Status of treatment-related severe hypoglycemia in Japanese patients with diabetes

Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web‐based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility‐specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the “presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)”, the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility‐specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4,962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2,237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1,171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480 and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively; those with type 2 diabetes were shown to be significantly older (median [interquartile range], 77.0 [68.0–83.0]) than those with type 1 diabetes (54.0 [41.0–67.0]) (P < 0.001); and the BMI was shown to be significantly higher for those with type 2 diabetes (22.0 [19.5–24.8] kg/m2) than for those with type 1 diabetes (21.3 [18.9–24.0] kg/m2) (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes (50.6 mL [31.8–71.1]/min/1.73 m2) than among those with type 1 diabetes (73.3 [53.5–91.1] mL/min/1.73 m2) (P < 0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3–8.1)% among all patients examined, 7.5 (6.9–8.6)% among those with type 1 diabetes, and 6.8 (6.1–7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P < 0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin‐naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment‐related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia not only through education on hypoglycemia but through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia

Structural and functional analyses of calcium ion response factors in the mantle of Pinctada fucata

The pearl oyster, Pinctada fucata, is cultured for pearl production in Japan. The shell of the pearl oyster consists of calcium carbonate and a small amount of organic matrix. Despite many studies of the shell matrix proteins, the mechanism by which calcium elements are transported from the mantle to the shell remains unclear. Investigating the molecular mechanism of calcium transportation, we prepared artificial seawater with a high concentration of calcium ions (10ASW) to induce calcification in the pearl oyster. When pearl oysters were cultured in 10ASW, unusual nanoparticles were precipitated on the surface of the nacreous layer. SDS-PAGE and 2D-PAGE analyses revealed that some calcium-sensing proteins (Sarcoplasmic Ca-binding Protein (Pf-SCP) and Pf-filamin A) might be related to the synthesis of these nanoparticles. The recombinant proteins of Pf-SCP can bind to calcium ions and accumulate nanoparticles of calcium carbonate crystals. However, transcriptomic analysis of the pearl oysters grown in 10ASW showed that the matrix protein genes in the shell did not differ before and after treatment with 10ASW. These results suggest that, despite increasing calcium transportation to the shell, treatment with a high concentration of calcium ions does not induce formation of the organic framework in the shell microstructure. These findings offer meaningful insights into the transportation of calcium elements from the mantle to the shell

Systems Genetics Analysis of Mouse Chondrocyte Differentiation

One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research

Clonal reproduction and genetic caste differences in a queen-polymorphic ant, Vollenhovia emeryi

Most social Hymenoptera are characterized by simple haploid sex determination and environment-based caste differentiation. This appears to be strikingly different in the queen-polymorphic ant Vollenhovia emeryi. Almost all long- and short-winged queens from a population in Central Japan were homozygous at three microsatellite loci, whereas workers were mostly heterozygous, suggesting either a complex system of genetic caste determination or, more likely, the production of female sexuals from unfertilized eggs by thelytokous parthenogenesis and of workers from fertilized eggs. Furthermore, male genotypes were not compatible with those of the queens and had exclusively the paternal allele found in the sterile, heterozygous workers, probably because males are produced from fertilized eggs after the exclusion of maternal nuclear DNA as recently reported for Wasmannia auropunctata. The genus Vollenhovia might provide an interesting model system to trace the evolution of unusual caste and sex determination systems

Effects of forced expression of M6a on retinal differentiation and proliferation

Sublayer distributions of virus-transduced enhanced green fluorescent protein (EGFP)-positive cells in retinal explants. Retinal explants were infected with retorovirus particles that encode M6a and EGFP. After 14 days, the explants were harvested and frozen-sections prepared. Immunostaining was performed using an anti-EGFP antibody. The percentages of cells in each sublayer are shown. More than 200 cells were counted for each sample, and the standard deviation (SD) was calculated from three independent experiments. Differentiation of virus-infected cells examined by immunostaining to identify subpopulations within the retina. The percentages of marker-positive cells in the EGFP-positive population are shown. Rhodopsin for rod, HuC/HuD for amacrine, glutamine synthetase for Müller glia, and protein kinase C for bipolar were used as markers. More than 100 cells were examined for each sample, and the average value from three independent experiments is shown with the SD. ,: Proliferation of M6a-expressing retinal cells was examined by measuring incorporation of bromodeoxyuridine (BrdU; ) or expression of the Ki67 antigen (). BrdU was present for the final 24 h of four days of culture of retinal explants, and frozen sections were immunostained using antibodies against BrdU. The same samples were immunostained with the anti-Ki67antibody. The percentage of positive cells with SD are shown. Listed below each panel is the stage when each retinal explant was prepared and its culture period. The following abbreviations are in effect: outer nuclear layer (ONL); inner nuclear layer (INL); ganglion cell layer (GCL).<p><b>Copyright information:</b></p><p>Taken from "M6a is expressed in the murine neural retina and regulates neurite extension"</p><p></p><p>Molecular Vision 2008;14():1623-1630.</p><p>Published online 03 Sep 2008</p><p>PMCID:PMC2529470.</p><p></p