Measurement of bioactive parathyroid hormone (PTH) is essential for optimal management of bone abnormalities in dialysis patients. This can be accomplished by PTH measurements using third-generation PTH assays, which detect more or less of the first six amino acids of the PTH structure. Such assays do not detect non-(1-84) PTH fragments, such as human PTH (7-84), which are recognized by the second-generation PTH assays that use a detection antibody that recognizes an epitope within the 13-34 region of the PTH structure. Therefore, third-generation PTH results are expected to be lower than those that are obtained with second-generation PTH assays. Rare exceptions to this rule have been reported for patients with severe primary hyperparathyroidism or parathyroid cancer. Sera and gland extracts were analyzed from a dialysis patient with high bone turnover disease and with surprising higher PTH levels by a third-generation assay than by a second-generation assay. This finding normalized after the surgical removal of an enlarged gland with a single nodule, an advanced type of nodular hyperplasia. HPLC fractionation of sera and gland extracts revealed the overproduction and secretion of a PTH molecule with an intact amino-terminus structure distinct from (1-84) PTH. This form of PTH was readily detectable by third-generation PTH assays but was poorly reactive in second-generation PTH assays. Therefore, parathyroid glands with advanced uremic nodular hyperplasia may overproduce and secrete a novel, biologically active form of PTH with an intact 1-6 region but a presumably modified 12-18 region required for the detection in second-generation PTH assays.

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.Materials and Methods:  A total of 167 health‐check examinees were classified into normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) according to 75 g oral glucose tolerance test (OGTT). Pancreatic and hepatic CT values were estimated at decreasing stages of glucose tolerance. The association of CT values of the pancreas and the indices of glucose tolerance were analyzed.Results:  Insulinogenic index (II) was decreased from NGT through IGT to DM. Mean pancreatic CT value was decreased significantly from NGT through IGT to DM. Mean area under the curves of glucose (AUC‐G) was significantly associated with II and insulin sensitivity index (ISI) composite in univariate analysis. In multiple regression analysis, II was most strongly inversely correlated with mean AUC‐G, suggesting that II is the strongest determinant of glucose tolerance in Japanese. In addition, II was significantly associated with mean pancreatic CT value in univariate analysis. In multiple regression analysis, mean pancreatic CT value was strongly correlated with II.Conclusions:  Pancreatic CT values were significantly decreased from NGT through IGT to DM. II was the strongest determinant of glucose tolerance, and was significantly influenced by pancreatic CT values. Thus, pancreatic fat deposition might impair insulin secretion in the early stage of development of type 2 diabetes, before overt deterioration of glucose tolerance. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00212.x, 2012)

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.

A dipeptidyl peptidase (DPP)-4 inhibitor, commonly used to treat patients with type 2 diabetes, has caused concern because of immune system side effects. We report a 48-year-old woman with type 2 diabetes who was diagnosed with rheumatoid arthritis (RA) after continued polyarthritis and an increase in rheumatoid factor up to 86 IU/mL after three months of treatment with sitagliptin, a DPP-4 inhibitor. The shared epitope (SE)-containing human leukocyte antigen (HLA)-DRB1 alleles, which are important predisposing factors for RA, were positive. RA might have been triggered by sitagliptin due to a predisposing condition.

This 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. We 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.

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.

We describe a patient who had a metastatic gastrointestinal stromal tumor (GIST) after previous failed extensive therapy, including multiple surgeries and hepatic artery embolization. Within a few months of starting administration of imatinib mesylate, the patient exhibited a clinical response with grade 3 neutropenia, when pulmonary tuberculosis developed. A c-kit mutation in exon 11 was detected only in metastatic liver specimens. It is unclear whether or not pulmonary tuberculosis may be induced by imatinib mesylate treatment, but caution is warranted in immunocompromised GIST patients. This is the first report of tuberculosis associated with neutropenia during imatinib mesylate treatment.

Lipids, apoproteins and associated enzyme activities in type 2 diabetic end-stage renal disease (ESRD) were compared with that in nondiabetic ESRD and normal controls. Of the 40 uremic patients with non-insulin-dependent diabetes mellitus, 20 patients were receiving stable continuous hemodialysis treatment (CHT). Of the 39 patients with nondiabetic ESRD, 21 were undergoing CHT. Patients with nondiabetic ESRD exhibited elevated levels of serum triglyceride and a marked reduction in high-density-lipoprotein (HDL) cholesterol. Concentrations of serum apolipoprotein (Apo) C-3 were higher than in controls, whereas mean levels of serum Apo E were lower. The concentrations of serum Apo A-1 and Apo A-2 decreased with diminished lecithin: cholesterol acyltransferase activity. Lipoprotein lipase activity decreased in undialysed patients, and hepatic triglyceride lipase activity decreased significantly throughout the observation. Patients with diabetic ESRD exhibited elevated serum Apo B and normal serum Apo E levels, besides the lipid and Apo abnormalities observed in nondiabetic ESRD. Moreover, a prominent reduction in serum Apo A-1 was found in dialysed diabetic patients. The Apo B/Apo A-1 ratio was significantly higher in diabetic ESRD than in nondiabetic patients undergoing CHT. These results indicate that lipid abnormalities are accelerated in diabetic ESRD and may constitute a serious risk for the development of atherosclerosis.