Impact of Anthracyclines on Diabetes Mellitus Development in B-Cell Lymphoma Patients: A Nationwide Population-based Study
Background and Objectives
Although anthracyclines are effective chemotherapeutic agents for treating B-cell lymphoma, adverse effects, such as bone marrow suppression and cardiotoxicity, limit their clinical application. We assessed whether anthracycline treatment also increases the risk for diabetes mellitus in patients with B-cell lymphoma.
Using data obtained from the Taiwanese National Health Insurance Research Database from 2004 to 2011, we compared overall survival and clinical features for B-cell lymphoma patients administered anthracyclines (n = 3147) and those not administered anthracyclines (n = 837). The impact of anthracycline treatment on diabetes risk was further investigated using a Gray’s test and multivariate competing-risk regression models in a dose-dependent manner.
Anthracycline administration was associated with a higher incidence of diabetes (HR: 1.75; 95% CI 1.11–2.75; p = 0.0163) after adjustments for age, gender, cumulative dose of prednisolone, and co-morbidities. Cumulative anthracycline doses of 253–400 mg (HR: 2.35; 95% CI 1.41–3.91; p = 0.0010), 401–504 mg (HR: 2.26; 95% CI 1.26–4.05; p = 0.0063), and > 504 mg (HR: 2.29; 95% CI 1.25–4.18; p = 0.0072) increased the incidence density of diabetes in a dose-dependent manner (p = 0.0006). The annual alteration of adapted diabetes complications severity index score was not significantly different between B-cell lymphoma patients with or without anthracycline treatment (p = 0.4924).
Anthracycline therapy increases diabetes risk in a dose-dependent manner in B-cell lymphoma patients. Intensive blood glucose monitoring and control should be recommended for B-cell lymphoma patients receiving anthracycline treatment.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflicts of interest.
This work was supported by grants from the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital, Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10701010021), Taiwan Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.
The institutional review board of the China Medical University Hospital approved this study (CMUH104-REC2-115). For this type of study, formal informed consent is not required by the institutional review board.
- 1.Coiffier B, Thieblemont C, Den Van, Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Ferme C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116:2040–5.CrossRefPubMedPubMedCentralGoogle Scholar
- 2.Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, Lopez-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M, MabThera International Trial G. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–91.CrossRefPubMedGoogle Scholar
- 3.Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell’olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013;31:1506–13.CrossRefPubMedGoogle Scholar
- 4.Chihara D, Westin JR, Oki Y, Ahmed MA, Do B, Fayad LE, Hagemeister FB, Romaguera JE, Fanale MA, Lee HJ, Turturro F, Samaniego F, Neelapu SS, Rodriguez MA, Fowler NH, Wang M, Davis RE, Nastoupil LJ. Management strategies and outcomes for very elderly patients with diffuse large B-cell lymphoma. Cancer. 2016;122:3145–51.CrossRefPubMedGoogle Scholar
- 5.Xu L, Wu X, Hu C, Zhang Z, Zhang L, Liang S, Xu Y, Zhang F. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials. Onco Targets Ther. 2016;9:4061–74.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Biondo LA, Lima Junior EA, Souza CO, Cruz MM, Cunha RD, Alonso-Vale MI, Oyama LM, Nascimento CM, Pimentel GD, Dos Santos RV, Lira FS, Rosa Neto JC. Impact of doxorubicin treatment on the physiological functions of white adipose tissue. PLoS One. 2016;11:e0151548.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.de Lima Junior EA, Yamashita AS, Pimentel GD, De Sousa LG, Santos RV, Goncalves CL, Streck EL, de Lira FS, Rosa Neto JC. Doxorubicin caused severe hyperglycaemia and insulin resistance, mediated by inhibition in AMPk signalling in skeletal muscle. J Cachexia Sarcopenia Muscle. 2016;7:615–25.CrossRefPubMedPubMedCentralGoogle Scholar