Diagnostic criteria for acute-onset type 1 diabetes mellitus (2012): Report of the Committee of Japan Diabetes Society on the Research of Fulminant and Acute-onset Type 1 Diabetes Mellitus

Type 1 diabetes is a disease characterized by destruction of pancreatic β-cells, which leads to absolute deficiency of insulin secretion. Depending on the manner of onset and progression, it is classified as fulminant, acute-onset or slowly progressive type 1 diabetes. Here, we propose the diagnostic criteria for acute-onset type 1 diabetes mellitus. Among the patients who develop ketosis or diabetic ketoacidosis within 3 months after the onset of hyperglycemic symptoms and require insulin treatment continuously after the diagnosis of diabetes, those with anti-islet autoantibodies are diagnosed with \u27acute-onset type 1 diabetes mellitus (autoimmune)\u27. In contrast, those whose endogenous insulin secretion is exhausted (fasting serum C-peptide immunoreactivity <0.6 ng/mL) without verifiable anti-islet autoantibodies are diagnosed simply with \u27acute-onset type 1 diabetes mellitus\u27. Patients should be reevaluated after certain periods in case their statuses of anti-islet autoantibodies and/or endogenous insulin secretory capacity are unknown

The glycated albumin to HbA1c ratio is elevated in patients with fulminant type 1 diabetes mellitus with onset during pregnancy

Fulminant type 1 diabetes mellitus (FT1DM) develops as a result of very rapid and almost complete destruction of pancreatic β cell. The most common form of type 1 diabetes mellitus with onset during pregnancy has been shown to be FT1DM at least in Japan. We previously reported that the ratio of glycated albumin (GA) to HbA1c (GA/HbA1c ratio) is elevated in FT1DM patients at the diagnosis. In the present study, we investigated whether the GA/HbA1c ratio is also elevated in FT1DM with onset during pregnancy (P-FT1DM). The study subjects consisted of 7 patients with P-FT1DM. Ten patients with untreated type 2 diabetes mellitus (T2DM) discovered during pregnancy (P-T2DM) and 9 non-pregnant women with untreated T2DM (NP-T2DM) were used as controls. All study patients satisfied HbA1c<8.7%, the diagnostic criteria for FT1DM. The GA/HbA1c ratio in the P-FT1DM patients at the diagnosis was significantly higher than that in the P-T2DM patients and the NP-T2DM patients. The GA/HbA1c ratio was ≥3.0 in all P-FT1DM patients, whereas it was <3.0 in 8 of 10 P-T2DM patients and all NP-T2DM patients. The GA/HbA1c ratio was also elevated in P-FT1DM patients at the diagnosis compared with T2DM with or without pregnancy

Insulin-producing cells derived from ‘induced pluripotent stem cells’ of patients with fulminant type 1 diabetes: vulnerability to cytokine insults and increased expression of apoptosis-related genes

Aims/Introduction: The present study was carried out to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes, and evaluate the cytokine‐induced apoptotic reactions of β‐like insulin‐producing cells differentiated from the iPSCs.Materials and Methods: iPSCs were generated from fibroblasts of patients with fulminant type 1 diabetes by inducing six reprogramming factors. Insulin‐producing cells were differentiated from the iPSCs in vitro. The proportion of cleaved caspase‐3‐positive or terminal deoxynucleotidyl transferase 2′‐deoxyuridine, 5′‐triphosphate nick end labeling‐positive cells among insulin (INS)‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines was evaluated under treatment with tumor necrosis factor‐α, interleukin‐1β and interferon‐γ. Ribonucleic acid sequencing was carried out to compare gene expressions in INS‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines.Results: Two iPSC clones were established from each of three patients with fulminant type 1 diabetes. The differentiation of insulin‐producing cells from fulminant type 1 diabetes iPSC was confirmed by immunofluorescence analysis and KCl‐induced C‐peptide secretion. After treatment with pro‐inflammatory cytokines, these INS‐positive cells showed higher expression of cleaved caspase‐3 than those derived from control human iPSCs. Altered expression levels of several apoptosis‐related genes were observed in INS‐positive cells derived from the fulminant type 1 diabetes iPSCs by ribonucleic acid sequencing.Conclusions: We generated iPSCs from patients with fulminant type 1 diabetes and differentiated them into insulin‐producing cells. This in vitro disease model can be used to elucidate the disease mechanisms of fulminant type 1 diabetes

Re-Enlightenment of Fulminant Type 1 Diabetes under the COVID-19 Pandemic

Fulminant type 1 diabetes (FT1D) is a subtype of type 1 diabetes (T1D) that is characterized by the rapid progression to diabetic ketoacidosis against the background of rapid and almost complete pancreatic islet destruction. The HbA1c level at FT1D onset remains normal or slightly elevated despite marked hyperglycemia, reflecting the rapid clinical course of the disease, and is an important marker for diagnosis. FT1D often appears following flu-like symptoms, and there are many reports of its onset being linked to viral infections. In addition, disease-susceptibility genes have been identified in FT1D, suggesting the involvement of host factors in disease development. In most cases, islet-related autoantibodies are not detected, and histology of pancreatic tissue reveals macrophage and T cell infiltration of the islets in the early stages of FT1D, suggesting that islet destruction occurs via an immune response different from that occurring in autoimmune type 1 diabetes. From 2019, coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread worldwide and became a serious problem. Reports on the association between SARS-CoV-2 and T1D are mixed, with some suggesting an increase in T1D incidence due to the COVID-19 pandemic. When discussing the association between COVID-19 and T1D, it is also necessary to focus on FT1D. However, it is not easy to diagnose this subtype without understanding the concept. Therefore, authors hereby review the concept and the latest findings of FT1D, hoping that the association between COVID-19 and T1D will be adequately evaluated in the future

Pathogenesis of Fulminant Type 1 Diabetes

Fulminant type 1 diabetes is a new subtype of type 1 diabetes. The term was established in 2000. It is a syndrome characterized by a markedly rapid and almost complete destruction of pancreatic β-cells. Several lines of evidence suggest that both genetic factors, such as human leukocyte antigen (HLA), and environmental factors, such as viral infection, contribute to the development of this disease. It is also suggested that autoimmune processes contribute less critically to fulminant type 1 diabetes than to classic type 1A diabetes. Based on the findings made to date, both viral infection and the subsequent immune reaction in genetically susceptible individuals cause β-cell destruction and lead to fulminant type 1 diabetes

A Case of Type 2 Diabetes Mellitus with Lung Cancer Suffered from Euglycemic Diabetic Ketosis Accompanied by Adrenal Insufficiency after Immune Checkpoint Inhibitors

A 74-year-old patient with type 2 diabetes mellitus received basal-bolus insulin, insulin secretagogues, and sodium glucose transporter 2 (SGLT2) inhibitors. After immune checkpoint inhibitor treatment for lung cancer, he suffered from depressed consciousness with a urinary ketone body (3+). When all hypoglycemic treatments were discontinued, his serum blood glucose remained at 121 mg/dL. He was diagnosed with euglycemic diabetic ketosis. Endocrine loading tests revealed isolated adrenocorticotropic hormone (ACTH) deficiency as an immune-related adverse event. It was suggested that euglycemic diabetic ketosis was induced by the self-suspension of insulin and insulin secretagogues, adrenal insufficiency, SGLT2 inhibitors, and carbohydrate intake shortage