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Aims To assess the association between dipstick hematuria and estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. Methods Longitudinal data were obtained from 3068 Japanese patients with type 2 diabetes. To assess the independent association between dipstick hematuria and eGFR decline, we used Cox proportional hazard model adjusted for potential confounders. Results Median follow-up period was 699.7 days. Mean age, body mass index (BMI), and HbA1c level were 65.7 years, 24.6 kg/m2, and 7.5% (58.1 mmol/mol), respectively. Positive dipstick hematuria was significantly associated with baseline eGFR and severity of albuminuria (p Conclusion Positive dipstick hematuria was associated with severity of albuminuria and renal function. A significant association was found between dipstick hematuria and increased risk of eGFR decline among patients with type 2 diabetes. Therefore, our results suggest that dipstick hematuria is perhaps indicative of more severe diabetic nephropathy.

Aims/Introduction We investigated the association between four insulin regimens and increase in HbA1c and insulin dose in a real-life clinical setting because there is no data about them among insulin regimens. Materials and Methods Subjects included 757 patients with type 2 diabetes having been treated with insulin therapy for more than 1 year. The four insulin regimens were regimen 1 (long-acting insulin, once daily), regimen 2 (biphasic insulin, twice daily), regimen 3 (biphasic insulin, three times daily), and regimen 4 (basal-bolus therapy). Main outcomes were increases in HbA1c levels >0.5% and increases in daily insulin units after 1 year. We performed multivariable analyses to examine differences in glycemic control and insulin dose with adjustment for possible confounders. Results Mean HbA1c level and duration of insulin therapy were 7.8% and 11.3 years, respectively. HbA1c levels increased by >0.5% at follow-up in 22.8%, 24.9%, 20.7%, and 29.3% of subjects using regimen 1, 2, 3, and 4, respectively, with no significant differences between groups. Daily insulin doses increased in 62.3%, 68.8%, 65.3%, and 38.6% of patients, respectively (P

Thyroid storm is an endocrine emergency which is characterized by multiple organ failure due to severe thyrotoxicosis, often associated with triggering illnesses. Early suspicion, prompt diagnosis and intensive treatment will improve survival in thyroid storm patients. Because of its rarity and high mortality, prospective intervention studies for the treatment of thyroid storm are difficult to carry out. We, the Japan Thyroid Association and Japan Endocrine Society taskforce committee, previously developed new diagnostic criteria and conducted nationwide surveys for thyroid storm in Japan. Detailed analyses of clinical data from 356 patients revealed that the mortality in Japan was still high (∼11%) and that multiple organ failure and acute heart failure were common causes of death. In addition, multimodal treatment with antithyroid drugs, inorganic iodide, corticosteroids and beta-adrenergic antagonists has been suggested to improve mortality of these patients. Based on the evidence obtained by nationwide surveys and additional literature searches, we herein established clinical guidelines for the management of thyroid storm. The present guideline includes 15 recommendations for the treatment of thyrotoxicosis and organ failure in the central nervous system, cardiovascular system, and hepato-gastrointestinal tract, admission criteria for the intensive care unit, and prognostic evaluation. We also proposed preventive approaches to thyroid storm, roles of definitive therapy, and future prospective trial plans for the treatment of thyroid storm. We hope that this guideline will be useful for many physicians all over the world as well as in Japan in the management of thyroid storm and the improvement of its outcome.

SummaryObjective Thyroid storm (TS) is a life-threatening endocrine emergency. This study aimed to achieve a better understanding of the management of TS by analyzing therapeutic modalities and prognoses reported by nationwide surveys performed in Japan. Design, patients and measurements Retrospective analyses were performed on clinical parameters, outcomes, and treatments in 356 TS patients. Results Patient disease severities assessed via Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores significantly correlated with mortality. Free triiodothyronine (FT3) and the FT3/free thyroxine (FT4) ratio inversely correlated with disease severity. Methimazole (MMI) was used in the majority of patients (78·1%), and there were no significant differences in mortality or disease severity between those treated with MMI and those receiving propylthiouracil (PTU). Patients who received inorganic iodide (KI) demonstrated higher disease severity but no change in mortality compared to those who did not. Patients treated with corticosteroids (CSs) demonstrated significantly higher disease severity and mortality than those who were not. Disease severity in patients treated with intravenous administration of beta-adrenergic antagonists (AAs) was significantly higher than those treated with oral preparations, although no significant difference in mortality was observed between these groups. In addition, mortality was significantly higher in patients treated with non-selective beta-AAs as compared with other types of beta-AAs. Conclusion In Japan, MMI was preferentially used in TS and showed no disadvantages compared to PTU. In severe TS, multimodal treatment, including administration of antithyroid drugs, KI, CSs and selective beta1-AAs may be preferable to improve outcomes.

We investigated the association between diabetes treatment-related quality of life (QOL) and levels of self-care activities in insulin injection among Japanese patients with type 2 diabetes. Data from 1394 patients with type 2 diabetes on insulin therapy were obtained from a diabetes registry in Japan. We used the Diabetes Therapy-Related QOL (DTR-QOL) questionnaire and relative risk regression analysis to assess the independent association of high levels of self-care activities in insulin injection and DTR-QOL scores while adjusting for possible confounders. The mean age, BMI and HbA1c level were 65.8 years, 24.8 kg/m2 and 62 mmol/mol (7.8 %), respectively. The frequency of insulin injection omission was associated with DTR-QOL scores. In the multivariable-adjusted model, the relative risks for high levels of self-care activities in insulin injection was 1.15 (95 % confidence interval, 1.05–1.26) in the highest quintile compared with those in the lowest quintile of DTR-QOL scores. Subgroup analysis confirmed this association in patients

A 44-year-old man with type 2 diabetes of five years' duration was admitted for the management of poor glycemic control despite the administration of insulin therapy. On admission, he received vigorous treatment for a 28-year history of Crohn's disease and a 14-year history of a psychiatric disorder. His glycosylated hemoglobin A1c (HbA1c) level was 11.3%, his fasting blood glucose level was 567 mg/dL and his C-peptide level was 1.0 ng/mL. His quality of life (QOL) was severely impaired as a result of frequent episodes of hyperglycemia and hypoglycemia. Treatment with liraglutide was commenced in place of insulin, which improved the patient's glycemic control to an HbA1c level of 5.5% and markedly increased his QOL score with no hypoglycemia.

To elucidate the sustainable effects of laughter on gene expression, we recruited type 2 diabetic patients who were in-patient for receiving self-management education and examined time-dependent regulation for gene expression by laughter. Two-day experiment was performed. On one day, the patients watched comic video and laughed together with hospital staffs. On the other day, they participated in an inpatient diabetes educational program. Blood samples were collected before and 1.5, 4 h after watching comic video or spending lecture time, and changes in gene expression were comprehensively analyzed by microarray technique. Of the 41,000 genes analyzed, the laughter relatively up-regulated 39 genes, among which, 27 genes were relatively increased in the expression for all the observation period after watching comic video. By functional classification of these genes, 14 genes were found to be related to natural killer cell activity. No genes were included that are directly involved in blood glucose regulation, though successive suppression of postprandial blood glucose levels was observed. These results suggest that the laughter influences the expression of many genes classified into immune responses, and may contribute to amelioration of postprandial blood glucose elevation through a modulation of NK cell activity caused by up-regulation of relating genes.

Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively.We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2.We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration3 mg/dL.TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.