Homocysteine levels are associated with hippocampus volume in type 2 diabetic patients.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are associated with cognitive dysfunction, in which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that elevated tHcy levels are correlated with hippocampus volume and insulin resistance in nondementia patients with type 2 diabetes. MATERIALS AND METHODS: The study included 43 nondementia patients with type 2 diabetes, who were divided into two groups: a high tHcy group (age: 65 ± 8 years, mean ± standard deviation, n = 16) and a normal tHcy group (64 ± 9 years, n = 27). Hippocampus volume was quantified with a computer-assisted analysis using a magnetic resonance imaging (MRI) voxel-based specific regional analysis system developed for the study of Alzheimer's disease (VSRAD), which yields a Z-score as the end point for the assessment of hippocampal volume. Results The Z-score was higher in the high tHcy group compared to the normal tHcy group (P < 0·0001). The fasting plasma glucose (P < 0·01) and insulin (P < 0·0001) concentrations and the homoeostasis model assessment (HOMA) index (P < 0·0001) were higher in the high tHcy group than in the normal tHcy group. Multiple regression analysis showed that the main factors that influenced tHcy levels may be the Z-score and the HOMA index. CONCLUSIONS: Our results indicate that the elevated levels of tHcy in Japanese nondementia patients with type 2 diabetes are characterised by hippocampal atrophy and insulin resistance and that the Z-score and HOMA index may be the primary factors that influence tHcy levels.

Abdominal visceral fat accumulation is associated with hippocampus volume in non-dementia patients with type 2 diabetes mellitus.

Obesity is associated with cognitive dysfunction, for which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that an elevated level of visceral fat accumulation (VFA) correlates with hippocampus volume and insulin resistance in non-dementia patients with type 2 diabetes. Subjects included 48 non-dementia patients with type 2 diabetes, who were divided into two groups, high VFA group (mean+/-standard deviation: age=65+/-6 years, n=30) and normal VFA group (65+/-5 years, n=18). Hippocampus volume has been quantitated with computer-assisted analysis using a magnetic resonance imaging (MRI) voxel-based specific regional analysis system developed for the study of Alzheimer's disease (VSRAD), which yields a Z-score as the end point for assessment of hippocampal volume. The Z-score was higher in the high VFA group than in the normal VFA group (p<0.0001). The fasting plasma glucose (p<0.05) and insulin concentrations (p<0.0001) and the homeostasis model assessment (HOMA) index (p<0.0001) were higher in the high VFA group than in the normal VFA group. Multiple regression analysis showed that VFA levels were independently predicted by Z-score and HOMA index. Our results indicate that the elevated level of VFA in Japanese non-dementia patients with type 2 diabetes is characterized by increased hippocampus volume and insulin resistance, and that the Z-score and HOMA index are independent predictors of VFA.

Hepatocyte growth factor is a significant risk factor for white matter lesions in Japanese type 2 diabetic patients.

BACKGROUND: The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Elevated hepatocyte growth factor (HGF) levels are associated with a high mortality rate in type 2 diabetic patients. The preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with HGF and insulin resistance in type 2 diabetic patients not receiving insulin treatment. MATERIAL AND METHODS: Based on brain magnetic resonance imaging, 92 type 2 diabetic patients were divided into two groups: WML-positive group (age 60 +/- 5 years, mean +/- SD, n = 35) and WML-negative group (age 59 +/- 6 years, mean +/- SD, n = 57. The level of blood glucose was assessed by fasting plasma glucose, fasting immunoreactive insulin, homeostasis model assessment (HOMA) index and haemoglobin A1c (HbA1c). RESULTS: The body mass index was higher in the WML-positive group than that in the WML-negative group (P < 0.005). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < 0.01 and P < 0.0001 respectively). Fasting plasma glucose (P < 0.0001), insulin concentrations (P < 0.0001), HOMA index (P < 0.0001) and HGF (< 0.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high HGF and insulin resistance (P < 0.0001 and P < 0.0001 respectively). CONCLUSION: The results of this preliminary study indicate that the presence of WML was associated with the high HGF and insulin resistance in Japanese patients with type 2 diabetes mellitus.

Baroreflex sensitivity predicts cardiovascular events in patients with type 2 diabetes mellitus without structural heart disease.

BACKGROUND: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM). However, the relationship between cardiovascular autonomic neuropathy and the incidence of cardiovascular events has been poorly investigated in type 2 DM. The present study aimed to assess the long-term cardiovascular predictive value of baroreflex sensitivity (BRS) in Japanese patients with type 2 DM without structural heart disease. METHODS AND RESULTS: BRS was evaluated using the phenylephrine method in 210 patients with type 2 DM who did not have structural heart disease or other severe complications. BRS was considered depressed if <6 ms/mmHg. Accurate follow-up information for 3-10 years (mean 4.7 years) was obtained in 184 patients (90 females, 94 males; mean age 58+/-12 years). The initial onset of a major adverse cardiovascular event (MACE) was investigated. During follow-up, 19 patients presented with a MACE (4 cardiovascular deaths, 3 nonfatal myocardial infarctions, 4 coronary revascularizations, 5 strokes, 2 congestive heart failures). Cox proportional hazards regression analysis revealed that depressed BRS was independently associated with the incidence of MACE (hazard ratio 1.93, 95% confidence interval 1.09-3.82, P=0.0236). CONCLUSIONS: Depressed BRS at baseline has long-term cardiovascular predictive value in Japanese patients with type 2 DM without structural heart disease.

Visceral Fat Accumulation Is Associated with Asthma in Patients with Type 2 Diabetes.

OBJECTIVE: The number of patients with type 2 diabetes has increased in Japan, and type 2 diabetes has attracted attention as a risk factor for asthma. However, the risk factors for the development of asthma in patients with type 2 diabetes have not been determined. This study was performed to clarify whether visceral fat accumulation (VFA) and insulin resistance are risk factors for the development of asthma in patients with type 2 diabetes. MATERIALS AND METHODS: A cross-sectional study was conducted. The study group comprised 15 patients with type 2 diabetes with asthma, and the control group comprised 145 patients with type 2 diabetes without asthma. Their fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. Their glucose status was assessed by measuring the fasting plasma glucose (FPG) concentration, fasting immunoreactive insulin concentration, homeostasis model assessment (HOMA) index, and hemoglobin A1c concentration. RESULTS: Among patients with type 2 diabetes, VFA was significantly greater in patients with asthma than those without asthma (P < 0.0001). The FPG concentration, fasting immunoreactive insulin concentration, and HOMA index were higher in patients with asthma than those without asthma (P < 0.05, P < 0.0001, and P < 0.0001, respectively). Multiple logistic regression analysis showed that VFA and the HOMA index were significantly associated with asthma in patients with type 2 diabetes (odds ratio, 1.78; 95% confidence interval, 1.31-3.89; P = 0.0115 and odds ratio, 3.65; 95% confidence interval, 1.37-7.85; P = 0.0078, respectively). CONCLUSIONS: Our data suggest that VFA and insulin resistance are associated with the development of asthma in patients with type 2 diabetes.

Correlations of visceral fat accumulation and atherosclerosis in Japanese patients with type 2 diabetes mellitus.

We tested the hypothesis that increased abdominal visceral fat accumulation (VFA) is associated with insulin resistance and aortic stiffness in patients with type 2 diabetes mellitus not receiving insulin treatment. The study consisted of 22 Japanese patients with type 2 diabetes mellitus and high VFA (> or =100 cm(2); age, 61 +/- 7 years; high VFA group) and a control group of 18 age-matched patients with normal VFA (<100 cm(2); age, 60 +/- 8 years; normal VFA group). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. The BaPWV was used as an index of atherosclerosis. The body mass index values (P < .05), waist circumferences (P < .0005), and waist-to-hip ratios (P < .05) were larger in the high VFA group than in the normal VFA group. The BaPWV was higher in the high VFA group than in the normal VFA group (P < .0001). Fasting plasma glucose (P < .05), insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .001) were higher in the high VFA group than in the normal VFA group. Multiple regression analysis showed that the VFA level was independently predicted by BaPWV and the HOMA index. Our results indicate that the elevation of VFA in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance and that BaPWV and the HOMA index are independent predictors of VFA.

High-sensitivity C-reactive protein level is a significant risk factor for silent cerebral infarction in patients on hemodialysis.

In patients with chronic renal failure on hemodialysis (HD), silent cerebral infarctions (SCIs) are associated with high mortality. The levels of high-sensitivity C-reactive protein (HSCRP), a marker of inflammation and atherosclerosis, elevate with increasing renal dysfunction. We tested the hypothesis that increased HSCRP levels correlate with the occurrence of SCI in HD patients. By brain magnetic resonance imaging findings, we divided 54 patients undergoing HD into a with-SCI group (61 +/- 8 years, n = 30) and a without-SCI group (60 +/- 7 years, n = 24). We compared sex, body mass index, metabolic profiles, HSCRP levels, and smoking habits in Japanese patients on HD with and without SCI. We made the following observations: (1) The number of patients with diabetes or hypertension did not differ between the 2 groups. (2) The levels of HSCRP were higher in the with-SCI group in comparison with the without-SCI group (P < .0001). (3) The proportion of smokers was higher in the with-SCI group than in the without-SCI group (P < .05). (4) Plasma levels of high-density lipoprotein cholesterol were lower, whereas uric acid was higher, in the with-SCI group than in the without-SCI group (P < .05 and P < .0001, respectively). (5) Multivariate logistic analysis identified HSCRP levels as being significantly associated with the presence of SCI (odds ratio, 1.61; 95% confidence interval, 1.17-2.85; P < .001). This study indicates that patients in chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI and that HSCRP is significantly associated with the presence of SCI in HD patients.

Postchallenge plasma glucose and glycemic spikes are associated with pulse pressure in patients with impaired glucose tolerance and essential hypertension.

Elevated pulse pressure (PP) is associated with an increased risk of cardiovascular events. We examined whether PP is associated with post-challenge hyperglycemia in Japanese patients with essential hypertension and impaired glucose tolerance (IGT). In a total of 70 untreated essential hypertensive patients (age: 57+/-4 years, mean+/-SD; males=35, females=35), 24-h ambulatory blood pressure (ABP) monitoring, 75 g oral glucose tolerance testing (OGTT), metabolic analysis and echocardiography were performed. Patients were categorized into a high PP group (PP>or=60 mmHg, n=33) or a normal PP group (PP<60 mmHg, n=37). In all patients, 24-h systolic ABP, daytime systolic ABP, nighttime systolic ABP, and nighttime heart rate were significantly higher in the high PP group. Additionally, fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index, left ventricular mass index (LVMI) were also elevated in the high PP group. Finally, the high PP group exhibited impaired insulin secretion, increased post-challenge glucose concentrations and greater glucose spikes (PGS) during 75 g OGTT. Of the parameters measured, 24-h PP correlated positively with age, triglyceride, uric acid, F-IRI, HOMA index, 1-h postload glucose and insulin, 2-h postload glucose and insulin, PGS60, PGS120, PGSmax, LVMI, and deceleration time but correlated negatively with HDL-cholesterol and E/A ratio. Multiple regression analysis revealed that PP level was independently predicted by age, LVMI, and PGS120. Our results show that age, LVMI, and PGS120 are significantly associated with high PP in Japanese patients with IGT and essential hypertension.

Predictors for prehypertension in patients with impaired glucose tolerance.

Prehypertension (PHT) is associated with increased risk of cardiovascular disease and progression to hypertension. Insulin resistance and hyperinsulinemia have been reported among patients with hypertension. In addition, impaired glucose tolerance (IGT) is a strong predictor of not only of type 2 diabetes but also of cardiovascular disease. However, little is known about the impact of insulin resistance on recently defined categories of hypertension and IGT. The aim of this study was to examine associations of surrogate makers of insulin resistance with PHT and IGT. In a total of 102 IGT patients with normotension and PHT (age: 58+/-5 years; mean+/-SD), blood pressure measurement, 75 g oral glucose tolerance testing (OGTT), metabolic analysis and echocardiography were performed. Body mass index was higher in the PHT group than in the normotension group (p<0.05). The fasting immnunoreactive insulin (F-IRI) (p<0.0001), homeostasis model assessment (HOMA) index (p<0.0001), 30 min postload glucose (p<0.05), 60 min postload glucose (p<0.05), 120 min postload glucose (p<0.01), 120 min postload insulin (p<0.0001) and left ventricular mass index (LVMI) (p<0.0005) were higher in the PHT group than in the normotension group. Multivariate logistic analysis revealed that the presence of PHT was independently predicted by F-IRI. Our findings indicate that the presence of PHT was associated with hyperinsulinemia and that the F-IRI was an independent predictor of PHT in these Japanese patients with IGT.

Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients.

BACKGROUND: The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. MATERIAL AND METHODS: The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis. RESULTS: The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index. CONCLUSIONS: Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.

Correlations between homocysteine levels and atherosclerosis in Japanese type 2 diabetic patients.

Elevated total plasma homocysteine (tHcy) level and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that tHcy correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 40 Japanese patients with type 2 diabetes mellitus and high tHcy levels (mean age +/- SD, 57 +/- 7 years) and a control group of 45 age-matched patients with normal tHcy levels (mean age +/- SD, 57 +/- 6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by an automatic oscillometric method. Brachial-ankle pulse wave velocity was used as an index of atherosclerosis. Body mass index values (P < .05), waist circumferences (P < .05), and the waist-to-hip ratios (P < .05) were larger in the high-tHcy group than in the normal-tHcy group. The BaPWV was higher in the high-tHcy group than in the normal-tHcy group (P < .0001). Fasting plasma glucose (P < .005) and insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .0001) were higher in the high-tHcy group than in the normal-tHcy group. Multiple regression analysis showed that tHcy levels were independently predicted by BaPWV and the HOMA index. In conclusion, our results indicate that the elevated level of tHcy in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and the HOMA index are independent predictors of tHcy.

Smoking is associated with urinary albumin excretion: an evaluation of premenopausal patients with type 2 diabetes mellitus.

Cigarette smoking and an increase in urinary albumin excretion are associated with high mortality in patients with type 2 diabetes mellitus. We tested the hypothesis that the presence of a smoking habit correlates with increased urinary albumin excretion in premenopausal Japanese women with type 2 diabetes mellitus. The study consisted of 20 premenopausal Japanese patients with type 2 diabetes mellitus in the current-smokers group (age, 45 +/- 4 years, mean +/- SD). The control group consisted of 35 age-matched never-smoker patients (age, 45 +/- 5 years). Serum triglyceride levels were higher and high-density lipoprotein cholesterol levels were lower in the current-smokers group than in the never-smokers group (P < .05 and P < .01, respectively). Furthermore, fasting plasma insulin concentrations and the homeostasis model assessment index were higher in the current-smokers group than in the never-smokers group (P < .005 and P < .001, respectively). Urinary albumin excretion also was higher in the current-smokers group than in the never-smokers group (P < .0001). Multivariate logistic analysis revealed that urinary albumin excretion is independently associated with current smoking in Japanese premenopausal with type 2 diabetes mellitus (odds ratio, 1.79; 95% confidence interval, 1.08-3.87; P < .01). The results of this study show that current smoking is associated with an increased level of urinary albumin excretion, suggesting that smoking was a risk factor in the development of increased urinary albumin excretion in these patients.

Hypoadiponectinemia in type 2 diabetes mellitus in men is associated with sympathetic overactivity as evaluated by cardiac 123I-metaiodobenzylguanidine scintigraphy.

Hypoadiponectinemia is associated with insulin resistance. However, there is very limited information about the relationship between plasma adiponectin and cardiac autonomic nervous function. We tested the hypothesis that hypoadiponectinemia is associated with cardiac sympathetic overactivity in patients with type 2 diabetes mellitus. Thirty-three male type 2 diabetic patients not on insulin treatment were classified into a hypoadiponectinemia group (plasma adiponectin concentration, <4.0 microg/mL; age, 58.6 +/- 8.6 years [mean +/- SD]; n = 14) and an age-matched normoadiponectinemia group (serum adiponectin concentration, >/=4.0 microg/mL; age, 58.2 +/- 8.1 years; n = 19). In each patient, baroreflex sensitivity, heart rate variability, plasma norepinephrine concentration, and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings were assessed. Compared with the normoadiponectinemia group, the hypoadiponectinemia group had a higher body mass index (P < .01), higher plasma concentrations of glucose and insulin (P < .05 and P < .01, respectively), higher homeostasis model assessment of insulin resistance (HOMA-IR) values (P < .005), higher plasma triglyceride levels (P < .05), and lower plasma high-density lipoprotein cholesterol levels (P < .05). In the hypoadiponectinemia group, the autonomic function measurements included a lower baroreflex sensitivity (P< .05) and a lower delayed myocardial uptake of (123)I-MIBG (P < .01) with a higher washout rate (P < .05). Multiple regression analysis revealed that the plasma adiponectin level was independently associated with HOMA-IR (F = 9.916) and the percent washout rate of (123)I-MIBG (F = 5.985). Our results suggest that in middle-aged men with type 2 diabetes mellitus, hypoadiponectinemia is associated with cardiac sympathetic overactivity as determined by (123)I-MIBG scintigraphy.

Predictors for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis.

In patients with chronic renal failure undergoing hemodialysis (HD), silent cerebral infarctions (SCIs) are associated with high mortality. Levels of hepatocyte growth factor (HGF) increase with renal dysfunction and may be a novel predictor of cerebrovascular events. We examined if HGF is a predictor of SCI in HD patients. Brain magnetic resonance imaging findings were used to divide 50 patients undergoing HD into 2 groups, a group with SCI (age, 61 +/- 8 years, mean +/- SD; n = 27) and a group without SCI (age, 60 +/- 7 years; n = 23). These patients received 24-hour ambulatory blood pressure monitoring. The number of patients with diabetes or hypertension was not different between the 2 groups. We made the following observations: (1) The percentage of smokers was higher in the group with SCI than in the group without SCI (P < .05). (2) Plasma levels of high-density lipoprotein cholesterol were lower and HGF levels were higher in the group with SCI compared with the group without SCI (P < .05 and P < .005, respectively). (3) Systolic ambulatory blood pressure and mean heart rate at night were higher in the group with SCI than in the group without SCI (P < .05). Multiple logistic regression analysis identified HGF as a significant risk factor for SCI (odds ratio, 1.89; 95% confidence interval, 1.57-3.38; P < .005). Our findings indicate that HGF may be a novel useful predictor of SCI in patients with chronic renal failure undergoing HD.

High-density lipoprotein cholesterol and insulin resistance are independent and additive markers of left ventricular hypertrophy in essential hypertension.

We examined whether plasma high-density lipoprotein-cholesterol (HDL-C) levels and glucose metabolism parameters are independent or additive predictors of left ventricular hypertrophy (LVH) in patients with untreated essential hypertension. The study group consisted of 41 Japanese patients with untreated essential hypertension and LVH (left ventricular mass index [LVMI] >125 g/m2; age 58+/-6 years, mean+/-SD), and the control group consisted of 39 age-matched patients with untreated essential hypertension without LVH (LVMI

Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus.

This study aims to investigate the relationship between the circulating level of homocysteine and body adiposity in Japanese patients with type 2 diabetes mellitus. We measured the body mass index (BMI), waist and hip circumferences, visceral and subcutaneous adiposities, visceral/subcutaneous (V/S) adiposity ratio, and insulin resistance as assessed by the Homeostasis Model Assessment (HOMA) index in patients with hyperhomocysteinemia. The study group consisted of 17 Japanese patients with type 2 diabetes and hyperhomocysteinemia (age: 62+/-10 years, mean+/-S.D.), and the control group consisted of 24 age-matched type 2 diabetes patients with normohomocysteinemia (60+/-11 years). The visceral adiposity, HOMA index, and V/S ratio were significantly higher in the hyperhomocysteinemia group than in the normohomocysteinemia group (P<0.05). In contrast, the BMI, hip circumference, and subcutaneous adiposity were similar between the two groups (P>0.1). Furthermore, multiple regression analysis showed that hyperhomocysteinemia was closely related to insulin resistance and visceral adiposity. Our results indicate that the presence of hyperhomocysteinemia in our population of Japanese patients with type 2 diabetes-associated insulin resistance was associated with increased visceral but not subcutaneous adiposity.

Correlations of urinary albumin excretion and atherosclerosis in Japanese type 2 diabetic patients.

Microalbuminuria and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 36 Japanese patients with type 2 diabetes and microalbuminuria (age: 56+/-9 years, mean+/-S.D.) and a control group of 44 age-matched patients with normoalbuminuria (56+/-7 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. BaPWV was used as an index of atherosclerosis. The BaPWV was higher in the microalbuminuria group than in the normoalbuminuria group (p<0.005). Fasting plasma glucose (p<0.05) and insulin concentrations (p<0.005), and the homeostasis model assessment (HOMA) index (p<0.0005), were higher in the microalbuminuria group than in the normoalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by BaPWV and HOMA index. Our results indicate that the presence of microalbuminuria in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV, HOMA index are independent predictors of urine albumin excretion.

Hyperhomocysteinemia is a significant risk factor for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis.

In patients with chronic renal failure undergoing hemodialysis (HD), the presence of silent cerebral infarction (SCI) is associated with high mortality. Plasma total homocysteine (tHcy), which increases with renal dysfunction, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of SCI correlates with tHcy in HD patients. Based on brain magnetic resonance imaging findings, 44 patients undergoing HD were divided into a with-SCI group (61+/-9 years [mean+/-SD]; n=24) and a without-SCI group (60+/-8 years, n=20), in whom 24-hour ambulatory blood pressure monitoring was performed. The number of patients with diabetes or hypertension was not different between the 2 groups. We made the following observations: (1) the percentage of smokers was higher in the with-SCI group than in the without-SCI group (P<.05); (2) plasma levels of high-density lipoprotein cholesterol were lower and tHcy was higher in the with-SCI group than in the without-SCI group (P<.05 and P<.0001, respectively); (3) and systolic ambulatory blood pressure and mean heart rate during nighttime were higher in the with-SCI group than in the without-SCI group (P<.05). Multivariate logistic analysis identified hyperhomocysteinemia as an independent and significant risk factor for SCI (odds ratio, 1.22; 95% CI, 1.10-1.36; P<.01). Our findings indicate that plasma tHcy may be a novel useful predictor for SCI in patients with chronic renal failure undergoing HD.

Diazoxide-induced cardioprotection via DeltaPsim loss depending on timing of application.

Although the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in cardioprotection is widely accepted, it remains unclear when their opening is critical for protection. We tested the hypothesis that the mitoKATP channel acts as a trigger or mediator of protection against apoptosis through loss of mitochondrial inner membrane potential (DeltaPsim). Exposure of neonatal rat cardiomyocytes to H2O2 (0.5 mmol/L) resulted in apoptosis associated with severe DeltaPsim loss. Pretreatment with diazoxide (20 to 100 micromol/L) prevented H2O2-induced apoptosis and DeltaPsim loss at 2 but not 18 h after exposure, while the latter was prevented by cotreatment with diazoxide. Lack of protection by pretreatment with diazoxide was observed in cardiomyocytes cultured in a medium containing H2O2 for 2 h and then not containing for 16 h. The slopes of the regression lines of the relationship between the proportion of apoptotic cells and DeltaPsim loss (y = -0.89 vs. -0.42) and the proportion of cells with high side scatter signal differed between cardiomyocytes exposed H2O2 for 2 and 18 h. Diazoxide per se caused a transient DeltaPsim loss (within 30 min) with a recovery followed by persistent DeltaPsim loss (after 6 h). Inhibition of the former by 5-hydroxydecanoate (5-HD, 0.5 mmol/L) abolished protection of pretreatment with diazoxide (trigger phase), while that of the latter prevented the protection of cotreatment with diazoxide (mediator phase). Our results suggest that mitoKATP channels act as a trigger and mediator of cardioprotection through a transient or persistent DeltaPsim loss depending on phenotypic consequence in response to oxidants.

[Evaluation of autonomic function using posture change].

There are several examinations to evaluate cardiac autonomic function. Autonomic neuropathy is a common complication of diabetes mellitus and is associated with increased mortality. Baroreflex sensitivity (BRS) is a marker for the ability to augment vagal activity. Several studies have shown that BRS is impaired in diabetes with autonomic neuropathy. The head-up tilt test is the most useful tool to diagnose the neurally mediated syncope. We have developed a new non-invasive method to evaluate the baroreflex using downward tilting (DT-BRS). In our previous study conducted in healthy volunteers and diabetic patients, we demonstrated a strong correlation between systolic blood pressure increase and corresponding RR interval lengthening during downward tilting, which yielded DT-BRS values that correlated well with the BRS value obtained by the phenylephrine method (Phe-BRS). Heart rate responses observed after both squatting and standing (squatting test) are assumed to be a simple and useful tool to assess autonomic activity. We reported that indices of the squatting test showed a significant correlation with BRS assessed by Phe-BRS in diabetes. DT-BRS and the squatting test may provide promising information for the assessment of reflex vagal activity in diabetes.