Anti PD-1 monoclonal antibody induced autoimmune diabetes mellitus: a case report and brief review

Abstract

Nowadays, immune checkpoint inhibitor therapy has been used in more and more cancer patients. These agents were associated with immune-related adverse effects, and autoimmune diabetes mellitus is one of them. And it is not common but can be potentially fatal. Anti PD-1 monoclonal antibody is a humanized IgG4 antibody against PD-1, which has been applied in advanced non-small cell lung cancer (NSCLC) treatment. In this paper, we reported the case of autoimmune diabetes mellitus induced by anti PD-1 monoclonal antibody in NSCLC treatment. Here is a 73-year-old male patient with no diabetes history who had anti PD-1 monoclonal antibody 200 mg every 3 weeks for NSCLC treatment. After 10 cycles of the therapy, his blood glucose level elevated and he suffered diabetic ketoacidosis (DKA). And his C-peptide was significantly decreased with negative relative auto-antibodies. Combined with his medical history and the laboratory examination, anti PD-1 monoclonal antibody induced autoimmune diabetes mellitus was diagnosed. After recovering from DKA and controlling his blood glucose, his anti PD-1 therapy was continued and he still got some benefit. This report suggested that glycemic monitoring is imperative during this anti PD-1 monoclonal antibody treatment. Moreover, after controlling the blood glucose level, continuing the immune therapy could still be benefit and safe for the patient.

Anti-programmed Cell Death Protein-1 Therapy in Intrahepatic Cholangiocarcinoma Induced Type 1 Diabetes: A Case Report and Literature Review

“…Hemoglobin A1c (HbA1c), a measure of average blood glucose over the preceding 3 months, is a common indicator for diabetes monitoring. Different from traditional diabetes, HbA1c levels in patients with anti-PD-1 diabetes were mostly close to normal or slightly elevated, ranging from 5.8 to 11.4% ( 1 , 4 , 5 , 18 , 21 , 22 , 27 ). In this case, the patient's HbA1c was 7.6%.…”

“…Since the acute onset of diabetes induced by anti-PD-1, the early HbA1c level is mostly normal, which might not be a good screening indicator ( 11 ). Nevertheless, continuous monitoring of HbA1c is significant for patients to minimize the risk of diabetes development and adjust the treatment regimen ( 15 , 22 ). Routine monitoring of HbA1c after anti-PD-1 treatment is still of importance.…”

“…C-peptide, which is secreted by islet β cells, is an indicator of islet β cell function and is not influenced by exogenous insulin. In patients with anti-PD-1 diabetes, C-peptide levels might be low or even absent, which suggests the rapid destruction of β cells ( 1 , 3 , 4 , 14 , 21 , 22 ). A retrospective study in 2021 indicated that the patients' C-peptide level were 0.1 ng/mL (0.012–3.16 ng/mL) ( 18 ).…”

“…The diagnostic criteria ( 28 ) are as follows: hyperglycemia develops into ketosis or ketoacidosis within 1 week; Blood glucose ≥16.0 mmol/L and HbA1c <8.5% at first diagnosis; Urinary C-peptide <10 μg/d or fasting serum C-peptide <0.3 ng/mL and postprandial C-peptide <0.5 ng/mL. As an important diagnostic indicator of fulminant diabetes, C-peptide should be closely monitored, especially for patients with rapidly elevated blood glucose ( 22 ).…”

“…For patients with autoimmune diabetes, diabetes-related autoantibodies, including glutamic acid decarboxylase antibody (GADA), islet-cell antibody (ICA), insulin antibody (IAA), anti-insulinoma antigen-2 antibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8), are usually tested ( 22 ). Among patients with anti-PD-1 diabetes, 50–56% were detected at least one diabetes-related autoantibody, and the most prevalent were GADA ( 1 , 4 , 5 , 9 , 11 , 16 ).…”