Glycemic control, associated factors and stress levels are altered in chronological order. Post-disaster diabetic medical care must consider these corresponding points in accordance with the time-period.

Because the renin-angiotensin-aldosterone system influences glucose homeostasis, the mineralocorticoid receptor (MR) signal in pancreatic islets may regulate insulin response upon glucose load. Glucagon-like peptide-1 (GLP-1) production is stimulated by interleukin-6 (IL-6) in pancreatic α-cells. To determine how glucose homeostasis is regulated by interactions of MR, IL-6 and GLP-1 in islets, we performed glucose tolerance and histological analysis of islets in primary aldosteronism (PA) model rodents and conducted in vitro experiments using α-cell lines. We measured active GLP-1 concentration in primary aldosteronism (PA) patients before and after the administration of MR antagonist eplerenone. In PA model rodents, aldosterone decreased insulin-secretion and the islet/pancreas area ratio and eplerenone added on aldosterone (E+A) restored those with induction of IL-6 in α-cells. In α-cells treated with E+A, IL-6 and GLP-1 concentrations were increased, and anti-apoptotic signals were enhanced. The E+A-treatment also significantly increased MR and IL-6 mRNA and these upregulations were blunted by MR silencing using small interfering RNA (siRNA). Transcriptional activation of the IL-6 gene promoter by E+A-treatment required an intact MR binding element in the promoter. Active GLP-1 concentration was significantly increased in PA patients after eplerenone treatment. MR signal in α-cells may stimulate IL-6 production and increase GLP-1 secretion, thus protecting pancreatic β-cells and improving glucose homeostasis.

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities, but is deteriorated by chronic metabolic insults. Heat shock (HS) with appropriate mild electrical stimulation (MES) activates HSR, and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (2 times/week, n=10), patients with metabolic syndrome (4 times/week, n=40), and patients with T2DM (n=100; 4 times/week (n=40) and 2, 4, 7 times/week (n=20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.

Background: Nonalcoholic fatty liver disease (NAFLD) often accompanies with metabolic disorders, such as metabolic syndrome (Mets) and type 2 diabetes (T2D). Effective treatment strategy to control NAFLD is not fully established yet. Cellular stress adaptation is one of the most important homeostatic ability, but this response can be deteriorated by metabolic insults. Heat shock (HS) with appropriate mild electrical stimulation (MES) activates stress adaptive heat shock response and improves metabolic abnormalities such as insulin resistance, hyperglycemia and inflammation in Mets and T2D. Methods: Retrospective analysis of the effects of MES+HS treatment on NAFLD biomarkers was performed in the subject with healthy men (n=10), Mets (n=40) and the patient with T2D (n=100). Results: In healthy males, there were no alterations in NAFLD steatosis or fibrosis biomarkers. In subjects with Mets, many of the NAFLD steatosis markers, such as AST/ALT ratio (from 0.80 to 0.94. p<0.01), fatty liver index (FLI: from 62.3 to 57.3. p<0.01), NAFLD-liver fat score (NAFLD-LFS: from 0.002 to - 0.276. p<0.01), liver/spleen (L/S) ratio (from 0.994 to 1.098. p<0.01) and hepatic steatosis index (HSI: from 37.2 to 36.0. p<0.01) were ameliorated upon MES+HS treatment, but NAFLD fibrosis markers were not. In patients with T2D, all those investigated NAFLD steatosis markers including AST/ALT ratio (from 0.94 to 1.08. p<0.05), FLI (from 64.0 to 59.6. p<0.01), LFS (from 1.40 to 0.90. p<0.05), L/S ratio (from 0.987 to 1.096. p<0.01) and HSI (from 40.2 to 39.4. p<0.01), visceral adiposity index (VAI: from 219.4 to 197.2. p<0.01) and triglyceride × fasting glucose index (TyG: from 4.05 to 3.95. p<0.01) were improved and NAFLD fibrosis markers such as Fib4 index (from 1.72 to 1.62. p<0.05) and NAFLD-fibrosis score (from - 0.23 to - 0.18. p<0.05) were ameliorated upon MES+HS treatment. Conclusions: Thus MES+HS, a physical interventional medicine may become a novel treatment strategy for NAFLD as well as metabolic disorders. Disclosure T. Kondo: None. S. Kitano: None. N. Miyakawa: None. T. Watanabe: None. R. Goto: None. M. Sakaguchi: None. M. Igata: None. J. Kawashima: None. H. Motoshima: None. T. Matsumura: None. E. Araki: Advisory Panel; Self; Abbott. Speaker’s Bureau; Self; ARKRAY, Astellas Pharma Inc., AstraZeneca, Eli Lilly Japan K.K., Merck & Co., Inc., Novo Nordisk Inc., WebMD LLC. Other Relationship; Self; Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Japan Ministry of Economy, Trade and Industry (24-065)

In April 14th and 16th, 2016, Kumamoto area was severely damaged by massive M7 class earthquakes. To examine the effects of these earthquakes on glycemic control and stress factors in diabetic outpatients regularly cared in diabetic clinic of Kumamoto University Hospital, sequential HbA1c, glycated albumin, other biochemical parameters, life style associated questionnaire and Impact of Event Scale-Revised (IES-R) scores were analyzed. A total of 557 patients were enrolled and data were collected from 13 months before to 13 months after the earthquakes. In patients with type 1 diabetes (T1D) or specific types of diabetes due to other causes, glycemic control was not altered during the observational period. This glycemic stability in T1D may result from self-management of insulin doses (increase in 7% and decrease in 20% of patients). In patients with type 2 diabetes (T2D), HbA1c was decreased by 0.11% (from 7.33% to 7.22%) at 1-2 months after the earthquakes compared to that before the earthquakes, and increased at 3-4, 6-7 and 12-13 months after the earthquakes. The reduction of HbA1c at after 1-2 months in T2D was associated with “quick restoration of life-lines” and “sufficiency of sleep.” The glycemic deterioration at after 3-4 months was related to “shortage of antidiabetic agents” and “insufficient amount of food”, and at after 12-13 months that was connected to “large-scale partial destruction of houses” and “changes in working environments.” IES-R, representing disaster associated stress levels were positively correlated with “age”, “delayed restoration of life-lines”, “self-managements of antidiabetic agents” and “increased amount of activity”, and negatively associated with “early restoration of life-lines” and “sufficiency of sleep.” Thus, the glycemic control, associated factors and stress levels are altered in chronological order. Post-disaster diabetic medical care must consider these corresponding points in accordance with the time period. Disclosure T. Kondo: None. N. Miyakawa: None. H. Motoshima: None. N. Ishii: None. M. Igata: None. K. Yoshinaga: None. D. Kukidome: None. T. Senokuchi: None. J. Kawashima: None. T. Matsumura: None. E. Araki: Speaker's Bureau; Self; Astellas Pharma US, Inc., MSD K.K., Kowa Pharmaceuticals America, Inc., Sanofi, Novo Nordisk Inc.. Research Support; Self; Astellas Pharma US, Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Takeda Pharmaceuticals U.S.A., Inc., Daiichi Sankyo Company, Limited, Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Novo Nordisk Inc., Sanofi, Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co..