Association between Prolactinoma and Incident Type 2 Diabetes Mellitus: Evidence from a Korean Nationwide Cohort

Background: The effect of prolactinoma on the development of type 2 diabetes mellitus (T2DM) has not been evaluated at the population level. We investigated the association between prolactinoma and incident T2DM in a nationwide cohort. Methods: We analyzed data from the Korean National Health Insurance Service-National Sample Cohort, which includes 2% of the total national population selected by random sampling, covering the period from 2002 to 2019. A total of 335 patients with newly diagnosed prolactinoma and 1,562 age- and sex-matched controls were included. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM using Cox proportional hazards regression. Time-dependent HRs were also estimated. Results: The proportion of prolactinoma patients who developed T2DM was significantly higher than that of controls (10.1% vs. 5.5%; relative risk, 1.84; 95% CI, 1.26 to 2.69). After adjustment for age, sex, income, and comorbidities, the risk of T2DM remained significantly higher in the prolactinoma group (HR, 1.56; 95% CI, 1.01 to 2.41). Subgroup analysis showed a markedly increased risk among individuals aged ≥50 years (HR, 4.47; 95% CI, 1.66 to 12.08). The positive association between prolactinoma and T2DM decreased over time but remained significant for up to 3 years after prolactinoma diagnosis (HR, 9.28 95% CI, 3.45 to 24.97; HR, 3.15 95% CI, 1.55 to 6.38; and HR, 0.82 95% CI, 0.44 to 1.53 for ≤1, 1-3, and >3 years, respectively). Conclusion: Newly diagnosed prolactinoma was independently associated with a higher risk of T2DM, with the association diminishing over 3 years. These findings highlight the importance of monitoring for T2DM during the early management of prolactinoma, particularly in middle-aged patients who may have been previously overlooked.