Skip to main content

Advertisement

SpringerLink
Log in

Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Acarbose has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on PDMP, selectins, and adiponectin in these patients is poorly understood. We investigated the effect of acarbose on circulating levels of PDMP, selectins, and adiponectin in patients with type 2 diabetes. Acarbose (300 mg/day) was administered for 3 months. Levels of PDMP, sP-selectin, sL-selectin, and adiponectin were measured by ELISA at baseline and after 1 and 3 months of treatment. The levels of PDMP, sP-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients (PDMP; 35.1 ± 34.2 vs. 53.3 ± 56.7 U/ml, P < 0.05: sP-selectin; 134 ± 52 vs. 235 ± 70 ng/dl, P < 0.01: sL-selectin; 569 ± 183 vs. 805 ± 146 ng/ml, P < 0.05), while there were no significant differences between hypertensive and hyperlipidemic patients. Before acarbose treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Acarbose therapy significantly decreased the plasma PDMP level relative to baseline. Acarbose also caused a significant decrease of sP-selectin and sL-selectin. On the other hand, acarbose therapy led to a significant increase of adiponectin after 3 months of administration compared with baseline (adiponectin: diabetes versus hypertension, 3.61 ± 1.23 vs. 5.87 ± 1.92 μg/ml, P < 0.05; diabetes versus controls, 2.81 ± 0.95 vs. 6.13 ± 1.24 μg/ml, P < 0.01). Twelve of the 30 diabetic patients had a history of thrombotic complications. Furthermore, the reduction of PDMP and selectins during acarbose therapy was significantly greater in the thrombotic group (12 of 30) than in the nonthrombotic group (18 of 30) of diabetic patients. Acarbose may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. However, it requires a large clinical trial to test this hypothesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chobanian AV (1991) Single risk factor intervention may be inadequate to inhibit atherosclerosis progression when hypertension and hypercholesterolemia co-exist. Hypertension 18:130–131

    CAS  PubMed  Google Scholar 

  2. Schafer AI (1985) The hypercoagulable states. Ann Intern Med 102:814–818

    CAS  PubMed  Google Scholar 

  3. Frade LJG, de la Calle H, Alava I et al (1987) Diabetes as a hypercoagulable state: its relationship with fibrin fragments and vascular damage. Thromb Res 47:533–540. doi:10.1016/0049-3848(87)90358-6

    Article  Google Scholar 

  4. Nomura S (2001) Function and clinical significance of platelet-derived microparticles. Int J Hematol 74:397–404. doi:10.1007/BF02982082

    Article  CAS  PubMed  Google Scholar 

  5. Nomura S, Ozaki Y, Ikeda Y (2008) Function and role of microparticles in various clinical settings. Thromb Res 123:8–23. doi:10.1016/j.thromres.2008.06.006

    Article  CAS  PubMed  Google Scholar 

  6. Cominacini L, Pasini AF, Garbin U et al (1995) Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control. Diabetologia 38:1122–1124. doi:10.1007/BF00402185

    Article  CAS  PubMed  Google Scholar 

  7. Lim YC, Snapp K, Kansas GS et al (1998) Important contributions of P-selectin glycoprotein ligand-1-mediated secondary capture to human monocyte adhesion to P-selectin, E-selectin, and TNF-α-activated endothelium under flow in vitro. J Immunol 161:2501–2508

    CAS  PubMed  Google Scholar 

  8. Tschope D, Esser J, Schwippert B et al (1991) Large platelets circulate in an activated state in diabetes. Semin Thromb Hemost 17:433–439. doi:10.1055/s-2007-1002650

    Article  Google Scholar 

  9. Nomura S, Shouzu A, Omoto S et al (2000) Significance of chemokines and activated platelets in patients with diabetes. Clin Exp Immunol 121:437–443. doi:10.1046/j.1365-2249.2000.01324.x

    Article  CAS  PubMed  Google Scholar 

  10. Rodriguez BL, Lau N, Burchfiel CM et al (1999) Glucose intolerance and 23-year risk of coronary heart disease and total mortality: the Honolulu Heart Program. Diabetes Care 22:1262–1265. doi:10.2337/diacare.22.8.1262

    Article  CAS  PubMed  Google Scholar 

  11. Coutinho M, Gerstein HC, Wang Y et al (1999) The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95, 783 individuals followed for 12.4 years. Diabetes Care 22:233–240. doi:10.2337/diacare.22.2.233

    Article  CAS  PubMed  Google Scholar 

  12. The DECODE study group on behalf of the European Diabetes Epidemiology Group (1999) Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria. Diabetes Epidemiology: collaborative analysis of diagnostic criteria in Europe. Lancet 354:617–621

    Article  Google Scholar 

  13. Nakagami T (2004) Hyperglycaemia and mortality from all cause and from cardiovascular disease in five populations of Asian origin. Diabetologia 47:385–394. doi:10.1007/s00125-004-1334-6

    Article  CAS  PubMed  Google Scholar 

  14. Puls W, Keup U, Krause HP et al (1977) Glucosidase inhibition. A new approach to the treatment of diabetes, obesity, and hyperlipoproteinaemia. Naturwissenschaften 64:536–537. doi:10.1007/BF00483562

    Article  CAS  PubMed  Google Scholar 

  15. Chiasson JL, Josse RG, Gomis R et al (2002) Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomized trial. Lancet 359:2072–2077. doi:10.1016/S0140-6736(02)08905-5

    Article  CAS  PubMed  Google Scholar 

  16. Chiasson JL, Josse RG, Gomis R et al (2003) Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 290:486–494. doi:10.1001/jama.290.4.486

    Article  CAS  PubMed  Google Scholar 

  17. Hanefield M, Chiasson JL, Koehler C et al (2004) Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. Stroke 35:1073–1078. doi:10.1161/01.STR.0000125864.01546.f2

    Article  Google Scholar 

  18. Hanefeld M, Cagatay M, Petrowitsch T et al (2004) Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J 25:10–16. doi:10.1016/S0195-668X(03)00468-8

    Article  CAS  PubMed  Google Scholar 

  19. Osumi K, Ozeki Y, Saito S et al (2001) Development and assessment of enzyme immunoassay for platelet-derived microparticles. Thromb Haemost 85:326–330

    CAS  PubMed  Google Scholar 

  20. Nomura S, Uehata S, Saito S (2003) Enzyme immunoassay detection of platelet-derived microparticles and RANTES in acute coronary syndrome. Thromb Haemost 89:506–512

    CAS  PubMed  Google Scholar 

  21. Packham MA, Mustard JF (1986) The role of platelets in the development and complications of atherosclerosis. Semin Hematol 23:8–19

    CAS  PubMed  Google Scholar 

  22. Sims PJ, Faioni EM, Wiedmer T et al (1988) Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J Biol Chem 263:18205–18212

    CAS  PubMed  Google Scholar 

  23. Nomura S, Suzuki M, Katsura K et al (1995) Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus. Atherosclerosis 116:235–240. doi:10.1016/0021-9150(95)05551-7

    Article  CAS  PubMed  Google Scholar 

  24. Nomura S, Tandon NN, Nakamura T et al (2001) High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis 158:277–287. doi:10.1016/S0021-9150(01)00433-6

    Article  CAS  PubMed  Google Scholar 

  25. Nomura S, Shouzu A, Omoto S et al (1998) Effect of cilostazol on soluble adhesion molecules and platelet-derived microparticles in patients with diabetes. Thromb Haemost 80:388–392

    CAS  PubMed  Google Scholar 

  26. Nomura S, Inami N, Iwasaka T et al (2004) Platelet activation markers, microparticles and soluble adhesion molecules are elevated in patients with arteriosclerosis obliterans: therapeutic effects by cilostazol and potentiation by dipyridamole. Platelets 15:167–172. doi:10.1080/09537100410001682779

    Article  CAS  PubMed  Google Scholar 

  27. Nomura S, Takahashi N, Inami N et al (2004) Probucol and ticlopidine: effect on platelet and monocyte activation markers in hyperlipidemic patients with and without type 2 diabetes. Atherosclerosis 174:329–335

    CAS  PubMed  Google Scholar 

  28. Ceriello A (1999) Hyperglycaemia: the bridge between non-enzymatic glycation and oxidative stress in the pathogenesis of diabetic complications. Diabetes Nutr Metab 12:42–46

    CAS  PubMed  Google Scholar 

  29. Yamagishi S, Nakamura K, Takeuchi M (2005) Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome. Med Hypotheses 65:152–154. doi:10.1016/j.mehy.2004.12.008

    Article  CAS  PubMed  Google Scholar 

  30. Ouchi N, Kihara S, Arita Y et al (1999) Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein, adiponectin. Circulation 100:2473–2476

    CAS  PubMed  Google Scholar 

  31. Ouchi N, Kihara S, Arita Y et al (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappa B signaling through a cAMP-dependent pathway. Circulation 102:1296–1301

    CAS  PubMed  Google Scholar 

  32. Hotta K, Funahashi T, Arita Y et al (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetes patients. Arterioscler Thromb Vasc Biol 20:1595–1599

    CAS  PubMed  Google Scholar 

  33. Shimabukuro M, Higa N, Asahi T et al (2003) Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J Clin Endocrinol Metab 88:3236–3240. doi:10.1210/jc.2002-021883

    Article  CAS  PubMed  Google Scholar 

  34. Chen H, Montagnani M, Funahashi T et al (2003) Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 278:45021–45026. doi:10.1074/jbc.M307878200

    Article  CAS  PubMed  Google Scholar 

  35. Hattori Y, Suzuki M, Hattori S et al (2003) Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 46:1543–1549. doi:10.1007/s00125-003-1224-3

    Article  CAS  PubMed  Google Scholar 

  36. Nomura S, Shouzu A, Omoto S et al (2008) Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus. Thromb Res 122:39–45. doi:10.1016/j.thromres.2007.08.013

    Article  CAS  PubMed  Google Scholar 

  37. Wang Y, Lam KS, Chan L et al (2006) Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex. J Biol Chem 281:16391–16400. doi:10.1074/jbc.M513907200

    Article  CAS  PubMed  Google Scholar 

  38. Fülöp N, Marchase RB, Chatham JC (2007) Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system. Cardiovasc Res 73:288–297. doi:10.1016/j.cardiores.2006.07.018

    Article  PubMed  Google Scholar 

  39. Fülöp N, Mason MM, Dutta K et al (2007) Impact of Type 2 diabetes and aging on cardiomyocyte function and O-linked N-acetylglucosamine levels in the heart. Am J Physiol Cell Physiol 292:C1370–C1378. doi:10.1152/ajpcell.00422.2006

    Article  PubMed  Google Scholar 

  40. Ochiai H, Ooka H, Shida C et al (2008) Acarbose treatment increases serum total adiponectin levels in patients with type 2 diabetes. Endocr J 55:549–556. doi:10.1507/endocrj.K07E-107

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was partly supported by a grant from the Japan Foundation of Neuropsychiatry and Hematology Research, a Research Grant for Advanced Medical Care from the Ministry of Health and Welfare of Japan, and a Grant (13670760 to S. Nomura) from the Ministry of Education, Science and Culture of Japan.

Author information

Authors and Affiliations

  1. Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan

    Takayuki Shimazu, Norihito Inami, Daisuke Satoh, Takayuki Kajiura, Kohichi Yamada & Toshiji Iwasaka

  2. Division of Hematology, Kishiwada City Hospital, 1001 Gakuhara-cho, Kishiwada, Osaka, 596-8501, Japan

    Shosaku Nomura

Authors
  1. Takayuki Shimazu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norihito Inami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daisuke Satoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takayuki Kajiura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kohichi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshiji Iwasaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shosaku Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shosaku Nomura.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shimazu, T., Inami, N., Satoh, D. et al. Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients. J Thromb Thrombolysis 28, 429–435 (2009). https://doi.org/10.1007/s11239-008-0301-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-008-0301-3

Keywords

Search

Navigation