Journal of Nephropharmacology (Jun 2023)
Association between type 2 diabetes mellitus and multiple myeloma: Fact or fiction
Abstract
Multiple myeloma is a plasma cell cancer causing bone and marrow damage, resulting in hypercalcemia, anemia, and renal insufficiency. Diabetes mellitus occurs in 6-24% of multiple myeloma cases, associated with immunosuppression, inflammation, and lymphocyte dysfunction, possibly contributing to multiple myeloma development. Insulin and insulin-like growth factor-1 also contribute to multiple myeloma pathogenesis. The incidence of both multiple myeloma and diabetes mellitus is expected to rise due to the aging population, lifestyle changes, genetic predisposition, and improved diagnostic methods. Although the link between diabetes mellitus and hematological malignancy risk is less conclusive, insulin resistance and growth factors may promote tumor cell proliferation. Genetic variants linked to type 2 diabetes mellitus (T2DM) influence multiple myeloma risks. The insulin like growth factor 1 (IGF1) gene triggers malignant plasma cell proliferation. Additionally, poorly managed T2DM-induced acidosis creates a favorable environment for cancer cell growth, including multiple myeloma. T2DM and metabolic syndrome (MetS) increase multiple myeloma risks through insulin resistance, hyperinsulinemia, inflammation, and dyslipidemia. Inflammatory cytokines [interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β)] contribute to insulin resistance, chronic inflammation, and multiple myeloma cell survival too. The coexistence of diabetes and multiple myeloma presents challenges in managing complications like neuropathy, nephropathy, and retinopathy. In conclusion, the association between T2DM and multiple myeloma has been established, with a discernible influence from distinct genetic variations. Notably, IL-6, TNF-alpha, and IL-1β exert significant influence on the development of insulin resistance and the proliferation of cancer cells, and also their viability. Consequently, the involvement of inflammatory cytokines, dyslipidemia, and IGF1 in the progression of MM among patients with T2DM and MetS is noteworthy.
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