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E Ishimura

Publications and source records attributed to E Ishimura.

At least 19 recordsLinked to original sources

Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients.

INTRODUCTION: Fibroblast growth factor (FGF) 23 is a recently identified circulating factor that regulates phosphate (Pi) metabolism. Since the derangement of Pi control is an important risk factor for vascular calcification, we investigated the importance of plasma FGF-23 in the development of vascular calcification in the aorta and peripheral artery in hemodialysis patients with and without diabetes mellitus (DM). METHODS: Male hemodialysis patients with DM (n=32) and without DM (n=56) were examined. Plasma samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Roentgenography of the aorta and hand artery was performed, and visible vascular calcification was evaluated by one examiner, who was blinded to the patient characteristics. RESULTS: In the 56 non-DM hemodialysis patients, vascular calcification was found in the hand artery in 5 patients (8.9%) and in the aorta in 23 patients (41.1%). These levels were significantly lower (p<0.05) than in the 32 DM patients, of whom, 19 (59.4%) and 21 (65.6%) had vascular calcification of the hand artery and aorta, respectively. Multiple regression analyses performed separately in the non-DM and DM patients showed that the plasma FGF-23 level, CaxPi product, and body weight are independent factors significantly associated with hand-artery calcification and that diastolic blood pressure is associated with aorta calcification in non-DM patients. In DM patients, the plasma FGF-23 level and hemodialysis duration emerged as independent factors associated with hand-artery calcification and diastolic blood pressure was associated with aorta calcification. The independent association of the plasma FGF-23 level with hand-artery calcification was retained in both non-DM and DM patients when adjusted for the CaxPi product. CONCLUSION: Our findings show that the plasma FGF-23 level is an independent factor negatively associated with peripheral vascular calcification in the hand artery, but not in the aorta, in both male non-DM and DM hemodialysis patients, even when adjusted for the CaxPi product. This study raises the possibility that the plasma FGF-23 level may provide a reliable marker for Moenckeberg's medial calcification in male hemodialysis patients, independent of its regulatory effect on Pi metabolism.

Adult↗

Body fat mass and lean mass as predictors of survival in hemodialysis patients.

A higher body mass index (BMI) is a predictor of better survival in hemodialysis patients, although the relative importance of body fat and lean mass has not been examined in the dialysis population. We performed an observational cohort study in 808 patients with end-stage renal disease on maintenance hemodialysis. At baseline, fat mass was measured by dual-energy X-ray absorptiometry and expressed as fat mass index (FMI; kg/m2). Lean mass index (LMI) was defined as BMI minus FMI. During the mean follow-up period of 53 months, 147 deaths, including 62 cardiovascular (CV) and 85 non-CV fatal events, were recorded. In univariate analysis, LMI was not significantly associated with CV or non-CV death, whereas a higher FMI was predictive of lower risk for non-CV death. Analyses with multivariate Cox models, which took other confounding variables as covariates, indicated the independent associations between a higher LMI and a lower risk of CV death, as well as between a higher FMI and a lower risk of non-CV death. These results indicate that increased fat mass and lean mass were both conditions associated with better outcomes in the dialysis population.

Absorptiometry, Photon↗

Butyrate modulates TGF-beta1 generation and function: potential renal benefit for Acacia(sen) SUPERGUM (gum arabic)?

Anecdotal evidence suggests that high fibre supplementation of dietary intake may have health benefits in renal disease related to alterations in circulating levels of short-chain fatty acids. The aim of the study was to examine the hypothesis that dietary manipulation may increase serum butyrate and thus have potential beneficial effects in renal disease. We examined the effect of dietary supplementation with a gum arabic sample of standardized molecular characteristics, Acacia(sen) SUPERGUM EM2 (SUPERGUM), on systemic levels of butyrate in normal human subjects. In an in vitro study, we also examined the potential role of butyrate in modifying the generation of the profibrotic cytokine transforming growth factor-beta (TGF-beta1) by renal epithelial cells. Following 8 weeks of dietary supplementation with 25 g/day of SUPERGUM, there was a two-fold increase in serum butyrate (n=7, P=0.03). In vitro work demonstrated that exposure of renal epithelial cells to elevated concentrations of butyrate suppressed both basal and stimulated TGF-beta1 synthesis. The action of butyrate was mediated by suppression of the extracellular signal-regulated kinase/mitogen-activated protein kinase signalling pathway. In addition, butyrate exposures reduced the response of renal epithelial cells to TGF-beta1 as assessed by luciferase activity of a TGF-beta-responsive reporter construct. Attenuation of TGF-beta1 signalling was associated with reduced phosphorylation of Smad 3 and decreased trafficking of TGF-beta1 receptors into signalling, non-lipid raft-associated membrane fractions. In conclusion, the data demonstrate that dietary supplementation with SUPERGU increased serum butyrate, which at least in vitro has beneficial effects on renal pro-fibrotic cytokine generation.

Butyrates↗

Increased incidence of vertebral fracture in older female hemodialyzed patients with type 2 diabetes mellitus.

Bone disease in hemodialysis (HD) patients with type 2 diabetes mellitus (DM) is characterized by low bone turnover (Inaba M, et al. Am J Kidney Dis 2002; 39:1261-1269), although their bone quality is yet to be determined. The present study was designed to examine whether the prevalence of vertebral fracture in female HD patients with type 2 DM, age 65 years and older, might be increased, and the relation of this fracture to bone mineral density (BMD) determined by dual X-ray absorptiometry (DXA), since few data are available on the effect of DM on bone strength at lumbar spine. The prevalence of vertebral fracture in type 2 DM HD patients was 32.3%, which was greater than that of non-DM HD patients (13.3%) when adjusted for age and HD duration. Logistic regression analysis elucidated the presence of DM and age as independent risk factors for an increased prevalence of vertebral fracture in HD patients. In non-DM HD patients, those with vertebral fracture showed age significantly higher and BMD in either lumbar spine or distal one third of radius significantly lower than the respective value in those without fracture. However, in DM HD patients, neither BMD in lumbar spine nor distal one third of radius was significantly lower in those with vertebral fracture than in those without. Furthermore, age did not differ significantly between DM HD patients with and without fracture. In conclusion, female type 2 DM HD patients, age 65 years and older, showed significantly higher incidence of vertebral fracture than non-DM HD patients. Although age and low BMD emerged as independent risk factors for vertebral fracture in non-DM HD patients, those factors failed to be a risk factor in DM HD patients, suggesting that BMD determined by DXA might not be reliable in assessing bone strength in DM HD patients.

Absorptiometry, Photon↗

Serum N-terminal midfragment vs. intact osteocalcin immunoradiometric assay as markers for bone turnover and bone loss in hemodialysis patients.

Although labile, assay of intact osteocalcin (iOC) is established as the standard assay for evaluating osteoblastic function. The present study examines the clinical usefulness of the newly developed immunoradiometric assay for osteocalcin (OC), which identifies the stable N-terminal midfragment of OC (N-MID OC assay), in hemodialysis (HD) patients. The performance of N-MID OC assay was compared to that of iOC assay in the sera obtained from 137 male HD patients, by comparing these assays with those of other bone metabolic markers and bone loss during a 1-year period before determination of serum markers. Serum N-MID OC values did not decrease significantly during 24 h incubation at room temperature, whereas serum iOC decreased significantly after 1 h incubation. Serum N-MID and iOC in the 137 male HD patients were 197.3 +/- 57.8 and 34.6 +/- 30.0 ng/ml, respectively, or 3.9 +/- 3.1 and 2.8 +/- 2.4 times above the respective reported normal upper limits. Serum N-MID OC correlated significantly in a positive manner with serum iOC (r = 0.934, P < 0.0001). Serum N-MID OC correlated no less significantly in a positive manner with serum levels of bone alkaline phosphatase, deoxypyridinoline, and intact parathyroid hormone compared to serum iOC. Of interest was the fact that serum N-MID OC, but not iOC, correlated significantly with both the amount and the rate of bone loss at the distal radius 1/3. In summary, the findings suggest that N-MID OC immunoreactivity is much more stable than iOC immunoreactivity and that N-MID OC assay may be less susceptible to the OC fragments reported to accumulate in uremic serum. It may, therefore, prove more reliable than iOC assay for evaluating bone turnover, and thus for reflecting bone loss, in HD patients.

Adult↗

Different risk factors for peripheral vascular calcification between diabetic and non-diabetic haemodialysis patients--importance of glycaemic control.

AIM/HYPOTHESIS: Although derangements of calcium and phosphate control have been emphasized as important risk factors for vascular calcification in non-diabetic haemodialysis patients, similar risk factors for diabetic haemodialysis patients are not known. We compared factors affecting peripheral vascular calcification between haemodialysis patients with and without diabetes. METHODS: We examined 421 patients on maintenance haemodialysis. There were 89 patients with Type II (non-insulin-dependent) diabetes mellitus (53 men and 36 women, 62+/-10 years old) and 332 patients without diabetes (192 men and 140 women, 59+/-13 years old). Hand roentgenography was carried out, and visible vascular calcification of the hand arteries was evaluated. RESULTS: There were 42 diabetic patients and 45 non-diabetic patients with vascular calcification. The prevalence of vascular calcification in diabetic patients (47.1%) was higher than in non-diabetic patients (13.6%) ( p<0.001). In multivariate logistic regression, the main factors affecting vascular calcification in non-diabetic patients were advanced age, longer duration of haemodialysis, increased phosphate concentrations, male gender, and lower predialysis diastolic pressure. In diabetic patients, predictors for vascular calcification were higher values of HbA(1C) and longer duration of haemodialysis. In diabetic patients, a 1% increase in HbA(1C) increased the risk of calcification by 2.1-fold (95% CI 1.282-3.575, p=0.0029). CONCLUSION/INTERPRETATION: We have shown that poor glycaemic control, rather than calcium and phosphate concentrations, is a predictor of peripheral vascular calcification in diabetic patients on haemodialysis. This study emphasizes that glycaemic control remains critical even in diabetic patients with end-stage renal disease.

Blood Glucose↗

Increased stiffness in common carotid artery in hyperthyroid Graves' disease patients.

The present study was undertaken to assess the effect of hyperthyroidism on stiffness in the common carotid artery (CCA) in patients with Graves' disease (GD) and elucidate the mechanism by which arterial stiffness is increased in hyperthyroidism. The arterial stiffness index beta (stiffness beta) was evaluated in the CCA using an ultrasonic phase-locked echo-tracking system. Stiffness beta was defined as the logarithm of the ratio of systolic to diastolic blood pressure divided by the fractional diameter increase during the cardiac cycle and thus established as a measure of arterial stiffness uninfluenced by the change in blood pressure. Seventy euthyroid GD patients were measured for CCA stiffness beta to determine its relationship to retinal blood flow and plasma levels of vascular injury markers. To investigate the effect of hyperthyroidism, 27 GD patients were measured for changes during antithyroid drug (ATD) therapy in stiffness beta and in hemodynamic parameters, retinal blood flow and plasma vascular injury markers. In euthyroid GD patients, stiffness beta in the CCA showed a significant and positive correlation with systolic blood pressure and pulse pressure, but not with peripheral blood flow in the central retinal artery. ATD therapy significantly reduced stiffness beta from 5.23 +/- 2.10 to 4.36 +/- 1.48. The fractional reduction of stiffness beta during ATD therapy correlated significantly with reductions in pulse pressure and retinal blood flow, but not with the reductions in systolic and mean blood pressure, or any of the plasma injury markers. In summary, the significant increase in stiffness beta in the hyperthyroid state may reflect the harmful effect of hyperthyroidism on the arterial wall, which may in turn result from increased stroke volume.

Adolescent↗

Modulation by cAMP of 1alpha,25-dihydroxyvitamin D3 sensitivity of murine erythroleukemia cells.

As we previously reported, 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) dose-dependently inhibited not only proliferation of undifferentiated murine erythroleukemia (MEL) cells but also activin A-induced erythroid differentiation of MEL cells. However, the effect of 1,25(OH)2D3 on MEL cell proliferation was significantly greater by one order of magnitude than that on differentiation (IC(50): 9.2 vs 0.8 nM, respectively). The response of activin A-treated mature MEL cells to 1,25(OH)2D3 in the induction of 1,25(OH)2D3-24-hydroxylase (24-OHase) activity, a rapid effect of 1,25(OH)2D3, was enhanced to the same degree as in untreated immature cells, suggesting that differences in capacity of cells to inactivate 1,25(OH)2D3 did not contribute to augmentation of 1,25(OH)2D3 effect in activin A-treated mature cells. Furthermore, neither the number nor the affinity of vitamin D receptors (VDR) differed significantly between activin A-treated cells and untreated immature cells. The intracellular cAMP level, which affects 1,25(OH)2D3-mediated induction of 24-OHase activity, was significantly less in activin A-treated mature cells than in immature MEL cells. The addition of dibutyryl cAMP (dbc AMP) to activin A-treated MEL cells dose-dependently attenuated 1,25(OH)2D3-mediated induction of 24-OHase activity, finally to a level comparable to that of the untreated cells at the final concentration of 100 nM dbcAMP, while dbcAMP itself by 100 nM did not affect MEL cell differentiation by 24 h. In summary, we have shown for the first time that 1,25(OH)2D3 exerted its effect on leukemia cells at physiological concentration and that the magnitude of this effect depended on the changes in intracellular cAMP level through stages of differentiation, suggesting that the cAMP-protein kinase A system may be useful as a target for clinical application of vitamin D analogs by improving the sensitivity of leukemic cells to 1,25(OH)2D3.

Activins↗

Atherogenic lipoprotein changes in diabetic nephropathy.

Cardiovascular risk is increased in patients with diabetic nephropathy. The aim of this study was to examine the relative impacts of albuminuria and renal failure, the two important features of diabetic nephropathy, on potentially atherogenic lipoprotein changes in this condition. The subjects were 160 non-diabetic healthy controls and a total of 200 type 2 diabetes patients with various degrees of nephropathy. The diabetic patients were divided into four groups by urinary albumin/creatinine ratio (U-ACR) and serum creatinine (S-Cr) levels: DM-1 (U-ACR< 30 mg/g, N=85), DM-2 (U-ACR=30-300 mg/g, N=48), DM-3 (U-ACR > 300 mg/g, N=29) and DM-4 (S-Cr>177 micromol/l or 2.0mg/dl, N=38). Lipids in very low (VLDL), intermediate (IDL), low (LDL), and high density (HDL) lipoproteins were measured following ultracentrifugation. VLDL-cholesterol (VLDL-C) was elevated (by 73-100%) in diabetic patients and it did not differ among the stages of nephropathy. IDL-C was higher as the nephropathy stage was advanced, and the elevation was significant in the DM-3 (by 75%) and DM-4 (by 131%) groups. LDL-C was not elevated in diabetic patients and was not different among the stages of nephropathy. Reduction of HDL-C was significant in DM-1, DM-2 and DM-3 (by 12-16%) and it was more exaggerated in DM-4 (by 35%). Multiple regression analyses indicated that elevated S-Cr, but not U-ACR, was an independent factor associated with raised IDL-C and lowered HDL-C in diabetic patients. These results indicate that diabetic patients with nephropathy show multiple lipoprotein changes, and that renal failure has greater impact than albuminuria on abnormalities in IDL and HDL. These lipoprotein alterations may contribute to an increased cardiovascular risk in diabetic nephropathy, especially in diabetic renal failure.

Aged↗

Femoral artery wall thickness and stiffness in evaluation of peripheral vascular disease in type 2 diabetes mellitus.

Stiffening and thickening of arterial wall are two important components of atherosclerosis. The purpose of this study was to evaluate the effects of femoral artery wall stiffness on clinical manifestation of peripheral vascular disease (PVD) in type 2 diabetes mellitus. The subjects were 315 patients with type 2 diabetes. Presence of intermittent claudication and/or leg pain at rest and reduced ankle-brachial blood pressure index (ABI<0.9) were used as a subjective and an objective index of PVD, respectively. Femoral artery intima-media thickness (FA-IMT) and stiffness parameter beta (FA-stiffness beta) were measured by ultrasound methods. Symptomatic patients (N=58) showed greater values for both FA-IMT and FA-stiffness beta than those without symptom (N=257). Similarly, patients with reduced ABI (N=56) had greater FA-IMT and FA-stiffness beta than those without (N=259). However, correlation between FA-IMT and FA-stiffness beta was not impressive, especially in the symptomatic patients. To evaluate the effect of FA-stiffness beta on PVD symptoms, the subjects were divided into three subgroups according to FA-IMT, and then FA-stiffness beta was compared between those with and without PVD symptoms in each subgroup. The symptomatic patients had greater FA-stiffness beta values than the asymptomatic subjects in all the three subgroups. Multiple logistic regression analysis indicated that the presence of PVD symptoms was associated more closely with increased FA-stiffness beta than with increased FA-IMT, whereas reduced ABI was associated more closely with FA-IMT than with FA-stiffness beta. These data suggest that stiffening of arterial wall has a significant impact on PVD manifestations, particularly on the leg symptoms, in patients with type 2 diabetes.

Adolescent↗

Hypertrophic pachymeningitis with anti-neutrophil cytoplasmic antibody (p-ANCA), and diabetes insipidus.

We treated a patient with idiopathic cranial hypertrophic pachymeningitis and elevated serum titer of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactive against myeloperoxidase. This 67-year-old man showed multiple cranial nerve-palsies, central diabetes insipidus (DI), and an intrasellar mass. DI and intrasellar mass had been present for 3 years, and DI had been well controlled by intranasal desmopressin. His nerve-palsies were most likely caused by thickened dura matter detected by the brain MRI. Granuloma may develop in the sella, and MRI findings in our patient are compatible to it. Corticosteroid and oral cyclophosphamide therapy improved his neurological symptoms and serum p-ANCA level with showing good correlation. DI improved temporally for 2 months. Few other cases of hypertrophic pachymeningitis with elevated p-ANCA have been reported, however the etiology is unknown. As p-ANCA antibodies have been detected in many of vasculitides, microvasculitis may be involved in some cases of idiopathic hypertrophic pachymeningitis.

Aged↗

Paradox of risk factors for cardiovascular mortality in uremia: is a higher cholesterol level better for atherosclerosis in uremia?

Patients with chronic uremia have a substantially elevated risk of death from cardiovascular disease than do the general population. Although uremic and nonuremic groups share some of the risk factors for cardiovascular mortality, such as older age, diabetes, and inflammation, other factors appear to affect cardiovascular mortality in the opposite direction. For example, being overweight and having hyperlipidemia are established risk factors in the general population, whereas lower body mass index and lower plasma cholesterol have been shown to be risk factors for cardiovascular mortality in end-stage renal disease (ESRD). This paradoxical phenomenon is explained by two facts: (1) that malnutrition is a strong predictor of cardiovascular mortality in ESRD and (2) that plasma lipid levels are lowered in malnutrition. However, it is not known whether atherosclerosis is promoted by malnutrition or by low cholesterol level. Because the cardiovascular mortality rate is theoretically the product of event rate and fatality rate after an event, risk factors for cardiovascular mortality could fall into two categories: those raising the event rate and those affecting the fatality rate. Some factors could work both ways. Patients with ESRD show a significant increase in both event rate and fatality rate. Dyslipidemia is an independent factor affecting atherosclerotic arterial wall changes and cardiovascular events in ESRD. Other factors affecting the cardiovascular event rate in ESRD include diabetes and an elevated homocysteine level. In contrast, factors associated with poor survival after an event include diabetes and anemia. Malnutrition could be a factor causing the fatality rate to rise, although there is no direct evidence supporting this possibility. Further studies are needed to show the differential effects of a risk factor on event rate and fatality rate. Patients with ESRD would have a better chance of living longer by better management of the two categories of risk factors.

Arteriosclerosis↗

Atherogenic lipoproteins in end-stage renal disease.

Cardiovascular mortality is substantially higher in patients with end-stage renal disease (ESRD). Lipoprotein abnormality in ESRD is one of the possible risk factors for advanced atherosclerosis. Uremic dyslipidemia is characterized by increased plasma triglycerides due to elevated very low density lipoprotein (VLDL) and decreased high-density lipoprotein (HDL). Plasma total or low-density lipoprotein (LDL) cholesterol is rarely elevated in hemodialysis patients. The "LDL" by standard assay methods consists of intermediate-density lipoprotein (IDL) and LDL devoid of IDL. Although "LDL" is not increased, IDL is markedly elevated in uremic plasma. We previously showed that aortic stiffness of hemodialysis patients was associated positively with VLDL, IDL, and LDL devoid of IDL and that IDL is the best lipoprotein predictor of aortic stiffness. The IDL level is correlated positively with plasma total cholesterol, triglyceride, and "LDL" levels. Importantly, increased IDL is found in ESRD patients with "normal" "LDL"cholesterol levels, indicating that the target "LDL" level should be lower than that for the general population. More than 40% of hemodialysis patients exceeded the upper limit (15 mg/dL, 95th percentile level) of IDL cholesterol in healthy subjects. Based on a linear relationship between IDL and "LDL," the normal range of IDL cholesterol (<15 mg/dL) corresponds to "LDL" cholesterol by the Friedewald equation below 100 mg/dL in hemodialysis patients. Statins effectively and safely reduce "LDL," including IDL in patients treated with hemodialysis or peritoneal dialysis. The effect of lipid-lowering therapy on cardiovascular mortality in ESRD, however, awaits the results of ongoing prospective trials.

Cardiovascular Diseases↗

Impaired secretion of parathyroid hormone is coherent to diabetic hemodialyzed patients.

Diabetic bone disease is characterized by low bone turnover resulting from impaired secretion of parathyroid hormone (PTH). However, it was suggested that the difference in duration of hemodialysis (HD) therapy and age of patients between HD patients with and without diabetes mellitus (DM) may be responsible for a significant reduction in serum intact PTH (iPTH) level in HD patients with DM. The present study showed that although such major factors affecting PTH secretion as age, sex, HD duration, and serum calcium, phosphate, and magnesium levels did not differ significantly between HD patients with and without DM, serum iPTH levels were still significantly lower in HD patients with than without DM. Among biochemical markers for bone metabolism, serum levels of intact osteocalcin (iOC) and deoxypyridinoline (DPD) were significantly lower in HD patients with than without DM, whereas serum bone-specific alkaline phosphatase, pyridinoline, and beta-crosslaps did not differ significantly between the two groups of patients. In summary, our findings indicate that PTH secretion may be significantly impaired in HD patients with DM compared with those without DM, and serum iOC and DPD are bone markers sensitive enough to detect low bone turnover in HD patients with DM.

Aged↗

Renal insufficiency accelerates atherosclerosis in patients with type 2 diabetes mellitus.

Diabetes mellitus is a strong risk factor for the progression of atherosclerosis. In patients with chronic renal failure on hemodialysis, advanced atherosclerosis is reported to be present. We examined how renal insufficiency affects intima-medial thickness (IMT) of the carotid and femoral arteries in patients with type 2 diabetes mellitus. IMT was measured by B-mode ultrasonography in 115 patients with type 2 diabetes mellitus (65 men, 50 women; 58 +/- 13 years old). The IMT of the carotid and the femoral artery of patients with creatinine clearance less than 80 mL/min (n = 55) were significantly greater than those of patients with creatinine clearance 80 mL/min or greater (n = 60; P < 0.01 and P < 0.05). Linear regression analyses showed that there was a significant negative correlation between creatinine clearance and IMT of the carotid artery (r = -0.330; P < 0.001) and femoral artery (r = -0.336; P < 0.001). Multiple regression analyses revealed that age and creatinine clearance significantly and independently affected the IMT of the carotid artery (R(2) = 0.176; P < 0.0001), and age, duration of diabetes, and smoking affected the IMT of the femoral artery (R(2) = 0.287; P < 0.0001). These findings show that decreased renal function accelerates atherosclerosis in patients with type 2 diabetes mellitus and that chronic renal failure is a significant, independent risk factor for carotid atherosclerosis in these patients.

Age Factors↗

Changes in body fat mass in male hemodialysis patients: a comparison between diabetics and nondiabetics.

Nutritional status is an important factor that affects morbidity and mortality of hemodialysis patients. We investigated 1-year changes in body fat mass of male patients undergoing hemodialysis (duration, 4.9 +/- 2.5 years). Fat mass of 217 male patients (age 60 +/- 13 years) was measured by dual x-ray absorptiometry twice in a 1-year interval. The patients consisted of 70 with diabetes mellitus and 147 without diabetes. At the second measurement compared with the first, a significant decrease in fat mass was observed in diabetic patients (12.1 +/- 4.4 kg versus 11.0 +/- 4.7 kg; P < 0.01); there were no significant changes in fat mass in nondiabetic patients (12.2 +/- 5.0 kg versus 11.9 +/- 4.9 kg; P = 0.15). Significant differences in percent fat mass changes per year were seen between diabetic and nondiabetic patients (P < 0.05). Protein catabolic rates of diabetic patients were significantly lower than those of nondiabetic patients (0.86 +/- 0.18 g/kg/d versus 0.93 +/- 0.19 g/kg/d; P < 0.05). In all patients, there was a significant correlation between protein catabolic rates and percent fat mass changes per year (r = 0.15; P < 0.05). These results showed that body fat mass was decreased significantly in 1 year in male diabetic patients with maintenance hemodialysis, suggesting poorer nutritional status in these patients. Poor protein intake may be one of the risk factors for the decrease in fat mass. Dual x-ray absorptiometry assessment of fat mass changes is suggested as a useful method to examine clinically the nutritional status of hemodialysis patients.

Absorptiometry, Photon↗

Correlation between peritoneal mesothelial cell cytology and peritoneal histopathology with respect to prognosis in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a serious complication seen in patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We have previously reported that mesothelial cells in effluent dialysate significantly increased in size as the duration of CAPD progressed. In this study, we investigated the relationship between mesothelial cytology, histopathology of the peritoneum, and clinical outcomes of 34 CAPD patients. METHODS: When peritoneal dialysis catheters were inserted (n = 7) or removed (n = 27), a peritoneal biopsy was performed and results compared with mesothelial cytology in effluent dialysate. RESULTS: A significant positive correlation was noted between the duration of CAPD and the surface area of peritoneal mesothelial cells (r = 0.721, p < 0.0001). The surface area of mesothelial cells in peritoneal sclerosis (n = 9; 584 +/- 97 microm(2)) was significantly greater than in peritoneal fibrosis (n = 14; 389 +/- 26 microm(2), p < 0.05), pathologic acute peritonitis (n = 3; 223 +/- 10 microm(2), p < 0.005), and normal peritoneum (n = 7; 247 +/- 12 microm(2), p < 0.001). The surface area in sclerosing peritonitis (n = 1; 1,200 microm(2)) was greater than that of all the others. Giant cells were found in the 1 case with sclerosing peritonitis and in 3 of 9 cases with peritoneal sclerosis, although they were found in only 1 of 14 patients with peritoneal fibrosis and in none of those with pathologic acute peritonitis or normal peritoneum. As the surface area of mesothelial cells increased to more than 400 microm(2) and giant cells appeared in the effluent, the frequency of peritoneal sclerosis and/or clinical SEP increased. CONCLUSION: An increase in the mesothelial cell surface area and the emergence of giant cells in the effluent indicate advanced peritoneal histopathology, and may be useful indicators to determine appropriate timing of discontinuation of CAPD to prevent the development of SEP.

Adult↗

Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes.

OBJECTIVE: To assess the impacts of insulin resistance and renal function on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes with a wide range of nephropathy. RESEARCH DESIGN AND METHODS: Plasma tHcy levels were measured using the enzyme immunoassay method in 75 patients with type 2 diabetes and compared with those in 54 healthy control subjects. Insulin sensitivity indexes were assessed in patients with type 2 diabetes by hyperinsulinemic-euglycemic clamp using artificial pancreas. RESULTS: Plasma tHcy levels and their log-translormed values (log tHcy) were significantly higher in all patients with diabetes than in control subjects (tHcy, 12.0 +/- 0.7 [SE] vs. 8.7 +/- 0.3 micromol/l, P < 0.0001; log tHcy, 1.040 +/- 0.021 vs. 0.920 +/- 0.016 micromol/l, P < 0.0001). Plasma tHcy levels in patients with diabetes were significantly increased according to degree of nephropathy (P < 0.0001). On simple regression analyses, log tHcy correlated with insulin sensitivity indexes (r = -0.319, P = 0.005) as well as creatinine clearance (r = 0.634, P < 0.0001) in all patients with diabetes. Multiple regression analyses showed that insulin sensitivity indexes (beta = -0.245) as well as creatinine clearance were independent contributors to log tHcy in all patients with diabetes (R2 = 0.750, P < 0.0001). For the 59 patients with diabetes with creatinine clearance >60 ml/min, insulin sensitivity indexes were also shown to be a significant contributor to log tHcy (beta = -0.438, R2 = 0.561, P < 0.001). CONCLUSION: Insulin resistance and renal function are independent determinants of tHcy levels in patients with type 2 diabetes.

Blood Glucose↗