Pioglitazone Slows Progression of Atherosclerosis in Prediabetes Independent of Changes in Cardiovascular Risk Factors
Open accessAbstract
Objective—: To determine whether changes in standard and novel risk factors during the Actos Now for Prevention of Diabetes trial explained the slower rate of carotid intima media thickness (CIMT) progression with pioglitazone treatment in persons with prediabetes. Methods and Results—: CIMT was measured in 382 participants at the beginning and up to 3 additional times during follow-up of the Actos Now for Prevention of Diabetes trial. During an average follow-up of 2.3 years, the mean unadjusted annual rate of CIMT progression was significantly ( P =0.01) lower with pioglitazone treatment (4.76×10 –3 mm/year; 95% CI: 2.39×10 –3 –7.14×10 –3 mm/year) compared with placebo (9.69×10 –3 mm/year; 95% CI: 7.24×10 –3 –12.15×10 –3 mm/year). High-density lipoprotein cholesterol, fasting and 2-hour glucose, HbA 1c , fasting insulin, Matsuda insulin sensitivity index, adiponectin, and plasminogen activator inhibitor-1 levels improved significantly with pioglitazone treatment compared with placebo ( P <0.001). However, the effect of pioglitazone on CIMT progression was not attenuated by multiple methods of adjustment for traditional, metabolic, and inflammatory risk factors and concomitant medications, and was independent of changes in risk factors during pioglitazone treatment. Conclusion—: Pioglitazone slowed progression of CIMT, independent of improvement in hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation in prediabetes. These results suggest a possible direct vascular benefit of pioglitazone.
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The IRIS results agree with a secondary outcome in PROactive, where death, MI, or stroke was significantly lower with pioglitazone, and with trials showing a favorable effect of pioglitazone on subclinical atherosclerosis progression.
“However, the IRIS results are consistent with findings regarding a secondary outcome in the PROactive trial (i.e., that the rates of death, myocardial infarction, or stroke were significantly lower with pioglitazone than with placebo) and with findings of trials showing a favorable effect of pioglitazone on the progression of subclinical atherosclerosis among patients with and those without”
From Pioglitazone after Ischemic Stroke or Transient Ischemic Attack (2016) · cites this paper as [34]
The Discussion reports a reduction in PROactive’s secondary composite cardiovascular endpoint and describes slower atherosclerosis progression with pioglitazone in trials involving people with and without type 2 diabetes. It does not specify that PROactive’s secondary endpoint comprised death, myocardial infarction, or stroke, so that detail cannot be verified from this paper. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPioglitazone reduced PAI-1.
“Pioglitazone also reduced PAI-1 and slowed the rate of progression of carotid intima-media thickening.204”
From The Vasculature in Prediabetes (2018) · cites this paper as [204]
Pioglitazone slowed the rate of progression of carotid intima-media thickening.
“Pioglitazone also reduced PAI-1 and slowed the rate of progression of carotid intima-media thickening.204”
From The Vasculature in Prediabetes (2018) · cites this paper as [204]
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Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · see citing works
Tuomilehto, J., Lindström, J., Eriksson, J. G., Valle, T. T., Hämäläinen, H., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Laakso, M., Louheranta, A., Rastas, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200105033441801 · Cited by 10,873 · see citing works
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Self-citationDormandy, 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., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67528-9 · Cited by 4,129 · see citing works
The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., & Glass, C. K. (1998) · Nature · doi:10.1038/34178 · Cited by 3,525 · see citing works
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
Jiang, C., Ting, A. T., & Seed, B. (1998) · Nature · doi:10.1038/34184 · Cited by 2,899 · see citing works
PPARγ Promotes Monocyte/Macrophage Differentiation and Uptake of Oxidized LDL
Tontonoz, P., Nagy, L., Alvarez, J. G. A., Thomázy, V. A., & Evans, R. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81575-5 · Cited by 1,800 · see citing works
Maeda, N., Takahashi, M., Funahashi, T., Kihara, S., Nishizawa, H., Kishida, K., Nagaretani, H., Matsuda, M., Komuro, R., Ouchi, N., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.9.2094 · Cited by 1,659 · see citing works
Bergman, R. N., Phillips, L. S., & Cobelli, C. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110398 · Cited by 1,640 · see citing works
Diabetes and cardiovascular disease
Howard, B. V., & Magee, M. F. (2000) · Current Atherosclerosis Reports · doi:10.1007/s11883-000-0046-8 · Cited by 1,386 · see citing works
Haffner, S. M., Greenberg, A. S., Weston, W. M., Chen, H., Williams, K., & Freed, M. I. (2002) · Circulation · doi:10.1161/01.cir.0000025403.20953.23 · Cited by 882 · see citing works
Nissen, S. E., Nicholls, S. J., Wolski, K., Nesto, R., Kupfer, S., Perez, A., Jure, H., De Larochellière, R., Staniloae, C. S., Mavromatis, K., et al. (2008) · JAMA · doi:10.1001/jama.299.13.1561 · Cited by 850 · see citing works
Li, A. C., Brown, K. K., Silvestre, M., Willson, T. M., Palinski, W., & Glass, C. K. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10370 · Cited by 833 · see citing works
Goldberg, R. B., Kendall, D. M., Deeg, M. A., Buse, J. B., Zagar, A. J., Pinaire, J. A., Tan, M. H., Khan, M. A., Perez, A. T., Jacober, S. J., et al. (2005) · Diabetes Care · doi:10.2337/diacare.28.7.1547 · Cited by 790 · see citing works
Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance
DeFronzo, R. A., Tripathy, D., Schwenke, D. C., Banerji, M., Bray, G. A., Buchanan, T. A., Clement, S. C., Henry, R. R., Hodis, H. N., Kitabchi, A. E., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1010949 · Cited by 752 · see citing works
Self-citationDiabetes and Cardiovascular Disease: The “Common Soil” Hypothesis
Stern, M. P. (1995) · Diabetes · doi:10.2337/diab.44.4.369 · Cited by 739 · see citing works
Estrogen in the Prevention of Atherosclerosis
Hodis, H. N., Mack, W. J., Lobo, R. A., Shoupe, D., Sevanian, A., Mahrer, P. R., Selzer, R. H., Liu, C., Ci-hua, L., & Azen, S. P. (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-135-11-200112040-00005 · Cited by 688 · see citing works
Self-citationMazzone, T., Meyer, P. M., Feinstein, S. B., Davidson, M. H., Kondos, G. T., D’Agostino, R. B., Perez, A., Provost, J.-C., & Haffner, S. M. (2006) · JAMA · doi:10.1001/jama.296.21.joc60158 · Cited by 674 · see citing works
Marx, N., Schönbeck, U., Lazar, M. A., Libby, P., & Plutzky, J. (1998) · Circulation Research · doi:10.1161/01.res.83.11.1097 · Cited by 587 · see citing works
Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation
Choi, J. H., Banks, A. S., Kamenecka, T. M., Busby, S. A., Chalmers, M. J., Kumar, N., Kuruvilla, D. S., Shin, Y., He, Y., Bruning, J. B., et al. (2011) · Nature · doi:10.1038/nature10383 · Cited by 541 · see citing works
Graham, D. J., Ouellet‐Hellstrom, R., MaCurdy, T. E., Ali, F. N., Sholley, C., Worrall, C. M., & Kelman, J. A. (2010) · JAMA · doi:10.1001/jama.2010.920 · Cited by 512 · see citing works
Prevention of Type 2 Diabetes With Troglitazone in the Diabetes Prevention Program
The Diabetes Prevention Program Research Group* (2005) · Diabetes · doi:10.2337/diabetes.54.4.1150 · Cited by 474 · see citing works
Expression and Function of PPARγ in Rat and Human Vascular Smooth Muscle Cells
Law, R. E., Goetze, S., Xi, X.-P., Jackson, S. M., Kawano, Y., Demer, L. L., Fishbein, M. C., Meehan, W. P., & Hsueh, W. A. (2000) · Circulation · doi:10.1161/01.cir.101.11.1311 · Cited by 442 · see citing works
Collins, A. R., Meehan, W. P., Kintscher, U., Jackson, S. M., Wakino, S., Noh, G. J., Palinski, W., Hsueh, W. A., & Law, R. E. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.21.3.365 · Cited by 384 · see citing works
Troglitazone Inhibits Atherosclerosis in Apolipoprotein E–Knockout Mice
Chen, Z., Ishibashi, S., Perrey, S., Osuga, J.-I., Gotoda, T., Kitamine, T., Tamura, Y., Okazaki, H., Yahagi, N., Iizuka, Y., et al. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.21.3.372 · Cited by 320 · see citing works
Increased CD36 protein as a response to defective insulin signaling in macrophages
Liang, C.-P., Han, S., Okamoto, H., Carnemolla, R., Tabas, I. A., Accili, D., & Tall, A. R. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19528 · Cited by 225 · see citing works
Insulin signaling in the arterial wall
Hsueh, W. A., & Law, R. E. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00353-7 · Cited by 200 · see citing works
Boyle, P. J., King, A. B., Olansky, L., Marchetti, A. E., Lau, H., Magar, R., & Martin, J. P. (2002) · Clinical Therapeutics · doi:10.1016/s0149-2918(02)85040-8 · Cited by 161 · see citing works
Orasanu, G., Ziouzenkova, O., Devchand, P. R., Nehra, V., Hamdy, O., Horton, E. S., & Plutzky, J. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.04.055 · Cited by 129 · see citing works
Calkin, A. C., Forbes, J. M., Smith, C. M., Lassila, M., Cooper, M. E., Jandeleit-Dahm, K. A. M., & Allen, T. J. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000177813.99577.6b · Cited by 128 · see citing works
Davidson, M., Meyer, P., Haffner, S. M., Feinstein, S. B., D’Agostino, R. B., Kondos, G. T., Pérez, A., Chen, Z., & Mazzone, T. (2008) · Circulation · doi:10.1161/circulationaha.107.746610 · Cited by 126 · see citing works
Nicholls, S. J., Tuzcu, E. M., Wolski, K., Bayturan, Ö., Lavoie, A., Uno, K., Kupfer, S., Pérez, A., Nesto, R. W., & Nissen, S. E. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.06.055 · Cited by 114 · see citing works
Actos Now for the prevention of diabetes (ACT NOW) study
DeFronzo, R. A., Banerji, M., Bray, G. A., Buchanan, T. A., Clement, S., Henry, R. R., Kitabchi, A. E., Mudaliar, S., Musi, N., Ratner, R., et al. (2009) · BMC Endocrine Disorders · doi:10.1186/1472-6823-9-17 · Cited by 89 · see citing works
Self-citationMiyazaki, Y., & DeFronzo, R. A. (2008) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2008.00880.x · Cited by 89 · see citing works
Self-citationChacko, B. K., Scott, D. W., Chandler, R. T., & Patel, R. P. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.247981 · Cited by 75 · see citing works
Levi, Z., Shaish, A., Yacov, N., Levkovitz, H., Trestman, S., Gerber, Y., Cohen, H. W., Dvir, A., Rhachmani, R., Ravid, M., et al. (2003) · Diabetes Obesity and Metabolism · doi:10.1046/j.1463-1326.2003.00240.x · Cited by 71 · see citing works
for the ACT NOW Study Group, DeFronzo, R. A., Banerji, M. A., Bray, G. A., Buchanan, T. A., Clément, S., Henry, R. R., Kitabchi, A. E., Mudaliar, S. R. D., Musi, N., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1614-2 · Cited by 71 · see citing works
Self-citationXiang, A. H., Peters, R. K., Kjos, S. L., Ochoa, C., Marroquin, A., Goico, J., Tan, S., Wang, C., Azen, S. P., Liu, C., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1685 · Cited by 68 · see citing works
Self-citationLonn, E., Gerstein, H. C., Sheridan, P., Smith, S. L., Díaz, R., Mohan, V., Bosch, J., Yusuf, S., & Dagenais, G. R. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.12.072 · Cited by 56 · see citing works
Xiang, A. H., Hodis, H. N., Kawakubo, M., Peters, R. K., Kjos, S. L., Marroquin, A., Goico, J., Ochoa, C., Liu, C., Ci-hua, L., et al. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.10.016 · Cited by 41 · see citing works
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MacDonald, M. R., Petrie, M. C., Home, P., Michel Komajda, N., Jones, N. P., Beck‐Nielsen, H., Gomis, R., Markolf Hanefeld, E., Pocock, S., Curtis, P. S., et al. (2011) · Diabetes Care · doi:10.2337/dc10-2398 · Cited by 32 · see citing works
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- Authors
- Saremi, A., Schwenke, D. C., Buchanan, T. A., Hodis, H. N., Mack, W. J., Banerji, M., Bray, G. A., Clement, S. C., Henry, R. R., Kitabchi, A. E., Mudaliar, S., Ratner, R. E., Stentz, F. B., Musi, N., Tripathy, D., DeFronzo, R. A., & Reaven, P. D.
- Affiliations
- Pennington Biomedical Research Center (US)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2013-02
- Volume
- 33
- Issue
- 2
- Pages
- 393-399
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC3908828
- OpenAlex
- W2093794516
- Cited by
- 101
- References
- 41
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 9 · 2017: 12 · 2016: 13 · 2015: 7 · 2014: 11 · 2013: 6
- FWCI
- 6.16
- Type
- journal article
- Language
- en
- Update notices
- correction (2013-05-01)
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Eli Lilly and Company
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- University of Southern California
- Halozyme
- Daiichi-Sankyo
- National Institutes of Health (5ul1rr031986-02)
- Genentech
- University of Texas Health Science Center at San Antonio
- National Center for Research Resources (UL1-RR031986)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- pioglitazone, prediabetes, atherosclerosis progression, carotid intima-media thickness, insulin sensitizers, insulin resistance, hyperglycemia, dyslipidemia, systemic inflammation, adiponectin, plasminogen activator inhibitor-1, cardiovascular risk factors
- MeSH terms
- Pioglitazone, Adult, Aged, Blood Glucose, Carotid Artery Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Cholesterol, HDL, Male, Middle Aged, Prediabetic State, Prospective Studies, Risk Factors, Time Factors, United States, Biomarkers, Multivariate Analysis, Chi-Square Distribution, Linear Models, Treatment Outcome, Plasminogen Activator Inhibitor 1, Disease Progression, Risk Assessment, Thiazolidinediones, Adiponectin, Carotid Intima-Media Thickness
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