Naoya Igaki

Increased Serum High-Molecular-Weight Complex of Adiponectin in Type 2 Diabetic Patients with Impaired Renal Function

Background/Aim: Adiponectin, an adipocyte-derived protein, has been shown to exert antidiabetic, anti-inflammatory, and antiatherosclerotic effects. Although recent reports show an increase in the total adiponectin levels in chronic kidney disease patients and in patients with end-stage renal disease, the nature of biodegradation and renal involvement of adiponectin is largely unknown. We aimed at determining whether the high-molecular-weight (HMW) complex of adiponectin is associated with renal insufficiency in type 2 diabetic patients. Methods: A total of 179 type 2 diabetic patients were selected from among outpatients and divided into four groups according to their albumin-to-creatinine ratio: patients with normoalbuminuria (n = 86), patients with microalbuminuria (n = 44), patients with macroalbuminuria (n = 23), and patients on hemodialysis (n = 26). The serum HMW adiponectin was specifically assayed with a commercially available enzyme-linked immunosorbent assay kit. Results: The HMW adiponectin levels were higher in patients on hemodialysis (17.1 ± 8.2 µg/ml) and in those with macroalbuminuria (14.3 ± 8.7 µg/ml) than in patients with normoalbuminuria (7.2 ± 5.6 µg/ml) and microalbuminuria (10.8 ± 7.0 µg/ml). Univariate linear regression analysis showed that the HMW adiponectin concentrations correlated negatively with the estimated glomerular filtration rate in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria (r = –0.42, p < 0.001). Multiple stepwise regression analysis disclosed that estimated glomerular filtration rate, pioglitazone therapy, gender differences, and systolic blood pressure were independently associated with HMW adiponectin levels (r = 0.56). Conclusions: The serum HMW adiponectin concentrations are higher in type 2 diabetic patients with nephropathy, and these levels are also associated with renal insufficiency.

An outbreak of fulminant hepatitis B in immunocompromised hemodialysis patients

BackgroundWe aimed to clarify the pathogenesis of an outbreak of fulminant hepatitis B in hemodialysis (HD) patients whose compromised cell-mediated immunity in turn contributed to chronic hepatitis B virus (HBV) carriage.MethodsFive consecutive adult HD patients with acute hepatitis B were evaluated. Viral genotype, mutations, and HBV-DNA levels were studied in relation to viral clearance, liver disease severity, and liver histology by immunostaining.ResultsAll five patients had hepatitis B surface antigen (HBsAg) genotype C, a G-to-A stop codon mutation at nucleotide (nt) 1896 in the precore region, an A-to-T mutation at nt 1762 and an G-to-A mutation at nt 1764 in the basal core promoter. The possible index patient, who suffered from liver cirrhosis, had HBsAg genotype C, anti-hepatitis B envelope (HBe), and these mutations. The level of HBV-DNA declined by about 10 percent per week and no difference in viral kinetics between the patients who died and the survivor was found, irrespective of therapies. The amount of liver cell apoptosis, as assessed by single-stranded DNA, was scarce. The risk of fulminant hepatic failure did not correlate with the preexistent liver histopathological changes. Acute HBV superinfection was associated with hepatitis C virus (HCV) elimination and increased mortality.ConclusionsThis outbreak of fulminant hepatitis B suggests that HD patients can foster highly virulent HBV strains (possibly owing to their compromised immune responses), which may place others at risk of severe, life-threatening acute liver damage and at increased risk of mortality if chronic carriers of HCV should be infected.

Adiponectin is associated with brain natriuretic peptide and left ventricular hypertrophy in hemodialysis patients with type 2 diabetes mellitus.

Background: Adiponectin, an adipocyte-derived hormone, has been shown to prevent the progression of left ventricular hypertrophy (LVH). However, recent studies have demonstrated increased levels of adiponectin according to the severity of chronic heart failure. We therefore investigated the relationships between adiponectin, brain natriuretic peptide (BNP), and LVH in type 2 diabetic patients on hemodialysis. Methods: The study population comprised 41 type 2 diabetic patients on hemodialysis. Left ventricular mass index (LVMI) and criteria for LVH were determined on the basis of echocardiographic findings. Serum adiponectin and plasma BNP levels were assayed with a commercially available kit. Results: Serum adiponectin levels significantly correlated with BMI (r = –0.49, p < 0.01), HDL-C (r = 0.36, p < 0.05) and TG (r = –0.49, p < 0.01). In addition, serum adiponectin levels correlated significantly and positively with plasma BNP levels (r = 0.36, p < 0.05). This relationship remained significant after adjustment for age, gender, and BMI (r = 0.34, p < 0.05). Serum adiponectin levels as well as plasma BNP levels were significantly higher than in patients without LVH (p < 0.05; p < 0.01, respectively), accompanied by a positive correlation between these levels and LVMI (r = 0.42, p < 0.01; r = 0.32, p < 0.05, respectively). Conclusion: Increased levels of adiponectin were associated with elevated BNP levels and LVH in hemodialysis patients with type 2 diabetes mellitus. It is speculated that adiponectin levels may be modulated by chronic hypervolemic state in this population.

Acceleration of Fructose Mediated Collagen Glycation

The effect of fructose on the formation of advanced Maillard reaction products which show fluorescence and have crosslinking was investigated. Type I collagen was added to various concentrations of glucose and fructose which were then incubated at 37°C for 4 weeks. The level of furosine and the fluorescence intensity both increased in direct proportion to glucose and fructose levels and to the duration of incubation. Incubation with fructose produced less furosine but more intense fluorescence than incubation with glucose. Furthermore, collagen was significantly less soluble after incubation with fructose than after incubation with glucose. These results suggest that fructose in the polyol pathway plays an important role in the formation of advanced Maillard products.

Purification of α-ketoaldehyde dehydrogenase from the human liver and its possible significance in the control of glycation

Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body.

Age- and diabetes-accelerated glycation in the human aorta.

The extent of glycation in pieces of human aorta was estimated by determining the content of furosine, which is derived from fructose-lysine through acid hydrolysis. Glycation of human aorta was found to increase with advancing age. A significant positive correlation was found between the degree of atherosclerosis and the furosine level in the aorta in subjects over 60 years of age. Furthermore, the furosine level in the aortae of diabetic patients was significantly higher than that in normal subjects of the same age. These results suggest not only that glycation in the aorta may increase with aging and with the development of arteriosclerosis, but also that diabetes may be related as well to premature aging as to arteriosclerosis.

Insulin secretion and computed tomography values of the pancreas in the early stage of the development of diabetes

Aims/Introduction:  The computed tomography (CT) value of the pancreas was examined across the range of glucose tolerance, and the relationships between pancreatic CT values and factors responsible for glucose intolerance were analyzed.

Fructose-related glycation

We investigated in vitro the effect of the polyol pathway on the formation of advanced Maillard reaction products which have fluorescence and cross-links. Bovine serum albumin supplemented with various concentrations of glucose, fructose or sorbitol was incubated for 14 days. The fluorescence intensity was higher after incubation with fructose than after incubation with glucose. However, no significant increase in fluorescence intensity was found after incubation with sorbitol. These results suggest that in the polyol pathway fructose plays an important role in the formation of advanced Maillard products.

Calcium, Phosphorus, Cardiovascular Events and All‐cause Mortality in Hemodialysis Patients: A Single‐center Retrospective Cohort Study to Reassess the Validity of the Japanese Society for Dialysis Therapy Guidelines

Abstract:  Mineral and bone disorders frequently cause cardiovascular complications and mortality in hemodialysis patients, but few observational studies of Japanese patients have investigated this matter. A retrospective cohort study of 99 patients (53 males, 46 females; mean age: 65 ± 12 year; 38% with diabetes mellitus) on maintenance hemodialysis in our dialysis center was conducted. Mean serum Ca, P and intact parathyroid hormone (iPTH) levels were 9.2 ± 0.9 mg/dL, 6.1 ± 1.7 mg/dL, and 233 ± 333 pg/mL, respectively. The cutoff values for each of these three parameter were defined according to the target ranges recommended by the Japanese Society for Dialysis Therapy (JSDT) guidelines (Ca: 8.4–10.0 mg/dL; P: 3.5–6.0 mg/dL; iPTH: 60–180 pg/mL). During a 45‐month follow up, patients with all parameters outside the target ranges showed the highest incidence of cardiovascular events and all‐cause deaths (16.6 and 29.2 per 1000 person‐years, respectively). The relative risks of cardiovascular events and all‐cause deaths were analyzed by multivariate Cox regression models. The hazard ratio (HR) for cardiovascular events was significantly lower for patients who achieved serum Ca and P objectives compared with others (HR: 2.12; 95% CI: 1.04–4.34; P < 0.05), and similar differences were observed for all‐cause deaths (HR: 3.10; 95% CI: 1.13–8.53; P < 0.05). However, the relationship between iPTH levels and each of the endpoints was less pronounced. The results of this study provide support for the JSDT guidelines, which give priority to the control of serum Ca and P levels over the control of parathyroid function.

The beneficial effect of effective control of anemia on hyperinsulinemia and hypoxemia in a hemodialysis patient with corrected transposition of the great arteries

We report the beneficial effect of control of anemia on hyperinsulinemia and hypoxemia in a hemodialysis patient with corrected transposition of the great arteries. The patient’s hemoglobin (Hb) level of 10.3 g/dl on admission represents good control for hemodialysis (HD) patients, but it was too low for this patient with secondary polycythemia because of a right-to-left shunt. Control of anemia for a 10-month period was followed by a marked increase in Hb level (from 10.3 g/dl to 13.9 g/dl) and in aerobic work capacity, while the fasted insulin level decreased from 36.7 µU/ml to 8.0 µU/ml, without changes in leptin level, body mass index (BMI), fat mass, Kt/V, or protein catabolic rate (PCR). Additionally, hypoxemia was ameliorated, from PO2 33.1 mmHg to PO2 56.2 mmHg, and the hyperdynamic cardiac state was improved. The degree of anemia, together with deteriorating tissue oxygenation, may have predisposed this patient to developing insulin resistance and consequent hyperinsulinemia. The most appropriate target Hb concentration should be tailored for the clinical condition of each individual patient, bearing in mind an insulin-resistance state, especially in hemodialysis patients with hypoxemia. A more complete understanding of what regulates insulin resistance and consequent hyperinsulinemia in endstage renal disease (ESRD) awaits the elucidation of carbohydrate and insulin metabolism.