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The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia

  • Tsuyoshi ItoEmail author
  • Taku Ichihashi
  • Hiroshi Fujita
  • Tomonori Sugiura
  • Junki Yamamoto
  • Shuichi Kitada
  • Kosuke Nakasuka
  • Yu Kawada
  • Nobuyuki Ohte
Original Article
  • 31 Downloads

Abstract

Impaired glucose metabolism is associated with an increased risk of cardiovascular complications, and coronary artery spasm is thought to underlie the development of coronary artery disease. Intraday glucose variability (GV) accelerates oxidative stress and inflammatory cytokine release, but its impact on coronary artery spasm remains unclear. This study investigated the relationship between intraday GV and coronary artery spasm. The study included 50 patients with dysglycemia and suspected coronary spastic angina. GV was analyzed by 24-h monitoring of the blood glucose concentration using a flash glucose monitoring system. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of GV. Coronary artery spasm was assessed using the intracoronary acetylcholine provocation test. Coronary spasm was defined as acetylcholine-induced total or subtotal coronary occlusion. Changes in vessel diameter in response to acetylcholine were evaluated with quantitative coronary angiography. Coronary artery spasms were observed in 21 patients (42%). MAGE was significantly higher in patients with spasms compared to those without spasms (127.5 ± 33.5 vs. 91.4 ± 37.6, p < 0.01). Regression analysis showed a positive correlation between MAGE levels and coronary diameter changes induced by acetylcholine (r = 0.47, p < 0.01). In multiple regression analysis, MAGE was independently associated with acetylcholine-induced coronary diameter change (β = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

Keywords

Dysglycemia Glucose variability Flash glucose monitoring Coronary spasm 

Notes

Compliance with ethical standards

Conflict of interest

This work was supported by a Grant-in-Aid for Research from Nagoya City University.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Collaboration Emerging Risk Factors, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222CrossRefGoogle Scholar
  2. 2.
    Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njølstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J, Collaboration Emerging Risk Factors (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364:829–841CrossRefGoogle Scholar
  3. 3.
    ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572CrossRefGoogle Scholar
  4. 4.
    Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559CrossRefGoogle Scholar
  5. 5.
    Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687CrossRefGoogle Scholar
  6. 6.
    Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D (2002) Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106:2067–2072CrossRefGoogle Scholar
  7. 7.
    Su G, Mi S, Tao H, Li Z, Yang H, Zheng H, Zhou Y, Ma C (2011) Association of glycemic variability and the presence and severity of coronary artery disease in patients with type 2 diabetes. Cardiovasc Diabetol 10:19CrossRefGoogle Scholar
  8. 8.
    Gohbara M, Hibi K, Mitsuhashi T, Maejima N, Iwahashi N, Kataoka S, Akiyama E, Tsukahara K, Kosuge M, Ebina T, Umemura S, Kimura K (2016) Glycemic variability on continuous glucose monitoring system correlates with non-culprit vessel coronary plaque vulnerability in patients with first-episode acute coronary syndrome—optical coherence tomography study. Circ J 80:202–210CrossRefGoogle Scholar
  9. 9.
    Su G, Mi SH, Li Z, Tao H, Yang HX, Zheng H (2013) Prognostic value of early in-hospital glycemic excursion in elderly patients with acute myocardial infarction. Cardiovasc Diabetol 12:33CrossRefGoogle Scholar
  10. 10.
    Oliva PB, Potts DE, Pluss RG (1973) Coronary arterial spasm in Prinzmetal angina. Documentation by coronary arteriography. N Engl J Med 288:745–751CrossRefGoogle Scholar
  11. 11.
    Nakamura M, Takeshita A, Nose Y (1987) Clinical characteristics associated with myocardial infarction, arrhythmias, and sudden death in patients with vasospastic angina. Circulation 75:1110–1116CrossRefGoogle Scholar
  12. 12.
    Sueda S, Kohno H (2018) Impact of pharmacological spasm provocation test in patients with a history of syncope. Heart Vessel 33:126–133CrossRefGoogle Scholar
  13. 13.
    Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U (2008) Coronary artery spasm as a frequent cause of acute coronary syndrome: the CASPAR (Coronary Artery Spasm in Patients with Acute Coronary Syndrome) study. J Am Coll Cardiol 52:523–527CrossRefGoogle Scholar
  14. 14.
    Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF (1970) Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 19:644–655CrossRefGoogle Scholar
  15. 15.
    JCS Joint Working Group (2014) Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ J 78:2779–2801CrossRefGoogle Scholar
  16. 16.
    Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, STOP-NIDDM Trail Research Group (2002) Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359:2072–2077CrossRefGoogle Scholar
  17. 17.
    Hu Y, Liu W, Huang R, Zhang X (2010) Postchallenge plasma glucose excursions, carotid intima-media thickness, and risk factors for atherosclerosis in Chinese population with type 2 diabetes. Atherosclerosis 210:302–306CrossRefGoogle Scholar
  18. 18.
    Ólafsdóttir AF, Attvall S, Sandgren U, Dahlqvist S, Pivodic A, Skrtic S, Theodorsson E, Lind M (2017) A clinical trial of the accuracy and treatment experience of the flash glucose monitor freestyle libre in adults with type 1 diabetes. Diabetes Technol Ther 19:164–172CrossRefGoogle Scholar
  19. 19.
    Torimoto K, Okada Y, Mori H, Tanaka Y (2013) Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus. Cardiovasc Diabetol 12:1CrossRefGoogle Scholar
  20. 20.
    Ito T, Fujita H, Tani T, Sugiura T, Ohte N (2015) Increased circulating malondialdehyde-modified low-density lipoprotein levels in patients with ergonovine-induced coronary artery spasm. Int J Cardiol 184:475–480CrossRefGoogle Scholar
  21. 21.
    Cosentino F, Hishikawa K, Katusic ZS, Lüscher TF (1997) High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 96:25–28CrossRefGoogle Scholar
  22. 22.
    Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JP (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106:987–992CrossRefGoogle Scholar
  23. 23.
    Takei Y, Tomiyama H, Tanaka N, Yamashina A (2007) Close relationship between sympathetic activation and coronary microvascular dysfunction during acute hyperglycemia in subjects with atherosclerotic risk factors. Circ J 71:202–206CrossRefGoogle Scholar
  24. 24.
    Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D (2008) Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57:1349–1354CrossRefGoogle Scholar
  25. 25.
    Otsuka A, Azuma K, Iesaki T, Sato F, Hirose T, Shimizu T, Tanaka Y, Daida H, Kawamori R, Watada H (2005) Temporary hyperglycaemia provokes monocyte adhesion to endothelial cells in rat thoracic aorta. Diabetologia 48:2667–2674CrossRefGoogle Scholar
  26. 26.
    Azuma K, Kawamori R, Toyofuku Y, Kitahara Y, Sato F, Shimizu T, Miura K, Mine T, Tanaka Y, Mitsumata M, Watada H (2006) Repetitive fluctuations in blood glucose enhance monocyte adhesion to the endothelium of rat thoracic aorta. Arterioscler Thromb Vasc Biol 26:2275–2280CrossRefGoogle Scholar
  27. 27.
    Gresele P, Guglielmini G, De Angelis M, Ciferri S, Ciofetta M, Falcinelli E, Lalli C, Ciabattoni G, Davì G, Bolli GB (2003) Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus. J Am Coll Cardiol 41:1013–1020CrossRefGoogle Scholar
  28. 28.
    Sueda S, Kohno H, Fukuda H, Watanabe K, Ochi N, Kawada H, Uraoka T (2003) Limitations of medical therapy in patients with pure coronary spastic angina. Chest 123:380–386CrossRefGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  • Tsuyoshi Ito
    • 1
    Email author
  • Taku Ichihashi
    • 1
  • Hiroshi Fujita
    • 1
  • Tomonori Sugiura
    • 1
  • Junki Yamamoto
    • 1
  • Shuichi Kitada
    • 1
  • Kosuke Nakasuka
    • 1
  • Yu Kawada
    • 1
  • Nobuyuki Ohte
    • 1
  1. 1.Department of Cardio-Renal Medicine and HypertensionNagoya City University Graduate School of Medical SciencesNagoyaJapan

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