Uncontrolled Diabetes Mellitus and the Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma in US Veterans.

7551 Background: Studies have shown that, independent of obesity, the metabolic effects of diabetes mellitus (DM) promote the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). However, it is unclear whether glycemic control is associated with MGUS progression in DM patients. We aimed to evaluate the association between poor glycemic control, measured by HbA1c >6.5%, and progression. Methods: Patients diagnosed with MGUS from 1999-2021 in the Veterans Health Administration (VHA) were identified using a published natural language processing (NLP)-based algorithm. We focused on patients whose MGUS subtype was IgG, IgA, or light chain. We excluded patients lacking body weight measurements from the time of MGUS diagnosis to the end of follow-up to ensure receiving care in the VHA. We further excluded patients with extended gaps >1 year between HbA1c measurements. Time-varying HbA1c measurements during the follow-up, evaluated at 1-day intervals and categorized into uncontrolled (HbA1c >6.5%) or controlled (≤6.5%) DM was the exposure variable. Progression of MGUS to MM was also confirmed by a published NLP algorithm. The association between the time-varying controlled/uncontrolled DM and progression was estimated by multivariable-adjusted hazard ratio (aHR) with death as a competing event. The covariates included sex, race, MGUS subtype as well as age, body mass index, monoclonal protein level, Charlson Comorbidity Index, DM medication, and DM type (type 1, type 2 with insulin-dependency status, type 2 without insulin-dependency status), all at MGUS diagnosis. Same analysis was conducted in a subgroup of patients with non-insulin dependent DM type 2 (NIDDMT2) without insulin use between MGUS diagnosis and the end of follow-up. Results: After applying inclusion and exclusion criteria, we identified 9,682 patients with both DM and MGUS. The multivariable analysis revealed a positive association between poor glycemic control and MM progression (see Table): (aHR 1.27, 95% CI 1.13-1.42). In NIDDMT2 without insulin use (n=3,498), poor glycemic control was associated with MM progression (aHR 1.81; 95% CI 1.57-2.10). Conclusions: For patients with DM and MGUS, the risk of MGUS progression to MM was 27% higher in uncontrolled DM and 81% higher in patients with NIDDMT2. This finding highlights a modifiable risk factor for MM progression in MGUS patients. Future studies should examine if interventions to enhance glycemic control could potentially reduce MGUS progression.