Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study.

BACKGROUND: Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) plays a crucial role in lipolytic processing. Previous studies have shown that GPIHBP1 mutations cause severe hypertriglyceridemia and that serum GPIHBP1 levels are marginally higher in patients with coronary heart disease; however, the role of GPIHBP1 in type 2 diabetes mellitus (T2DM) remains unknown. OBJECTIVE: We investigated the association between circulating GPIHBP1 levels and the prevalence of microvascular complications in T2DM. METHODS: A total of 237 subjects with T2DM and 235 non-diabetic control subjects were enrolled in this study. Their serum GPIHBP1 levels were evaluated using ELISA assays. RESULTS: Circulating GPIHBP1 levels were higher in patients with T2DM (952.7 pg/mL [761.3-1234.6], p < 0.0001) than in non-diabetic subjects (700.6 [570.8-829.6]), but did not differ in T2DM patients with or without hypertriglyceridemia. Serum GPIHBP1 levels were significantly higher in patients with T2DM with diabetic retinopathy (DR), diabetic nephropathy (DN), and microvascular complications than in those without these complications. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses revealed that the presence of microvascular complications, but not macrovascular complications, was independently associated with serum GPIHBP1 levels, which could predict the presence of diabetic microvascular complications. CONCLUSIONS: Elevated GPIHBP1 levels are associated with microvascular complications in T2DM and may help to predict their progression.

Identification of circulating miR-101, miR-375 and miR-802 as biomarkers for type 2 diabetes.

PURPOSE: The unique circulating microRNAs (miRNAs) observed in patients with type 2 diabetes (T2D) are candidates as new biomarkers and therapeutic targets. In order to identify circulating miRNAs relevant to the disease process in case of type 2 diabetes, we performed the Illumina sequencing of miRNAs derived from the serum, liver and epididymal white adipose tissue (WAT) of diet-induced obese male C57BL/6J mice. BASIC PROCEDURES: We selected four miRNAs, miR-101, miR-335, miR-375, and miR-802, which are increased in the sera and tissues of obese mice, and measured the serum levels of miRNAs in T2D and subjects with normal glucose tolerance (NGT). MAIN FINDINGS: The serum concentrations of miRNAs, log(10)miR-101, log(10)miR-375, and log(10)miR-802, were significantly increased in the T2D patients compared with NGT subjects (1.41±2.01 v.s. -0.57±1.05 (P=1.36×10(-5)), 0.20±0.58 v.s. 0.038±1.00 (P=3.06×10(-6)), and 2.45±1.27 v.s. 0.97±0.98 (P=0.014), respectively). The log(10)miR-335 values did not demonstrate any significant differences between the T2D and NGT groups (-1.08±1.35 v.s. -0.38±1.21 (P=0.25)). According to the stepwise regression analysis, the HbA1c was an independent predictor of miR-101. Regarding the serum miR-802 levels, eGFR, HbA1c and HDL-C values were identified as significant determinants. PRINCIPAL CONCLUSIONS: The present findings demonstrated that the circulating miR-101, miR-375 and miR-802 levels are significantly increased in T2D patients versus NGT subjects and they may become the new biomarkers for type 2 diabetes.

Accumulated cytokines in stored autologous blood do not cause febrile nonhemolytic transfusion reactions.

Accumulated inflammatory cytokines are considered to be a cause of febrile nonhemolytic transfusion reactions (FNHTRs) of platelet transfusions. Inflammatory cytokines have been found in red cell components stored at 4 degrees C; however, their relationship to FNHTRs has not been clearly demonstrated following red cell transfusions. We measured cytokine levels in stored blood, and determined whether inflammatory marker concentrations were elevated in subjects infused with autologous blood stored for 5 weeks. In conclusion, cytokines accumulated in blood stored at 4 degrees C, but their increases were small. No changes were seen in recipients' inflammatory markers after blood transfusion. Our results indicate that cytokines in stored autologous blood are not responsible for FNHTRs.

Changes of gene expression profiles in macrophages stimulated by angiotensin II--angiotensin II induces MCP-2 through AT1-receptor.

INTRODUCTION: Macrophages play critical roles in the development of atherosclerosis and diabetic nephropathy as well as many inflammatory diseases. Angiotensin II type 1 receptor antagonists (AIIA) are beneficial for the prevention of atherosclerosis and diabetic nephropathy suggesting that angiotensin II (Ang II) promotes the development of these diseases. It has recently been reported that Ang II exerts proinflammatory actions in vivo and in vitro. This study was aimed to clarify the direct effects of Ang II on monocytes/macrophages. MATERIALS AND METHODS: PMA-treated THP-1 cells, a human monocytic leukaemia cell line, were treated with Ang II (10-6 mol/L) for 24 hours with or without AIIA (CV11974). We evaluated gene expression profiles of these cells using DNA microarray system and quantified them by real-time RT-PCR. RESULTS: DNA microarray revealed that in total 19 genes, including monocyte chemoattractant protein (MCP)-2, were up-regulated by Ang II and down-regulated by AIIA. Real-time RT-PCR showed that up-regulation of MCP-2 with Ang II is blocked by the AIIA (CV11974) but not by an AT2-receptor antagonist. CONCLUSIONS: These results suggest that Ang II directly stimulates MCP-2 expression through AT1-receptors in activated macrophages. Ang II may contribute to the persistence or amplification of microinflammation in vessel walls, heart and kidney. Vasculoprotective or renoprotective effects of AIIA might partly depend on direct anti-inflammatory effects on macrophages.

Pre-transfusion screening for platelet-reactive antibodies.

We retrospectively compared the cost of platelet concentrates (PCs) used for patients whose serum had already been screened for platelet-reactive antibodies with the cost for patients whose serum was examined after the commencement of treatment using platelets. On the basis of 774 patients' data, the mean cost of PCs for the latter group of patients ($5562) was higher than that for the former group ($2547). Screening beforehand ensured a prompt supply of specific PCs, and costs were suppressed by the avoidance of multiple transfusions. We conclude that screening for platelet-reactive antibodies followed by administration of crossmatch-negative PCs appears to be both clinically and economically advantageous.

Transfusion-related problems following major ABO-incompatible bone marrow transplantation.

A case of acute myelocytic leukemia has been reported in which the patient's surviving original B lymphocytes after pretransplant-conditioning chemotherapy probably reproduced hemagglutinins that reacted with red blood cells (RBCs) derived from engrafted donor marrow for a prolonged period of time. Although the direct antiglobulin test was negative and hemagglutinins were not detectable in the patient's sera but only in the eluate, the antibodies reappeared in the sera. Therefore, it is important to confirm that the eluate does not contain antibodies that would react with donor-derived RBCs when the type of red cell used for transfusion is switched from the patient's type to the donor's type in a major ABO-mismatched bone marrow transplantation (BMT). Testing of ABO subgroups using lectins is also recommended to avoid a delayed hemolytic transfusion reaction following BMT.