Multiple Myeloma and Type 2 Diabetes Mellitus: A Clinical Challenge

Poorly controlled type 2 diabetes mellitus in patients with multiple myeloma (MM) may increase the risk of adverse cardiovascular outcomes, kidney damage, and peripheral neuropathy. Considering the effect of medications to treat MM on blood glucose control may be an important part of choosing a treatment regimen for some patients.

Type 2 diabetes mellitus (T2DM) may complicate management of patients with multiple myeloma (MM), according to an article published in the International Journal of Hematology-Oncology and Stem Cell Research. The authors estimated that 11% to 22% of patients with MM also have T2DM.

MM places patients at risk for kidney disease, anemia, hypercalcemia, and bone deterioration. The risk of kidney disease, which is a common long-term comorbidity of T2DM, may be compounded in patients with both T2DM and MM. In addition, both T2DM and MM independently increase the risk of coronary heart disease and stroke. The additive effect of poorly controlled T2DM in patients with MM may further increase the risk of these adverse outcomes.

With the availability of novel agents, including bortezomib, thalidomide, and lenalidomide, clinicians must be aware of the potential for some of these medications to affect control of T2DM, especially as survival rates in MM improve. In some patients with MM, especially with the advent of novel life-prolonging agents, MM is increasingly becoming a chronic disease state.

Although the importance of aggressive MM management may intuitively seem to outweigh the importance of managing T2DM, Chiu et al found that very high glucose levels 2 hours after a meal in patients with MM was associated with a 3-fold increase in the risk of mortality (hazard ratio [HR]: 3.06; 95% CI, 1.05 to 8.93). Because control of blood glucose levels may influence survival outcomes in patients with MM, the influence of medication on blood sugar control may be an important consideration in choosing an appropriate therapeutic regimen.

Some agents used to treat MM—notably glucocorticoids (eg, prednisone, dexamethasone)—may affect blood sugar control. Although some studies are now advocating use of proteasome inhibitors like thalidomide and lenalidomide, some evidence indicates that these agents may also adversely affect control of blood glucose levels.

In 2001, a study by Figg et al demonstrated that dosage reductions in thalidomide were associated with improvements in glycemic control. In an older study, conducted when thalidomide was used for morning sickness, a higher proportion of women (83%) developed insulin resistance compared with a minority (28%) of pregnant woman in a control group.

The use of certain medications for MM may increase the risk of neuropathy, which is also a potential complication of T2DM. In an analysis of data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA) trial, investigators analyzed various factors that increased the risk of neuropathy with bortezomib therapy. Although preexisting T2DM did not increase the risk of neuropathy appreciably, existing neuropathic symptoms increased the risk of developing neuropathy with bortezomib by 79% (HR: 1.785, P = .0065).

Balancing the risks and benefits of different treatments for patients with both MM and T2DM is a clinical challenge. As more evidence accumulates, it is conceivable that control of T2DM will be increasingly recognized as an important part of improving quality of life and, potentially, prolonging survival in patients with MM who also have T2DM.