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The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for "a definitive diagnosis of SPIDDM": (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement of insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity < 0.6 ng/mL) at the last observed point in time. When a patient fulfills the only (1) and (2), but not (3), he/she is diagnosed with "SPIDDM (probable)" because the diabetes is non-insulin-dependent state., Competing Interests: Conflict of interestAkira Shimada: lecture fee (Sanofi, Novo, Lilly, Terumo, Sumitomo, Abbott). Norio Abiru: lecture fee (Novo, Lilly). Haruhiko Osawa: research funding (Sysmex), scholarship donation (Daiichi-Sankyo, Novo). Tomoyasu Fukui: research funding (Cosmic). Junnosuke Miura: lecture fee (Terumo). Kazuki Yasuda: scholarship donation (Ono). Akihisa Imagawa: research funding (Parexel International, Taiho, MSD, Ono). Hiroshi Ikegami: lecture fee (Sanofi, Sumitomo, Terumo, Novo), scholarship donation (Sumitomo, Taisho, Life Scan, Novo). Other authors: nothing to declare., (© The Japan Diabetes Society 2023.)

Type 1 diabetes (T1D) is classified into three subtypes: acute-onset, slowly progressive, and fulminant T1D, according to the heterogeneity of clinical course in Japan. Although several cross-sectional databases of T1D have been reported, prospective longitudinal databases to investigate clinical outcomes are lacking in our country. Therefore, we herein construct multi-center prospective longitudinal database of the three subtypes of T1D, accompanied with genetic information and biobanking, which is named Japanese Type 1 Diabetes Database Study (TIDE-J). Inclusion criteria of this study are as follows: (1) the duration of T1D was less than 5 years, (2) the patients had one or more islet-related autoantibodies and/or fasting serum C-peptide levels were less than 1.0 ng/mL, (3) the patients could clearly understand the study consent in writing. In the TIDE-J, clinical data, including glycemic control, endogenous insulin secretion, islet-related autoantibodies, diabetic complications, and treatment, are collected annually using electric data collection system, which is named REDCap. Furthermore, HLA genotypes of each participant were analyzed at entry and the blood samples were stored for assessing exploratory markers and further genetic analysis annually. The TIDE-J certainly helps in revealing distinct clinical course of each T1D subtype. Moreover, this database may help in identifying novel markers for diagnosing each subtype of T1D and predicting clinical outcomes (including pancreatic beta cell function and disease severity) in patients., Competing Interests: Conflict of interestDaisuke Chujo received honorarium for lectures from Eli Lilly and Company; research funding from Novo Nordisk Pharma Ltd., and Sanofi K.K.; Akihisa Imagawa received honorarium for lectures from Astellas Pharma Inc.; clinical commissioned/joint research grant from Astra Zeneca, Soiken Inc., Taiho Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Merck KGaA, and Parexel International Inc.; research grant from Shionogi Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company, and Ono Pharmaceutical Co., Ltd.; Norio Abiru received honorarium for lectures from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., and Eli Lilly and Company; research funding from Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb, Taisho Pharmaceutical Co., Ltd., and Astellas Pharma Inc.; Takuya Awata received honorarium for lectures from Astellas Pharma Inc.; Hiroshi Ikegami received honorarium for lectures from Astellas Pharma Inc., Eli Lilly and Company, MSD K.K., Novo Nordisk Pharma Ltd., Novartis Pharma K.K., Sumitomo Dainippon Pharma Co., Ltd., and Terumo Corporation; donations from Abbott Japan Co., Ltd., LifeScan Japan K.K., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Otsuka Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company. Akira Shimada received honorarium for lectures from Novo Nordisk Pharma Ltd., Eli Lilly and Company, and Sanofi K.K.; Other authors have no conflict of interest to declare., (© The Japan Diabetes Society 2021.)

Aims: We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to anti-programmed cell death-1 therapy., Methods: We analyzed the detailed data of 22 patients that were collected using a Japan Diabetes Society survey and a literature database search., Results: Among the 22 patients, 11 (50.0%) met the criteria for fulminant type 1 diabetes and 11 (50.0%) met the criteria for acute-onset type 1 diabetes. The average patient age was 63 years. The mean duration between the date of the first anti-PD-1 antibody injection and development of type 1 diabetes was 155 days and ranged from 13 to 504 days. Flu-like symptoms, abdominal symptoms, and drowsiness were observed in 27.8, 31.6, and 16.7% patients, respectively. Mean ± standard deviation or median (first quartile-third quartile) glucose levels, HbA1c levels, urinary C-peptide immunoreactivity levels, and fasting serum C-peptide immunoreactivity levels were 617 ± 248 mg/dl, 8.1 ± 1.3%, 4.1 (1.4-9.4) μg/day, and 0.46 (0.20-0.70) ng/ml, respectively. Seventeen of 20 patients (85.0%) developed ketosis, and 7 of 18 patients (38.9%) developed diabetic ketoacidosis. Ten of 19 patients (52.6%) showed at least one elevated pancreatic enzyme level at the onset and two of seven patients showed this elevation before diabetes onset. Only one of 21 patients was anti-glutamic acid decarboxylase antibody positive., Conclusions: Anti-programmed cell death-1 antibody-related type 1 diabetes varies from typical fulminant type 1 diabetes to acute-onset type 1 diabetes. However, diabetic ketoacidosis was frequently observed at the onset of diabetes. An appropriate diagnosis and treatment should be provided to avoid life-threatening metabolic alterations., Competing Interests: Akihisa Imagawa received scholarship donations from Ono Pharmaceutical Co., Ltd. and MSD and honoraria for lectures from Ono Pharmaceutical Co., Ltd. Norio Abiru received research grants from Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb. Hiroshi Ikegami received a scholarship grant from Ono Pharmaceutical Co., Ltd. Yumiko Kawabata received a scholarship grant from Ono Pharmaceutical Co., Ltd. Other authors declare that they have no conflicts of interest.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (The Ethics Committees of the JDS, date of approval: 26 August 2016, approval number: 28-003-(2), Osaka University Hospital, date of approval: 27 April 2016, approval number: 15589, and Osaka Medical College, date of approval: 10 January 2017, approval number: 2098) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

Abrupt disease onset and severe metabolic disorders are main characteristics of fulminant type 1 diabetes. Diffusion-weighted magnetic resonance imaging (DWI) is an imaging technique that reflects restricted diffusion in organs and can detect mononuclear cell infiltration into the pancreas at the onset of the disease. Fourteen patients with fulminant type 1 diabetes who underwent abdominal magnetic resonance imaging were recruited for the measurement of apparent diffusion coefficient (ADC) values of the pancreas that were compared with those of 21 non-diabetic controls. The ADC values of all parts of the pancreas were significantly lower in fulminant type 1 diabetes than in controls (head, 1.424 ± 0.382 × 10 -3 vs. 1.675 ± 0.227 × 10 -3 mm 2 /s; body, 1.399 ± 0.317 × 10 -3 vs. 1.667 ± 0.170 × 10 -3 mm 2 /s; tail, 1.336 ± 0.247 × 10 -3 vs. 1.561 ± 0.191 × 10 -3 mm 2 /s; mean, 1.386 ± 0.309 × 10 -3 vs. 1.634 ± 0.175 × 10 -3 mm 2 /s) ( p  < 0.01). The best cut-off value indicated that the sensitivity was 86% and the specificity was 71% when using DWI, which was also efficient in two atypical patients with fulminant type 1 diabetes without elevated levels of exocrine pancreatic enzymes or with high HbA1c levels due to the preexistence of type 2 diabetes. The ADC values were significantly correlated to plasma glucose levels and arterial pH, and tended to increase with the lapse of time. DWI may be an additional tool for making an efficient diagnosis of fulminant type 1 diabetes., Competing Interests: The authors declare no conflicts of interest.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Opt-out opportunities are provided to study subjects.

[This corrects the article DOI: 10.1007/s13340-015-0207-1.].

The pathogenesis of type 1 diabetes is different from that of type 2 diabetes, and anti-glutamic acid decarboxylase antibody (GADA) helps to diagnose autoimmune type 1 diabetes. Some studies reported that GADA seroconversion occurs during the clinical course of type 2 diabetes, leading to development of "type 1 on type 2 diabetes". To clarify the clinical characteristics and triggers of GADA seroconversion, we performed a nationwide questionnaire survey for clinical cases identified by literature search, and obtained information on 38 cases (24 with insulin therapy and 14 without it). The diabetes duration up to determination of GADA seroconversion was significantly longer in the group with insulin therapy than that without it. This finding was particularly noted in insulin-treated non-obese patients with lower serum C-peptide levels. In these patients, insulin therapy could have masked sudden increases in plasma glucose and HbA1c levels, possibly leading to delayed determination of GADA seroconversion. In non-obese patients without insulin therapy, an abrupt rise in the plasma glucose and HbA1c levels was observed at immediately before the determination, a finding which may help to predict GADA seroconversion. From the results of the present survey, we could not determine apparent triggers of GADA seroconversion. Thus, physicians may need to consider the possibility of concurrent type 1 diabetes during the therapeutic course of type 2 diabetes; GADA measurement should be considered when non-obese type 2 diabetic patients not receiving insulin therapy experience unexpected abrupt hyperglycemia and when those receiving insulin therapy show low serum C-peptide levels., Competing Interests: Author HI received scholarship grants from Sumitomo Dainippon Pharma Co., Ltd, Ono Pharmaceutical Co., LTD., Otsuka Pharmaceutical Co., Ltd., Boehringer Ingelhaim Japan, Inc., Daiichi Sankyo Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Johnson & Johnson K.K. Author HI received honoraria for lectures from Novo Nordisk Pharma Ltd., Sumitomo Dainippon Pharma Co., Ltd, Kowa Co., Ltd., Astellas Pharma Inc., Eli Lilly Japan K.K. Author AI received a clinical research grant from Mochida Pharmaceutical Co., Ltd. Author AI received scholarship grants from Daiichi Sankyo Company Ltd., Astellas Pharma Inc., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., AstraZeneca K.K. Author YK received scholarship grants from Sumitomo Dainippon Pharma Co., Ltd, Ono Pharmaceutical Co., LTD., Otsuka Pharmaceutical Co., Ltd., Boehringer Ingelhaim Japan, Inc., Daiichi Sankyo Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Johnson & Johnson K.K. Author TH received a scholarship grant from Astellas Pharma Inc. Authors YO, AS, TA, TF, HK, EK, JM, HO, KT, ST, YU, HY, KY, and TK declare that they have no conflict of interest.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

Aims: The onset of fulminant type 1 diabetes mellitus is sometimes accompanied by sudden death or cardiac arrest. The aim of this study was to determine the risk factors for the development of these conditions at the onset of fulminant type 1 diabetes mellitus., Methods: We conducted a search of the literature on fulminant type 1 diabetes and sudden death or cardiac arrest published up to 2012 in PubMed and Ichushi (a Japanese article database), and a questionnaire survey was administered to the authors of the articles and to diabetes specialists affiliated to the Japan Diabetes Society. We analyzed the clinical data at disease onset of 17 patients with fulminant type 1 diabetes mellitus who experienced sudden death or cardiac arrest, and those of 257 patients who did not develop these conditions., Results: Patients with sudden death or cardiac arrest were younger, had a higher rate of impaired consciousness, more severe acidosis, hyperglycemia, hyponatremia, hyperkalemia, and hypochloremia, a higher serum blood urea nitrogen level, a higher serum creatinine level, and a higher plasma osmolality level than the other patients. In multiple logistic regression analyses, plasma glucose level was positively associated with sudden death or cardiac arrest. Receiver operating characteristic curve analyses showed that patients with a plasma glucose level over 1000 mg/dl (55.5 mmol/l) were at a high risk of cardiac arrest., Conclusions: Severe metabolic derangement, especially a high plasma glucose level, is associated with sudden death or cardiac arrest at the onset of fulminant type 1 diabetes mellitus., Competing Interests: Toshiaki Hanafusa received honoraria for lectures from Ono Pharmaceutical, Mitsubishi Tanabe Pharma, and Sumitomo Dainippon Pharma. Hiroshi Ikegami received honoraria for lectures from Novo Nordisk Pharmaceuticals Industries, Inc., Sumitomo Dainippon Pharma, and Kowa Company, and scholarship grants from Ono Pharmaceutical and Novo Nordisk Pharmaceuticals Industries, Inc. Yumiko Kawabata received scholarship grants from Ono Pharmaceutical and Novo Nordisk Pharmaceuticals Industries, Inc. Other authors declare that they have no conflict of interest.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or a substitute for it was obtained from all patients before they were included in the study.

Aims: Both sitagliptin (SIT) and mitiglinide (MIT) can lower postprandial hyperglycemia. The purpose of this study was to examine differences in insulin and glucagon secretion after SIT or MIT administration when similar levels of plasma glucose (PG) were achieved for both agents following an oral glucose load., Patients and Methods: We directly compared the effects of these two agents in 16 type-2 diabetic patients (M/F = 10/6, age 66 ± 3 years old, HbA1c 6.6 ± 0.5 %). Patients received SIT (50 mg qd for 1 week and 100 mg qd for an additional week) or MIT (10 mg tid for 2 weeks). After 2 weeks, patients crossed over to the other treatment. 75-g oral glucose tolerance tests were conducted before the study and after interventions., Results: The area under the curve (AUC) up to 180 min for the PG response was similar for both agents. While basal insulin secretion rates (ISR) were similar, incremental AUC of ISR was significantly lower in the SIT treatment (522 ± 108 vs 702 ± 288 pmol/min min, p  < 0.01), although the difference between the SIT and MIT treatments in the Matsuda index-which reflects insulin sensitivity-remained nonsignificant. Glucose-stimulated insulin secretion was similarly increased by the MIT and SIT treatments. Suppression of the AUC for glucagon was observed in the SIT treatment, while MIT treatment failed to suppress the glucagon concentration (-432 ± 2322 vs MIT 1116 ± 2520 pg/ml min, p  < 0.05). The basal proinsulin/insulin ratio was lower in the SIT treatment (0.23 ± 0.04 vs MIT 0.26 ± 0.36, p  < 0.05)., Conclusions: Although either SIT or MIT can be employed to reduce postprandial hyperglycemia, SIT induces changes in hormonal profiles that are more favorable to islet functions than MIT does.