We present a case of a 32-year-old diabetic woman with Prader–Willi syndrome who developed severe ketoacidosis caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents, during a strict low-carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was relatively low, though laboratory evaluations showed severe ketoacidosis. This is the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to not only pay attention when using a SGLT2 inhibitor in patients following a low-carbohydrate diet, but also to start a low-carbohydrate diet in patients treated with a SGLT2 inhibitor because of a high risk for developing ketoacidosis.

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Introduction: It is indicated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucose lowering agents, may increase a level of glucagon, and simultaneously, compete with their antiglycemic effect. Aim: To elucidate the alteration of glucagon concentration and blood glucose level during administration of SGLT2i, Empagliflozin (EMPA) was administered to diabetic mice with homozygous (gcg−/−) or heterozygous (gcg+/−) deficiency of glucagon gene. Methods: After induction of diabetes using 150 mg/kg of streptozotocin, gcg−/− and control gcg+/− mice of 12-14 weeks old were administered 30 mg/kg/day of EMPA for 3-5 weeks. Casual blood glucose, fasting blood glucose, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), blood glucagon, blood insulin, blood beta-hydroxybutyric acid were evaluated. Additionally, metabolic parameters including respiratory exchange ratio (RER), activity, feeding, and drinking, were monitored utilizing a home-cage chronic laboratory animal monitoring system (CLAMS). Results: Glucagon concentration in control gcg+/− mice were not altered by induction of diabetes or administration of EMPA. In gcg−/−, blood glucagon was not detected. The OGTT of diabetic gcg+/− and gcg−/− revealed that the area under the curve (AUC) of blood glucose in mice treated with EMPA were decreased compared with that without EMPA (p<0.05). However, reduction ratios of the AUC showed no significant difference between gcg+/− and gcg−/−. In ITT, there was no significant difference in the reduction rate of glucose levels between mice treated with or without EMPA. CLAMS revealed no significant difference induced by EMPA in metabolic parameters: RER, activity, food intake, and drinking. Conclusion: Administration of EMPA for almost one month in mice did not induce noticeable change in glucagon level or metabolic parameters. The gcg deficiency did not have any impact on glucose lowering effect of EMPA. Disclosure H. Shimoda: None. Y. Seino: None. T. Himeno: None. R. Inoue: None. M. Motegi: None. T. Hayami: None. E. Asano: None. S. Asano: None. M. Kato: None. Y. Yamada: None. E. Miura-Yura: None. M. Kondo: None. S. Tsunekawa: None. Y. Kato: Speaker's Bureau; Self; Merck & Co., Inc. K. Kato: None. Y. Hayashi: Speaker's Bureau; Self; Astellas Pharma Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K.

Background: Diabetic complications (DCs) are conventionally classified as micro- or macro-angiopathies. However, in the case of diabetic neuropathy (DPN), it is thought that impairments of neurons and glial cells of the peripheral nervous system, which do not consist of the vascular system, occupy a pivotal role in the pathology. Furthermore, recent accumulated evidences indicate that diabetic retinopathy (DR) which has been mentioned as a microangiopathy, should be also considered as adisease with complex pathogenesis consist of neurodegeneration and angiopathy. Based on this fact, we hypothesized that retinal function can predict the presence or absence of early stage DCs. The current study aimed to elucidate the relationship between DCs and retinal function in diabetic patients (DM) using a handheld device of electroretinogram (ERG) RETevalTM. Methods: Subjects: 175 hospitalized DM. Microvascular complications were assessed using urine albumin creatinine ratio (ACR) measurements, digital retinal images, and nerve conduction studies. Atherosclerosis was assessed utilizing baPWV, ABI, TBI, and carotid IMT. The Pearson’s or Spearman’s coefficient was used for data analysis. Results: Patient background: 112 males, average 60.4±14.0 years old, mean duration of disease 10.7±11.3 years, and mean HbA1c 10.1±2.3%. Prevalence of DCs were 29.4% of DR, 32.9% of nephropathy (DN), and 43.8% of DPN. Relationships with significant correlation between indices of ERG and DCs: ERG latency (LAT) and DR (p = 0.003); ERG amplitude (AMP) and DR (p < 0.001), DN (p = 0.024), or DPN (p = 0.019). Relationships with significant correlation between indices of ERG and indices of DCs: LAT and minimal F-wave latency of the tibial nerves or sural nerve NCVs; AMP and T-Chol, LDL-C, eGFR, urinary C-peptide, ACR, IMT, baPWV, TBI, or SNAP of the sural nerves. Conclusion: AMP and LAT were correlated with prevalence of DCs and their indices. The handheld ERG might predict DCs. Disclosure M. Kawai: None. T. Himeno: None. Y. Yamada: None. E. Asano: None. Y. Sugiura: None. H. Shimoda: None. Y. Shibata: None. M. Kondo: None. S. Tsunekawa: None. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation.

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