• In myeloma, diabetes is more prevalent in Black patients (25%) compared to White patients (12%) and associated with worse survival (p<0.001)

  • In a mouse model of type 2 diabetes the progression of MM xenografts is faster in mice with diabetes than mice without diabetes (p<0.05).

Multiple myeloma (MM) is twice as common in Black individuals compared to White, and diabetes mellitus (DM) disproportionately affects Black patients. While numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (12% White and 25% Black). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (HR 1.27; 95% CI 1.11, 1.47; p<0.001). This appeared to be driven by a marked difference in OS between White patients with and without DM, but not Black patients. In contrast, obesity was associated with better OS in Black patients, but not White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised non-obese diabetic (Rag1-/-/MKR) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phospho-S6 ribosomal protein(Ser235/236) levels indicating greater activation of the mammalian target of rapamycin pathway. Our study is the first to evaluate racial differences in DM prevalence and survival in MM as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients, and to improve survival in MM DM management cannot be ignored.

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