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Background: Increased visceral adiposity is strongly associated with non-alcoholic fatty liver disease (NAFLD). However, little attention has been paid to the association between the change in subcutaneous adipose mass and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate whether increased subcutaneous adipose tissue (gynoid fat mass) could be protective against the progression of NAFLD in Japanese patients with type 2 diabetes. Methods: This is a retrospective observational study of 294 Japanese patients with type 2 diabetes (65 ± 10 years old, 40% female). Liver attenuation index (LAI) measured by abdominal computed tomography was used for the assessment of hepatic steatosis. Both gynoid (kg) and android (kg) fat masses were measured by the whole body dual-energy X-ray absorptiometry. One-year changes in LAI, gynoid, and android fat masses were evaluated in both male and female patients. Linear regression analysis with a stepwise procedure was used for the statistical analyses to investigate the association of the changes in gynoid and android fat masses with the change in LAI. Results: LAI levels at baseline were 1.15 ± 0.31 and 1.10 ± 0.34 in female and male patients (p = 0.455). The change in gynoid fat mass was significantly and positively associated with the change in LAI in both univariate (standardized β 0.331, p = 0.049) and multivariate (standardized β 0.360, p = 0.016) models in the female patients. However, no significant association was observed in males. In contrast, the increase in android fat mass was significantly associated with the reduced LAI in both genders in the multivariate models (standardized β -0.651, p < 0.001 in females and standardized β -0.519, p = 0.042 in males). Conclusions: This study provides evidence that increased gynoid fat mass may be protective against the progression of NAFLD in female Japanese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV. Methods: Type 2 diabetic patients with HbA1c 6.5-9.0% and body mass index (BMI, kg/m2) ≥25.0 were enrolled in this single arm pilot study. Participants were administered luseogliflozin 2.5 mg daily and the dosage was tolerated to be increased up to 5.0 mg daily. EFV [median (interquartile range), cm3] was measured by magnetic resonance imaging. Primary endpoint was the decrease in EFV at 12 weeks. Visceral fat area (VFA, cm2) and liver attenuation index (LAI) measured by the abdominal computed tomography, and skeletal muscle index (SMI) and body fat (%) measured by the whole body dual-energy X-ray absorptiometry were also determined at baseline and at 12 weeks. Results: Nineteen patients (mean age: 55 ± 12 years; 26% female) completed this study. Luseogliflozin treatment significantly reduced EFV at 12 weeks [117 (96-136) to 111 (88-134), p = 0.048]. The body weight, BMI, systolic and diastolic blood pressure, HbA1c, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, SMI, and body fat were significantly reduced by luseogliflozin at 12 weeks. The reduction of EFV was significantly correlated with the reduction of C-reactive protein (r = 0.493, p = 0.019). Neither VFA nor LAI were significantly reduced by the luseogliflozin treatment. No severe adverse events were observed. Conclusions: Our data suggest that luseogliflozin could reduce the EFV in parallel with the improvement of systemic micro-inflammation and the reduction of body weight in Japanese patients with type 2 diabetes. The reduction of muscle mass after the administration of SGLT2 inhibitors may require a particular attention. [ABSTRACT FROM AUTHOR]

Background: Whole body dual-energy X-ray absorptiometry (DXA) can simultaneously measure both regional fat and non-fat mass. Android-to-gynoid (A/G) ratio measured by DXA has been reported to be associated with cardiovascular risks and visceral adiposity; however, little is known regarding its relationship with fatty liver disease and atherosclerosis among patients with diabetes. This study was designed to investigate the association of android and gynoid fat mass measured by DXA with fatty liver disease and atherosclerosis in patients with type 2 diabetes. Methods: This is a cross-sectional study of 259 patients with type 2 diabetes (mean age 64 ± 13 years; 40.2 % female). Android and gynoid fat mass (kg) were measured by DXA. Skeletal muscle index (SMI) was calculated as appendicular non-fat mass (kg) divided by height (m²). Visceral fat area (VFA, cm²), subcutaneous fat area (SFA, cm²), and liver attenuation index (LAI) were assessed by abdominal computed tomography. Intima media thickness (IMT, mm) in common carotid arteries was determined by carotid ultrasonography. Results: A/G ratio was significantly correlated with VFA (r = 0.72, p < 0.001), SFA (r = 0.32, p < 0.001) and LAI (r = -0.26, p < 0.001). A/G ratio (standardized β -0.223, p = 0.002) as well as VFA (standardized β -0.226, p = 0.001) were significantly associated with LAI in the univariate model. A/G ratio remained to be significantly associated with LAI (standardized β -0.224, p = 0.005) after adjusting for covariates including body mass index and transaminases. Among patients with low SMI (SMI < 7.0 in male and < 5.4 in female), A/G ratio was significantly associated with carotid IMT in the multivariate model (standardized β 0.408, p = 0.014). Conclusions: DXA can be used to simultaneously estimate the risks for both fatty liver disease and atherosclerosis in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate whether visceral adiposity could modify the impact of blood pressure on arterial stiffness and albuminuria in patients with type 2 diabetes. Methods: This cross-sectional study examines the interaction of visceral adiposity with increased blood pressure on arterial stiffness and albuminuria. 638 patients with type 2 diabetes (mean age 64 ± 12 years; 40% female) were enrolled. Visceral fat area (VFA, cm2) was assessed by a dual-impedance analyzer, whereby patients were divided into those with VFA < 100 (N = 341) and those with VFA ≥ 100 (N = 297). Albuminuria was measured in a single 24-h urine collection (UAE, mg/day) and brachial-ankle pulse wave velocity (ba-PWV, cm/s) was used for the assessment of arterial stiffening. Linear regression analyses were used to investigate the association of systolic blood pressure (SBP) and VFA with UAE and baPWV. Results: Patients with VFA ≥ 100 were significantly younger, had higher SBP, HbA1c, triglycerides, UAE, alanine aminotransferase, C-reactive protein and lower high-density lipoprotein and shorter duration of diabetes than those with VFA < 100. SBP was significantly and almost equivalently associated with ba-PWV both in VFA < 100 (standardized β 0.224, p = 0.001) and VFA ≥ 100 (standardized β 0.196, p = 0.004) patients in the multivariate regression analysis adjusting for covariates including age, gender, HbA1c, diabetic complications and the use of insulin and anti-hypertensive agents. By contrast, the association of SBP with UAE was stronger in patients with VFA ≥ 100 (standardized β 0.263, p = 0.001) than that in patients with VFA < 100 (standardized β 0.140, p = 0.080) in the multivariate regression model. In the whole cohort, the significant interaction between SBP and VFA on UAE (standardized β 0.172, p = 0.040) but not on ba-PWV (standardized β -0.008, p = 0.916) was observed. Conclusions: The effect of increased blood pressure on arterial stiffness is almost similar in type 2 diabetic patients with both low and high visceral adiposity, while its association with albuminuria is stronger in the latter. [ABSTRACT FROM AUTHOR]

Background: Abdominal 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. Methods: This 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. Results: Among 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. Conclusions: This 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. [ABSTRACT FROM AUTHOR]

Background: Although the maze procedure is an established surgical treatment for eliminating atrial fibrillation (AF), its efficacy in patients with mitral valve disease has remained unsatisfactory. A useful predictive marker for the outcome of the maze procedure is needed. The aim of this study was to investigate whether the preoperative ratio of atrial natriuretic peptide (ANP) to brain natriuretic peptide (BNP) reflects atrial fibrosis and can be used to predict the maze procedure outcome in patients with mitral valve disease. Methods: A total of 23 consecutive patients who underwent the radial approach to the maze procedure combined with mitral valve surgery were included in this study and were divided into a sinus rhythm (SR) group (n=16) and an AF group (n=7) based on postoperative cardiac rhythm. Plasma samples were obtained at rest before the operation and were analysed for ANP and BNP levels. Atrial tissue samples taken during surgery were used to quantify interstitial fibrosis. Results: The preoperative ANP-to-BNP ratio in the SR group was significantly higher than that in the AF group (0.74 +/- 0.29 vs. 0.42 +/- 0.28, respectively; p=0.025). Receiver operating characteristic (ROC) curve analysis was used to identify factors that predict outcomes after the maze procedure. The area under the ROC curve for the ANP-to-BNP ratio (0.81) was greater than for any other preoperative factors. Moreover, the preoperative ANP-to-BNP ratio demonstrated a negative correlation with left atrial fibrosis (r=-0.69; p=0.003). Conclusions: The preoperative ANP-to-BNP ratio can predict maze procedure outcome in patients with mitral valve disease, and it represents a potential biomarker for left atrial fibrosis. [ABSTRACT FROM AUTHOR]

Background: Increased visceral adiposity is strongly associated with non-alcoholic fatty liver disease (NAFLD). However, little attention has been paid to the association between the change in subcutaneous adipose mass and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate whether increased subcutaneous adipose tissue (gynoid fat mass) could be protective against the progression of NAFLD in Japanese patients with type 2 diabetes., Methods: This is a retrospective observational study of 294 Japanese patients with type 2 diabetes (65 ± 10 years old, 40% female). Liver attenuation index (LAI) measured by abdominal computed tomography was used for the assessment of hepatic steatosis. Both gynoid (kg) and android (kg) fat masses were measured by the whole body dual-energy X-ray absorptiometry. One-year changes in LAI, gynoid, and android fat masses were evaluated in both male and female patients. Linear regression analysis with a stepwise procedure was used for the statistical analyses to investigate the association of the changes in gynoid and android fat masses with the change in LAI., Results: LAI levels at baseline were 1.15 ± 0.31 and 1.10 ± 0.34 in female and male patients ( p  = 0.455). The change in gynoid fat mass was significantly and positively associated with the change in LAI in both univariate (standardized β 0.331, p  = 0.049) and multivariate (standardized β 0.360, p  = 0.016) models in the female patients. However, no significant association was observed in males. In contrast, the increase in android fat mass was significantly associated with the reduced LAI in both genders in the multivariate models (standardized β -0.651, p  < 0.001 in females and standardized β -0.519, p  = 0.042 in males)., Conclusions: This study provides evidence that increased gynoid fat mass may be protective against the progression of NAFLD in female Japanese patients with type 2 diabetes.

Background: Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV., Methods: Type 2 diabetic patients with HbA1c 6.5-9.0% and body mass index (BMI, kg/m 2 ) ≥25.0 were enrolled in this single arm pilot study. Participants were administered luseogliflozin 2.5 mg daily and the dosage was tolerated to be increased up to 5.0 mg daily. EFV [median (interquartile range), cm 3 ] was measured by magnetic resonance imaging. Primary endpoint was the decrease in EFV at 12 weeks. Visceral fat area (VFA, cm 2 ) and liver attenuation index (LAI) measured by the abdominal computed tomography, and skeletal muscle index (SMI) and body fat (%) measured by the whole body dual-energy X-ray absorptiometry were also determined at baseline and at 12 weeks., Results: Nineteen patients (mean age: 55 ± 12 years; 26% female) completed this study. Luseogliflozin treatment significantly reduced EFV at 12 weeks [117 (96-136) to 111 (88-134), p = 0.048]. The body weight, BMI, systolic and diastolic blood pressure, HbA1c, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, SMI, and body fat were significantly reduced by luseogliflozin at 12 weeks. The reduction of EFV was significantly correlated with the reduction of C-reactive protein (r = 0.493, p = 0.019). Neither VFA nor LAI were significantly reduced by the luseogliflozin treatment. No severe adverse events were observed., Conclusions: Our data suggest that luseogliflozin could reduce the EFV in parallel with the improvement of systemic micro-inflammation and the reduction of body weight in Japanese patients with type 2 diabetes. The reduction of muscle mass after the administration of SGLT2 inhibitors may require a particular attention. Trial registration umin.ac.jp, UMIN000019072.

Background: Whole body dual-energy X-ray absorptiometry (DXA) can simultaneously measure both regional fat and non-fat mass. Android-to-gynoid (A/G) ratio measured by DXA has been reported to be associated with cardiovascular risks and visceral adiposity; however, little is known regarding its relationship with fatty liver disease and atherosclerosis among patients with diabetes. This study was designed to investigate the association of android and gynoid fat mass measured by DXA with fatty liver disease and atherosclerosis in patients with type 2 diabetes., Methods: This is a cross-sectional study of 259 patients with type 2 diabetes (mean age 64 ± 13 years; 40.2 % female). Android and gynoid fat mass (kg) were measured by DXA. Skeletal muscle index (SMI) was calculated as appendicular non-fat mass (kg) divided by height (m(2)). Visceral fat area (VFA, cm(2)), subcutaneous fat area (SFA, cm(2)), and liver attenuation index (LAI) were assessed by abdominal computed tomography. Intima media thickness (IMT, mm) in common carotid arteries was determined by carotid ultrasonography., Results: A/G ratio was significantly correlated with VFA (r = 0.72, p < 0.001), SFA (r = 0.32, p < 0.001) and LAI (r = -0.26, p < 0.001). A/G ratio (standardized β -0.223, p = 0.002) as well as VFA (standardized β -0.226, p = 0.001) were significantly associated with LAI in the univariate model. A/G ratio remained to be significantly associated with LAI (standardized β -0.224, p = 0.005) after adjusting for covariates including body mass index and transaminases. Among patients with low SMI (SMI < 7.0 in male and < 5.4 in female), A/G ratio was significantly associated with carotid IMT in the multivariate model (standardized β 0.408, p = 0.014)., Conclusions: DXA can be used to simultaneously estimate the risks for both fatty liver disease and atherosclerosis in patients with type 2 diabetes.

Background: We aimed to investigate whether visceral adiposity could modify the impact of blood pressure on arterial stiffness and albuminuria in patients with type 2 diabetes., Methods: This cross-sectional study examines the interaction of visceral adiposity with increased blood pressure on arterial stiffness and albuminuria. 638 patients with type 2 diabetes (mean age 64 ± 12 years; 40 % female) were enrolled. Visceral fat area (VFA, cm(2)) was assessed by a dual-impedance analyzer, whereby patients were divided into those with VFA < 100 (N = 341) and those with VFA ≥ 100 (N = 297). Albuminuria was measured in a single 24-h urine collection (UAE, mg/day) and brachial-ankle pulse wave velocity (ba-PWV, cm/s) was used for the assessment of arterial stiffening. Linear regression analyses were used to investigate the association of systolic blood pressure (SBP) and VFA with UAE and baPWV., Results: Patients with VFA ≥ 100 were significantly younger, had higher SBP, HbA1c, triglycerides, UAE, alanine aminotransferase, C-reactive protein and lower high-density lipoprotein and shorter duration of diabetes than those with VFA < 100. SBP was significantly and almost equivalently associated with ba-PWV both in VFA < 100 (standardized β 0.224, p = 0.001) and VFA ≥ 100 (standardized β 0.196, p = 0.004) patients in the multivariate regression analysis adjusting for covariates including age, gender, HbA1c, diabetic complications and the use of insulin and anti-hypertensive agents. By contrast, the association of SBP with UAE was stronger in patients with VFA ≥ 100 (standardized β 0.263, p = 0.001) than that in patients with VFA < 100 (standardized β 0.140, p = 0.080) in the multivariate regression model. In the whole cohort, the significant interaction between SBP and VFA on UAE (standardized β 0.172, p = 0.040) but not on ba-PWV (standardized β -0.008, p = 0.916) was observed., Conclusions: The effect of increased blood pressure on arterial stiffness is almost similar in type 2 diabetic patients with both low and high visceral adiposity, while its association with albuminuria is stronger in the latter.