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. 2009 Oct;70(5):377–389. doi: 10.1016/j.curtheres.2009.10.002

Effectiveness and tolerability of rosiglitazone on insulin resistance and body composition in nondiabetic Thai patients undergoing continuous ambulatory peritoneal dialysis: A 12-week pilot study

Pornanong Aramwit 1,*, Panipat Bunmee 1, Ouppatham Supasyndh 2
PMCID: PMC3967294  PMID: 24683246

Abstract

Background: Patients with chronic renal insufficiency, especially those undergoing continuous ambulatory peritoneal dialysis (CAPD), normally have insulin resistance due to deficiencies in insulin secretion and degradation, as well as tissue resistance to insulin at both receptor and postreceptor levels.

Objective: The aim of this study was to investigate the effectiveness and tolerability of rosiglitazone on insulin resistance and body composition in patients without diabetes mellitus (DM) undergoing CAPD.

Methods: This pilot study included a pretest and posttest with a repeated-measure design in a small number of patients. CAPD patients without DM received rosiglitazone 2-mg tablets BID for 12 weeks. Homeostasis Model Assessment Index of Insulin Resistance (HOMA-IR) and bioelectrical impedance analysis (BIA) were used to assess insulin resistance and body composition, respectively. Tolerability was assessed using laboratory analyses as well as physical examination findings to evaluate peripheral edema. Peripheral edema was assessed by the study investigators.

Results: Thirteen Thai patients (mean [SD] age, 54.17 [11.42] years [range, 35–85 years]; body mass index [BMI], >20 to <30 kg/m2; fasting blood glucose [FBG] concentration, <5.39 mmol/L) were included in the study. One patient was withdrawn due to illness unrelated to the study. No significant difference was found in FBG concentration between baseline and posttreatment (after 12 weeks of treatment) (5.45 [0.59] vs 5.24 [0.51] mmol/L), but fasting plasma insulin concentrations (28.50 [23.70] vs 10.15 [4.22] μIU/mL; P = 0.005) and HOMA-IR score (6.70 [5.23] vs 2.40 [1.15]; P = 0.011) were significantly lower. There were no significant changes in weight or BMI from baseline to posttreatment. Seven subjects (58.3%) experienced weight gain at week 4, while 2 patients (16.7%) still had weight gain after 12 weeks of treatment. A significant increase was found between baseline and posttreatment in total body water (38.03 [4.55] vs 42.44 [5.99] L; P = 0.018), extracellular fluid (20.24 [3.75] vs 26.22 [8.69] L; P = 0.005), plasma fluid (4.29 [0.80] vs 5.20 [0.93] L; P = 0.005), and interstitial fluid (14.99 [2.78] vs 17.68 [3.07] L; P = 0.040). Using BIA, no significant changes were observed in intracellular fluid, fat mass, or liver function. After 12 weeks of rosiglitazone administration, 2 patients (16.7%) had mild edema.

Conclusions: Rosiglitazone 2 mg BID for 12 weeks was associated with significantly improved insulin resistance in this small group of nondiabetic Thai patients undergoing CAPD. There was a significant increase in total body water and extracellular fluid after administration of rosiglitazone for 12 weeks. There were no significant changes in FBG, weight, or BMI.

Key words: rosiglitazone, insulin resistance, body composition, nondiabetic, CAPD

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References

  • 1.Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539–553. doi: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  • 2.Sarafidis PA, Whaley-Connell A, Sowers JR, Bakris GL. Cardiometabolic syndrome and chronic kidney disease: What is the link? J Cardiometab Syndr. 2006;1:58–65. doi: 10.1111/j.0197-3118.2006.05470.x. [DOI] [PubMed] [Google Scholar]
  • 3.Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med. 1974;290:697–701. doi: 10.1056/NEJM197403282901301. [DOI] [PubMed] [Google Scholar]
  • 4.Canbakan M, Sahin GM. Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis patients. Ren Fail. 2007;29:289–293. doi: 10.1080/08860220601166271. [DOI] [PubMed] [Google Scholar]
  • 5.Wu HY, Hung KY, Huang JW. Initial glucose load predicts technique survival in patients on chronic peritoneal dialysis. Am J Nephrol. 2008;28:765–771. doi: 10.1159/000128608. [DOI] [PubMed] [Google Scholar]
  • 6.Maggs DG, Buchanan TA, Burant CF. Metabolic effects of troglitazone monotherapy in type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998;128:176–185. doi: 10.7326/0003-4819-128-3-199802010-00002. [DOI] [PubMed] [Google Scholar]
  • 7.Schwartz S, Raskin P, Fonseca V, Graveline JF, Troglitazone and Exogenous Insulin Study Group Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. N Engl J Med. 1998;338:861–866. doi: 10.1056/NEJM199803263381302. [DOI] [PubMed] [Google Scholar]
  • 8.Raskin P, Rendell M, Riddle MC, Rosiglitazone Clinical Trials Study Group A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Diabetes Care. 2001;24:1226–1232. doi: 10.2337/diacare.24.7.1226. [DOI] [PubMed] [Google Scholar]
  • 9.Liazos E, Broadbent DM, Beare N, Kumar N. Spontaneous resolution of diabetic macular oedema after discontinuation of thiazolidenediones. Diabet Med. 2008;25:860–862. doi: 10.1111/j.1464-5491.2008.02491.x. [DOI] [PubMed] [Google Scholar]
  • 10.Berlie HD, Kalus JS, Jaber LA. Thiazolidinediones and the risk of edema: A meta-analysis. Diabetes Res Clin Pract. 2007;76:279–289. doi: 10.1016/j.diabres.2006.09.010. [DOI] [PubMed] [Google Scholar]
  • 11.Karalliedde J, Buckingham R, Starkie M, Rosiglitazone Fluid Retention Study Group Effect of various diuretic treatments on rosiglitazone-induced fluid retention. J Am Soc Nephrol. 2006;17:3482–3490. doi: 10.1681/ASN.2006060606. [DOI] [PubMed] [Google Scholar]
  • 12.Nesto RW, Bell D, Bonow RO. Thiazolidinedione use, fluid retention, and congestive heart failure: A consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care. 2004;27:256–263. doi: 10.2337/diacare.27.1.256. [DOI] [PubMed] [Google Scholar]
  • 13.Starner CI, Schafer JA, Heaton AH, Gleason PP. Rosiglitazone and pioglitazone utilization from January 2007 through May 2008 associated with five risk-warning events. J Manag Care Pharm. 2008;14:523–531. doi: 10.18553/jmcp.2008.14.6.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Hong G, Lockhart A, Davis B. PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells. FASEB J. 2003;17:1966–1968. doi: 10.1096/fj.03-0181fje. [DOI] [PubMed] [Google Scholar]
  • 15.Rossier BC, Canessa CM, Schild L, Horisberger JD. Epithelial sodium channels. Curr Opin Nephrol Hypertens. 1994;3:487–496. doi: 10.1097/00041552-199409000-00003. [DOI] [PubMed] [Google Scholar]
  • 16.Ciaraldi TP, Kolterman OG, Scarlett JA. Role of glucose transport in the postreceptor defect of non-insulin-dependent diabetes mellitus. Diabetes. 1982;31:1016–1022. doi: 10.2337/diacare.31.11.1016. [DOI] [PubMed] [Google Scholar]
  • 17.Ciaraldi TP, Kong AP, Chu NV. Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects. Diabetes. 2002;51:30–36. doi: 10.2337/diabetes.51.1.30. [DOI] [PubMed] [Google Scholar]
  • 18.Kelly IE, Han TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes [published correction appears in Diabetes Care. 1999;22:536] Diabetes Care. 1999;22:288–293. doi: 10.2337/diacare.22.2.288. [DOI] [PubMed] [Google Scholar]
  • 19.Larsen PJ, Jensen PB, Sørensen RV. Differential influences of peroxisome proliferator-activated receptors gamma and -alpha on food intake and energy homeostasis. Diabetes. 2003;52:2249–2259. doi: 10.2337/diabetes.52.9.2249. [DOI] [PubMed] [Google Scholar]
  • 20.Matthews DR, Hosker JP, Rudenski AS. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–419. doi: 10.1007/BF00280883. [DOI] [PubMed] [Google Scholar]
  • 21.Keskin M, Kurtoglu S, Kendirci M. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics. 2005;115:e500–e503. doi: 10.1542/peds.2004-1921. [DOI] [PubMed] [Google Scholar]
  • 22.Ikeda Y, Suehiro T, Nakamura T. Clinical significance of the insulin resistance index as assessed by homeostasis model assessment. Endocr J. 2001;48:81–86. doi: 10.1507/endocrj.48.81. [DOI] [PubMed] [Google Scholar]
  • 23.Shoji T, Emoto M, Nishizawa Y. HOMA index to assess insulin resistance in renal failure patients. Nephron. 2001;89:348–349. doi: 10.1159/000046098. [DOI] [PubMed] [Google Scholar]
  • 24.Kim MG, Park SY, Ha SH. Objective interpretation of severity of SLS induced edema by stereoimaging. J Dermatol Sci. 2004;35:125–131. doi: 10.1016/j.jdermsci.2004.05.002. [DOI] [PubMed] [Google Scholar]
  • 25.Lin SH, Lin YF, Kuo SW. Rosiglitazone improves glucose metabolism in nondiabetic uremic patients on CAPD. Am J Kidney Dis. 2003;42:774–780. doi: 10.1016/s0272-6386(03)00844-8. [DOI] [PubMed] [Google Scholar]
  • 26.Stenvinkel P, Heimbürger O, Paultre F. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999;55:1899–1911. doi: 10.1046/j.1523-1755.1999.00422.x. [DOI] [PubMed] [Google Scholar]
  • 27.Shoji T, Emoto M, Shinohara K. Diabetes mellitus, aortic stiffness, and cardiovascular mortality in end-stage renal disease. J Am Soc Nephrol. 2001;12:2117–2124. doi: 10.1681/ASN.V12102117. [DOI] [PubMed] [Google Scholar]
  • 28.O’Moore-Sullivan TM, Prins JB. Thiazolidinediones and type 2 diabetes: New drugs for an old disease [published correction appears in Med J Aust. 2002;177:396] Med J Aust. 2002;176:381–386. doi: 10.5694/j.1326-5377.2002.tb04461.x. [DOI] [PubMed] [Google Scholar]
  • 29.Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004;351:1106–1118. doi: 10.1056/NEJMra041001. [DOI] [PubMed] [Google Scholar]
  • 30.Keidar S, Guttmann H, Stam T. High incidence of reduced plasma HDL cholesterol in diabetic patients treated with rosiglitazone and fibrate. Pharmacoepidemiol Drug Saf. 2007;11:1192–1194. doi: 10.1002/pds.1448. [DOI] [PubMed] [Google Scholar]
  • 31.Normén L, Frohlich J, Montaner J. Combination therapy with fenofibrate and rosiglita-zone paradoxically lowers serum HDL cholesterol. Diabetes Care. 2004;27:2241–2242. doi: 10.2337/diacare.27.9.2241. [DOI] [PubMed] [Google Scholar]
  • 32.Kim SK, Hur KY, Kim HJ. The increase in abdominal subcutaneous fat deposit is an independent factor to determine the glycemic control after rosiglitazone treatment. Eur J Endocrinol. 2007;157:167–174. doi: 10.1530/EJE-07-0043. [DOI] [PubMed] [Google Scholar]
  • 33.Carey DG, Cowin GJ, Galloway GJ. Effect of rosiglitazone on insulin sensitivity and body composition in type 2 diabetic patients [published correction appears in Obes Res. 2002;10: following table of contents] Obes Res. 2002;10:1008–1015. doi: 10.1038/oby.2002.137. [DOI] [PubMed] [Google Scholar]
  • 34.Fonseca V. Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med. 2003;115(Suppl 8A):42S–48S. doi: 10.1016/j.amjmed.2003.09.005. [DOI] [PubMed] [Google Scholar]
  • 35.Mayerson AB, Hundal RS, Dufour S. The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes. 2002;51:797–802. doi: 10.2337/diabetes.51.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Mori Y, Murakawa Y, Okada K. Effect of troglitazone on body fat distribution in type 2 diabetic patients. Diabetes Care. 1999;22:908–912. doi: 10.2337/diacare.22.6.908. [DOI] [PubMed] [Google Scholar]
  • 37.Okuno A, Tamemoto H, Tobe K. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest. 1998;101:1354–1361. doi: 10.1172/JCI1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Chen J, Muntner P, Hamm LL. Insulin resistance and risk of chronic kidney disease in nondiabetic US adults. J Am Soc Nephrol. 2003;14:469–477. doi: 10.1097/01.asn.0000046029.53933.09. [DOI] [PubMed] [Google Scholar]

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