平塚 いづみ

OBJECTIVE: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ. We investigated the association between IgG4-RD and the main characteristics of Graves' disease (GD) at the time of diagnosis. Additionally, we evaluated whether serum IgG4 levels change during treatment. DESIGN AND PATIENTS: Twenty-eight patients with newly diagnosed GD were enrolled into this longitudinal follow-up study. Serum IgG4 levels and thyroid function were measured in all the participants at the time of diagnosis. Further, the serum IgG4 levels of nine of 28 patients with untreated GD were measured after the achievement of euthyroid state (through the use of methimazole). RESULTS: Two (7.1%) of 28 patients with untreated GD had elevated serum IgG4 levels of >135 mg/dL. There was no significant difference in the average IgG4 levels before and after the achievement of euthyroid state (66.2±74.0 mg/dL vs. 50.5±47.3 mg/dL). In two patients, the elevated serum IgG4 levels returned to normal after treatment. However, one patient had an elevated serum IgG4 level of 136.6 mg/dL after treatment. CONCLUSIONS: This study showed that serum IgG4 levels varied with treatment in patients with GD, independent of thyroid function, suggesting that IgG4 might be indirectly related to GD.

AIMS: The aim of this study is to investigate the effects of a low-carbohydrate staple food (i.e., low-carbohydrate bread) on glucose and lipid metabolism and pancreatic and enteroendocrine hormone secretion in comparison with meals containing normal-carbohydrate bread, without consideration of the carbohydrate content of the side dishes. METHODS: T2DM patients (n = 41) were provided meals containing low-carbohydrate bread (LB) together with side dishes or normal-carbohydrate bread (NB) together with side dishes every other day as a breakfast. Blood glucose levels were evaluated by using a continuous glucose monitoring system; blood samples were collected before and 1 and 2 h after the breakfast. RESULTS: Postprandial blood glucose levels, plasma insulin, plasma glucose-dependent insulinotropic polypeptide (GIP) and plasma triglyceride were significantly lower and plasma glucagon levels were significantly higher in LB compared with those in NB. Plasma glucagon-like peptide-1 (GLP-1) levels did not differ in the LB and NB groups. CONCLUSIONS: These results indicate that changing only the carbohydrate content of the staple food has benefits on glucose and lipid metabolism in T2DM patients concomitant with the decrease of insulin and GIP secretion, which ameliorate body weight gain and insulin resistance.

<p>  A 34-year-old woman with type 1 diabetes on hemodialysis was admitted to our hospital for simultaneous pancreas kidney transplantation received from her father. She had suffered from type 1 diabetes mellitus since age 13, and had complained of serious atonic gastroenteropathy and orthostatic hypotension. After the transplantation, she became free from hemodialysis and insulin injection. At the same time, her gastrointestinal symptoms disappeared. However, she still had orthostatic hypotension, which was improved by taking fludrocortisone. Two months after the transplantation, orthostatic hypotension with marked polyuria became obvious. By hypertonic saline challenge test, she was diagnosed as partial central diabetes insipidus. Although treatment with desmopressin was necessary for 5 months, she became free from medication afterwards. Diabetes insipidus seems to be a rare but could be an important complication after simultaneous pancreas kidney transplantation and/or or kidney transplantation.</p>

Background: Understanding the roles of circulating microRNAs (miRNAs) can provide important and novel information regarding disease pathogenesis and a patient's clinical condition. Circulating miRNAs, such as exosomal miRNA, may regulate various bioactivities related to intercellular communication. However, the circulation of miRNAs in Graves' disease (GD) in relation to disease activity has never been elucidated. This study aimed to identify circulating miRNAs in GD in relation to disease activity and whether their exosomes play a role in the pathogenesis of GD. Methods: Circulating miRNAs were measured in serum obtained from seven intractable GD patients, seven GD patients in remission, and seven healthy controls using the miScript miRNA PCR Array. Altered miRNAs selected from array data were validated in 65 subjects. To investigate exosome biology, peripheral blood mononuclear cells (PBMCs) were incubated with exosomes isolated from the subjects' sera. mRNAs were quantified for cytokines using quantitative real-time polymerase chain reaction. Results: Circulating miR-23b-5p and miR-92a-39 were increased in GD patients in remission compared with intractable GD patients (p&lt;0.05). On the other hand, let-7g-3p and miR-339-5p were decreased in GD patients in remission compared with intractable GD patients (p&lt;0.05). Exosomes from intractable GD patients stimulated mRNA expression for IL-1 and TNF- compared with GD patients in remission or healthy controls. Conclusions: This study demonstrates that different levels of circulating miRNAs are associated with intractable GD. Moreover, serum exosomes of patients with intractable GD may activate immune cells, which may play an important role in GD pathogenesis.

Objective: Traditional Japanese food appears to be healthy but contains a small amount of milk products. Type 2 diabetes (T2DM) patients commonly reduce their energy intake to control their blood glucose levels. However, nutritional guidance for diabetes does not emphasize calcium (Ca) consumption. The aim of this study is to estimate the nutritional status of Ca and other nutrients, which affect bone and Ca metabolism, in T2DM patients. Methods: This observational study was conducted with Japanese T2DM patients (n = 96 M/F = 50/46 age: 61.6 � 10.1 years). We estimated nutrient intake using a simple food frequency questionnaire. Results: Median total energy intake was 1750 kcal/day (1440-1970). Their median daily intake of Ca, vitamin D, and vitamin K was 451 mg (336-560), 10.2 μg (8.5-12), and 206 μg (84-261), respectively. Only 17.7% of the study subjects were found to take more than 600 mg/day of Ca. Protein and salt intake was 78 (64-90) and 10.6 (9.3-12.2) g/day, respectively. Male subjects had more salt, less Ca and vitamin K than female. Daily Ca intake was positively associated with total energy, protein, and lipid intake but not with carbohydrates. Vitamin D intake correlated only with protein intake. Conclusion: The daily Ca intake of Japanese T2DM patients appears to be insufficient and could depend on protein and lipid intake. Additionally, these patients should have specific recommendations to ensure sufficient intake of Ca with protein and lipid during energy restriction.

Autoimmune thyroid diseases (AITDs), including Graves' diseases (GD) and Hashimoto's thyroiditis (HT), are the most common autoimmune diseases, and are mainly mediated by T cells that produce cytokines and chemokines in abnormal amounts. Few reports have described the circulating chemokines active in AITDs. Recently, we used a new multiplex immunobead assay to simultaneously measure cytolcines and chemokines in small volume serum samples from patients with AITDs. We measured 23 selected serum chemokines in patients with GD (n=45) or HT (n=26), and healthy controls (n=9). GD patients were further classified as either untreated, intractable, or in remission, while HT patients were classified as either hypothyroid or euthyroid. Of the 23 serum chemokines assayed, only the serum level of IP-10 (CXCL10/interferon-gamma-inducible protein 10) was elevated, depending on disease activity, in GD or HT compared with healthy controls. However, the serum level of IP-10 was also increased in both untreated GD patients and hypothyroid HT patients, suggesting that levels of this cytokine may not be affected by disease specificity. In conclusion, autoimmune inflammation in patients with AITD is closely related to the level of the serum chemokine, IP-10. Therefore, IP-10 might be a good biomarker for tissue inflammation in the thyroid, but not a useful biomarker for predicting disease specific activity, the progression of AITDs, or responsiveness to treatment because of its independence from thyroid function or disease specificity.

Context Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are the most common autoimmune diseases. MicroRNAs (miRNAs) are small noncoding RNAs, which can play pivotal roles in immune functions and development of autoimmunity. Recently, it has been recognized that identification of circulating miRNAs can provide important and novel information regarding disease pathogenesis and clinical condition. However, the role circulating miRNAs in AITD has not yet been described. Objective The aim of this study was to characterize the different circulating levels of miRNA in patients with AITD. Design and methods Sixty-four participants who met the criteria for HT or GD and healthy subjects were recruited. Microarrays were used to analyse the expression patterns of miRNA in serum obtained from patients with HT and GD and healthy subjects. After analysing the microarray data, four interesting miRNAs (miR-16, miR-22, miR-375 and miR-451) were selected and validated by quantitative real-time PCR. Results Several miRNAs were observed to be differently expressed in serum from patients with AITD compared with healthy subjects by microarray analysis. Further analysis consistently showed that serum levels of miR-22, miR-375 and miR-451 were increased in patients with HT. On the other hand, the serum levels of miR-16, miR-22, miR-375 and miR-451 were increased in patients with GD compared with healthy subjects. Conclusions We revealed that different levels of serum miRNAs were associated with GD and HT, which may play a role in the pathogenesis of these diseases.