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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2020

Open Access 01-12-2020 | Type 2 Diabetes | Original investigation

Visit-to-visit HbA1c variability is associated with in-stent restenosis in patients with type 2 diabetes after percutaneous coronary intervention

Authors: Chen Die Yang, Ying Shen, Lin Lu, Zhen Kun Yang, Jian Hu, Rui Yan Zhang, Wei Feng Shen, Feng Hua Ding, Xiao Qun Wang

Published in: Cardiovascular Diabetology | Issue 1/2020

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Abstract

Background

Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation.

Methods

We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR.

Results

From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P < 0.001), and this trend was more prominent in patients with optimal glycemic control (HbA1c ≤ 7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI 1.14–7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings.

Conclusions

This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation.
Trial registration NCT02089360: NCT
Appendix
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Literature
1.
Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus—mechanisms, management, and clinical considerations. Circulation. 2016;133(24):2459–502.PubMedPubMedCentralCrossRef
2.
Natali A, Vichi S, Landi P, Severi S, L’Abbate A, Ferrannini E. Coronary atherosclerosis in Type II diabetes: angiographic findings and clinical outcome. Diabetologia. 2000;43(5):632–41.PubMedCrossRef
3.
Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339(4):229–34.PubMedCrossRef
4.
Shen Y, Ding FH, Dai Y, Wang XQ, Zhang RY, Lu L, Shen WF. Reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion. Cardiovasc Diabetol. 2018;17(1):26.PubMedPubMedCentralCrossRef
5.
West NE, Ruygrok PN, Disco CM, Webster MW, Lindeboom WK, O’Neill WW, Mercado NF, Serruys PW. Clinical and angiographic predictors of restenosis after stent deployment in diabetic patients. Circulation. 2004;109(7):867–73.PubMedCrossRef
6.
Qin Z, Zhou K, Li YP, Wang JL, Cheng WJ, Hu CP, Shi C, He H, Zhou YJ. Remnant lipoproteins play an important role of in-stent restenosis in type 2 diabetes undergoing percutaneous coronary intervention: a single-centre observational cohort study. Cardiovasc Diabetol. 2019;18(1):11.PubMedPubMedCentralCrossRef
7.
Fröbert O, Lagerqvist B, Carlsson J, Lindbäck J, Stenestrand U, James SK. Differences in restenosis rate with different drug-eluting stents in patients with and without diabetes mellitus. SCAAR. 2009;53(18):1660–7.
8.
Gilbert J, Raboud J, Zinman B. Meta-analysis of the effect of diabetes on restenosis` rates among patients receiving coronary angioplasty stenting. Diabetes Care. 2004;27(4):990–4.PubMedCrossRef
9.
Mathew V, Gersh BJ, Williams BA, Laskey WK, Willerson JT, Tilbury RT, Davis BR, Holmes DR Jr. Outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention in the current era: a report from the Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) trial. Circulation. 2004;109(4):476–80.PubMedCrossRef
10.
Corpus RA, George PB, House JA, Dixon SR, Ajluni SC, Devlin WH, Timmis GC, Balasubramaniam M, O’Neill WW. Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention. J Am Coll Cardiol. 2004;43(1):8–14.PubMedCrossRef
11.
Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, Skatchkov M, Thaiss F, Stahl RA, Warnholtz A, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res. 2001;88(2):E14–22.PubMedCrossRef
12.
Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes. 2000;49(11):1939–45.PubMedCrossRef
13.
Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004;63(4):582–92.PubMedCrossRef
14.
Kassaian SE, Goodarzynejad H, Boroumand MA, Salarifar M, Masoudkabir F, Mohajeri-Tehrani MR, Pourhoseini H, Sadeghian S, Ramezanpour N, Alidoosti M, et al. Glycosylated hemoglobin (HbA1c) levels and clinical outcomes in diabetic patients following coronary artery stenting. Cardiovasc Diabetol. 2012;11:82.PubMedPubMedCentralCrossRef
15.
Pu Z, Lai L, Yang X, Wang Y, Dong P, Wang D, Xie Y, Han Z. Acute glycemic variability on admission predicts the prognosis in hospitalized patients with coronary artery disease: a meta-analysis. Endocrine. 2020;67(3):526–34.PubMedCrossRef
16.
Gerbaud E, Darier R, Montaudon M, Beauvieux MC, Coffin-Boutreux C, Coste P, Douard H, Ouattara A, Catargi B. Glycemic variability is a powerful independent predictive factor of midterm major adverse cardiac events in patients with diabetes with acute coronary syndrome. Diabetes Care. 2019;42(4):674–81.PubMedCrossRef
17.
Takahashi H, Iwahashi N, Kirigaya J, Kataoka S, Minamimoto Y, Gohbara M, Abe T, Okada K, Matsuzawa Y, Konishi M, et al. Glycemic variability determined with a continuous glucose monitoring system can predict prognosis after acute coronary syndrome. Cardiovasc Diabetol. 2018;17(1):116.PubMedPubMedCentralCrossRef
18.
Besch G, Pili-Floury S, Morel C, Gilard M, Flicoteaux G, Salomon du Mont L, Perrotti A, Meneveau N, Chocron S, Schiele F et al: Impact of post-procedural glycemic variability on cardiovascular morbidity and mortality after transcatheter aortic valve implantation: a post hoc cohort analysis. Cardiovasc Diabetol 2019, 18(1):27.
19.
Kilpatrick ES, Rigby AS, Atkin SL. A1C variability and the risk of microvascular complications in type 1 diabetes: data from the diabetes control and complications trial. Diabetes Care. 2008;31(11):2198–202.PubMedPubMedCentralCrossRef
20.
Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Morano S, Cavalot F, Lamacchia O, Laviola L. HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study. Diabetes Care. 2013;36(8):2301–10.PubMedPubMedCentralCrossRef
21.
Hirakawa Y, Arima H, Zoungas S, Ninomiya T, Cooper M, Hamet P, Mancia G, Poulter N, Harrap S, Woodward M, et al. Impact of visit-to-visit glycemic variability on the risks of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial. Diabetes Care. 2014;37(8):2359–65.PubMedCrossRef
22.
Orsi E, Solini A, Bonora E, Fondelli C, Trevisan R, Vedovato M, Cavalot F, Gruden G, Morano S, Nicolucci A, et al. Haemoglobin A1c variability is a strong, independent predictor of all-cause mortality in patients with type 2 diabetes. Diabetes Obes Metab. 2018;20(8):1885–93.PubMedCrossRef
23.
Xia J, Xu J, Hu S, Hao H, Yin C, Xu D. Impact of glycemic variability on the occurrence of periprocedural myocardial infarction and major adverse cardiovascular events (MACE) after coronary intervention in patients with stable angina pectoris at 6 months follow-up. Clin Chim Acta. 2017;471:196–200.PubMedCrossRef
24.
Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998, 15(7):539–53.
25.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.PubMedPubMedCentralCrossRef
26.
Yang CD, Shen Y, Lu L, Ding FH, Yang ZK, Zhang RY, Shen WF, Jin W, Wang XQ. Insulin resistance and dysglycemia are associated with left ventricular remodeling after myocardial infarction in non-diabetic patients. Cardiovasc Diabetol. 2019;18(1):100.PubMedPubMedCentralCrossRef
27.
Echouffo-Tcheugui JB, Zhao S, Brock G, Matsouaka RA, Kline D, Joseph JJ. Visit-to-visit glycemic variability and risks of cardiovascular events and all-cause mortality: the ALLHAT Study. Diabetes Care. 2019;42(3):486–93.PubMedPubMedCentralCrossRef
28.
Marfella R, Sardu C, Calabrò P, Siniscalchi M, Minicucci F, Signoriello G, Balestrieri ML, Mauro C, Rizzo MR, Paolisso G, et al. Non-ST-elevation myocardial infarction outcomes in patients with type 2 diabetes with non-obstructive coronary artery stenosis: effects of incretin treatment. Diabetes Obes Metab. 2018;20(3):723–9.PubMedCrossRef
29.
Marfella R, Sardu C, Balestrieri ML, Siniscalchi M, Minicucci F, Signoriello G, Calabrò P, Mauro C, Pieretti G, Coppola A, et al. Effects of incretin treatment on cardiovascular outcomes in diabetic STEMI-patients with culprit obstructive and multivessel non obstructive-coronary-stenosis. Diabetology & metabolic syndrome. 2018;10:1.CrossRef
30.
Elezi S, Kastrati A, Pache J, Wehinger A, Hadamitzky M, Dirschinger J, Neumann FJ, Schomig A. Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement. J Am Coll Cardiol. 1998;32(7):1866–73.PubMedCrossRef
31.
Ike A, Nishikawa H, Shirai K, Mori K, Kuwano T, Fukuda Y, Takamiya Y, Yanagi D, Kubota K, Tsuchiya Y, et al. Impact of glycemic control on the clinical outcome in diabetic patients with percutaneous coronary intervention–from the FU-registry. Circ J. 2011;75(4):791–9.PubMedCrossRef
32.
Monnier L, Colette C. Contributions of fasting and postprandial glucose to hemoglobin A1c. Endocrine Pract. 2006;12(Suppl 1):42–6.CrossRef
33.
Wadén J, Forsblom C, Thorn LM, Gordin D, Saraheimo M, Groop P-H. A1C variability predicts incident cardiovascular events, microalbuminuria, and overt diabetic nephropathy in patients with type 1 diabetes. Diabetes. 2009;58(11):2649–55.PubMedPubMedCentralCrossRef
34.
Critchley JA, Carey IM, Harris T, DeWilde S, Cook DG. Variability in glycated hemoglobin and risk of poor outcomes among people with type 2 diabetes in a large primary care cohort study. Diabetes Care. 2019;42(12):2237–46.PubMedCrossRef
35.
Su G, Mi SH, Tao H, Li Z, Yang HX, Zheng H, Zhou Y, Tian L. Impact of admission glycemic variability, glucose, and glycosylated hemoglobin on major adverse cardiac events after acute myocardial infarction. Diabetes Care. 2013;36(4):1026–32.PubMedPubMedCentralCrossRef
36.
Sun J, Xu Y, Dai Z, Sun Y. Intermittent high glucose stimulate MCP-l, IL-18, and PAI-1, but inhibit adiponectin expression and secretion in adipocytes dependent of ROS. Cell Biochem Biophys. 2009;55(3):173–80.PubMedCrossRef
37.
Sardu C, Barbieri M, Balestrieri ML, Siniscalchi M, Paolisso P, Calabrò P, Minicucci F, Signoriello G, Portoghese M, Mone P, et al. Thrombus aspiration in hyperglycemic ST-elevation myocardial infarction (STEMI) patients: clinical outcomes at 1-year follow-up. Cardiovasc Diabetol. 2018;17(1):152.PubMedPubMedCentralCrossRef
38.
D’Onofrio N, Sardu C, Paolisso P, Minicucci F, Gragnano F, Ferraraccio F, Panarese I, Scisciola L, Mauro C, Rizzo MR, et al. MicroRNA-33 and SIRT1 influence the coronary thrombus burden in hyperglycemic STEMI patients. J Cell Physiol. 2020;235(2):1438–52.PubMedCrossRef
39.
Marfella R, Rizzo MR, Siniscalchi M, Paolisso P, Barbieri M, Sardu C, Savinelli A, Angelico N, Del Gaudio S, Esposito N, et al. Peri-procedural tight glycemic control during early percutaneous coronary intervention up-regulates endothelial progenitor cell level and differentiation during acute ST-elevation myocardial infarction: effects on myocardial salvage. Int J Cardiol. 2013;168(4):3954–62.PubMedCrossRef
40.
Sasso FC, Pafundi PC, Marfella R, Calabrò P, Piscione F, Furbatto F, Esposito G, Galiero R, Gragnano F, Rinaldi L, et al. Adiponectin and insulin resistance are related to restenosis and overall new PCI in subjects with normal glucose tolerance: the prospective AIRE Study. Cardiovasc Diabetol. 2019;18(1):24.PubMedPubMedCentralCrossRef
41.
Kohnert KD, Augstein P, Zander E, Heinke P, Peterson K, Freyse EJ, Hovorka R, Salzsieder E. Glycemic variability correlates strongly with postprandial beta-cell dysfunction in a segment of type 2 diabetic patients using oral hypoglycemic agents. Diabetes Care. 2009;32(6):1058–62.PubMedPubMedCentralCrossRef
42.
Torimoto K, Okada Y, Mori H, Tanaka Y. Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus. Cardiovasc Diabetol. 2013;12:1.PubMedPubMedCentralCrossRef
43.
Sardu C, Paolisso P, Sacra C, Mauro C, Minicucci F, Portoghese M, Rizzo MR, Barbieri M, Sasso FC, D’Onofrio N, et al. Effects of metformin therapy on coronary endothelial dysfunction in patients with prediabetes with stable angina and nonobstructive coronary artery stenosis: the CODYCE multicenter prospective study. Diabetes Care. 2019;42(10):1946–55.PubMedCrossRef
44.
Kitta Y, Nakamura T, Kodama Y, Takano H, Umetani K, Fujioka D, Saito Y, Kawabata K, Obata JE, Ichigi Y, et al. Endothelial vasomotor dysfunction in the brachial artery is associated with late in-stent coronary restenosis. J Am Coll Cardiol. 2005;46(4):648–55.PubMedCrossRef
45.
Lafont A, Durand E, Samuel JL, Besse B, Addad F, Lévy BI, Desnos M, Guérot C, Boulanger CM. Endothelial dysfunction and collagen accumulation: two independent factors for restenosis and constrictive remodeling after experimental angioplasty. Circulation. 1999;100(10):1109–15.PubMedCrossRef
46.
Kilpatrick ES, Rigby AS, Atkin SL. The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care. 2006;29(7):1486–90.PubMedCrossRef
Metadata
Title
Visit-to-visit HbA1c variability is associated with in-stent restenosis in patients with type 2 diabetes after percutaneous coronary intervention
Authors
Chen Die Yang
Ying Shen
Lin Lu
Zhen Kun Yang
Jian Hu
Rui Yan Zhang
Wei Feng Shen
Feng Hua Ding
Xiao Qun Wang
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Type 2 Diabetes
Published in
Cardiovascular Diabetology / Issue 1/2020
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-020-01111-7

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