Yusuke Mineoka

Visit-to-visit variability in systolic blood pressure is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes

OBJECTIVE Recent studies make remarks on the effect of variability in systolic blood pressure (SBP) on the development of cardiovascular disease. The aim of this study was to investigate the relationship between the variability in SBP and the degree of diabetic nephropathy and atherosclerosis in patients with type 2 diabetes. METHODS We measured SBP in 422 consecutive patients with type 2 diabetes at every visit during a year, and we calculated the coefficient of variation (CV) of SBP. Then, we evaluated relationships of variability of SBP to degree of urinary albumin excretion (UAE), which is a useful marker for cardiovascular disease as well as diabetic nephropathy, ankle-brachial index (ABI) and pulse wave velocity (PWV). RESULTS CV of SBP positively correlated with logUAE (r=0.210, P<0.0001) or PWV (r=0.409, P<0.0001), whereas CV of SBP inversely correlated with ABI (r=-0.098, P=0.0463). Multiple regression analysis demonstrated that CV of SBP independently correlated with logUAE (β=0.149, P=0.0072), PWV (β=0.337, P<0.0001) or ABI (β=-0.162, P=0.0101). CONCLUSIONS Not only average SBP but also variability in SBP is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.

Visit-to-Visit Blood Pressure Variability Is a Novel Risk Factor for the Development and Progression of Diabetic Nephropathy in Patients With Type 2 Diabetes

OBJECTIVE Recent study has suggested that not only the presence of hypertension but also the variability in systolic blood pressure (SBP) are risk factors for vascular disease and organ damage. The aim of this study was to investigate the relationship between visit-to-visit variability in SBP and change in urinary albumin excretion (UAE) or development of albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We measured SBP in 354 consecutive patients at every visit during 1 year and calculated the coefficient of variation (CV) of SBP. We performed a follow-up study to assess change in UAE or development of albuminuria, the mean interval of which was 3.76 ± 0.71 years. Then, we evaluated relationships of variability of SBP to diabetic nephropathy using multiple regression analysis and multiple Cox regression model. RESULTS Multiple regression analysis demonstrated that CV of SBP was independently associated with change in UAE (β = 0.1758; P = 0.0108). Adjusted Cox regression analyses demonstrated that CV of SBP was associated with an increased hazard of development of albuminuria; hazard ratio was 1.143 (95% CI 1.008–1.302). CONCLUSIONS Visit-to-visit variability in SBP could be a novel risk factor for the development and progression of diabetic nephropathy in patients with type 2 diabetes.

Testosterone deficiency induces markedly decreased serum triglycerides, increased small dense LDL, and hepatic steatosis mediated by dysregulation of lipid assembly and secretion in mice fed a high-fat diet

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 4weeks 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.

Visit-to-visit variability in systolic blood pressure is a novel risk factor for the progression of coronary artery calcification

Recent studies have suggested that variability in the systolic blood pressure (SBP) is a risk factor for cardiovascular disease (CVD). The aim of this study was to investigate the relationship between variability in the SBP and the progression of coronary artery calcification (CAC), which is a useful marker for CVD. We measured SBP in 164 consecutive patients at every visit over the course of a year and calculated the coefficient of variation and s.d. of the SBP. We performed a follow-up study using multislice computed tomography to assess the progression of the CAC score, the mean interval of which was 3.93±1.36 years. We then evaluated the relationship between variability in the SBP and progression of the CAC score. The coefficient of variation for the SBP correlated positively with the progression of the CAC score (r=0.4382, P<0.0001). Multiple regression analysis demonstrated that the coefficient of variation of the SBP (β=0.3826, P<0.0001) was independently associated with the progression of the CAC score. The visit-to-visit variability in SBP could be a novel risk factor for the progression of CAC.

A difference in systolic blood pressure between arms and between lower limbs is a novel risk marker for diabetic nephropathy in patients with type 2 diabetes.

Recent studies have demonstrated that a difference in systolic blood pressure (SBP) between arms is associated with both vascular disease and mortality. The aim of this study was to investigate the relationship between a difference in SBP between arms and between lower limbs and the degree of albuminuria, which is an established marker for cardiovascular disease and diabetic nephropathy in patients with Type 2 diabetes. We measured blood pressure in the arms and lower limbs of 314 consecutive patients with Type 2 diabetes, and we calculated a difference in SBP between arms and between lower limbs. We then evaluated the relationship of the difference in SBP between arms and between lower limbs to the degree of urinary albumin excretion (UAE). The average difference in SBP between arms and between lower limbs was 3.52±3.94 and 9.66±14.1 mm Hg, respectively. Multiple regression analyses demonstrated that a difference in SBP between arms (β=0.172, P=0.0239) and between lower limbs (β=0.238, P=0.0033) independently correlated with the logarithm of the UAE. Multiple logistic regression analyses showed that a difference in SBP of ⩾10 mm Hg between arms (odds ratio 12.23 (95% CI 1.130–132.35), P<0.0393) and a difference in SBP of ⩾15 mm Hg between lower limbs (odds ratio 4.291 (95% CI 1.403–13.123), P<0.0106) correlated with the risk of albuminuria. A difference in SBP between arms and between lower limbs, therefore, could be a novel risk marker for diabetic nephropathy in patients with Type 2 diabetes.

Morning pulse pressure is associated more strongly with elevated albuminuria than systolic blood pressure in patients with type 2 diabetes mellitus: Post hoc analysis of a cross-sectional multicenter study

AIMS Recently, focus has been directed toward pulse pressure as a potentially independent risk factor for micro- and macrovascular disease. This study was designed to examine the relationship between pulse pressure taken at home and elevated albuminuria in patients with type 2 diabetes. METHODS This study is a post hoc analysis of a cross-sectional multicenter study. Home blood pressure measurements were performed for 14 consecutive days in 858 patients with type 2 diabetes. We investigated the relationship between systolic blood pressure or pulse pressure in the morning or in the evening and urinary albumin excretion using univariate and multivariate analyses. Furthermore, we measured area under the receiver-operating characteristic curve (AUC) to compare the ability to identify elevated albuminuria, defined as urinary albumin excretion equal to or more than 30 mg/g creatinine, of systolic blood pressure or pulse pressure. RESULTS Morning systolic blood pressure (β=0.339, P<0.001) and morning pulse pressure (β=0.378, P<0.001) were significantly associated with logarithm of urinary albumin excretion independent of other potential co-factors. AUC for elevated albuminuria in morning systolic blood pressure and morning pulse pressure were 0.668 (0.632-0.705; P<0.001) and 0.694 (0.659-0.730; P<0.001), respectively. AUC of morning pulse pressure was significantly greater than that of morning systolic blood pressure (P=0.040). CONCLUSIONS Our findings implicate that morning pulse pressure is associated with elevated albuminuria in patients with type 2 diabetes, which suggests that lowering morning pulse pressure could prevent the development and progression of diabetic nephropathy.

Relationship between limited joint mobility of the hand and diabetic foot risk in patients with type 2 diabetes.

Foot ulceration is a serious problem for patients with type 2 diabetes (T2D), and the early detection of risks for this condition is important to prevent complications. The present cross‐sectional study in T2D patients determined the relationship between limited joint mobility (LJM) of the hand and diabetic foot risk classified using the criteria of the International Working Group on the Diabetic Foot (IWGDF).

E-012 UNCONTROLLED HOME BLOOD PRESSURE IN THE MORNING IS ASSOCIATED WITH NEPHROPATHY IN JAPANESE PATIENTS WITH TYPE 2 DIABETES

Backgrounds Nephropathy in diabetic patients is the leading cause of end-stage renal failure. The significance of home blood pressure measurement has been widely recognized. In this study, we have investigated the state of blood pressure control level by measuring clinic and home blood pressure, and investigated the relationship between blood pressure control and nephropathy in Japanese patients with type 2 diabetes. Methods We measured clinic and home blood pressure in 923 patients with type 2 diabetes. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH). Results Of all patients, 13.9%, 12.6%, 13.3% and 60.2% were identified as having CH, WCH, MH and SH, respectively. The average number of drugs prescribed was 1.8. Degree of urinary albumin excretion and the prevalence of nephropathy in diabetic patients were higher in MH and SH groups than those in CH group. The majority of patients had poor blood pressure control, regardless of ongoing conventional antihypertensive therapy, and diabetic patients with MH and SH were associated with nephropathy in diabetic patients. Conclusions More aggressive antihypertensive treatment is recommended to prevent nephropathy in patients with type 2 diabetes.

E-009 THE COEFFICIENT VARIATION OF HOME BLOOD PRESSURE IS A NOVEL FACTOR ASSOCIATED WITH MACROALBUMINURIA IN TYPE 2 DIABETES MELLITUS

Backgrounds Home blood pressure (HBP) measurement has been found to have a stronger relationship with target organ damage. Recent studies have explored the association between variabilities of BP and target organ damage. Therefore, we investigated the relationship between day-by-day variabilities of HBP and diabetic nephropathy in Japanese patients with type 2 diabetes. Methods We compared the coefficient variation (CV) of HBP in 858 Japanese patients withand withoutmacroalbuminuria. Next, we analyzed the relationship between logarithm of urinary albumin excretion and the CV of HBP using linear regression analysis. Then, we evaluated the association of the CV of HBP with macroalbuminuria using logistic regression analysis. Results The CV of morning systolic blood pressure in patients with macroalbuminuria was significantly greater than that without (8.08 ± 3.35% vs. 7.19 ± 2.25%, p < 0.05). Multivariate linear regression analyses indicated that CV of morning systolic (P < 0.05) was the independent explanatory variables for logarithm of urinary albumin excretion. Multivariate logistic regression analysis demonstrated that the odds ratio of the CV of morning systolic blood pressure for macroalbuminuria was 1.35 (P < 0.05). Conclusions The CV of HBP correlated with macroalbuminuria independent of the known risk factors in Japanese patients with type 2 diabetes.

B-008 N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE COULD BE A MARKER OF SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH TYPE 2 DIABETES

Background Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in patients 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. Furthermore, alterations in vascular structure and function are also recognized increasingly as significant independent predictors of adverse cardiovascularoutcomes. In this study, we investigated the relationships between NT-proBNP and markers of subclinical atherosclerosis in patients with type 2 diabetes. Methods Relationships of NT-proBNP to pulse wave velocity (PWV) or ankle-brachial index (ABI) as wellas to major metabolic risk parameters, including body mass index, blood pressure, serum lipid concentration, serum uric acid concentration,and glycemic control (hemoglobinA1c), age, hemoglobin, serum creatinine concentration, severity of diabetic nephropathy orretinopathy, current treatment of diabetes, smoking status, and presence of CVD were investigated in 323 consecutive patients with type 2 diabetes. Results 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 (&bgr; = 0.267, p < 0.0001), systolic blood pressure (&bgr; = 0.249, p < 0.0001), uric acid (&bgr; = 0.121, p = 0.0383), creatinine (&bgr; = −0.139, p = 0.0239) and log (NT-proBNP) (&bgr; = 0.173, p = 0.0043) were independent determinants of PWV and that log triglyceride (&bgr; = −0.130, p = 0.0390) andlog (NT-proBNP) (&bgr; = −0.153 p = 0.0256) were independent determinants of ABI. Conclusions NT-proBNP was associated with PWV and ABI in patients with type 2 diabetes. NT-proBNP could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.