Effects of Exenatide in a Morbidly Obese Patient with Type 2 Diabetes

INTRODUCTION: The effect of exenatide in weight loss has been reported. Presented here is a case of a morbidly obese patient with type 2 diabetes using exenatide who dramatically lost her body weight in a year and experienced improved glycemic control. CASE REPORT: Exenatide therapy was initiated for a 59-year-old morbidly obese Japanese woman with type 2 diabetes. To examine the effects of the exenatide treatment, continuous glucose monitoring was performed, and blood was drawn at 0, 30, 60, 120, and 180 min after breakfast to measure insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) levels. After 1 year of exenatide therapy, the patient lost 37.5 kg, her glycemic control improved, and her insulin sensitivity recovered. The patient’s levels of insulin, glucagon, active GLP-1, and total GIP also decreased after 1 year of exenatide treatment. CONCLUSION: The exenatide treatment was effective for reducing body weight and improving glycemic control. After 1 year of exenatide treatment, decreased glucagon, active GLP-1, and total GIP levels were observed following a meal, suggesting that exenatide might affect these hormonal reactions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13300-014-0050-6) contains supplementary material, which is available to authorized users

Verification of glycemic profiles using continuous glucose monitoring : cases with steroid use, liver cirrhosis, enteral nutrition, or late dumping syndrome

Glycemic control is often difficult to achieve in patients with diabetes, especially in the presence of comorbid diseases or conditions such as steroid-use or liver cirrhosis, or in patients receiving enteral nutrition. Moreover, reactive hypoglycemia due to late dumping syndrome in people having undergone gastrectomy is also a matter of concern. Empirically and theoretically, the typical glycemic profiles associated with these conditions have been determined ; however, what actually happens during a 24-h span is still somewhat obscure. In order to verify and provide information about the 24-h glycemic profiles associated with these conditions, 8 patients with the 4 above-mentioned conditions were monitored using a continuous glucose monitoring system (CGMS). For all 8 patients, CGMS provided detailed information regarding the 24-h glycemic profiles. The CGM results showed typical glycemic patterns for each condition, and we were moreover able to observe the effects of various practical treatments. Based on these cases, we conclude that the CGMS is highly useful for determining the glycemic patterns of patients with the aforementioned conditions in a practical setting ; and this system may be used to monitor the treatment success of such cases

Factors complicating the diabetes management of visitors to Japan : advices from a Japanese National Center for overseas medical staff

Linguistic, cultural, and geographical differences might challenge the management of diabetes patients travelling in a culturally and linguistically homogeneous country. This article presents an instructive case and identifies various factors that can help in effective diabetes management of such cases. A Russian female patient aged 23 came to Japan and visited our hospital for a second opinion regarding glycemic control. She was diagnosed with type 1 diabetes at age three and started insulin injections and diet therapy with carbohydrate counting methods. Her HbA1c level was 11.0% with multiple daily insulin injections. She showed neuropathy, nephropathy, and blindness due to her progressed retinopathy. Because of the language barrier, suggestions for lifestyle modification were not effectively conveyed to the patient. We analyzed possible barriers to effective diabetes management in such foreign patients. In addition to language barriers and difficulties in diet therapy, dissimilar diabetes treatment guidelines, inadequate healthcare insurance, and stress-inducing conditions can be barriers to effective diabetes management. Foreign diabetes patients might face several barriers in effective management while travelling in Japan. Use of medical interpreters, adequate medical insurance, and trained medical staff will help in overcoming these barriers

Immunohistochemical findings in the pancreatic islets of a patient with transfusional iron overload and diabetes : case report

Excessive iron storage sometimes causes diabetes in patients with hemochromatosis, a disease caused by iron overloading. We performed an immunohistochemical analysis to study an autopsy case of aplastic anemia and diabetic hemochromatosis caused by frequent blood transfusions, and extensive hemosiderin deposition was observed in the liver and pancreas. The pancreatic islets of the patient and a control subject were stained to detect glucagon, insulin, and proinsulin. Significantly lower levels of immunoreactivity with both insulin antibodies and proinsulin antibodies, but not with glucagon antibodies, was observed in the islet cells in the patient’s tissue than in the islet cells of the control. Hemosiderin deposition in the islets is known to be exclusively distributed in the β-cells, thus, selective iron-induced damage to the β-cells may have affected insulin synthesis and secretion and led to glucose intolerance in the patient

フォン・ヴィレブランド因子の機能を調節することで、マウスの急性腎虚血再灌流障害を緩和できる

Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. In addition to its hemostatic functions, von Willebrand factor (VWF) is known to play a role in cross-talk between inflammation and thrombosis. We hypothesized that VWF may be involved in the pathophysiology of AKI, major causes of which include insufficient renal circulation or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the role of VWF in AKI using a mouse model of acute ischemia-reperfusion (I/R) kidney injury. We analyzed renal function and blood flow in VWF-gene deleted (knock-out; KO) mice. The functional regulation of VWF by ADAMTS13 or a function-blocking anti-VWF antibody was also evaluated in this pathological condition. Greater renal blood flow and lower serum creatinine were observed after reperfusion in VWF-KO mice compared with wild-type (WT) mice. Histological analysis also revealed a significantly lower degree of tubular damage and neutrophil infiltration in kidney tissues of VWF-KO mice. Both human recombinant ADAMTS13 and a function-blocking anti-VWF antibody significantly improved renal blood flow, renal function and histological findings in WT mice. Our results indicate that VWF plays a role in the pathogenesis of AKI. Proper functional regulation of VWF may improve the microcirculation and vessel function in the kidney, suggesting a novel therapeutic option against AKI.博士（医学）・甲第744号・令和2年3月16日© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Efficacy of ezetimibe as monotherapy or combination therapy in hypercholesterolemic patients with and without diabetes

Ezetimibe selectively inhibits dietary and biliary cholesterol absorption and reduces serum cholesterol levels when administered alone (monotherapy) and along with common lipid-regulating agents (combination therapy). To evaluate the effect of ezetimibe therapy on the lipid profile, glucose metabolism, and levels of cholesterol absorption and synthesis markers, we administered 10 mg ezetimibe to 50 hypercholesterolemic patients with or without diabetes. The serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly reduced at 4 and 12 weeks of ezetimibe therapy in diabetic patients of both the monotherapy and combination-therapy groups and in nondiabetic patients of the combination-therapy group. The serum levels of the cholesterol absorption markers were significantly reduced, while those of the cholesterol synthesis markers were significantly increased at 12 weeks of ezetimibe therapy. No significant differences were noted in the values of the parameters of glucose metabolism in all patients. We also investigated the clinical characteristics of patients who exhibited a good response to ezetimibe (ezetimibe responders) ; however, multivariate regression analysis did not reveal a correlation between ezetimibe efficacy and patient characteristics such as gender, age, BMI, diabetic condition, method of ezetimibe administration, and the initial absolute values of cholesterol absorption/synthesis markers levels. In conclusion, ezetimibe therapy significantly improved the lipid profile without disturbing glucose metabolism. We were unable to identify the specific characteristics of ezetimibe responders among our subjects. However, we may interpret this result as suggesting that ezetimibe can be used in any population to lower low-density lipoprotein cholesterol levels

犬モデルにおける ex vivo および in vivo 遺伝子治療のための代替遺伝子導入技術の開発

Introduction: Gene therapy have recently attracted much attention as a curative therapeutic option for inherited single gene disorders such as hemophilia. Hemophilia is a hereditary bleeding disorder caused by the deficiency of clotting activity of factor VIII (FVIII) or factor IX (FIX), and gene therapy for hemophilia using viral vector have been vigorously investigated worldwide. Toward further advancement of gene therapy for hemophilia, we have previously developed and validated the efficacy of novel two types of gene transfer technologies using a mouse model of hemophilia A. Here we investigated the efficacy and safety of the technologies in canine model. Especially, validations of technical procedures of the gene transfers for dogs were focused. Methods: Green fluorescence protein (GFP) gene were transduced into normal beagle dogs by ex vivo and in vivo gene transfer techniques. For ex vivo gene transfer, blood outgrowth endothelial cells (BOECs) derived from peripheral blood of normal dogs were transduced with GFP gene using lentivirus vector, propagated, fabricated as cell sheets, then implanted onto the omentum of the same dogs. For in vivo gene transfer, normal dogs were subjected to GFP gene transduction with non-viral piggyBac vector by liver-targeted hydrodynamic injections. Results: No major adverse events were observed during the gene transfers in both gene transfer systems. As for ex vivo gene transfer, histological findings from the omental biopsy performed 4 weeks after implantation revealed the tube formation by implanted GFP-positive BOECs in the sub-adipose tissue layer without any inflammatory findings, and the detected GFP signals were maintained over 6 months. Regarding in vivo gene transfer, analyses of liver biopsy samples revealed more than 90% of liver cells were positive for GFP signals in the injected liver lobes 1 week after gene transfers, then the signals gradually declined overtime. Conclusions: Two types of gene transfer techniques were successfully applied to a canine model, and the transduced gene expressions persisted for a long term. Toward clinical application for hemophilia patients, practical assessments of therapeutic efficacy of these techniques will need to be performed using a dog model of hemophilia and FVIII (or FIX) gene.博士（医学）・乙第1517号・令和3年12月21日© 2021, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/)

Reduced serum level of leukocyte cell-derived chemotaxin 2 is associated with the presence of diabetic retinopathy

AbstractBackgroundVascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR.MethodsThe study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR. Serum LECT2 levels were measured using an enzyme-linked immunosorbent assay. Data were evaluated using Spearman's rank correlation, univariate and multivariate logistic regression.ResultsSerum LECT2 levels were significantly lower in participants with DM having DR than in those not having DR (35.6±14.9ng/ml vs. 44.5±17.6ng/ml, P<0.001). Spearman's rank correlation analysis revealed a significant association between serum LECT2 levels and the presence of DR (P<0.001). Multiple regression analysis revealed that serum LECT2 levels were independently related to DR (P<0.001).ConclusionsThese findings indicated that serum LECT2 level is negatively associated with the presence of DR and suggest that low circulating LECT2 level is a risk factor for DR