Improved preservation of residual beta cell function by atorvastatin in patients with recent onset type 1 diabetes and high CRP levels (DIATOR trial)

PLoS ONE

Volumn 7, Issue 3, 2012, Pages

  Strom, Alexander ^a   Kolb, Hubert ^b   Martin, Stephan ^c   Herder, Christian ^a   Simon, Marie Christine ^a   Koenig, Wolfgang ^d   Heise, Tim ^e   Heinemann, Lutz ^e   Roden, Michael ^a,b   Schloot, Nanette C ^a,b,f   The DIATOR Study Group, ^g  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b UNIVERSITY HOSPITAL DÜSSELDORF   (Germany)

^c West German Centre of Diabetes and Health   (Germany)

^d UNIVERSITY HOSPITAL ULM   (Germany)

^e Profil Institute for Metabolic Research   (Germany)

^f LILLY DEUTSCHLAND GMBH   (Germany)

^g BU Diabetes Lilly Deutschland GmbH ^*

Author keywords

[No Author keywords available]

Indexed keywords

ATORVASTATIN; C PEPTIDE; C REACTIVE PROTEIN; CHOLESTEROL; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 18; INTERLEUKIN 6; INTERLEUKIN 8; MACROPHAGE DERIVED CHEMOKINE; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; MONOCYTE CHEMOTACTIC PROTEIN 1; MONOCYTE CHEMOTACTIC PROTEIN 4; PANCREAS ISLET CELL ANTIBODY; PLACEBO; THYMUS AND ACTIVATION REGULATED CHEMOKINE; HEPTANOIC ACID DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; PYRROLE DERIVATIVE;

ADULT; AGE DISTRIBUTION; ANTIBODY TITER; ARTICLE; BODY MASS; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DRUG DOSE INCREASE; DRUG EFFICACY; FEMALE; FOOD INTAKE; GERMANY; HUMAN; IMMUNE RESPONSE; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; MAJOR CLINICAL STUDY; MALE; MEAL; METABOLIC PARAMETERS; MULTICENTER STUDY; OUTCOME ASSESSMENT; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; SECONDARY ANALYSIS; SEX DIFFERENCE; TREATMENT DURATION; ADOLESCENT; BLOOD; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CYTOLOGY; DRUG EFFECT; METABOLISM; ONSET AGE;

ADOLESCENT; ADULT; AGE OF ONSET; C-PEPTIDE; C-REACTIVE PROTEIN; DIABETES MELLITUS, TYPE 1; FEMALE; GERMANY; HEPTANOIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INSULIN; INSULIN-SECRETING CELLS; MALE; PYRROLES; YOUNG ADULT;

EID: 84858631179     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0033108     Document Type: Article

References (38)

1. Kanda H, Yokota K, Kohno C, Sawada T, Sato K, et al. (2007) Effects of low-dosage simvastatin on rheumatoid arthritis through reduction of Th1/Th2 and CD4/CD8 ratios. Mod Rheumatol 17: 364-368.
2. McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, et al. (2004) Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 363: 2015-2021.
3. Tang TT, Song Y, Ding YJ, Liao YH, Yu X, et al. (2011) Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patients with rheumatoid arthritis. J Lipid Res 52: 1023-1032.
4. Contreras JL, Smyth CA, Bilbao G, Young CJ, Thompson JA, et al. (2002) Simvastatin induces activation of the serine-threonine protein kinase AKT and increases survival of isolated human pancreatic islets. Transplantation 74: 1063-1069.
5. Lozanoska-Ochser B, Barone F, Pitzalis C, Peakman M, (2006) Atorvastatin fails to prevent the development of autoimmune diabetes despite inhibition of pathogenic beta-cell-specific CD8 T-cells. Diabetes 55: 1004-1010.
6. Palomer X, Calpe-Berdiel L, Verdaguer J, Carrillo J, Pastor X, et al. (2005) Atorvastatin does not decrease or delay diabetes onset in two different mouse models of type 1 diabetes. Diabetologia 48: 1671-1673.
7. Rydgren T, Vaarala O, Sandler S, (2007) Simvastatin protects against multiple low-dose streptozotocin-induced type 1 diabetes in CD-1 mice and recurrence of disease in nonobese diabetic mice. J Pharmacol Exp Ther 323: 180-185.
8. Zhang S, Yan X, Zhou PC, Huang C, Yang L, et al. (2008) [Effects of pravastatin in prevention of diabetes and mechanism thereof: experiment with non-obese diabetic mice]. Zhonghua Yi Xue Za Zhi 88: 568-572.
9. Martin S, Herder C, Schloot NC, Koenig W, Heise T, et al. (2011) Residual beta cell function in newly diagnosed type 1 diabetes after treatment with atorvastatin: the Randomized DIATOR Trial. PLoS One 6: e17554.
10. Martin S, Pawlowski B, Greulich B, Ziegler AG, Mandrup-Poulsen T, et al. (1992) Natural course of remission in IDDM during 1st yr after diagnosis. Diabetes Care 15: 66-74.
11. Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, et al. (2004) C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes 53: 250-264.
12. Torn C, Landin-Olsson M, Lernmark A, Palmer JP, Arnqvist HJ, et al. (2000) Prognostic factors for the course of beta cell function in autoimmune diabetes. J Clin Endocrinol Metab 85: 4619-4623.
13. Wagner AM, Sanchez-Quesada JL, Benitez S, Bancells C, Ordonez-Llanos J, et al. (2011) Effect of statin and fibrate treatment on inflammation in type 2 diabetes. A randomized, cross-over study. Diabetes Res Clin Pract 93: e25-28.
14. Blank N, Schiller M, Krienke S, Busse F, Schatz B, et al. (2007) Atorvastatin inhibits T cell activation through 3-hydroxy-3-methylglutaryl coenzyme A reductase without decreasing cholesterol synthesis. J Immunol 179: 3613-3621.
15. Bu DX, Tarrio M, Grabie N, Zhang Y, Yamazaki H, et al. (2010) Statin-induced Kruppel-like factor 2 expression in human and mouse T cells reduces inflammatory and pathogenic responses. J Clin Invest 120: 1961-1970.
16. Kofler S, Schlichting C, Jankl S, Nickel T, Weis M, (2008) Dual mode of HMG-CoA reductase inhibition on dendritic cell invasion. Atherosclerosis 197: 105-110.
17. Kwak B, Mulhaupt F, Myit S, Mach F, (2000) Statins as a newly recognized type of immunomodulator. Nat Med 6: 1399-1402.
18. Amuro H, Ito T, Miyamoto R, Sugimoto H, Torii Y, et al. (2010) Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, function as inhibitors of cellular and molecular components involved in type I interferon production. Arthritis Rheum 62: 2073-2085.
19. Arnaud C, Burger F, Steffens S, Veillard NR, Nguyen TH, et al. (2005) Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins. Arterioscler Thromb Vasc Biol 25: 1231-1236.
20. Feng B, Xu L, Wang H, Yan X, Xue J, et al. (2011) Atorvastatin exerts its anti-atherosclerotic effects by targeting the receptor for advanced glycation end products. Biochim Biophys Acta 1812: 1130-1137.
21. Montecucco F, Burger F, Pelli G, Poku NK, Berlier C, et al. (2009) Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes. Rheumatology (Oxford) 48: 233-242.
22. Aktunc E, Kayhan B, Arasli M, Gun BD, Barut F, (2011) The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis. Immunopharmacol Immunotoxicol.
23. Kim YC, Kim KK, Shevach EM, (2010) Simvastatin induces Foxp3+ T regulatory cells by modulation of transforming growth factor-beta signal transduction. Immunology 130: 484-493.
24. Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, et al. (2002) The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420: 78-84.
25. Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, et al. (2011) Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation 124: 335-345.
26. Blum A, Shamburek R, (2009) The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis. Atherosclerosis 203: 325-330.
27. Bot I, Jukema JW, Lankhuizen IM, van Berkel TJ, Biessen EA, (2011) Atorvastatin inhibits plaque development and adventitial neovascularization in ApoE deficient mice independent of plasma cholesterol levels. Atherosclerosis 214: 295-300.
28. Yang J, Huang C, Jiang H, Ding J, (2010) Statins attenuate high mobility group box-1 protein induced vascular endothelial activation: a key role for TLR4/NF-kappaB signaling pathway. Mol Cell Biochem 345: 189-195.
29. Gabay C, Kushner I, (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340: 448-454.
30. Muller S, Martin S, Koenig W, Hanifi-Moghaddam P, Rathmann W, et al. (2002) Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia 45: 805-812.
31. Carstensen M, Herder C, Kivimaki M, Jokela M, Roden M, et al. (2010) Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes 59: 1222-1227.
32. Cartier A, Bergeron J, Poirier P, Almeras N, Tremblay A, et al. (2009) Increased plasma interleukin-1 receptor antagonist levels in men with visceral obesity. Ann Med 41: 471-478.
33. Herder C, Baumert J, Zierer A, Roden M, Meisinger C, et al. (2011) Immunological and cardiometabolic risk factors in the prediction of type 2 diabetes and coronary events: MONICA/KORA Augsburg case-cohort study. PLoS One 6: e19852.
34. Meigs JB, Hu FB, Rifai N, Manson JE, (2004) Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. Jama 291: 1978-1986.
35. Scholin A, Siegbahn A, Lind L, Berne C, Sundkvist G, et al. (2004) CRP and IL-6 concentrations are associated with poor glycemic control despite preserved beta-cell function during the first year after diagnosis of type 1 diabetes. Diabetes Metab Res Rev 20: 205-210.
36. Greenbaum CJ, Mandrup-Poulsen T, McGee PF, Battelino T, Haastert B, et al. (2008) Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care 31: 1966-1971.
37. Herder C, Peltonen M, Koenig W, Sutfels K, Lindstrom J, et al. (2009) Anti-inflammatory effect of lifestyle changes in the Finnish Diabetes Prevention Study. Diabetologia 52: 433-442.
38. Herder C, Baumert J, Thorand B, Koenig W, de Jager W, et al. (2006) Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984-2002. Diabetologia 49: 921-929.