Increased incidence of non-Hodgkin lymphoma, leukemia, and myeloma in patients with diabetes mellitus type 2: a meta-analysis of observational studies

Abstract

Hematologic malignancies are a heterogeneous group of conditions with an unclear etiology. We hypothesized that diabetes mellitus type 2 is associated with increased risk of developing lymphoma, leukemia, and myeloma. A literature search identified 26 studies (13 casecontrol and 13 cohort studies) evaluating such an association. Outcome was calculated as the odds ratio (OR) using a random effects model. Heterogeneity and publication bias were evaluated using the I 2 index and the trim-and-fill analysis, respectively. Quality was assessed using the Newcastle-Ottawa scale. The OR for non-Hodgkin lymphoma was increased at 1.22 (95% confidence interval [CI], 1.07-1.39; P < .01) but the OR for Hodgkin lymphoma was not. There was an increased OR for peripheral T-cell lymphoma (OR ‫؍‬ 2.42, 95% CI, 1.24-4.72; P ‫؍‬ .009) but not for other non-Hodgkin lymphoma subtypes. The OR for leukemia was 1.22 (95% CI, 1.03-1.44; P ‫؍‬ .02) and the OR for myeloma was 1.22 (95% CI, 0.98-1.53; P ‫؍‬ .08). Although diabetes mellitus type 2 seems to increase the risk of developing lymphoma, leukemia, and myeloma, future studies should focus on evaluating other potential confounders such as obesity, dietary habits, physical activity, and/or antidiabetic therapy. IntroductionHematologic malignancies are a heterogeneous group of diseases characterized by the malignant uncontrolled growth of hematopoietic cells. According to Surveillance Epidemiology and End Results data, approximately 75 000, 45 000, and 20 500 persons were diagnosed with lymphoma, leukemia, and myeloma, respectively, in 2011 in the United States alone. 1 The development of hematologic malignancies has been associated with different causes, such as infectious processes (eg, HTLV-1 and adult T-cell leukemia/lymphoma), autoimmune disorders (eg, rheumatoid arthritis, Sjogren syndrome, and systemic lupus erythematosus) or a positive family history. However, despite recent advances in the understanding of their pathophysiology, the etiology of these conditions remains largely unexplained.Diabetes affects approximately 25.8 million people in the United States. 2 It is estimated that diabetes mellitus type 2 (DM2) accounts for 90%-95% of all diabetes cases. DM2 has been studied as a potential risk factor for the development of hematologic malignancies; however, studies evaluating such an epidemiologic association have rendered conflicting results. In a previous metaanalysis evaluating the association between diabetes and incidence of lymphoma, 3 we found a stronger association for DM2 and non-Hodgkin lymphoma (NHL). However, NHL subtype analyses were not performed given the paucity of the data available at the time.The primary objective of the present study was to evaluate the potential association between DM2 and the incidence of lymphoma, leukemia, and myeloma. Secondary objectives were to evaluate the association between DM2 and specific subtypes of lymphoma and leukemia. Methods Literature searchTwo authors performed a literature search independently using PubMed/ MEDLINE a...

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