Skeletal muscle and whole body insulin resistance but not cardiac muscle insulin resistance could be improved by troglitazone therapy within 12 weeks in type-2 diabetes — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Skeletal muscle and whole body insulin resistance but not cardiac muscle insulin resistance could be improved by troglitazone therapy within 12 weeks in type-2 diabetes
Department of Cardiovascular Medicine, Clinical Research Center, Sanno Hospital of International University of Health and Welfare, Tokyo, Japan
,
Department of Clinical Engineering, Faculty of Medical Engineering, Suzuka University of Medical Science, Suzuka, Japan
,
JapanDepartment of Radiology, Institute of Medical Science, Graduate School of Medicine University of Tokyo, Tokyo, Japan
1 Department of Cardiovascular Medicine, Clinical Research Center, Sanno Hospital of International University of Health and Welfare, Tokyo, Japan
2 Department of Clinical Engineering, Faculty of Medical Engineering, Suzuka University of Medical Science, Suzuka, Japan
3 JapanDepartment of Radiology, Institute of Medical Science, Graduate School of Medicine University of Tokyo, Tokyo, Japan
Background: Existence of myocardial insulin resistance (IR) has been reported in type II diabetics (T2- DM) and coronary artery disease (CAD). Improvement in heart and skeletal muscle IR after thiazolidinedione’s therapy was reported in T2DM and CAD. However effects of troglitazone therapy (TRO) on myocardial IR remain uncertain. To clarify heart and skeletal muscle and whole body IR in T2DM without CAD by TRO to clarify whether TRO would provide different results. Methods: We analyzed data on 15 T2DM patients who underwent dynamic PET with 18 F-FDG under insulin clamping before and during TRO (200 mg/day) and 17 controls. Results: Whole body glucose disposal rate (WBGR mg/min/kg) in T2DM before TRO (3.41 ± 1.72) was significantly lower than in controls (9.76 ± 2.97, p < 0.01) as was the skeletal muscle glucose utilization rate (SMGU mg/min/kg); T2DM (0.367 ± 0.217) vs. controls (1.34 ± 0.613, p < 0.01) and myocardial glucose utilization rate (MGU mg/min/kg; T2DM 5.86 ± 2.03 vs. controls 7.34 ± 1.80, p < 0.05). WBGR in T2DM during TRO (5.17 ± 2.75, p < 0.05) was significantly higher than that before TRO, as was the SMGU (0.782 ± 0.20, p < 0.05). The MGU in T2DM during TRO (6.59 ± 0.72) was comparable with that before TRO. Conclusion: Myocardial IR response to TRO differed from that in skeletal muscle and the whole body in T2DM without CAD.
KeywordsInsulin ResistanceMyocardial Insulin ResistanceGlucose MetabolismSkeletal MuscleType II Diabetes Mellitus18F-FDGPET
Despres, J.P., Lamarche, B., Mauriège, P., Cantin, B., Dagenais, G.R., Moorjani, S. and Lupien, P.J. (1996) Hyperinsulinemia as an independent risk factor for ischemic heart disease. The New England Journal of Medicine, 334, 952-957. doi:10.1056/NEJM199604113341504
Voipio-Pulkki, L.M., Nuutila, P., Knuuti, M.J., Ruotsalainen, U., Haaparanta, M., Ter?s, M., Wegelius, U. and Koivisto, V.A.(1993) Heart and skeletal muscle glucose disposal in type 2 diabetic patients as determined by positron emission tomography. Journal of Nuclear Medicine, 34, 2064-2067.
Yokoyama, I., Ohtake, T., Momomura, S., Yonekura, K., Yamada, N., Nishikawa, J., Sasaki, Y. and Omata, M. (1998) Organ-specific insulin resistance in patients with noninsulin-dependent diabetes mellitus and hypertension. Journal of Nuclear Medicine, 39, 884-889.
Yokoyama, I., Yonekura, K., Moritan, T., Tateno, M., Momose, T., Ohtomo, K., Inoue, Y. and Nagai, R.(2001) Troglitazone improves whole-body insulin resistance and skeletal muscle glucose use in type II diabetic patients. Journal of Nuclear Medicine, 42, 1005-1010.
Yokoyama, I., Yonekura, K., Ohtake, T., Kawamura, H., Matsumoto, A., Inoue, Y., Aoyagi, T., Sugiura, S., Omata, M., Ohtomo, K. and Nagai, R. (2000) Role of insulin resistance in heart and skeletal muscle F-18 fluorodeoxy-glucose uptake in patients with non-insulin-dependent diabetes mellitus. Journal of Nuclear Cardiology, 7, 242-248. doi:10.1016/S1071-3581(00)70013-4
H?llsten, K., Virtanen, K.A., L?nnqvist, F., Janatuinen, T., Turiceanu, M., R?nnemaa, T., Viikari, J., Lehtim?ki, T., Knuuti, J. and Nuutila, P. (2004) Enhancement of insulin- stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone. Diabetic Medicine, 21, 1280-1287. doi:10.1111/j.1464-5491.2004.01332.x
Lautamaki, R., Airaksinen, K.E., Seppanen, M., Toikka, J., Luotolahti, M., Ball, E., Borra, R., Harkonen, R., Iozzo, P., Stewart, M., Knuuti, J. and Nuutila, P. (2005) Rosigli- tazone improves myocardial glucose uptake in patients with type 2 diabetes and coronary artery disease: A 16-week randomized, double-blind, placebo-controlled study. Diabetes, 54, 2787-2794. doi:10.2337/diabetes.54.9.2787
Naoumova, R.P., Kindler, H., Leccisotti, L., Mongillo, M., Khan, M.T., Neuwirth, C., Seed, M., Holvoet, P., Betteridge, J. and Camici, P.G. (2007) Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: A randomized, double-blind, placebo-controlled study. Jour- nal of the American College of Cardiology, 50, 2059- 2060. doi:10.1016/j.jacc.2007.07.070
Lincoff, A.M., Wolski, K., Nicholls, S.J. and Nissen, S.E. (2007) Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials. Journal of the American Medical Association, 298, 1180-1188. doi:10.1001/jama.298.10.1180
Barsheshet, A., Shotan, A., Cohen, E., Garty, M., Gold- enberg, I., Sandach, A., Behar, S., Zimlichman, E., Lewis, B.S., Gottlieb, S. and HFSIS Steering Committee and In- vestigators (2010) Predictors of long-term (4-year) mortality in elderly and young patients with acute heart failure. European Journal of Heart Failure, 12, 833-840. doi:10.1093/eurjhf/hfq079
Ehrenkaufer, R.E., Potocki, J.F. and Jewett, D.M. (1989) Simple synthesis of F-18 labeled 2-fluoro-2-deoxy-D-glu- cose. Journal of Nuclear Medicine, 25, 333-337.
Ohtake, T., Kosaka, N., Watanabe, T., Yokoyama, I., Moritan, T., Masuo, M., Iizuka, M., Kozeni, K., Momose, T., Oku, S., Sugimoto, T. and Iio, M. (1991) Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. Journal of Nuclear Medicine, 32, 1432-1438.
Ng, C.K., Soufer, R. and McNulty, P.H. (1998) Effect of hyperinsulinemia on myocardial fluorine-18-FDG uptake. Journal of Nuclear Medicine, 39, 379-383.
Kelly, D.E., Williams, K.V. and Goodpaster, B. (1999) Determination of the lumped constant for [18F]fluorodeo- xyglucose in human skeletal muscle. Journal of Nuclear Medicine, 40, 1798-1804.
Peltoniemi, P., L?nnroth, P., Laine, H., Oikonen, V., Tol- vanen, T., Gr?nroos, T., Strindberg, L., Knuuti, J. and Nuutila, P. (2000) Lumped constant for [18F]fluorodeoxy-glucose in skeletal muscles of obese and nonobese humans. American Journal of Physiology—Endocrinology and Metabolism, 279, E1120-E1130.
Yokoyama, I., Ohtake, T., Momomura, S., Yonekura, K., Shin, W.S., Nishikawa, J., Sasaki, Y. and Omata, M. (1998) Hyperglycemia rather than insulin resistance is related to coronary flow reserve in patients with non-insulin dependent diabetes mellitus. Diabetes, 47, 119-124. doi:10.2337/diabetes.47.1.119
Hsiao, A., Worrall, D.S., Olefsky, J.M. and Subramaniam, S. (2004) Variance-modeled posterior inference of microarray data: Detecting gene-expression changes in 3T3-L1 adipocytes. Bioinformatics, 20, 3108-3127. doi:10.1093/bioinformatics/bth371
Dormandy, J.A., Charbonnel, B., Eckland, D.J., Erdmann, E., Massi-Benedetti, M., Moules, I.K., Skene, A.M., Tan, M.H., Lefèbvre, P.J., Murray, G.D., Standl, E., Wilcox, R.G., Wilhelmsen, L., Betteridge, J., Birkeland, K., Golay, A., Heine, R.J., Korányi, L., Laakso, M., Mokán, M., Norkus, A., Pirags, V., Podar, T., Scheen, A., Scherbaum, W., Schernthaner, G., Schmitz, O., Skrha, J., Smith, U. and Taton, J. (2005) Secondary prevention of macrovas- cular events in patients with type 2 diabetes in the PRO- active Study (PROspective pioglitAzone Clinical Trial in macroVascular Events): A randomised controlled trial. Lancet, 366, 1279-1289. doi:10.1016/S0140-6736(05)67528-9
Nissen, S.E. and Wolski, K. (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. The New England Journal of Medicine, 356, 2457-2471. doi:10.1056/NEJMoa072761
Juurlinkm, D.N., Gomes, T., Lipscombe, L.L., Austin, P.C., Hux, J.E. and Mamdani, M.M. (2009) Adverse cardiovascular events during treatment with pioglitazone and rosiglitazone: Population based cohort study. British Medical Journal, 339, b2942. doi:10.1136/bmj.b2942
Graham, D.J., Ouellet-Hellstrom, R., MaCurdy, T.E., Ali, F., Sholley, C., Worrall, C. and Kelman, J.A. (2010) Risk of acute myocardial infarction, stroke, heart failure, and death in elderly medicare patients treated with rosi- glitazone or pioglitazone. Journal of the American Medi- cal Association, 3044, 411-418. doi:10.1001/jama.2010.920
Nuutila, P., Maeki, M., Laine, H., Knuuti, J., Ruotsalainen, U., Kuotohahiti, M., Haaparanta, M., Solin, O., Jula, A., Koivisto, V.A., Voipio-Pulkki, L.M. and Ykijaeynen, H. (1995) Insulin action on heart and skeletal muscle glucose uptake in essential hypertension. Journal of Clinical Investigation, 96, 1003-1009. doi:10.1172/JCI118085
Tanaka, T., Itoh, H., Doi, K., Fukunaga, Y., Hosoda, K., Shintani, M., Yamashita, J., Chun, T.H., Inoue, M., Masatsugu, K., Sawada, N., Saito, T., Inoue, G., Nishimura, H., Yoshimasa, Y. and Nakao, K. (1999) Down regulation of peroxisome proliferator-activated receptor gamma expression by inflammatory cytokines and its reversal by thiazolidinediones. Diabetologia, 42, 702-710. doi:10.1007/s001250051218
De Vos, P., Lefebvre, A.M., Miller, S.G., Guerre-Millo, M., Wong, K., Saladin, R., Hamann, L.G., Staels, B., Briggs, M.R. and Auwerx, J. (1996) Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor gamma. Journal of Clinical Investigation, 98, 1004-1009. doi:10.1172/JCI118860
Okuno, A., Tamemoto, H., Tobe, K., Ueki, K., Mori, Y., Iwamoto, K., Umesono, K., Akanuma, Y., Fujiwara, T., Horikoshi, H., Yazaki, Y. and Kadowaki, T. (1998) Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zuc- ker rats. Journal of Clinical Investigation, 101, 1354-1361. doi:10.1172/JCI1235
Yokoyama, I., Inoue, Y., Moritan, T., Ohtomo, K. and Nagai, R. (2006) Myocardial glucose utilisation in type II diabetes mellitus patients treated with sulphonylurea drugs. European Journal of Nuclear Medicine and Molecular, 33, 703-708.
Yokoyama, I., Ohtake, T., Momomura, S., Yonekura, K., Kobayakawa, N., Aoyagi, T., Sugiura, S., Yamada, N., Ohtomo, K., Sasaki, Y., Omata, M. and Yazaki, Y. (1999) Insulin action on Heart and skeletal muscle FDG uptake in patients with hypertriglyceridemia. Journal of Nuclear Medicine, 40, 1116-1121.