Type I Diabetes-A Rare Adverse Event Described in Patients Receiving Immunotherapy Versus a Side Effect from SARS-CoV-2 Infection

Abstract

Background and Clinical Significance: Lung cancer, a leading cause of global cancer diagnoses, maintains the highest mortality risk despite advances in treatment. Immunotherapy agents, such as anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1), have revolutionized care for non-small cell lung cancer (NSCLC). However, the success is tempered by the emergence of immune-mediated adverse reactions, including the rare onset of type I diabetes. The incidence of diabetes mellitus increased during the SARS-CoV-2 pandemic. While there are several cases of new-onset diabetes after COVID-19 and COVID-19 vaccination, no case of new-onset type 1 diabetes after COVID-19 was described in an immune checkpoint inhibitor (ICI)-treated patient. Case Presentation: A 57-year-old male with stage IV NSCLC (brain and liver metastases) who had been treated with nivolumab for 4 years appeared positive for SARS-CoV-2 infection at a routine check. After two weeks, he was admitted to our clinic with severe fatigue, hyperglycemia, hyponatremia, and hyperkalemia. HbA1c level was normal and serum peptide C was undetectable. Nivolumab treatment was ceased, and the patient became fully dependent on basal-bolus insulin. After 3 months, the patient showed a complete imagistic remission. Conclusions: The case presented significant challenges due to the unclear etiology of newly onset diabetes and the uncommon age at which type 1 diabetes is developed. The outcome suggests that anti-PD-1 and SARS-CoV-2 infection can act synergistically.

Keywords: SARS-CoV-2 pandemic; adverse effect; immunotherapy; lung cancer; type I diabetes.

Figure A1

(A) HE×200: Invasive lung adenocarcinoma-G3, solid predominant pattern: sheets of neoplastic cells with poorly formed glands. (B) HE×200: Invasive lung adenocarcinoma-G2, acinar pattern: variably sized and shaped glands in a fibrotic stroma. (C) IHC×400: Invasive lung adenocarcinoma negative for ALK (D5F3 clone Ventana).

Figure A2

Abdominal CT scan: complete remission of hepatic metastases.

Figure 1

Chest CT scan: left superior lung lobe tumor cT2cN0.

Figure 2

Brain CT scan: left occipital lobe metastases.

Figure 3

Abdominal CT scan: hepatic metastases.

Figure 4

Glucose levels evolution.

Figure 5

Complete remission. (a) Brain CT scan: complete remission of occipital lobe metastases. (b) Abdominal CT scan: complete remission of hepatic metastases.

Figure 6

Complete remission. (a) Abdominal CT scan: complete remission of hepatic metastases (b) Chest CT scan: complete remission.