Rosiglitazone in Diabetes Control in Hemodialysis Patients With and Without Viral Hepatitis Infection Effectiveness and side effects CHIH-KANG CHIANG, MD, PHD 1,2 TAI-I. HO, MD 2 YU-SEN PENG, MD 2 SHIH-PING HSU, MD 2 MEI-FEN PAI, MD 2 SHAO-YU YANG, MD 2 KUAN-YU HUNG, MD, PHD 1 KWAN-DUN WU, MD 1 OBJECTIVE — Thiazolidinedione (TZD) may provide an additional benefit of cardiovascu- lar protection in diabetic patients through targeting of insulin resistance. However, use of a TZD is hampered by possible effects of fluid retention and hepatotoxicity. In this study we aimed to determine whether the risk of TZD-induced fluid retention or hepatic injury is higher in hemo- dialysis patients with persistent viral hepatitis infection. RESEARCH DESIGN AND METHODS — This was a prospective, cohort study on hemodialysis patients. Type 2 diabetic patients with A1C levels of 8% were followed for at least 12 months. Rosiglitazone was initiated at 2– 4 mg/day. The primary outcome was the target A1C (7%) achieved and dosages of rosiglitazone. Secondary outcomes included changes in lipid profile and inflammatory biomarkers. Safety evaluations were number of hypoglycemic epi- sodes, changes in liver transaminase levels, cardiothoracic ratio (CTR), fluid status control during dialysis, and events of symptomatic heart failure. RESULTS — A total of 78 patients, including 15.4% (n = 12) hepatitis B surface antigen– positive and 16.7% (n = 13) anti– hepatis C virus (HCV)-positive patients, were enrolled. The mean follow-up period was 15.4  3.8 months. The diabetic response rate (A1C 7%) to rosiglitazone was 86.1%. The serum triglyceride level was reduced (194  112.5 to 168  88 mg/dl, P = 0.037) more significantly than the total cholesterol level (178  42.1 to 174  46.5 mg/dl, P = 0.13). High-dose rosiglitazone (8 mg/day) reduced the serum level of C-reactive protein and increased the serum adiponectin level significantly. After rosiglitazone, interdialysis weight gain (2.07  1.6 to 3.2  1.2 kg, P  0.01) and mean CTR (48.2  5.6 to 50.4  6.2%, P = 0.0213) of individuals increased significantly. Nevertheless, liver aminotransferase (aspar- tate aminotransferase and alanine aminotransferase) levels did not show a tendency to increase in patients (n = 25) with viral hepatitis B or C infections. CONCLUSIONS — Among regular hemodialysis patients with chronic viral hepatitis infec- tions, rosiglitazone may be safely used for diabetes control. However, one must be aware that a possible effect of its use is a deterioration in cardiovascular reserve. Diabetes Care 30:3–7, 2007 T aiwan has the highest incidence of end-stage renal disease (ESRD) in the world (1). Diabetes not only leads to ESRD but also predisposes pa- tients to higher cardiovascular risk and chronic inflammatory conditions through multifactorial mechanisms including in- sulin resistance (2,3). Previously, we demonstrated that the prevalence of insu- lin resistance in patients receiving long-term dialysis is high (4,5). Thiazo- lidinediones (TZDs) enable effective tar- geting of insulin resistance, which may provide an additional cardiovascular ben- efit with control of diabetes in ESRD pa- tients. Rosiglitazone, classified as a TZD, has been reported to possess cardiovascu- lar protection with its anti-inflammatory (2,6) and lipid-lowering effects (7). How- ever, because of concerns about fluid re- tention and hepatic injury associated with TZDs, their use is not recommended in patients with advanced heart failure (8,9) and/or liver insufficiency (10,11). Hemodialysis patients, because of their nearly absent urine output, may have additional risks of water retention if they are given TZDs. In contrast, we be- lieve that hemodialysis therapy may re- duce the risk of fluid retention by regular fluid removal every 2–3 days. Whether TZDs are associated with a net advantage or disadvantage among hemodialysis pa- tients remains undetermined. Taiwan is an endemic area for hepati- tis B virus (HBV) and hepatitis C virus (HCV) infections (12,13). Although there are a few reports of TZD-induced acute hepatic injury (10,11), a systemic study of safety issues with regular use of TZDs in high-risk patients, such as those with chronic HBV or HCV infections, is lack- ing. Thus, in this study, we elucidate whether the risk of TZD-induced hepatic injury is higher in ESRD patients with HBV or HCV infections. We had four aims in this study: 1) to evaluate the effectiveness of rosiglitazone in diabetic patients receiving regular he- modialysis; 2) to evaluate the impact of rosiglitazone on fluid control and cardio- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; and 2 Far-Eastern Memorial Hospital, Pan-Chiao, Taipei, Taiwan. Address correspondence and reprint requests to Kuan-Yu Hung, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China. E-mail: d820612@ ha.mc.ntu.edu.tw. Received for publication 10 May 2006 and accepted in revised form 17 September 2006. C.-K.C. and T.-I.H. contributed equally to this work. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; CTR, cardiothoracic ratio; ESRD, end-stage renal disease; HBV, hepatitis B virus; HCV, hepatitis C virus; TZD, thiazolidinedione. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. DOI: 10.2337/dc06-0956 © 2007 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Clinical Care/Education/Nutrition O R I G I N A L A R T I C L E DIABETES CARE, VOLUME 30, NUMBER 1, JANUARY 2007 3 Downloaded from http://diabetesjournals.org/care/article-pdf/30/1/3/594494/zdc00107000003.pdf by guest on 28 June 2022