SAT-564 - Observed Sex Differences in Time to Onset of Immune Checkpoint Inhibitor-Induced Diabetes

Background:
Immune checkpoint inhibitor–induced diabetes mellitus (CPI-DM) is a rare but severe endocrine immune-related adverse event (irAE) characterized by abrupt insulin dependence. While CPI-DM affects men and women at similar overall rates, sex-specific differences in autoantibody (Ab) profiles and timing of CPI-DM onset remain poorly defined.

Objective:
To evaluate sex differences in islet Ab positivity and time from immune checkpoint inhibitor (CPI) initiation to CPI-DM onset.

Methods:
We conducted a retrospective cohort study of adults with CPI-DM at a single academic medical center between 2016 and 2025. Patients were included if they developed insulin-dependent diabetes following CPI initiation and underwent islet Ab testing. Islet Ab positivity was defined as positivity for at least one Ab, including GAD65, insulin, ZnT8, ICA, or IA-2. Time from CPI initiation to CPI-DM diagnosis was analyzed using Kaplan–Meier curves and compared by sex and Ab status using log-rank tests.

Results:
The cohort included 61 individuals with CPI-DM (56% male). Median time from CPI initiation to CPI-DM onset showed a trend to faster onset for males than females (128 vs 209 days, respectively; log-rank p = 0.30).
When islet Ab positivity was defined as positivity prior to or within 30 days of diabetes diagnosis, rates were similar between males and females (26.5% vs. 32.0%, respectively, Fisher’s exact p = 0.77). When islet Ab positivity was defined across all available lab tests, rates of positivity were similar between males and females (50% vs 56%, Fisher’s exact p = 0.79). This higher cumulative prevalence reflected, in part, delayed seroconversion in a subset of patients, predominantly involving insulin (n=6) and GAD65 Ab (n=1).

Among individuals who were Ab positive at any time point, males developed CPI-DM significantly earlier than females (median 63 vs 170 days for males and females, respectively; log-rank p = 0.01), while no significant difference was observed among Ab negative individuals.

For Ab testing within or before 30 days of CPI-DM diagnosis, Ab positive males demonstrated a trend towards shorter median time to CPI-DM onset compared with females (63 vs 105.5 days, for males and females, respectively (log-rank p = 0.40)) and a consistent trend in Ab negative individuals (168 vs 262 days for males and females, respectively; log-rank p = 0.40).

Conclusion:
Islet Ab positivity occurs at similar rates in men and women with CPI-DM. Although no statistically significant sex-based differences in time to CPI-DM onset were observed when Ab positivity was defined at or near diagnosis, analyses using cumulative Ab status demonstrated earlier diabetes onset among Ab positive males following CPI initiation. These findings suggest sex-specific differences in immune-mediated β-cell vulnerability and may support incorporating sex into risk stratification for CPI-DM surveillance.

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