Renal arteriolar hyalinosis, not intimal thickening in large arteries, is associated with cardiovascular events in people with biopsy-proven diabetic nephropathy.

AIMS: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. METHODS: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. RESULTS: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. CONCLUSIONS: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy.

Frailty, health-related quality of life and mental well-being in older adults with cardiometabolic risk factors.

OBJECTIVE: Frailty is an emergent health-related problem in older adults. The aim of this study was to examine the health-related quality of life (HRQOL) and the effect of frailty in elderly patients with cardiometabolic risk factors. METHODS: One-hundred and one patients 65 years or older responded to an HRQOL assessment using the World Health Organization Quality of Life (WHOQOL)-26 questionnaire. Frailty was assessed using two indices: the Hebrew Rehabilitation Center for Aged (HRCA) vulnerability index and the Vulnerable Elders Survey (VES) index. In addition, these patients completed self-rating questionnaires assessing mental well-being [the 28-item version of the General Health Questionnaire (GHQ-28)] and depression (Geriatric Depression Scale). RESULTS: Based on the combination of HRCA and VES indices, 24 subjects (23.7%) met the criteria of frail. Persons > or = 75 years old and those with depressive mood or lower creatinine clearance had significantly lower WHOQOL-26 scores than their counterparts. Diabetes and macrovascular complications did not associate with the WHOQOL-26 scores. Compared with non-frail patients, the frail scored lower on the WHOQOL-26 questionnaire after adjusting for age, kidney dysfunction and depressive mood. Frail patients also reported significantly higher the GHQ-28 scores compared with non-frail patients. CONCLUSIONS: Frail older adults had a significant lower HRQOL, as well as lower mental well-being, independent of age, diabetes, macrovascular complication, kidney dysfunction and depressed mood.

Purification and characteristics of feruloyl esterase from Aspergillus awamori G-2 strain.

For food industry production processes and other uses, a mold that produces high levels of feruloyl esterase was obtained from laboratory mold collections and other sources. It was Aspergillus awanmori G-2 that produces high levels of feruloyl esterase. The feruloyl esterase was purified using ion-exchange chromatography, size-exclusion chromatography, and HPLC chromatography. The enzyme was identified as a monomer protein using size-exclusion chromatography. Its optimum temperature and pH were, respectively, 40 degrees C and pH 5. Its activity was stable at pH 3 to 5. The enzyme was combined with xylan and starch, but it was absorbed by cellulose. The km of the feruloyl esterase was 0.0019% (0.01 mM). The enzyme showed stable activity at pH 3 and 50 degrees C, making this enzyme useful for food production.

New "pre-diabetes" category and the metabolic syndrome in Japanese.

BACKGROUND: Recently, impaired fasting glucose (IFG) was redefined as fasting plasma glucose of 100-125 mg/dl, and individuals with IFG and/or impaired glucose tolerance (IGT) were referred to as having "pre-diabetes". However, there is a lack of data using the new definition of IFG and "pre-diabetes". OBJECTIVE: The aim of this study was to examine associations of the metabolic syndrome components with the new "pre-diabetes" category in relatively lean Japanese. METHODS: Six hundred and sixty-one Japanese study participants underwent a 75 g oral glucose tolerance test. They were classified into three groups-normal (n=225), pre-diabetes (n=308), and diabetes (n=128). The metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III, as modified for waist circumference criteria by the Regional Office for the Western Pacific Region of WHO. RESULTS: Prevalence of the metabolic syndrome in each group was 10.7%, 27.9%, and 53.9%, respectively. Of the metabolic syndrome components, the OR for prevalent pre-diabetes was 2.00 (95% CI, 1.73-2.31, p<0.001) for fasting glucose, 1.93 (95% CI, 1.54-2.42, p<0.001) for waist circumference, and 1.36 (95% CI, 1.10-1.68, p=0.005) for triglycerides. Similar associations were found in prevalent diabetes. Insulin resistance assessed using Stumvoll's index was significantly associated with both pre-diabetes and diabetes. CONCLUSION: Pre-diabetes and the metabolic syndrome frequently coexist in relatively lean Japanese. This association seems to link with abdominal adiposity and insulin resistance.

Beta-cell function and insulin sensitivity contribute to the shape of plasma glucose curve during an oral glucose tolerance test in non-diabetic individuals.

To clarify whether beta-cell function and/or insulin resistance contributes to the shape of plasma glucose curve during an oral glucose tolerance test (OGTT), we investigated 583 Japanese subjects with normal glucose tolerance (NGT, n = 306) or impaired glucose tolerance (IGT, n = 277). Each subject was subdivided into three shapes of plasma glucose curve as follows: monophasic pattern (M type), biphasic pattern (B type) and two peaks (T type). Homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and insulinogenic index were assessed by plasma glucose and insulin concentrations obtained at fasting or during an OGTT. There was a greater proportion of M type in the IGT group (M = 80.9%, B = 15.5% and T = 3.6%), whereas the prevalence of B and T types was much higher in the NGT group (M = 66.6%, B = 26.5% and T = 6.9%). There were significant differences in the proportions of shape types between the NGT and IGT groups (p = 0.0006). Among the NGT category, insulin sensitivity was significantly higher in the B type than in the M type, and beta-cell function adjusted for insulin resistance was significantly higher in the B and T types than in the M type. Among the IGT category, no significant differences were seen among the three shape types with respect to insulin sensitivity, but the beta-cell function adjusted for insulin resistance was significantly lower in the M type than in the B and T types. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of the shape of plasma glucose curve in Japanese subjects.

Use of novel assays to indicate that O-esters and S-esters are produced by the same enzyme in brewing yeast.

Ethanol- and methanethiol-dependent removal of acetyl-CoA by crude extracts of ale yeast has been monitored using a decrease in OD232. Activity has also been detected in these extracts after fractionation on polyacrylamide gels, in this case using a novel assay in which the coenzyme A produced in the reaction is linked via DCPIP reduction to color formation from nitroblue tetrazolium. Ethanol- and methanethiol-dependent activities migrate identically on such gels, and only one band of color formation was observed. Furthermore they displayed closely similar sensitivity to heating at 40 degrees C and 60 degrees C and pH optima, with activity maximal at pH 7.5. It is likely that a single enzyme is responsible for the formation of O-esters and S-esters in yeast. Initial kinetic studies indicate that methanethiol has higher affinity for the enzyme than has ethanol and a higher maximum velocity. However, the enzyme has a much lower Km for acetyl-CoA, suggesting that the alcohol or thiol substrate is the more likely substrate to be limiting.

Association of transforming growth factor-beta1 T29C polymorphism with the progression of diabetic nephropathy.

Diabetes mellitus is a leading cause of end-stage renal disease in the Western world. Histologically, mesangial expansion with increased extracellular matrix protein is observed in patients with diabetic nephropathy. Because transforming growth factor (TGF)-beta promotes extracellular matrix production in response to high glucose, TGF-beta is considered to play a central role in the pathogenesis of diabetic nephropathy. We investigated the association of TGF-beta1 T29C polymorphism and the progression of diabetic nephropathy. Forty patients with type 2 diabetes mellitus were enrolled. All patients had had diabetes for more than 10 years. DNA was extracted from peripheral blood cells, and genotype was determined using real-time polymerase chain reaction method. Patients were classified into three groups according to genotype: TT, TC, and CC. Grade of diabetic nephropathy was determined using the amount of urinary excretion of albumin. Demographic characteristics of the patients with each genotype were not statistically different. No differences in the glycemic control and the mode of therapy were observed. Among patients with three genotypes, the severity of diabetic nephropathy was not statistically different. The patients with TT genotype tended to have a higher rate of progression of nephropathy; however, no statistically significant difference was observed among the three groups. Our results suggest that TGF-beta1 T29C polymorphism is not associated with the progression of diabetic nephropathy. Further studies are required to determine the exact role of this polymorphism in the progression of diabetic nephropathy.

Serum levels of advanced glycosylation end products in diabetic nephropathy.

BACKGROUND/AIMS: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. METHODS: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. RESULTS: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 +/- 0.73 mU/ml; 15-24%, 4.01 +/- 0.71 mU/ml; 25% or more, 5.12 +/- 0.64 mU/ml). CONCLUSIONS: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.

[Two cases of exercise-induced acute renal failure with idiopathic renal hypouricemia].

Acute renal failure without oliguria developed in a 25-year-old male and a 19-year-old male after exercise. Marked hypouricemia became apparent during improvement of their renal function. Increased excretion of uric acid into the urine, increased fractional excretion of uric acid(clearance ratio of uric acid against creatinine), and normal concentration of plasma xanthine and hypoxanthine were observed in both cases. Probenecid and pyrazinamide loading test suggesting decreased reabsorption of uric acid in the proximal convoluted tubules revealed that presecretory reabsorption defect of uric acid resulted in the hypouricemia in both cases. These two cases were diagnosed as having idiopathic renal hypouricemia.

Advanced glycation end products in nondiabetic patients with coronary artery disease.

OBJECTIVE: To investigate whether advanced glycation end products (AGEs) participate in the development of coronary artery disease (CAD) in nondiabetic and diabetic subjects. RESEARCH DESIGN AND METHODS: Serum concentrations of AGEs were measured using a newly established enzyme-linked immunosorbent assay in 48 nondiabetic patients (normal glucose tolerance, n = 20; impaired glucose tolerance, n = 28) who received coronary angiography for the study of chest pain or suspected CAD. Insulin sensitivity was examined by the euglycemic-hyperinsulinemic glucose clamp technique and was estimated as the mean glucose infusion rate during the last 30 min of clamp time (M value). RESULTS: Patients were classified into four groups based on the number of significantly stenosed vessels, defined as 0-, 1-, 2-, or 3-vessel disease. Serum concentrations of AGEs were significantly higher in nondiabetic subjects with CAD than in control subjects (2.42 +/- 0.65 vs. 1.96 +/- 0.40 mU/ml, P < 0.01) and significantly correlated with the number of significantly stenosed vessels (r = 0.678, P < 0.001). M values significantly inversely correlated with serum concentrations of AGEs (r = -0.490, P < 0.05). In multiple regression analysis, with the number of significantly stenosed vessels as the dependent variable, serum concentrations of AGEs, 2-h plasma glucose, and areas under the plasma glucose response curve were independently associated. CONCLUSIONS: This pilot study indicates the relation between AGEs and the severity of CAD in nondiabetic patients. The measurement of serum AGE concentrations may be predictive of vascular damage.

Growth of Trichoderma viride on crude cell wall preparations from barley.

Trichoderma viride can utilize crude cell wall preparations from barley starchy endosperm as sole source of carbon and energy. In the process beta-(1-->3)(1-->4)-glucan and arabinoxylan are released. The onset of release of the latter preceded that of glucan, consistent with arabinoxylan being encountered and utilized first. The release of several enzymes was observed during growth of Trichoderma on this substrate: endo-beta-(1-->3)(1-->4)-glucanase, endo-beta-(1-->4)-glucanase, endo-xylanase, arabinofuranosidase, esterase, carboxypeptidase, and "beta-glucan solubilase". It is inferred that each of these activities is necessary for the digestion of this substrate.

Predictors of diabetic renal lesions in type 2 diabetes associated with microalbuminuria.

Not all type 2 diabetic patients with microalbuminuria show the same pattern of renal tissue injury, and heterogeneity in renal lesions has been reported. We determine clinical and laboratory findings that predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria. Twenty-three type 2 diabetic patients with microalbuminuria who underwent renal biopsy were investigated. Two patterns of renal biopsy findings were defined as type D (typical diabetic glomerulosclerosis) and type A (atherosclerotic nephropathy without evidence of diabetic glomerulopathy). Thirteen patients (57%) were classified as type D, and 10 (43%) as type A. In stepwise multiple regression analysis, severity of diabetic retinopathy (P = 0.0006), relatively high urinary N-acetyl-beta-D-glucosaminidase activity (P = 0.0013), and relatively low serum creatinine concentration (P = 0.0303) significantly predicted type D findings as opposed to type A (R2 = 0.734, P < 0.001). Certain patient characteristics can predict the presence of typical diabetic glomerulosclerosis in type 2 diabetic patients with microalbuminuria.

Serum IgA levels in patients with diabetic nephropathy and IgA nephropathy superimposed on diabetes mellitus.

The aim of this study was to examine the relationship between serum immunoglobulin A (IgA) levels and diabetic nephropathy in patients with type 2 diabetes mellitus, and to describe the role of IgA nephropathy superimposed on diabetes mellitus. A total of 127 type 2 diabetic patients were studied. Of these diabetics, 74 had no proteinuria, 35 had diabetic glomerulosclerosis confirmed by renal biopsy, 13 had superimposed IgA nephropathy, and five had superimposed non-IgA nephropathy. We also studied 93 non-diabetic patients with IgA nephropathy, 24 non-diabetic patients with non-IgA nephropathy, and 38 non-diabetic controls. Serum IgA levels were significantly higher in IgA nephropathy patients (350+/-130 mg/dl) than in non-diabetic controls (228+/-56 mg/dl) and diabetics without proteinuria (268+/-104 mg/dl). Serum IgA levels were also significantly higher in diabetics with superimposed IgA nephropathy (470+/-208 mg/dl) than in non-diabetic controls, non-IgA nephropathy patients (270+/-133 mg/dl), diabetics without proteinuria, diabetic glomerulosclerosis alone (302+/-126 mg/dl), and diabetics with superimposed non-IgA nephropathy (248+/-137 mg/dl). The prevalence of high serum IgA levels was significantly higher in diabetics with superimposed IgA nephropathy (76.9%) than in diabetic glomerulosclerosis alone (31.4%) and diabetics with superimposed non-IgA nephropathy (25.0%). In conclusion, our findings indicate that high serum IgA level is a sign of the existence of IgA nephropathy superimposed on diabetes mellitus.

Association of Chlamydia pneumoniae infection with diabetic nephropathy.

We evaluated the association of Chlamydia pneumoniae (CP) infection with progression of diabetic nephropathy. Type 2 diabetic patients (60) were divided into two groups, those with incipient nephropathy and those with advanced nephropathy, based on the severity of diffuse glomerular lesions using Gellman's criteria. Type 2 (34) diabetic patients without nephropathy (normoalbuminuria) and 59 nondiabetics served as control groups. Serum IgG-antibody against CP was measured using ELISA. CP antibody was detected in 45.8% of nondiabetic controls, in 47.1% of diabetic patients without nephropathy, in 52.6% of diabetic patients with incipient nephropathy, and 78% of diabetic patients with advanced nephropathy. There was 4.22-fold increase in the risk of advanced nephropathy associated with the presence of CP antibody. Our findings indicate an association between chronic CP infection and advanced diabetic nephropathy.