[Show abstract][Hide abstract] ABSTRACT: Objectives
To compare the efficacy and safety of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency.
Our study included 18 patients with type 2 diabetes and a mean (range) estimated glomerular filtration rate of 13.2 mL/minute/1.73 m2 (5.8-27.6), which corresponds to stage 4-5 chronic kidney disease.
After titration of doses, regular insulin was administered thrice daily on Day 1, along with continuous glucose monitoring for 24 h starting at 7 am. Exactly equal doses of insulin glulisine were administered on Day 2. Area under the curve (AUC) for blood glucose level variation after breakfast (AUC-B 0-4), lunch (AUC-L 0-6), and dinner (AUC-D 0-6) were evaluated.
AUC-B 0-4 and AUC-D 0-6 were significantly lower with insulin glulisine than with regular insulin (AUC-B 0-4: 3.3 ± 4.7 vs. 6.2 ± 5.4 × 102 mmol/L·minute, respectively, P = .028; AUC-D 0-6: 1.8 ± 7.3 vs. 6.5 ± 6.2 × 102 mmol/L·minute, respectively, P = .023). In contrast, AUC-L 0-6 was higher with insulin glulisine than with regular insulin (AUC-L 0-6: 7.6 ± 6.4 vs. 4.2 ± 8.7 × 102 mmol/L·minute, respectively, P = .099), suggesting a prolonged hypoglycemic action of regular insulin after lunch.
Insulin glulisine effectively suppressed postprandial hyperglycemia, whereas regular insulin caused a prolonged hypoglycemic action. These findings support the effectiveness and safety of insulin glulisine in patients with type 2 diabetes and severe renal insufficiency.
Full-text · Article · Jan 2014 · Journal of Renal Nutrition
[Show abstract][Hide abstract] ABSTRACT: Aim:
Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD.
The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD.
The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) μg/mL and 2.3 (1.7-3.0) μg/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables.
The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.
No preview · Article · Dec 2013 · Journal of atherosclerosis and thrombosis
[Show abstract][Hide abstract] ABSTRACT: Objective
Morning blood pressure surge (MBPS) is an independent predictor of cardiovascular events. However, little is known on the association between glycemic control and MBPS and its effect on vascular injury in patients with type 2 diabetes mellitus (T2DM). The present study examined the association between glycemic control and MBPS and the involvement of MBPS in the development of vascular dysfunction in T2DM patients.Research Design and Methods
We examined MBPS in T2DM patients (M/F; 25/25, age; 60.1±13.2 years, n=50) by 24-hour ambulatory blood pressure monitoring, and assessed vascular function by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD).ResultsHbA1c (ρ=0.373, p=0.009) and triglyceride (ρ=0.375, p=0.009) correlated significantly and positively with MBPS. In multiple regression analysis including triglyceride and HbA1c in addition to age, 24-hour systolic blood pressure (24h-SBP) as independent variables, HbA1c (β=0.328, p=0.016) and triglyceride (β=0.358, p=0.014) associated significantly in a positive manner with MBPS. In non-insulin user, when HOMA-R was included in place of TG, HOMA-R emerged as a significant factor. MBPS (ρ=-0.289, p=0.043), and HbA1c (ρ=-0.301, p=0.035) correlated significantly and negatively with FMD, while 24h-SBP correlated with both FMD (ρ=-0.359, p=0.012) and NMD (ρ=-0.478, p=0.004). In multiple regression analysis, including age, gender, 24h-SBP, MBPS, LDL-cholesterol, and HbA1c, MBPS (β=-0.284, p=0.044) alone associated significantly in a negative manner with FMD, but not with NMD.Conclusions
The present study demonstrated that poor glycemic control and insulin resistance are independently associated with the occurrence of MBPS in T2DM patients, which might be significantly associated with endothelial dysfunction.
[Show abstract][Hide abstract] ABSTRACT: Objective
Serum creatinine levels are lower in diabetic patients compared with their non-diabetic counterparts. Therefore, estimated glomerular filtration rate (eGFR) is higher in the former than in the latter group. Factors associated with overestimation of renal function in diabetic patients were examined, and new formulae reflecting precise eGFR were created.Research Design and Methods
Eighty subjects (age 56.5±15.4 years; 35 males (43.8%); 40 diabetics and 40 non-diabetics subjects) were enrolled. GFR was evaluated by inulin clearance (Cin). eGFR values were calculated based on serum creatinine and/or serum cystatin C levels. The factors related to the dissociation between eGFR and Cin in diabetic patients and the agreement between each of three eGFR and Cin were compared.ResultsAlthough Cin was not significantly different between the diabetic and non- diabetic subjects (p=0.2866), each of three eGFR measures from the diabetic patients was significantly higher than that of the non-diabetic subjects (p<0.01). There were significant and positive correlations between the ratio of each eGFR/Cin, hemoglobin A1c and glycated albumin. The intraclass correlation coefficients in diabetic patients were weaker than those in the non-diabetic subjects, and the intercepts of the regression lines between each eGFR measure and Cin in the diabetic patients were significantly higher than those of the non-diabetic subjects. New formulae for the calculation of eGFR corrected by the glycemic control indices were better than the original eGFR, particularly in diabetic patients.ConclusionseGFR overestimates Cin as glycemic controls worsen. eGFR corrected by hemoglobin A1c is considered to be clinically useful and feasible.
[Show abstract][Hide abstract] ABSTRACT: Background:
Extracellular magnesium (Mg) accounts for approximately 1% of the total body Mg. Clinically, serum Mg concentration is measured, but it does not necessarily reflect total body Mg status. Although relationships have been reported between reduced Mg and cardiovascular disease in non-dialysis patients, there have been few such studies in hemodialysis patients. It was hypothesized that reduced Mg, as represented by lower Mg concentration in the hair, would be associated with echocardiographic parameters in chronic hemodialysis patients.
Methods and results:
Hair Mg concentration was measured in 79 male hemodialysis patients using inductively coupled plasma mass spectrometry, and the relationships between hair Mg concentration and echocardiographic parameters were investigated. There was no significant correlation between Mg concentration in the hair and in serum. Hair Mg concentration in the patients with high-left ventricular mass index (LVMI) was significantly lower than that in the low-LVMI patients. Hair Mg concentration correlated significantly and negatively with posterior left ventricular wall thickness, interventricular septum thickness, left ventricular wall thickness (LVWT), and relative wall thickness. Serum Mg concentration, however, did not correlate with any of these echocardiographic parameters.
In hemodialysis patients, hair Mg concentration is a biomarker, independent of serum Mg concentration. Hair Mg, but not serum Mg, was significantly and negatively associated with LVWT. Reduced tissue Mg concentration, as measured in the hair, may be associated with left ventricular hypertrophy in hemodialysis patients.
No preview · Article · Aug 2013 · Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: Background:
In a previous proteomic study, we detected increased expression of nephronectin in the glomeruli from patients with diabetic nephropathy (DN). The aim of the present study was to clarify the usefulness of determining glomerular expression of nephronectin in kidney disease.
We performed immunohistochemical staining for nephronectin in renal biopsy specimens from patients with a variety of kidney diseases (n = 190). The percentage of nephronectin-positive areas in the glomeruli was analyzed using an image analyzer.
Nephronectin immunoreactivity was clearly, strongly positive in the mesangial expansion and nodular lesions of DN (n = 18), whereas nephronectin immunoreactivity was negative in IgA glomerulonephritis, membranoproliferative glomerulonephritis, lupus nephritis, membranous glomerulonephritis, minor glomerular abnormalities, crescentic glomerulonephritis, and other kidney diseases, such as amyloidosis and light chain deposition disease. Nephronectin was stained weakly in sclerotic lesions, such as focal segmental glomerulosclerosis and hypertensive nephropathy. The percentage of nephronectin-positive areas in the glomeruli from DN patients [15.1 ± 4.7% (n = 18)] was significantly higher than that for other kidney diseases [5.5 ± 3.6% (n = 172)] (p < 0.001). In multiple regression analyses, fasting plasma glucose and hemoglobin A1c were significantly associated with the increase in the percentage of nephronectin-positive areas in the glomeruli (β = 0.23, p < 0.001 and β = 0.16, p = 0.045, respectively).
The expression of nephronectin was sufficient to discriminate DN from other kidney diseases with mesangial matrix expansion and nodular lesions. We consider that nephronectin staining could be helpful in the diagnosis of DN.
No preview · Article · May 2013 · Nephron Clinical Practice
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Unlike the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), n-3-PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have beneficial effects on inflammation, thrombosis, and cardiovascular disease (CVD). We examined possible alterations in serum PUFA profiles in patients on maintenance hemodialysis therapy and its association with CVD risk. STUDY DESIGN: An observational study including cross-sectional and longitudinal analyses. SETTING & PARTICIPANTS: Single-center study of 517 maintenance hemodialysis patients in an urban area in Japan. PREDICTORS: Serum EPA, DHA, and AA concentrations and EPA:AA, DHA:AA, and (EPA+DHA):AA ratios. OUTCOMES: CVD events, including ischemic heart disease, stroke, peripheral artery disease, pulmonary edema, and valve disease. RESULTS: Hemodialysis patients showed lower (EPA+DHA):AA, EPA:AA, and DHA:AA ratios than 122 controls similar in age and sex. During follow-up, 190 CVD events were recorded. (EPA+DHA):AA ratio was not associated significantly with CVD in unadjusted analysis, but was associated significantly and inversely with CVD in Cox models adjusted for age and other confounding variables, with HRs in the range of 1.71-1.99 in the lowest versus highest quartile of (EPA+DHA):AA ratios. Similarly, EPA:AA and DHA:AA ratios showed inverse associations with CVD, whereas serum EPA, DHA, and AA concentrations were not predictive of CVD. LIMITATIONS: No information for dietary intake, use of dietary supplements, or cell membrane PUFA content. CONCLUSIONS: In hemodialysis patients, serum PUFA profile is unfavorably altered, and the low n-3-PUFA:AA ratios are independent predictors of CVD.
No preview · Article · Apr 2013 · American Journal of Kidney Diseases
[Show abstract][Hide abstract] ABSTRACT: Objective:
Low thyroid function may be associated with a reduced glomerular filtration rate (GFR) calculated on the basis of creatinine metabolism. Thyroid hormone directly affects serum creatinine in muscle and low thyroid function might exert a similar direct effect in the kidney. The goal of the study was to evaluate this possibility by assessment of the inulin-based GFR and to examine the mechanism underlying the reduction of GFR.
Patients and methods:
Renal and glomerular hemodynamics were assessed by simultaneous measurements of plasma clearance of para-aminohippurate (CPAH) and inulin (Cin) in 26 patients with serum creatinine <1.00 mg/dl and without thyroid disease. All subjects were normotensive with or without antihypertensive treatment and were kept in a sodium-replete state. Renal and glomerular hemodynamics were calculated using Gomez's formulae.
Serum TSH, including within the normal range (0.69-4.30 μIU/ml), was positively correlated with vascular resistance at the afferent arteriole (Ra) (r=0.609, P=0.0010), but not at the efferent arteriole (Re). Serum TSH was significantly and negatively correlated with renal plasma flow (RPF), renal blood flow (RBF), and GFR (r=-0.456, P=0.0192; r=-0.438, P=0.0252; r=-0.505, P=0.0086 respectively). In multiple regression analysis, serum TSH was significantly positively associated with Ra after adjustment for age and mean blood pressure.
These findings suggest that low thyroid function, even within the normal range, is associated with reduced RPF, RBF, and GFR, which might be caused by a preferential increase in Ra.
Preview · Article · Apr 2013 · European Journal of Endocrinology
[Show abstract][Hide abstract] ABSTRACT: Background:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was originally isolated as an inducer of apoptosis in transformed cells. In addition to tumor surveillance, recent findings suggest that TRAIL and its receptor system have a protective role against infection and cardiovascular disease (CVD). Patients undergoing hemodialysis have a high mortality rate with a unique risk factor profile. Considering that the leading causes of death in these patients are infection and CVD, TRAIL represents an attractive candidate for predicting mortality in this population. We therefore investigated whether TRAIL predicted mortality in hemodialysis patients.
The study was a retrospective observational cohort design of 45-month duration in 149 male hemodialysis patients. The subjects were divided into two groups according to their baseline TRAIL level measured by ELISA (low or high TRAIL group). The main outcome was all-cause mortality.
During the follow-up period, 33 patients died, mostly because of CVD (n=11) or infection (n=9). Crude survival analyses showed that a low TRAIL level was a powerful predictor of all-cause (p=0.011) and infectious mortality (p=0.048). The predictive power of TRAIL remained after adjustment for various confounding factors.
The serum TRAIL level may be a novel biomarker for predicting prognosis in hemodialysis patients.
[Show abstract][Hide abstract] ABSTRACT: Fetuin was first isolated from bovine serum in 1944. It is now most commonly known as either fetuin-A or alpha-2-HS-glycoprotein (AHSG), the protein product of Ahsg gene. A prominent feature of this protein is the functional diversity exerted in human physiology and pathophysiology. Fetuin-A plays a role in bone metabolism, metabolic disorders such as insulin resistance and diabetes mellitus (DM), and central nervous system (CNS) disorders such as ischemic stroke (IS) and neurodegenerative diseases. In addition, emerging evidence suggests involvement of fetuin-A in the cardiovascular system. However, there are many discordant findings on the associations between fetuin-A and vascular diseases. In other words, it is unknown whether fetuin-A is an exacerbating or a protective factor in the cardiovascular system. One reason for the seemingly inconsistent behavior is the dual functionality of fetuin-A in vascular diseases where it can act as an atherogenic factor or as a vascular calcification inhibitor. In addition, the existence of confounding factors such as DM and renal dysfunction can veil the primary association between fetuin-A and clinical parameters. Considering these issues, we discuss the role of fetuin-A for atherosclerosis and vascular calcification in this review.
No preview · Article · Dec 2012 · Advances in clinical chemistry
[Show abstract][Hide abstract] ABSTRACT: Background
Recent in vitro and in vivo studies have suggested a critical role of osteocalcin (OC), especially the undercarboxylated form (ucOC), in insulin secretion and insulin sensitivity. The objective of this study was to investigate the association between serum ucOC levels and insulin resistance in humans with type 2 diabetes mellitus.
We measured serum ucOC levels in 129 patients with type 2 diabetes. Insulin resistance was assessed using the euglycemic hyperinsulinemic clamp technique. The insulin resistance indices used were the M value, which is the total body glucose disposal rate, and the M/I value, which is the M value adjusted for the steady state plasma insulin level. ucOC levels were not correlated with the M value (ρ = −0.013, p = 0.886) or the M/I value (ρ = 0.001, p = 0.995).
We found no association between ucOC levels and insulin resistance in patients with type 2 diabetes mellitus.
Full-text · Article · Dec 2012 · Diabetology and Metabolic Syndrome
[Show abstract][Hide abstract] ABSTRACT: Aim:
The adipocyte-derived hormone leptin plays a key role in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-associated atherosclerosis and cardiovascular disease. In this study, we investigated the associations of leptin and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with type 2 diabetes.
Three hundred seventeen type 2 diabetic subjects were enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R concentrations were measured by enzyme-linked immunosorbent assays. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasound.
The IMT was significantly associated with sOb-R concentrations, age, diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= -0.404, p<0.001) and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT in subjects treated with insulin for glycemic control, but not in those treated with diet alone or oral hypoglycemic agents. Multiple regression analysis, including age, sex, diabetes duration, body mass index, SBP, HbA1c, triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that plasma leptin and the leptin/sOb-R ratio were independently associated with IMT in subjects treated with insulin.
Plasma leptin and the leptin/sOb-R ratio are associated with atherosclerosis in patients with type 2 diabetes on insulin therapy, and these associations were independent of obesity and other cardiovascular risk factors.
No preview · Article · Oct 2012 · Journal of atherosclerosis and thrombosis
[Show abstract][Hide abstract] ABSTRACT: Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown of high mobility group box-1 and S100b, both of which are RAGE ligands endogenously expressed in 3T3-L1 cells, also canceled RAGE-medicated adipocyte hypertrophy, implicating a fundamental role of ligands-RAGE ligation. Adipocyte hypertrophy induced by RAGE overexpression is associated with suppression of glucose transporter type 4 and adiponectin mRNA expression, attenuated insulin-stimulated glucose uptake, and insulin-stimulated signaling. Toll-like receptor (Tlr)2 mRNA, but not Tlr4 mRNA, is rapidly upregulated by RAGE overexpression, and inhibition of Tlr2 almost completely abrogates RAGE-mediated adipocyte hypertrophy. Finally, RAGE(-/-) mice exhibited significantly less body weight, epididymal fat weight, epididymal adipocyte size, higher serum adiponectin levels, and higher insulin sensitivity than wild-type mice. RAGE deficiency is associated with early suppression of Tlr2 mRNA expression in adipose tissues. Thus, RAGE appears to be involved in mouse adipocyte hypertrophy and insulin sensitivity, whereas Tlr2 regulation may partly play a role.
[Show abstract][Hide abstract] ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was originally identified as an inducer of apoptosis in cancer cells. Recent findings suggest that TRAIL is also inversely associated with the severity of atherosclerosis and the prognosis of patients with advanced atherosclerosis. However, whether TRAIL is associated with early-stage atherosclerosis remains obscure. Therefore, we examined the association between serum TRAIL levels and endothelial and vascular smooth muscle dysfunction. Serum TRAIL levels were measured by ELISA in 121 patients with type 2 diabetes mellitus and without overt renal dysfunction. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were assessed to evaluate endothelial and vascular smooth muscle dysfunction, respectively. Serum TRAIL levels were not associated with either FMD (r = 0.038, p = 0.678) or NMD (r = 0.096, p = 0.343). These results reveal that serum TRAIL levels are not associated with endothelial and vascular smooth muscle dysfunction, suggesting that TRAIL may not be associated with early-stage atherosclerosis.
No preview · Article · Sep 2012 · Diabetology International
[Show abstract][Hide abstract] ABSTRACT: Background:Fibroblast growth factor (FGF)-23, secreted from osteocytes/osteoblasts, plays major roles in phosphate (Pi)-mediated stimulation of PTH secretion and consequently in regulation of serum Pi. Osteocyte/osteoblast dysfunction develops in patients with type 2 diabetes mellitus (DM).Objective:Our objective was to examine whether increases in serum FGF-23 and PTH after oral Pi stimulation are impaired in type 2 DM.Design and Methods:The subjects were 10 DM and 10 non-DM patients without chronic kidney disease stage 3-5. Serum FGF-23, intact PTH (iPTH), and Pi were measured serially after oral Pi administration at a daily dose of 2.0 g.Results:Pi administration caused significant increases of FGF-23 by 2 h and iPTH by 4 h in non-DM patients. These increases were attenuated in DM patients. After 2 d of Pi stimulation, serum FGF-23 and iPTH remained elevated in non-DM patients but not in DM. In all subjects, initial changes of serum FGF-23 (0-2 h) and iPTH (0-4 h) were positively correlated (r = 0.528) and showed significant negative correlations with later changes in serum Pi (2-4 h) (r = -0.457 and r = -0.673, respectively). Serum Pi (2-4 h) significantly increased in DM patients, consistent with the lack of change in serum FGF-23 and iPTH, whereas serum Pi did not change significantly in non-DM patients.Conclusion:These results show that increases of serum FGF-23 and PTH in response to Pi stimulation are impaired in type 2 DM and that serum Pi is significantly increased thereafter. This may be a mechanism underlying advanced atherosclerosis in type 2 DM.
Full-text · Article · Aug 2012 · The Journal of Clinical Endocrinology and Metabolism
[Show abstract][Hide abstract] ABSTRACT: Background
Endocrine and metabolic abnormalities may affect the survival of hemodialysis patients. Serum dehydroepiandrosterone sulfate (DHEA-S), an adrenal androgen with anabolic properties, is known to be lowered in ill patients and predicts poor outcome in the general population and in those with cardiac disease. The aims of this study were to examine a possible change in the DHEA-S level in dialysis patients and its association with survival in this population.Methods
This was an observational cohort study in 494 prevalent hemodialysis patients (313 men and 181 women) in urban area of Osaka, Japan. The main exposure was the baseline DHEA-S level in December 2004 and the key outcome was all-cause mortality during the subsequent 5 years. Also, DHEA-S levels were compared between the hemodialysis patients and 122 matched healthy controls.ResultsThe median (inter-quartile range) DHEA-S levels were 771 (447-1351) and 414 (280-659) ng/mL for male and female dialysis patients, respectively, and these values were significantly lower by 40-53% than the healthy control levels. Among the hemodialysis patients, DHEA-S was lower in women, those with older age, pre-existing cardiovascular disease, lower serum albumin and higher C-reactive protein. During the follow-up, we recorded 101 deaths. A low DHEA-S level was a significant predictor of all-cause mortality independent of potential confounders in male, but not in female, hemodialysis patients.Conclusions
The serum DHEA-S level is decreased in hemodialysis patients and associated with mortality in men. These results support the growing observational evidence that uremia-induced endocrine alterations including decreased sex hormones may be linked to adverse clinical outcomes.
[Show abstract][Hide abstract] ABSTRACT: Although poor glycemic control is known as an independent predictor of mortality in diabetic hemodialysis patients, it is often difficult for some patients to perform standard self injection insulin therapy. Some practical methods are needed for such patients. We evaluated the usefulness of a new regimen of insulin therapy, namely thrice-weekly insulin injection with nurse's support (TWINS) using insulin NPH or glargine at the end of each hemodialysis sessions in 5 outpatients on hemodialysis with type 2 diabetes mellitus showing HbAlc levels > or = 8.0% (JDS). HbA1c levels were successfully decreased in all patients from 9.3 +/- 1.1% to 6.9 +/- 0.7% (mean +/- SD) in six months without hypoglycemia symptoms. These preliminary results suggest that this regimen can be one of the practical choices in poor-controlled diabetes patients on regular hemodialysis who have difficulty in self injection of insulin.
No preview · Article · Jun 2012 · Osaka city medical journal
[Show abstract][Hide abstract] ABSTRACT: Elemental concentrations in hair from hemodialysis (HD) patients have not been well investigated. We examined the relationships between the elemental concentrations in scalp hair and health-related quality of life (HRQOL) and nutritional status in HD patients. Twenty six elemental concentrations were measured in scalp hair samples from 60 male HD patients using inductively-coupled plasma mass spectrometry. To evaluate HRQOL, the Short Form 36 item health survey (SF36) was used. As indices of nutritional status, body mass index, serum parameters, and geriatric nutritional risk index (GNRI) were used. Phosphorus correlated positively with serum creatinine, blood urea nitrogen (BUN), GNRI and the physical domains of the SF36. Zinc correlated positively with serum creatinine, BUN and the physical domains of the SF36. Mercury and arsenic correlated positively with BUN. Cadmium correlated negatively with serum albumin, BUN and GNRI. Copper correlated positively with the physical domains of the SF36. Iodine correlated negatively with the physical domains of the SF36. Selenium correlated negatively with the mental domains of the SF36. In conclusion, phosphorus and zinc concentrations in scalp hair can be additional biomarkers of HRQOL and/or nutritional status in HD patients. Cadmium accumulation correlated with malnutrition. Iodine and selenium accumulation may adversely affect HRQOL. Further investigation is necessary to determine precisely how these elements affect these measures.
No preview · Article · Apr 2012 · Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
[Show abstract][Hide abstract] ABSTRACT: Poor muscle quality provides a clinically relevant measure for mortality in general population, particularly in the elderly people. Our previous reports indicating poorer muscle quality in diabetes mellitus (DM) hemodialysis patients than in non-DM counterparts prompted us to examine the association between two parameters in hemodialysis patients, independent of DM prevalence.
The study was performed from 1997 to 2005. Grip dynamometry and dual-energy X-ray absorptiometry (DXA) were used to measure handgrip strength (HGS) and arm lean mass (ALM), respectively, with the muscle quality defined as the ratio of HGS to ALM.
During the mean follow-up period of 77 months, 90 out of 272 patients died. The patients were divided into higher and lower groups based on the values of muscle quality. In Kaplan-Meier analysis, the higher group revealed lower mortality than the lower group. Cox regression hazards analysis identified higher muscle quality as a significant independent predictor for better survival in hemodialysis patients (HR; 0.889, 95% CI 0.814-0.971; P<0.05), after adjustment for age, sex and the prevalence of DM. Since DM prevalence is a major factor for poorer muscle quality, another analysis was performed after restriction of the subjects to non-DM patients. The result also indicated that muscle quality provides a relevant measure independent of the presence of DM to predict the mortality in hemodialysis patients (HR; 0.849, 95% CI 0.759-0.950; P<0.05).
The study suggested that muscle quality provides a good marker for survival in hemodialysis patients, independently of the presence DM, age and serum albumin.
No preview · Article · Dec 2011 · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
[Show abstract][Hide abstract] ABSTRACT: To date, little proteomic information has been available from the glomeruli of diabetic patients, possibly due to the clinical limitations of renal biopsy in diabetic patients and insufficient quantities of such specimens for proteome analysis. The purpose of the present study was to identify altered protein expression profiles in diabetic glomeruli using formalin-fixed paraffin-embedded (FFPE) kidney tissues from diabetic patients.
Glomeruli were laser microdissected from FFPE autopsy kidney tissues from 10 patients with diabetic nephropathy and 10 non-diabetic control patients and underwent proteome analysis using QSTAR Elite liquid chromatography with tandem mass spectrometry and iTRAQ technology. Immunohistochemical analysis was performed on 93 autopsy samples from diabetic patients with and without nephropathy (n = 45 and n = 48, respectively).
Thirty-one renal and urological disease-related proteins displayed a differential abundance in glomerular samples from patients with diabetic nephropathy compared with non-diabetic control patients. Among them, we found that nephronectin, which functions in the assembly of extracellular matrix, showed clearly positive immunoreactivity in diabetic glomeruli. The numerical fraction of nephronectin-positive glomerular cross sections was increased significantly in diabetic patients with nephropathy compared to those without nephropathy (32.1 ± 31.5 versus 4.14 ± 5.65%, P < 0.0001). Furthermore, there was a significant positive correlation between this numerical fraction of nephronectin-positive glomerular cross sections and the glomerular sclerosis index (ρ = 0.881, P < 0.0001, n = 93).
The present study demonstrated, for the first time, that nephronectin may be associated with the development of diabetic glomerulosclerosis and that proteome analysis with FFPE kidney tissues from diabetic patients with nephropathy is useful in understanding diabetic nephropathy.
No preview · Article · Dec 2011 · Nephrology Dialysis Transplantation