Immune Checkpoint Inhibitor–Associated Diabetes: A Single-Institution Experience

• DOI: 10.2337/dc20-0609
• Publication Date: 2020-10-14T02:25:13Z
• Authors: David J. Byun; Rebecca Braunstein; Jessica Flynn; Junting Zheng; Robert A. Lefkowitz; Sarah Kanbour; Monica Girotra
• Keywords: Adult; Male; Programmed Cell Death 1 Receptor; Middle Aged; B7-H1 Antigen; Diabetic Ketoacidosis; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Hyperglycemia; Neoplasms; Diabetes Mellitus; Humans; Female; Immune Checkpoint Inhibitors; Aged; Follow-Up Studies; Retrospective Studies

OBJECTIVE To characterize immune checkpoint inhibitor–associated diabetes mellitus (ICI-DM) in a single-institution case series.

RESEARCH DESIGN AND METHODS Retrospective chart review of 18 patients with new-onset ICI-DM following anti–programmed cell death protein 1 (PD-1)/anti–programmed cell death protein ligand 1 (PD-L1) therapy for advanced carcinomas.

RESULTS Of 18 patients, 9 had diabetic ketoacidosis (median glucose 27.92 mmol/L; median glucose before presentation 6.35 mmol/L). Median C-peptide at ICI-DM diagnosis was low, and it declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56–12.23 months). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those patients who were positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically.

CONCLUSIONS ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may occur both earlier following PD-L1 blockade compared with PD-1 inhibition and in those who have positive GAD65 autoantibodies.