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Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, they can lead to immune-related adverse events, including immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM). While fulminant T1DM is common in East Asia, ICI-T1DM has predominantly been reported in Western countries. In this report, we present the case of a 66-year-old Japanese man with type 2 diabetes mellitus undergoing dialysis for diabetic nephropathy. The patient was diagnosed with left upper lobe lung cancer, and treatment with nivolumab and ipilimumab was initiated. After 48 days, the patient experienced impaired consciousness and difficulty moving. His blood glucose levels were 815 mg/dL, and metabolic acidosis was detected, leading to a diagnosis of diabetic ketoacidosis. The patient was subsequently treated with continuous intravenous insulin. However, his C-peptide levels rapidly depleted, and new-onset ICI-T1DM was diagnosed. Although most Japanese patients with ICI-T1DM test negative for glutamic acid decarboxylase (GAD) antibodies, this case exhibited a strong positivity. Thus, we reviewed the literature on 15 similar Japanese cases, revealing a mean HbA1c level at onset of 8.7% and a mean time from ICI administration to onset of 9.7 weeks, which was shorter than that in GAD-negative cases. Moreover, human leukocyte antigen typing revealed five cases of DRB1*04:05-DQB1*04:01, including the present case, and one case of DRB1*09:01-DQB1*03:03, both of which were susceptible to T1DM haplotypes. These findings suggest that GAD antibody positivity may be associated with acute onset and disease progression in some cases of Japanese patients with ICI-T1DM. Given that the prediction of new-onset ICI-T1DM is challenging, monitoring GAD antibody levels might be useful. However, further studies with large sample sizes and validation across different racial and ethnic populations are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yabuki, Hirai, Moriya, Kusano and Hasegawa.)

Recently, along with increasing use of immune checkpoint inhibitors such as nivolumab, the incidence of immune-related adverse events, including type 1 diabetes mellitus, has become a serious problem. We report a patient who had immune checkpoint inhibitor‒associated type 1 diabetes mellitus that developed after a second mRNA-based SARS-CoV-2 vaccination.

Advances in insulin preparations and administration methods have produced a gradual improvement in glycemic control in patients with type 1 diabetes mellitus (DM). Nevertheless, glycated hemoglobin (HbA1c) levels in patients with type 1 DM are still poor compared to those in patients with type 2 DM. Here, we sought to assess the efficacy and safety of the sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin (IPRA) in patients with type 1 DM. This study was retrospectively conducted with data from type 1 DM patients who had a history of IPRA therapy. The primary endpoint was HbA1c level at 24 weeks. The baseline characteristics of a total of 12 subjects were as follows: age, 50.1 ± 13.2 years; diabetes duration, 17.3 ± 10.5 years; body mass index (BMI), 22.9 ± 2.1 kg/m 2 ; HbA1c, 8.8 ± 1.3%; and daily insulin dose, 0.60 ± 0.21 units/kg. IPRA decreased HbA1c levels to 8.2 ± 1.2% (p < 0.05) and reduced insulin dose to 0.52 ± 0.17 units/kg (p < 0.01) after 24 weeks. HbA1c value was particularly reduced in subjects with preserved C-peptide index. IPRA significantly reduced body weight by -1.4 ± 1.4 kg (p < 0.01) 16 weeks after starting treatment, with no further weight loss after 24 weeks. There were no instances of diabetic ketoacidosis or severe hypoglycemia. IPRA exerted beneficial effects on glycemic control without any severe adverse effects, and should be safe and effective when used in patients with type 1 DM with understanding of correspondence in sick day.

Objective: Interferon therapy can trigger induction of several autoimmune diseases, including type 1 diabetes. To assess the clinical, immunologic, and genetic characteristics of type 1 diabetes induced by interferon therapy, we conducted a nationwide cross-sectional survey., Research Design and Methods: Clinical characteristics, anti-islet autoantibodies, and HLA-DR typing were examined in 91 patients for whom type 1 diabetes developed during or shortly after interferon therapy., Results: Median age at the onset of type 1 diabetes was 56 (interquartile range 48-63) years and mean ± SD BMI was 20.8 ± 2.7 kg/m(2). The time period from the initiation of interferon therapy to type 1 diabetes onset in patients receiving pegylated interferon and ribavirin was significantly shorter than that in patients with nonpegylated interferon single therapy (P < 0.05). Anti-islet autoantibodies were detected in 94.5% of patients at diabetes onset. Type 1 diabetes susceptibility HLA-DRs in the Japanese population, DR4 and DR9, were also associated with interferon treatment-related type 1 diabetes. Furthermore, the prevalence of HLA-DR13 was significantly higher in interferon treatment-related type 1 diabetes than in healthy control subjects (odds ratio 3.80 [95% CI 2.20-7.55]; P < 0.0001) and classical type 1 diabetes (2.15 [1.17-3.93]; P < 0.05)., Conclusions: Anti-islet autoantibodies should be investigated before and during interferon therapy to identify subjects at high risk of type 1 diabetes. Stronger antiviral treatment may induce earlier development of type 1 diabetes. Furthermore, patients who develop interferon-induced type 1 diabetes are genetically susceptible.