Aims/Introduction: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder including polycystic ovary morphology (PCOM), ovulatory dysfunction and hyperandrogenism. PCOS is frequently associated with type 2 diabetes mellitus; however, it is unknown whether PCOM and PCOS are prevalent in Japanese patients with type 1 diabetes mellitus. The purpose of our study was to determine the frequency of PCOM and PCOS in women with type 1 diabetes mellitus. Materials and Methods: We evaluated clinical, hormonal and ovarian ultrasound data from 21 type 1 diabetes mellitus patients whose average glycated hemoglobin levels were 7.9 -1.5%. Results: Ultrasound identified PCOM in 11 patients (52.4%) and these patients also had higher levels of the androgen dehydroepiandrosterone sulfate (DHEA-S) than those without PCOM (P < 0.05). Of the patients with PCOM, five presented menstrual irregularities (45.5%) and three met the Japanese criteria for PCOS (27.2%); whereas all patients without PCOM had a normal menstrual cycle (P < 0.05). Conclusions: Japanese premenopausal women with type 1 diabetes mellitus had a high frequency of PCOM as well as PCOS. This is the first research of this area carried out in an Asian population. (J Diabetes Invest

Background and Aims: Metabolic surgery has been proven to be effective for improving long-term outcome in patients with obesity and T2DM in Western countries. We aimed to evaluate the effects of this treatment in Japanese patients. Methods: We enrolled Japanese patients with obesity and T2DM who underwent laparoscopic sleeve gastrectomy (LSG) in our hospital from October 2016 to November 2019. We compared changes in body weight, HbA1c, antidiabetic drugs, and various metabolic parameters from preoperative baseline and 6 months after LSG. Results: Fifty-one patients with obesity underwent LSG; 26 had T2DM (age, 46.2±9.2 years; duration of diabetes, 9.5±7.4 years; female sex, 65.0%). Patients’ body weight, BMI and HbA1c decreased significantly (108.1±16.7 to 88.4±15.7 kg, 39.9±5.8 to 32.7±5.9 kg/m2 and 7.4±1.2 to 6.0±0.8%, respectively). The number of antidiabetic drugs significantly decreased postoperatively (2.1±1.2 to 0.6±1.0). Among them, 18 patients completely discontinued antidiabetic drugs. And all of five patients on insulin preoperatively maintained good glycemic control without insulin injections after LSG. The T2DM remission rate (HbA1c &lt; 6.5% and no antidiabetic medications for 6 months) was 76.9%. ROC curve analysis revealed that the remission rates were low in patients with preoperative mABCD score ≤ 5 and DiaRem score ≥ 6. Dyslipidemia, hypertension and liver enzyme elevation improved significantly after LSG as well. There were no serious complications related to LSG; one patient experienced suture failure. Conclusion: LSG for Japanese patients with obesity and T2DM improved both body weight and glycemic control, as well as other various metabolic-related diseases. Six months after LSG, the T2DM remission rate was comparable in Japanese patients to Westerns. In addition, LSG significantly reduced the amount of antidiabetic drugs, suggesting that LSG has some advantage in healthcare costs. Disclosure Y. Oe: None. T. Takase: None. K. Cho: None. A. Nakamura: None. H. Nomoto: None. H. Kameda: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd.

Background and Aim: DPP-4 inhibitor is well known to flatten glucose fluctuation in patients with type 2 diabetes by exerting a hypoglycemic effect according to plasma glucose level. SGLT2 inhibitors also have powerful hypoglycemic effects depending on glucose level and renal function. However. few reports have compared them and their combination in detail. Methods: A multicenter, open-label, parallel-group, randomized, controlled study (UMIN000029628). The key inclusion criteria were: Japanese patients with type 2 diabetes; age, 20-80 years; HbA1c, 6.5%-9.0%; BMI, ≥22 kg/m2; eGFR, ≥45 mL/min/1.73m2; and treatment with 20 mg of Teneligliptin, DPP-4 inhibitor. Participants were randomized to the combination of Canagliflozin 100 mg/Teneligliptin 20 mg (C, combination) or Canagliflozin 100 mg (S, SGLT2 inhibitor) groups. Glycemic fluctuation was evaluated with flash glucose monitoring (FreeStyle Libre Pro) during test meals for 2 days before and more than 7 days after the switching. The primary endpoint was the mean amplitude of glycemic excursions (MAGE). Results: No significant differences were observed in the backgrounds of 50 patients in C group and 49 patients in S group. MAGE decreased significantly in C group, and the reduction was significantly larger in C group than in S group (C, 116.5 ± 39.8 to 92.2 ± 28.0 mg/dL; S, 110.7 ± 29.8 to 104.2 ± 27.6 mg/dL, p &lt;0.01). Mean blood glucose for 24-hour decreased significantly in both groups, but the extent of the reduction was significantly larger in C group than in S group (C, 142.3 ± 41.8 to 119.5 ± 34.8 mg/dL; S, 146.4 ± 41.3 to 135.5 ± 39.8 mg/dL, p &lt;0.001). HbA1c was decreased only in C group (C, −0.4 ± 0.3%; S, −0.1 ± 0.2%, p &lt;0.01). None of the patients dropped out of the trial for adverse events. Conclusions: SGLT2 inhibitor combined with DPP-4 inhibitor strongly flattened glycemic fluctuation compared with their single use, and this contributed to suppression of the progression of diabetic complications. Disclosure K. Cho: None. H. Nomoto: None. A. Nakamura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd. K. Omori: None. T. Atsumi: Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB, Inc. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Mitsubishi Tanabe Pharma Corporation

Background: SGLT2 inhibitors (SGLT2i) are used worldwide, because of their multiple benefits for patients with type 2 diabetes. The purpose of this study was to determine the efficacy and safety of SGLT2i in patients with type 1 diabetes. Methods: Patients with type 1 diabetes attending multiple centers who had been treated with SGLT2i for &gt;12 weeks were included in this retrospective study. Changes in body mass, insulin dose, blood test data, including HbA1c, and the frequency of adverse events were evaluated over 12 weeks. The changes in day-to-day and daily glucose variability were evaluated using continuous glucose monitoring (CGM) as the primary endpoints. Day-to-day glucose variability was evaluated using the interquartile range (P25/P75) of the ambulatory glucose data obtained using CGM. Results: Fifty-one patients (37 female; mean age 52.7 years) were included in the analysis. HbA1c and body mass significantly decreased by 0.4% and 1.2 kg, respectively. The total insulin dose decreased by 15.6% (43.6 ± 26.2 to 36.8 ± 25.2 units/day). CGM data were obtained from 29 patients. The P25/P75 significantly decreased by 17.6 ± 20.7% during SGLT2i treatment (P&lt;0.01). The TIR (time in range: % of readings and time 70-180 mg/dL) significantly increased (42.1% to 55.7%, P&lt;0.01) and the TAR (time above range) significantly decreased (56.4% to 42.5%, P&lt;0.01) although the TBR (time below range) was not affected (1.56% to 1.89%). During the observation period, 11 patients (21.2%) showed hypoglycemia. Urinary ketone bodies were detected in four patients (7.8%), but none developed ketoacidosis, urinary tract infections or dizziness. Conclusion: SGLT2i were effective at reducing HbA1c and body mass, and were safe in this clinical study. In addition, SGLT2i improved both day-to-day and daily glucose variability in patients with type 1 diabetes. The incidence of hypoglycemia could be reduced by reducing glucose fluctuations using SGLT2i, after which the dosage could be adjusted appropriately. Disclosure K. Chiba: None. K. Cho: None. H. Kameda: None. A. Nakamura: None. Y. Shibayama: None. H. Nomoto: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd.

We previously showed a sodium glucose co-transporter 2 (SGLT2) inhibitor, luseogliflozin, increased beta cell mass and improved beta cell function in db/db mice, but the mechanism has remained unclear. The aim of this study is to investigate the mechanism of favorable effects of luseogliflozin on beta cells. Six-week-old db/db mice were fed to standard chow (control group) or standard chow containing 0.01% luseogliflozin (luseo group) for 4 weeks. DNA microarray analysis, real-time PCR analysis, measurement of mitochondrial respiratory capacity and reactive oxygen species (ROS) generation, and metabolome analysis were performed using isolated islets. Immunohistochemistry and electron microscopy were performed using pancreatic tissues. DNA microarray and real-time PCR analysis showed gene expressions of solute carrier family 2 member 2 (Slc2a2) related to glucose uptake, pyruvate carboxylase (Pcx) and enzymes related to the tricarboxylic acid (TCA) cycle, and cytochrome c oxidase subunit 6A2 (Cox6a2) related to electron transport chain were upregulated in the luseo group. The luseo group had a higher mitochondrial complex II-linked oxidative phosphorylation capacity, and had a lower mitochondrial ROS generation compared with the control group. Electron microscopy showed mitochondrial swelling in the control group, while the mitochondrial size was normally maintained in the luseo group. Immunohistochemistry showed the proportion of Nkx6.1 positive cells/beta cells was significantly higher in the luseo group compared with the control group (89.8 ± 1.8% vs. 75.3 ± 3.5%, P &lt; 0.01). In metabolome analysis, the metabolites in the TCA cycle were greater in the luseo group compared with the control group. Relief of glucotoxicity by luseogliflozin may reduce mitochondrial ROS generation and elevate Nkx6.1 expression related to beta cell proliferation. The elevated expression of Nkx6.1 could improve glucose metabolism in the TCA cycle, resulting in protection of beta cells. Disclosure Y. Yamauchi: None. K. Cho: None. T. Anzai: None. S. Tanaka: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Novo Nordisk, Sanofi, Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker’s Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Miyoshi: Research Support; Self; Abbott Japan Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K. K., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Speaker’s Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K. K., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K. K., Sumitomo Dainippon Pharma Co., Ltd. T. Atsumi: Research Support; Self; Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K. K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., UCB Japan Co. Ltd., Speaker’s Bureau; Self; AbbVie Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Takeda Pharmaceutical Co., UCB Japan Co. Ltd. A. Nakamura: Research Support; Self; Boehringer Ingelheim International GmbH, Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K. K., Taisho Pharmaceutical Co., Ltd. T. Yokota: None. K. Takahashi: None. S. Kawata: None. K. Tsuchida: None. K. Omori: None. H. Nomoto: None. H. Kameda: None.