Ali Rastegar-Kashkouli
1 
, Mohsen Jafari
1* , Saina Karami
2 , Pourya Yousefi
1 , Amir Mohammad Taravati
1* , Ashkan Khavaran
3 , Dordaneh Rastegar
4 , Mohammad Reza Jafari
1 , Seyedeh Yasaman Alemohammad
5 , Ghader Dargahi Abbasabad
6, Mohammad Shahbaz
7 , Mohammad Ebrahimi Kalan
8 1 Nickan Research Institute, Isfahan, Iran
2 School of Pharmacy, University of Maryland, Baltimore, United States
3 Faculty of Medicine, University of Freiburg, Freiburg, Germany
4 Dr Maleknasab Pathology Lab, Shiraz, Iran
5 Robert Stemple College of Public Health and Social Work, Florida International University, Miami, Florida, United States
6 Applied Health Service Research, University of New Brunswick, Canada
7 Perinatal Science, University of Auckland, Auckland, New Zealand
8 Eastern Virginia Medical School, Norfolk, Virginia, United States
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.
Implication for health policy/practice/research/medical education:
According to our comprehensive review, there exists a correlation between T2DM and the onset and advancement of multiple myeloma, which can be attributed to a variety of distinct mechanisms.
Please cite this paper as: Rastegar-Kashkouli A, Jafari M, Karami S, Yousefi P, Taravati AM, Khavaran A, Rastegar D, Jafari MR, Alemohammad SY, Dargahi Abbasabad G, Shahbaz M, Ebrahimi Kalan M. Association between type 2 diabetes mellitus and multiple myeloma: fact or fiction. J Nephropharmacol. 2023;12(2):e10604. DOI: 10.34172/npj.2023.10604.