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Objective Previous studies have implicated PR interval (iPR) and QRS duration (dQRS) obtained by electrocardiography in independent predictors of cardiovascular disease, which often precedes renal dysfunction. The aim of this study was to examine whether iPR or dQRS could be a predictor of renal function decline in a community-based cohort. Methods We enrolled 1149 healthy subjects, and retrospectively evaluated the relationships between iPR or dQRS and renal function decline, observation period of which was 3 years, and assessed whether iPR or dQRS could predict renal function decline. Results The iPR ( r = −0.102, p = 0.0006) or dQRS ( r = −0.097, p = 0.0010) was negatively associated with a rate of decline in estimated glomerular filtration rate (eGFR). Multiple regression analyses revealed that iPR ( β = −0.095, p = 0.0023) or dQRS ( β = −0.069, p = 0.0351) was an independent determinant of the rate of decline in eGFR after adjustment for covariates. Logistic regression analyses demonstrated that the longest iPR (odds ratios (OR), 2.03; 95% confidence intervals (CI), 1.49 to 2.76; p p = 0.0043) tertile showed an increased OR for prevalence of the rate of decline in eGFR ≤ 1 ml/min/1.73 m 2 /year compared to the shortest iPR or dQRS tertile after adjustment for covariates. Conclusion The iPR and dQRS could be independent predictors of renal function decline in healthy subjects.

Aims/Introduction: Eicosapentaenoic acid (EPA) stimulates glucagon‐like peptide‐1 (GLP‐1) secretion in mice. We investigated the relationship between serum EPA concentrations and the efficacy of dipeptidyl‐peptidase IV (DPP‐4) inhibitor in patients with type 2 diabetes. Materials and Methods: Serum EPA concentrations were measured in 62 consecutive patients with type 2 diabetes who were newly given DPP‐4 inhibitor as a monotherapy or as an add‐on therapy to oral hypoglycemic agents. The dosage of oral hypoglycemic agents was maintained during the observation period. After 24 weeks of treatment with DPP‐4 inhibitor, we evaluated the relationships between a decrease in hemoglobin A1c from baseline and serum EPA concentrations, as well as age, sex, body mass index (BMI), hemoglobin A1c at baseline and usage of antidiabetic concomitant drugs. Results: Hemoglobin A1c was significantly decreased from 8.1 ± 1.1% to 7.2 ± 1.0% by DPP‐4 inhibitor. A decrease in hemoglobin A1c correlated with BMI (r = −0.396, P = 0.0013), age (r = 0.275, P = 0.0032), hemoglobin A1c at baseline (r = 0.490, P

Several studies have shown that prolongation of QT interval predicts the risks of all-cause and cardiovascular mortality. Moreover, a close association was reported between prolongations of QT interval and pulse wave velocity (PWV) in general population without preexisting cardiovascular disease. The aim of this study was to evaluate the relationship between QT interval and PWV in patients with type 2 diabetes without preexisting cardiovascular disease. In a cross-sectional study of 251 Japanese patients with type 2 diabetes, we examined the correlation of the heart rate-corrected QT interval duration (QTc) with PWV or other various parameters, including age, duration of diabetes, body mass index, systolic blood pressure, hemoglobin A1c, serum cholesterol, creatinine, uric acid, potassium, severity of diabetic nephropathy or retinopathy and current treatment of diabetes. The QTc correlated positively with PWV (r=0.268, p

Objective The aim of this study was to investigate whether serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), which mediates initiation and progression of atherosclerosis in endothelial cells, could be a novel marker for peripheral artery disease (PAD) in patients with type 2 diabetes. Methods We evaluated relationships of serum sLOX-1 to ankle–brachial index (ABI) and examined the association of serum sLOX-1 with PAD in 410 patients with type 2 diabetes. Results Serum sLOX-1 was inversely correlated with ABI (r = − 0.197, P

Objective Although low serum testosterone (T) is associated with metabolic disorders, the mechanism of this association is unclear. The objective of the present study was to investigate the combined effects of T deficiency and a high-fat diet (HFD) on hepatic lipid homeostasis in mice. Materials/Methods Orchiectomized (ORX) mice and sham-operated (SHAM) mice were randomly divided into five groups: SHAM mice fed a standard diet (SD), SHAM mice fed HFD, ORX mice fed SD, ORX mice fed HFD, and ORX mice fed HFD with T supplementation. After 4 weeks of treatment, we investigated the synthesis and secretion of lipids in the liver and detailed serum lipoprotein profiles in each group. Results ORX mice fed HFD showed increased hepatic steatosis, markedly decreased serum triglyceride (TG) and TG-VLDL content, and increased serum very small-LDL content. Gene expression analysis revealed that ORX mice fed HFD showed significantly decreased expression of microsomal triglyceride transfer protein, lipin-1, peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ coactivator 1-α, and significantly increased sterol regulatory element-binding protein-1, diacylglycerol acyltransferase-2 and fatty acid synthase. Reduction of hepatic AMPK phosphorylation was observed in ORX mice fed HFD. These perturbations in ORX mice fed HFD were normalized to the levels of SHAM mice fed HFD by T supplementation. Conclusion T deficiency is associated with failure of lipid homeostasis mediated by altered expression of genes involved in hepatic assembly and secretion of lipids.

Both high and low salt intakes have been reported to be associated with an increased risk of cardiovascular events. The aim of this study was to investigate the relationship between daily salt intake and albuminuria, a marker of diabetic nephropathy and cardiovascular disease, in patients with type 2 diabetes. We classified 270 patients with type 2 diabetes, who were not receiving antihypertensive medication into four groups according to their daily salt intake (8, 8-10, 10-12 and12 g per day). We investigated the relationship between daily salt intake and the logarithm of urinary albumin excretion (UAE). A multivariate linear regression analysis was used to evaluate whether daily salt intake independently correlated with the logarithm of UAE. In addition, we assessed the contribution of the variables, including age, sex, duration of diabetes, body mass index, systolic blood pressure, hemoglobin A(1C), low-density lipoprotein cholesterol, triglycerides, serum creatinine, alcohol intake, smoking status and square of (daily salt intake-10) on albuminuria, defined as a UAE30 mg g(-1) of creatinine, using a multiple logistic regression analysis. The logarithm of the UAE was lowest in the third quartile of daily salt intake. The multivariate linear regression analysis demonstrated that the logarithm of the UAE was significantly correlated with the quadratic term of daily salt intake centered at 10 g per day (β=0.170, P=0.008). The multivariate logistic regression analysis demonstrated that the odds ratio (95% confidence interval) of albuminuria was 3.996 (1.295-12.327; P=0.016) in patients whose daily salt intake was less than 8 g per day compared with patients whose daily salt intake was 10-12 g per day. In conclusion, low daily salt intake was correlated with albuminuria in patients with type 2 diabetes, who were not receiving antihypertensive medication.

Aim: There is increasing evidence of a strong link between erectile dysfunction and atherosclerosis. The aim of this study was to evaluate the relationships between the 5-item version of the International Index of Erectile Function (IIEF-5) score and albuminuria as well as markers of subclinical atherosclerosis in men with type 2 diabetes.Methods: We evaluated the relationship of the IIEF-5 score with the degree of urinary albumin excretion, pulse wave velocity, ankle-brachial index or toe-brachial index (n = 125) as well as with major cardiovascular risk factors, including age, blood pressure, serum lipid concentration and hemoglobin A1c, body mass index, severity of diabetic retinopathy or nephropathy, and presence of neuropathy or cardiovascular disease in 197 men with type 2 diabetes.Results: The mean IIEF-5 score was 10.0 ± 6.9. The IIEF-5 score was inversely correlated with age or duration of diabetes, and positively correlated with diastolic blood pressure or serum total cholesterol concentration. The IIEF-5 score inversely correlated with log (urinary albumin excretion; r =−0.190, p =0.0078) or pulse wave velocity (r =−0.255, p =0.0003), and positively correlated with the toe-brachial index (r = 0.379, p < 0.0001). The IIEF-5 score was lower in patients with proliferative diabetic retinopathy than in patients with no diabetic retinopathy, and in patients with macroalbuminuria than in patients with normoalbuminuria. The IIEF-5 score was also lower in patients with neuropathy or cardiovascular disease than without.Conclusions: The IIEF-5 score correlated with diabetic micro- and macroangiopathy in men with type 2 diabetes.

N-terminal pro-brain natriuretic peptide (NT-proBNP), which is a useful biomarker of chronic heart failure, has been shown to be a strong predictor of cardiovascular mortality. The aim of this study was to evaluate the relationships between NT-proBNP and markers of subclinical atherosclerosis in patients with type 2 diabetes. Relationships of NT-proBNP to pulse wave velocity (PWV) or ankle-brachial index (ABI) as well as to various parameters, including body mass index, blood pressure, serum lipid concentration, serum uric acid concentration, and glycemic control (hemoglobin A1c), age, hemoglobin, serum creatinine concentration, severity of diabetic nephropathy or retinopathy, current treatment of diabetes, cardiothoracic ratio on chest radiograph, presence of left ventricular hypertrophy and/or ST-T changes evaluated by electrocardiograph, smoking status and presence of cardiovascular disease were investigated in 323 consecutive patients with type 2 diabetes. Log (NT-proBNP) correlated positively with PWV (r = 0.283, p < 0.0001) and correlated negatively with ABI (r = −0.144, p = 0.0094). Multiple regression analysis demonstrated that age (β = 0.200, p = 0.0033), systolic blood pressure (β = 0.246, p < 0.0001), total cholesterol (β = −0.135, p = 0.0326), uric acid (β = 0.133, p = 0.0462), creatinine (β = −0.184, p = 0.0122), smoking status (β = −0.129, p = 0.0499) and log (NT-proBNP) (β = 0.177, p = 0.0149) were independently correlated with PWV and that systolic blood pressure (β = −0.145, p = 0.0310), log triglyceride (β = −0.151, p = 0.0397) and log (NT-proBNP) (β = −0.207, p = 0.0094) were independently correlated with ABI. In conclusion, NT-proBNP could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.

We investigated the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia simultaneously in a community-based observational cohort study ( n = 4304). When hypertension or dyslipidemia was present at baseline, hazard ratio (95% CI) of developing diabetes mellitus at year 5 is 3.014 (2.131–4.264) or 2.112 (1.520–2.936), respectively.

Background and objectives: Patients with allergic disorders such as allergic rhinitis or asthma have been reported to be at increased risk for atherosclerosis. In this study, we evaluated the relationships between peripheral eosinophil count and degree of albumin excretion rate, which is a useful marker of cardiovascular mortality as well as diabetic nephropathy in patients with type 2 diabetes. Design, setting, participants, & measurements: We evaluated relationships of peripheral eosinophil count to degree of albumin excretion rate as well as to major cardiovascular risk factors, including age, BP, serum lipid concentration, and glycemic control (glycosylated hemoglobin); body mass index; current treatment for diabetes; smoking status; and presence of cardiovascular disease in 783 patients (416 men and 367 women) with type 2 diabetes. Results: Log(eosinophil count) was positively associated with systolic BP (r = 0.124, P = 0.0108), serum triglyceride concentration (r = 0.108, P = 0.0284), and log(albumin excretion rate) (r = 0.301, P < 0.0001) in men; however, no association was found between log(eosinophil count) and log(albumin excretion rate) (r = 0.085, P = 0.1050) in women. Multivariate linear regression analysis demonstrated that log(eosinophil count) (β = 0.260, P < 0.0001), duration of diabetes (β = 0.203, P = 0.0003), glycosylated hemoglobin (β = 0.117, P = 0.0238), systolic BP (β = 0.205, P = 0.0001), and serum triglyceride concentration (β = 0.162, P = 0.0038) were independent determinants of log(albumin excretion rate) in men. Conclusions: Allergic disorders may be associated with microalbuminuria in men with type 2 diabetes.

Background Hemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages. Methods Continuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide. Results Nine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment. Conclusion These results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress.

BACKGROUND/AIMS: The senescence marker protein-30 (SMP30) is a 34 kDa protein originally identified in rat liver that shows decreased levels with age. Several functional studies using SMP30 knockout (Smp30(Y/-) ) mice established that SMP30 functions as an antioxidant and protects against apoptosis. To address the potential role of SMP30 in nonalcoholic fatty liver disease (NAFLD) pathogenesis, we established Smp30(Y/-) mice on a Lepr(db/db) background (Lepr(db/db)Smp30(Y/-) mice). RESEARCH DESIGN/PRINCIPAL FINDINGS: Male Lepr(db/db)Smp30(Y/-) mice were fed a standard diet (340 kcal/100 g, fat 5.6%) for 16 weeks whereupon the lipid/lipoprotein profiles, hepatic expression of genes related to lipid metabolism and endoplasmic reticulum stress markers were analyzed by HPLC, quantitative RT-PCR and western blotting, respectively. Changes in the liver at a histological level were also investigated. The amount of SMP30 mRNA and protein in livers was decreased in Lepr(db/db)Smp30(Y/+) mice compared with Lepr(db/+)Smp30(Y/+) mice. Compared with Lepr(db/db)Smp30(Y/+) mice, 24 week old Lepr(db/db)Smp30(Y/-) mice showed: i) increased small dense LDL-cho and decreased HDL-cho levels; ii) fatty liver accompanied by numerous inflammatory cells and increased oxidative stress; iii) decreased mRNA expression of genes involved in fatty acid oxidation (PPARα) and lipoprotein uptake (LDLR and VLDLR) but increased CD36 levels; and iv) increased endoplasmic reticulum stress. CONCLUSION: Our data strongly suggest that SMP30 is closely associated with NAFLD pathogenesis, and might be a possible therapeutic target for NAFLD.