA<100 cm2 (OB(+)VA(−)), BMI<25 kg/m2 and VFA≥100 cm2 (OB(−)VA(+)), and BMI≥25 kg/m2 and VFA≥100 cm2 (OB(+)VA(+)). Multivariate linear regression analysis was done to determine the impact of OB(−)VA(+) on arterial stiffness.ResultsAmong the patients, 7.2% were OB(−)VA(+) with higher baPWV levels (1956±444 cm/s) than those with OB(+)VA(−) (1671±416 cm/s, p=0.014), those with OB(+)VA(+) (1744±317 cm/s, p=0.048), and those with OB(−)VA(−) (1620±397 cm/s, p=0.024). In multivariate linear regression analysis, OB(−)VA(+) remained independently associated with baPWV (standardized β 0.184, p=0.001).ConclusionsThis study provides evidence for the burden of arterial stiffness in OB(−)VA(+) patients with type 2 diabetes; therefore, evaluation of visceral adiposity is of clinical relevance for the better management of non-obese individuals as well as obese populations.

Nine limonoids, 1-9, one apocarotenoid, 11, one alkaloid, 12, and one steroid, 13, from the leaf extract; and one triterpenoid, 10, five steroids, 14-18, and two flavonoids, 19 and 20, from the bark extract of Melia azedarach L. (Chinaberry tree; Meliaceae) were isolated. Among these compounds, three compounds, 4-6, were new, and their structures were established as 3-deacetyl-28-oxosalannolactone, 3-deacetyl-28-oxosalanninolide, and 3-deacetyl-17-defurano-17,28-dioxosalannin, respectively, on the basis of extensive spectroscopic analyses and comparison with literature data. All of the isolated compounds were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines. 3-Deacetyl-4'-demethyl-28-oxosalannin (3) against HL60 and AZ521 cells, and methyl kulonate (10) against HL60 cells exhibited potent cytotoxicities with IC50 values in the range of 2.8-5.8 μM. In addition, upon evaluation of compounds 1-13 against production of nitric oxide (NO) in mouse macrophage RAW 264.7 cells induced by lipopolysaccharide (LPS), seven, i.e., trichilinin B (1), 4, ohchinin (7), 23-hydroxyohchininolide (8), 21-hydroxyisoohchininolide (9), 10, and methyl indole 3-carboxylate (12), inhibited production of NO with IC50 values in the range of 4.6-87.3 μM with no, or almost no, toxicity to the cells (IC50 93.2-100 μM). Western blot analysis revealed that compound 7 reduced the expression levels of the inducible NO synthase (iNOS) and COX-2 proteins in a concentration-dependent manner. Furthermore, compounds 5, 6, 13, and 18-20 exhibited potent inhibitory effects (IC50 299-381 molar ratio/32 pmol TPA) against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cell line.

Aims/IntroductionTo investigate the impact of increased visceral adiposity with normal weight (OB[−]VA[+]) on the prevalence of non‐alcoholic fatty liver disease in patients with type 2 diabetes.Materials and MethodsThis was a cross‐sectional study of 140 Japanese patients with type 2 diabetes (mean age 65 ± 11 year; 44.6% women). Visceral fat area (VFA; cm2) and liver attenuation index (LAI) were assessed by abdominal computed tomography. The patients were divided into four groups by VFA and body mass index (BMI; kg/m2) as follows: BMI <25 kg/m2 and VFA <100 cm2 (OB[−]VA[−]), BMI ≥25 kg/m2 and VFA <100 cm2 (OB[+]VA[−]), BMI <25 kg/m2 and VFA ≥100 cm2 (OB[−]VA[+]), and BMI ≥25 kg/m2 and VFA ≥100 cm2 (OB[+]VA[+]). Multivariate linear regression and logistic regression analysis were carried out to determine the impact of OB(−)VA(+) on LAI.ResultsIn the present study, 25.0% were OB(−)VA(+) patients, where the LAI levels were lower (1.09 ± 0.22) than those in OB(−)VA(−) patients (1.23 ± 0.15), and were equivalent to those in OB(+)VA(+) patients (1.03 ± 0.26). In multivariate linear regression analysis, OB(−)VA(+) was independently associated with LAI (standardized β−0.212, P = 0.014). In multivariate logistic regression analysis, OB(−)VA(+) was a significant predictor of LAI <0.9 (odds ratio 5.88, 95% confidence interval 1.03−33.52, P = 0.046).ConclusionsThe present study provides evidence that increased visceral adiposity with normal weight is a strong predictor for the prevalence of non‐alcoholic fatty liver disease in Japanese patients with type 2 diabetes.