Association between diabetic control and progression of monoclonal gammopathy of undetermined significance to multiple myeloma

Abstract Diabetes Mellitus (DM) is a risk factor for multiple myeloma (MM), but the relationship between diabetic control and risk of progression to MM in patients with monoclonal gammopathy of undetermined significant (MGUS) is unclear. We conducted a retrospective cohort study of US Veterans diagnosed with MGUS from 10/1/1999-12/31/2023 with prior DM. MGUS and MM diagnoses were confirmed using published natural language processing-assisted models. The exposure was time-varying glycated hemoglobin (HbA1c) > 7% during the follow-up (time of MGUS to MM, death, or being censored on 4/15/2025, whichever occurred first). The outcome was time from MGUS to MM. The association was estimated by multivariable-adjusted hazard ratio (aHR) using a Fine-Gray subdistribution hazard model with death as a competing event, adjusted by inverse probability of treatment weighting (IPTW). Among 11,061 patients with DM, HbA1c > 7% was associated with increased progression risk (aHR 1.15; 95% confidence interval [CI] 1.01–1.32). This association was stronger in the subgroups of Type-2 DM (T2DM) with insulin use ( n = 7070; aHR 1.46; 95% CI 1.19–1.78) and non-use ( n = 3724; aHR 1.42; 95% CI 1.14–1.77) throughout follow-up. For patients with T2DM and MGUS, poorly controlled diabetes may be associated with progression risk to MM. Future studies are needed to confirm this relationship.