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ABSTRACT: 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 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.RESULTSMultiple regression analysis demonstrated that coefficient of variation of SBP was independently associated with change in UAE (β = 0.1758; P = 0.0108). Adjusted Cox regression analyses demonstrated that coefficient of variation of SBP was associated with an increased hazard of development of albuminuria; hazard ratio was 1.143 (95% confidence interval 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.
Diabetes care 01/2013; · 8.09 Impact Factor
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ABSTRACT: 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.Hypertension Research advance online publication, 17 January 2013; doi:10.1038/hr.2012.207.
Hypertension Research 01/2013; · 2.58 Impact Factor
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ABSTRACT: 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.
Metabolism: clinical and experimental 01/2013; · 2.59 Impact Factor
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Yoshitaka Kondo,
Goji Hasegawa, Hiroshi Okada,
Takafumi Senmaru,
Michiaki Fukui,
Naoto Nakamura,
Morio Sawada,
Jo Kitawaki,
Takeshi Okanoue,
Yuki Kishimoto,
Akiko Amano,
Naoki Maruyama,
Hiroshi Obayashi,
Akihito Ishigami
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ABSTRACT: BACKGROUNDAIMS: 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 DESIGNPRINCIPAL 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.
Our data strongly suggest that SMP30 is closely associated with NAFLD pathogenesis, and might be a possible therapeutic target for NAFLD.
PLoS ONE 01/2013; 8(6):e65698. · 4.09 Impact Factor
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Takafumi Senmaru,
Masahiro Yamazaki, Hiroshi Okada,
Mai Asano,
Michiaki Fukui,
Naoto Nakamura,
Hiroshi Obayashi,
Yoshitaka Kondo,
Naoki Maruyama,
Akihito Ishigami,
Goji Hasegawa
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ABSTRACT: We recently identified senescence marker protein-30 as the lactone-hydrolyzing enzyme gluconolactonase, which is involved in vitamin C biosynthesis. In this study, we investigated the effects of vitamin C on insulin secretion from pancreatic β-cells using senescence marker protein-30/gluconolactonase knockout mice. In intraperitoneal glucose tolerance tests, vitamin C-deficient senescence marker protein-30/gluconolactonase knockout mice demonstrated impaired glucose tolerance with significantly lower blood insulin levels at 30 and 120 min post-challenge than in wild type mice (p<0.01-0.05). In contrast, vitamin C-sufficient senescence marker protein-30/gluconolactonase knockout mice demonstrated significantly higher blood glucose and lower insulin only at the 30 min post-challenge time point (p<0.05). Senescence marker protein-30/gluconolactonase knockout mice showed enhanced insulin sensitivity regardless of vitamin C status. Static incubation of islets revealed that 20 mM glucose-stimulated insulin secretion and islet ATP production were significantly decreased at 60 min only in vitamin C-deficient SMP30/GNL knockout mice relative to wild type mice (p<0.05). These results indicate that the site of vitamin C action lies between glycolysis and mitochondrial oxidative phosphorylation, while SMP30 deficiency itself impairs the distal portion of insulin secretion pathway.
Journal of Clinical Biochemistry and Nutrition 03/2012; 50(2):114-8. · 1.98 Impact Factor
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Hiroshi Okada,
Michiaki Fukui,
Muhei Tanaka,
Shinobu Inada,
Yusuke Mineoka,
Naoko Nakanishi,
Takafumi Senmaru,
Kazumi Sakabe,
Emi Ushigome,
Mai Asano,
Masahiro Yamazaki,
Goji Hasegawa,
Naoto Nakamura
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ABSTRACT: 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.
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).
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).
Not only average SBP but also variability in SBP is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.
Atherosclerosis 11/2011; 220(1):155-9. · 3.79 Impact Factor
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Michiaki Fukui,
Muhei Tanaka, Hiroshi Okada,
Hiroya Iwase,
Yusuke Mineoka,
Takafumi Senmaru,
Masayoshi Ohnishi,
Shin-Ichi Mogami,
Yoshihiro Kitagawa,
Masahiro Yamazaki,
Goji Hasegawa,
Naoto Nakamura
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ABSTRACT: 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.
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.
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.
The IIEF-5 score correlated with diabetic micro- and macroangiopathy in men with type 2 diabetes.
Journal of atherosclerosis and thrombosis 07/2011; 18(11):991-7. · 2.69 Impact Factor
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ABSTRACT: Recent studies have demonstrated that hyperinsulinemia is a risk factor for cardiovascular disease. The aim of this study was to evaluate the relationship between serum insulin level and the cardio-ankle vascular index (CAVI), which was developed as a marker of arterial stiffness. We performed a cross-sectional study of 260 consecutive and nondiabetic subjects with clinical suspicion of coronary heart disease. We measured CAVI in all subjects. A standard 75-g oral glucose tolerance test was performed, and plasma glucose and serum insulin levels were measured in venous blood collected at 0, 30, 60 and 120 min after the test. Statistical analyses were conducted for four subgroups according to the insulin area under the concentration time curve (InsAUC). Mean CAVI and InsAUC were 8.7 and 109.5 μIUml(-1)h(-1), respectively. Unadjusted analysis demonstrated that the InsAUC quartiles were significantly associated with CAVI (P<0.0001), and the lowest InsAUC quartile (P=0.001) had a lower glucose AUC. Analysis of covariance demonstrated that the lowest InsAUC quartile had the highest CAVI, and, after adjusting for several coronary risk factors, the highest InsAUC quartile had a higher CAVI than the second and third InsAUC quartiles (P<0.0001). In conclusion, the lowest InsAUC quartile was related to CAVI, although the lowest InsAUC quartile maintained glucose homeostasis in this study population. Both hyperinsulinemia and low insulin level are independently associated with CAVI.
Hypertension Research 12/2010; 34(3):336-40. · 2.58 Impact Factor
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ABSTRACT: Chromosome numbers of 42 species and 3 varieties from 24 genera of theAnnonaceae have been determined (Table 1); reports for 15 of the genera are new. Among Asian genera 2n = 14 occurs only in the specializedMezzettia, while 2n = 16 is wide-spread and also has been found inAnaxagorea with some primitive characters. 2n = 18 is reported for 11 genera, and tetraploidy (2n = 36) has been observed inPolyalthia. Therefore, an original basic number of x = 8 or x = 9 is suggested at least for the Asian genera of theAnnonaceae.—Cytotaxonomical notes on the critical speciesPolyalthia rumphii andP. affinis are given, and the new combinationNeouvaria parallelivenia (Boerl.)Okada & Ueda is proposed.
Plant Systematics and Evolution 08/1984; 144(3):165-177. · 1.34 Impact Factor
