Table of Contents Author Guidelines Submit a Manuscript
International Journal of Endocrinology
Volume 2018, Article ID 8380192, 17 pages
https://doi.org/10.1155/2018/8380192
Review Article

Is Atorvastatin Associated with New Onset Diabetes or Deterioration of Glycemic Control? Systematic Review Using Data from 1.9 Million Patients

1Society of Junior Doctors, Athens, Greece
2Hypertension Center STRIDE-7, Third University Department of Medicine, Sotiria Hospital, Athens, Greece
3Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK

Correspondence should be addressed to Angeliki M. Angelidi; moc.liamg@9gnaeigna

Received 24 June 2018; Accepted 24 September 2018; Published 22 October 2018

Academic Editor: Matteo Monami

Copyright © 2018 Angeliki M. Angelidi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. D. Waters, J. E. Ho, S. M. Boekholdt et al., “Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes,” Journal of the American College of Cardiology, vol. 61, no. 2, pp. 148–152, 2013. View at Publisher · View at Google Scholar · View at Scopus
  2. E. Mandosi, M. Fallarino, A. Gatti et al., “Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and TNFalpha levels in type 2 diabetes,” Journal of Atherosclerosis and Thrombosis, vol. 17, no. 6, pp. 539–545, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Ogawa, K. Matsui, Y. Saito et al., “Differences between rosuvastatin and atorvastatin in lipid-lowering action and effect on glucose metabolism in Japanese hypercholesterolemic patients with concurrent diabetes. Lipid-lowering with highly potent statins in hyperlipidemia with type 2 diabetes patients (LISTEN) study,” Circulation Journal, vol. 78, no. 10, pp. 2512–2515, 2014. View at Google Scholar
  4. J. C. LaRosa, S. M. Grundy, D. D. Waters et al., “Intensive lipid lowering with atorvastatin in patients with stable coronary disease,” The New England Journal of Medicine, vol. 352, no. 14, pp. 1425–1435, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Sadeghi, M. Asadpour-Piranfar, M. Asadollahi, M. Taherkhani, and F. Baseri, “The effects of different doses of atorvastatin on serum lipid profile, glycemic control, and liver enzymes in patients with ischemic cerebrovascular accident,” ARYA Atherosclerosis, vol. 10, no. 6, pp. 298–304, 2014. View at Google Scholar
  6. M. Arca, “Atorvastatin efficacy in the prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome,” Drugs, vol. 67, Supplement 1, pp. 43–54, 2007. View at Publisher · View at Google Scholar · View at Scopus
  7. American Diabetes Association, “8. Cardiovascular disease and risk management,” Diabetes Care, vol. 38, Supplement 1, pp. S49–S57, 2016. View at Publisher · View at Google Scholar · View at Scopus
  8. N. J. Stone, J. G. Robinson, A. H. Lichtenstein et al., “2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines,” Circulation, vol. 129, Supplement 2, no. 25, pp. S1–S45, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. K. K. Koh, M. J. Quon, S. H. Han, Y. Lee, S. J. Kim, and E. K. Shin, “Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients,” Journal of the American College of Cardiology, vol. 55, no. 12, pp. 1209–1216, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Simsek, B. H. Wolffenbuttel, and C. G. Schalkwijk, “Effects of rosuvastatin and atorvastatin on glycaemic control in type 2 diabetes---the CORALL study,” Diabetic Medicine, vol. 29, no. 5, pp. 628–631, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. T. Yamakawa, T. Takano, S. Tanaka, K. Kadonosono, and Y. Terauchi, “Influence of pitavastatin on glucose tolerance in patients with type 2 diabetes mellitus,” Journal of Atherosclerosis and Thrombosis, vol. 15, no. 5, pp. 269–275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. A. A. Carter, T. Gomes, X. Camacho, D. N. Juurlink, B. R. Shah, and M. M. Mamdani, “Risk of incident diabetes among patients treated with statins: population based study,” BMJ, vol. 346, article f2610, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Tehrani, F. Mobarrez, P. E. Lins, U. Adamson, H. N. Wallén, and G. Jörneskog, “Impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes,” Diabetes & Vascular Disease Research, vol. 10, no. 6, pp. 483–488, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. T. Ma, M. H. Chang, L. Tien, Y. S. Liou, and G. P. Jong, “The long-term effect of statins on the risk of new-onset diabetes mellitus in elderly Taiwanese patients with hypertension and dyslipidaemia: a retrospective longitudinal cohort study,” Drugs & Aging, vol. 29, no. 1, pp. 45–51, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. A. L. Culver, I. S. Ockene, R. Balasubramanian et al., “Statin use and risk of diabetes mellitus in postmenopausal women in the Women’s Health Initiative,” Archives of Internal Medicine, vol. 172, no. 2, pp. 144–152, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. E. Y. Choe, H. J. Wang, O. Kwon et al., “HMG CoA reductase inhibitor treatment induces dysglycemia in renal allograft recipients,” Transplantation, vol. 97, no. 4, pp. 419–425, 2014. View at Publisher · View at Google Scholar · View at Scopus
  17. C. H. Chu, J. K. Lee, H. C. Lam et al., “Atorvastatin does not affect insulin sensitivity and the adiponectin or leptin levels in hyperlipidemic type 2 diabetes,” Journal of Endocrinological Investigation, vol. 31, no. 1, pp. 42–47, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. P. Grigoropoulou, I. Eleftheriadou, C. Zoupas et al., “Effect of atorvastatin on baroreflex sensitivity in subjects with type 2 diabetes and dyslipidaemia,” Diabetes & Vascular Disease Research, vol. 11, no. 1, pp. 26–33, 2013. View at Publisher · View at Google Scholar · View at Scopus
  19. H. L. Tam, S. W. M. Shiu, Y. Wong, W. S. Chow, D. J. Betteridge, and K. C. B. Tan, “Effects of atorvastatin on serum soluble receptors for advanced glycation end-products in type 2 diabetes,” Atherosclerosis, vol. 209, no. 1, pp. 173–177, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Tehrani, F. Mobarrez, A. Antovic et al., “Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia,” Thrombosis Research, vol. 126, no. 3, pp. e225–e231, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. M. K. Rutter, H. R. Prais, V. Charlton-Menys et al., “Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA): a randomized double-blind placebo-controlled trial of high- vs. low-dose atorvastatin(1),” Diabetic Medicine, vol. 28, no. 1, pp. 100–108, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. D. D. Waters, J. E. Ho, D. A. DeMicco et al., “Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials,” Journal of the American College of Cardiology, vol. 57, no. 14, pp. 1535–1545, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. N. Thongtang, M. Ai, S. Otokozawa et al., “Effects of maximal atorvastatin and rosuvastatin treatment on markers of glucose homeostasis and inflammation,” The American Journal of Cardiology, vol. 107, no. 3, pp. 387–392, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Martin, C. Herder, N. C. Schloot et al., “Residual beta cell function in newly diagnosed type 1 diabetes after treatment with atorvastatin: the randomized DIATOR trial,” PLoS One, vol. 6, no. 3, article e17554, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. J. Puurunen, T. Piltonen, K. Puukka et al., “Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study,” The Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 12, pp. 4798–4807, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. P. S. Sever, B. Dahlöf, N. R. Poulter et al., “Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial,” Lancet, vol. 361, no. 9364, pp. 1149–1158, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Goyal, S. Singh, N. Tandon, N. Gupta, and Y. K. Gupta, “Effect of atorvastatin on pancreatic beta-cell function and insulin resistance in type 2 diabetes mellitus patients: a randomized pilot study,” Canadian Journal of Diabetes, vol. 38, no. 6, pp. 466–472, 2014. View at Publisher · View at Google Scholar · View at Scopus
  28. R. N. A. Black, C. N. Ennis, I. S. Young, S. J. Hunter, A. B. Atkinson, and P. M. Bell, “The peroxisome proliferator-activated receptor alpha agonist fenofibrate has no effect on insulin sensitivity compared to atorvastatin in type 2 diabetes mellitus; a randomised, double-blind controlled trial,” Journal of Diabetes and its Complications, vol. 28, no. 3, pp. 323–327, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Tanaka, “Beneficial effect of atorvastatin on renal function in patients with type 2 diabetes,” The Journal of International Medical Research, vol. 39, no. 4, pp. 1504–1512, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. T. Shinozaki, Y. Matsuyama, S. Iimuro et al., “Effective prevention of cardiovascular disease and diabetes-related events with atorvastatin in Japanese elderly patients with type 2 diabetes mellitus: adjusting for treatment changes using a marginal structural proportional hazards model and a rank-preserving structural failure time model,” Geriatrics & Gerontology International, vol. 12, pp. 88–102, 2012. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Ma, L. Tien, C. L. Fang, Y. S. Liou, and G. P. Jong, “Statins and new-onset diabetes: a retrospective longitudinal cohort study,” Clinical Therapeutics, vol. 34, no. 9, pp. 1977–1983, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. N. L. Zaharan, D. Williams, and K. Bennett, “Statins and risk of treated incident diabetes in a primary care population,” British Journal of Clinical Pharmacology, vol. 75, no. 4, pp. 1118–1124, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. T. Takano, T. Yamakawa, M. Takahashi, M. Kimura, and A. Okamura, “Influences of statins on glucose tolerance in patients with type 2 diabetes mellitus,” Journal of Atherosclerosis and Thrombosis, vol. 13, no. 2, pp. 95–100, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. H. Cederberg, A. Stančáková, N. Yaluri, S. Modi, J. Kuusisto, and M. Laakso, “Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort,” Diabetologia, vol. 58, no. 5, pp. 1109–1117, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. Cho, E. Choe, Y. H. Lee et al., “Risk of diabetes in patients treated with HMG-CoA reductase inhibitors,” Metabolism, vol. 64, no. 4, pp. 482–488, 2015. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Y. Park, S. W. Rha, B. Choi et al., “Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: three-year clinical outcomes,” International Journal of Cardiology, vol. 184, pp. 502–506, 2015. View at Publisher · View at Google Scholar · View at Scopus
  37. C. W. Chen, T. C. Chen, K. Y. Huang, P. Chou, P. F. Chen, and C. C. Lee, “Differential impact of statin on new-onset diabetes in different age groups: a population-based case-control study in women from an asian country,” PLoS One, vol. 8, no. 8, article e71817, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Amarenco, J. Bogousslavsky, A. Callahan 3rd et al., “High-dose atorvastatin after stroke or transient ischemic attack,” The New England Journal of Medicine, vol. 355, no. 6, pp. 549–559, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. P. M. Ridker, A. Pradhan, J. G. MacFadyen, P. Libby, and R. J. Glynn, “Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial,” Lancet, vol. 380, no. 9841, pp. 565–571, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. B. Chogtu, R. Magazine, and K. L. Bairy, “Statin use and risk of diabetes mellitus,” World Journal of Diabetes, vol. 6, no. 2, pp. 352–357, 2015. View at Publisher · View at Google Scholar
  41. H. Naci, J. Brugts, and T. Ades, “Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials,” Circulation. Cardiovascular Quality and Outcomes, vol. 6, no. 4, pp. 390–399, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. D. Preiss, S. R. Seshasai, P. Welsh et al., “Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis,” JAMA, vol. 305, no. 24, pp. 2556–2564, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. B. Zafrir and M. Jain, “Lipid-lowering therapies, glucose control and incident diabetes: evidence, mechanisms and clinical implications,” Cardiovascular Drugs and Therapy, vol. 28, no. 4, pp. 361–377, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Laakso and J. Kuusisto, “Diabetes secondary to treatment with statins,” Current Diabetes Reports, vol. 17, no. 2, p. 10, 2017. View at Publisher · View at Google Scholar · View at Scopus
  45. K. K. Koh, I. Sakuma, and M. J. Quon, “Differential metabolic effects of distinct statins,” Atherosclerosis, vol. 215, no. 1, pp. 1–8, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. A. J. Rahal, A. I. ElMallah, R. J. Poushuju, and R. Itani, “Do statins really cause diabetes? A meta-analysis of major randomized controlled clinical trials,” Saudi Medical Journal, vol. 37, no. 10, pp. 1051–1060, 2016. View at Publisher · View at Google Scholar · View at Scopus
  47. D. Thakker, S. Nair, A. Pagada, V. Jamdade, and A. Malik, “Statin use and the risk of developing diabetes: a network meta-analysis,” Pharmacoepidemiology and Drug Safety, vol. 25, no. 10, pp. 1131–1149, 2016. View at Publisher · View at Google Scholar · View at Scopus
  48. E. P. Navarese, A. Buffon, F. Andreotti et al., “Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus,” The American Journal of Cardiology, vol. 111, no. 8, pp. 1123–1130, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. K. Ray, “Statin diabetogenicity: guidance for clinicians,” Cardiovascular Diabetology, vol. 12, Supplement 1, p. S3, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. Y. Zhou, Y. Yuan, R. R. Cai et al., “Statin therapy on glycaemic control in type 2 diabetes: a meta-analysis,” Expert Opinion on Pharmacotherapy, vol. 14, no. 12, pp. 1575–1584, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Sasaki, M. Iwashita, and S. Kono, “Statins: beneficial or adverse for glucose metabolism,” Journal of Atherosclerosis and Thrombosis, vol. 13, no. 3, pp. 123–129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Nakata, S. Nagasaka, I. Kusaka, H. Matsuoka, S. Ishibashi, and T. Yada, “Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control,” Diabetologia, vol. 49, no. 8, pp. 1881–1892, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. T. Yada, M. Nakata, T. Shiraishi, and M. Kakei, “Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+ signalling and insulin secretion due to blockade of L-type Ca2+ channels in rat islet beta-cells,” British Journal of Pharmacology, vol. 126, no. 5, pp. 1205–1213, 1999. View at Publisher · View at Google Scholar · View at Scopus
  54. H. Mabuchi, T. Higashikata, M. Kawashiri et al., “Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients,” Journal of Atherosclerosis and Thrombosis, vol. 12, no. 2, pp. 111–119, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Ishikawa, A. Namiki, T. Kubota et al., “Effect of pravastatin and atorvastatin on glucose metabolism in nondiabetic patients with hypercholesterolemia,” Internal Medicine, vol. 45, no. 2, pp. 51–55, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. G. Rena, D. G. Hardie, and E. R. Pearson, “The mechanisms of action of metformin,” Diabetologia, vol. 60, no. 9, pp. 1577–1585, 2017. View at Publisher · View at Google Scholar · View at Scopus
  57. J. Jin, H. Zeng, O. Yang, and J. Kong, “The endothelial protective effects of pioglitazone on insulin resistance in endothelial cells,” Clinical Laboratory, vol. 60, no. 7, pp. 1129–1134, 2014. View at Google Scholar
  58. U. Smith, “Pioglitazone: mechanism of action,” International Journal of Clinical Practice, vol. 121, pp. 13–18, 2001. View at Google Scholar
  59. T. Kimura, H. Kaneto, M. Shimoda et al., “Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: comparison of their effects between in an early and advanced stage of diabetes,” Molecular and Cellular Endocrinology, vol. 400, pp. 78–89, 2015. View at Publisher · View at Google Scholar · View at Scopus
  60. D. Sola, L. Rossi, G. P. C. Schianca et al., “Sulfonylureas and their use in clinical practice,” Archives of Medical Science, vol. 11, no. 4, pp. 840–848, 2015. View at Publisher · View at Google Scholar · View at Scopus
  61. K. Khunti, S. Chatterjee, H. C. Gerstein, S. Zoungas, and M. J. Davies, “Do sulphonylureas still have a place in clinical practice?” The Lancet Diabetes and Endocrinology, vol. 6, no. 10, pp. 821–832, 2018. View at Publisher · View at Google Scholar · View at Scopus
  62. D. J. Drucker, “Mechanisms of action and therapeutic application of glucagon-like peptide-1,” Cell Metabolism, vol. 27, no. 4, pp. 740–756, 2018. View at Publisher · View at Google Scholar · View at Scopus
  63. E. E. Mulvihill and D. J. Drucker, “Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors,” Endocrine Reviews, vol. 35, no. 6, pp. 992–1019, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Kalra, “Glucagon-like peptide-1 receptors agonists (GLP1 RA),” The Journal of the Pakistan Medical Association, vol. 63, no. 10, pp. 1312–1315, 2013. View at Google Scholar
  65. K. I. Cho, I. Sakuma, I. S. Sohn, T. Hayashi, K. Shimada, and K. K. Koh, “Best treatment strategies with statins to maximize the cardiometabolic benefits,” Circulation Journal, vol. 82, no. 4, pp. 937–943, 2018. View at Publisher · View at Google Scholar · View at Scopus
  66. P. C. Underwood and G. K. Adler, “The renin angiotensin aldosterone system and insulin resistance in humans,” Current Hypertension Reports, vol. 15, no. 1, pp. 59–70, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. F. Andreozzi, E. Laratta, A. Sciacqua, F. Perticone, and G. Sesti, “Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells,” Circulation Research, vol. 94, no. 9, pp. 1211–1218, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. Y. Izawa, M. Yoshizumi, Y. Fujita et al., “ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells,” Experimental Cell Research, vol. 308, no. 2, pp. 291–299, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. C. Tikellis, P. J. Wookey, R. Candido, S. Andrikopoulos, M. C. Thomas, and M. E. Cooper, “Improved islet morphology after blockade of the renin–angiotensin system in the ZDF rat,” Diabetes, vol. 53, no. 4, pp. 989–997, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. G. C. Weir, C. Aguayo-Mazzucato, and S. Bonner-Weir, “β-cell dedifferentiation in diabetes is important, but what is it?” Islets, vol. 5, no. 5, pp. 233–237, 2013. View at Publisher · View at Google Scholar · View at Scopus
  71. H. Chen, W. Zhou, Y. Ruan et al., “Reversal of angiotensin ll-induced β-cell dedifferentiation via inhibition of NF-κb signaling,” Molecular Medicine, vol. 24, no. 1, p. 43, 2018. View at Publisher · View at Google Scholar
  72. H. Takagi and T. Umemoto, “Telmisartan improves insulin sensitivity: a meta-analysis of randomized head-to-head trials,” International Journal of Cardiology, vol. 156, no. 1, pp. 92–96, 2012. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Paolisso, M. R. Tagliamonte, A. Gambardella et al., “Losartan mediated improvement in insulin action is mainly due to an increase in non-oxidative glucose metabolism and blood flow in insulin-resistant hypertensive patients,” Journal of Human Hypertension, vol. 11, no. 5, pp. 307–312, 1997. View at Publisher · View at Google Scholar · View at Scopus
  74. A. Moan, A. Høieggen, G. Nordby, I. K. Eide, and S. E. Kjeldsen, “Effects of losartan on insulin sensitivity in severe hypertension: connections through sympathetic nervous system activity?” Journal of Human Hypertension, vol. 9, Supplement 5, pp. S45–S50, 1995. View at Google Scholar
  75. K. Suzuki, O. Nakagawa, and Y. Aizawa, “Improved early-phase insulin response after candesartan treatment in hypertensive patients with impaired glucose tolerance,” Clinical and Experimental Hypertension, vol. 30, no. 5, pp. 309–314, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. T. S. Perlstein, R. R. Henry, K. J. Mather et al., “Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose,” Clinical Science, vol. 122, no. 4, pp. 193–202, 2012. View at Publisher · View at Google Scholar · View at Scopus
  77. S. H. Ko, H. S. Kwon, S. R. Kim et al., “Ramipril treatment suppresses islet fibrosis in Otsuka Long–Evans Tokushima fatty rats,” Biochemical and Biophysical Research Communications, vol. 316, no. 1, pp. 114–122, 2004. View at Publisher · View at Google Scholar · View at Scopus
  78. T. Shiuchi, T. X. Cui, L. Wu et al., “ACE inhibitor improves insulin resistance in diabetic mouse via bradykinin and NO,” Hypertension, vol. 40, no. 3, pp. 329–334, 2002. View at Publisher · View at Google Scholar · View at Scopus
  79. B. Singh, A. Mourya, S. P. Sah, and A. Kumar, “Protective effect of losartan and ramipril against stress induced insulin resistance and related complications: anti-inflammatory mechanisms,” European Journal of Pharmacology, vol. 801, pp. 54–61, 2017. View at Publisher · View at Google Scholar · View at Scopus
  80. R. S. Weisinger, T. K. Stanley, D. P. Begg, H. S. Weisinger, K. J. Spark, and M. Jois, “Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet,” Physiology & Behavior, vol. 98, no. 1-2, pp. 192–197, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. U. N. Das, “Renin–angiotensin–aldosterone system in insulin resistance and metabolic syndrome,” Journal of Translational Internal Medicine, vol. 4, no. 2, pp. 66–72, 2016. View at Publisher · View at Google Scholar
  82. K. Putnam, R. Shoemaker, F. Yiannikouris, and L. A. Cassis, “The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome,” American Journal of Physiology. Heart and Circulatory Physiology, vol. 302, no. 6, pp. H1219–H1230, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. Ç. Bitkin Eda, B. Mehmet, T. Necati et al., “Effects of ACE inhibitors on insulin resistance and lipid profile in children with metabolic syndrome,” Journal of Clinical Research in Pediatric Endocrinology, vol. 5, no. 3, pp. 164–169, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. E. L. Gillespie, C. M. White, M. Kardas, M. Lindberg, and C. I. Coleman, “The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes,” Diabetes Care, vol. 28, no. 9, pp. 2261–2266, 2005. View at Publisher · View at Google Scholar · View at Scopus
  85. J. J. McMurray, R. R. Holman, S. M. Haffner et al., “Effect of valsartan on the incidence of diabetes and cardiovascular events,” The New England Journal of Medicine, vol. 362, no. 16, pp. 1477–1490, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. L. V. Solski and D. S. Longyhore, “Prevention of type 2 diabetes mellitus with angiotensin-converting-enzyme inhibitors,” American Journal of Health-System Pharmacy, vol. 65, no. 10, pp. 935–940, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. H. Abuissa, P. G. Jones, S. P. Marso, and J. H. O’Keefe Jr, “Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials,” Journal of the American College of Cardiology, vol. 46, no. 5, pp. 821–826, 2005. View at Publisher · View at Google Scholar · View at Scopus
  88. L. M. Prisant, “Preventing type II diabetes mellitus,” Journal of Clinical Pharmacology, vol. 44, no. 4, pp. 406–413, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. M. M. Haluzík and M. Haluzík, “PPAR-alpha and insulin sensitivity,” Physiological Research, vol. 55, no. 2, pp. 115–122, 2006. View at Google Scholar
  90. T. Damci, S. Tatliagac, Z. Osar, and H. Ilkova, “Fenofibrate treatment is associated with better glycemic control and lower serum leptin and insulin levels in type 2 diabetic patients with hypertriglyceridemia,” European Journal of Internal Medicine, vol. 14, no. 6, pp. 357–360, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. S. M. H. Chan, R. Q. Sun, X. Y. Zeng et al., “Activation of PPARα ameliorates hepatic insulin resistance and steatosis in high fructose-fed mice despite increased endoplasmic reticulum stress,” Diabetes, vol. 62, no. 6, pp. 2095–2105, 2013. View at Publisher · View at Google Scholar · View at Scopus
  92. R. Elkeles, “Fibrates: old drugs with a new role in type 2 diabetes prevention?” The British Journal of Diabetes & Vascular Disease, vol. 11, no. 1, pp. 4–9, 2011. View at Publisher · View at Google Scholar
  93. M. J. Graham, R. G. Lee, T. A. Brandt et al., “Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides,” The New England Journal of Medicine, vol. 377, no. 3, pp. 222–232, 2017. View at Publisher · View at Google Scholar · View at Scopus
  94. M. S. Kostapanos, G. L. Liamis, H. J. Milionis, and M. S. Elisaf, “Do statins beneficially or adversely affect glucose homeostasis?” Current Vascular Pharmacology, vol. 999, no. 999, pp. 1–20, 2010. View at Publisher · View at Google Scholar
  95. T. R. Pedersen, O. Faergeman, J. J. Kastelein et al., “High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the ideal study: a randomized controlled trial–correction,” JAMA, vol. 294, no. 19, pp. 2437–2445, 2005. View at Publisher · View at Google Scholar · View at Scopus