title: Effects of daily glucose fluctuations on the healing response to everolimus-eluting stent implantation as assessed using continuous glucose monitoring and optical coherence tomography.
abstract: BACKGROUND
  Several studies have revealed that glucose fluctuations provoke oxidative stress that leads to endothelial cell dysfunction, progression of coronary atherosclerosis, and plaque vulnerability. However, little is known regarding their effect on neointimal growth after stenting in patients with coronary artery disease (CAD). We aimed to investigate the effects of glucose fluctuations on neointimal growth after everolimus-eluting stent (EES) implantation.
  
  
  METHODS
  This study examined 50 patients who underwent a 9-month follow-up using optical coherence tomography (OCT) after EES implantation. Glucose fluctuation was expressed as the mean amplitude of glycemic excursion (MAGE), and was determined via continuous glucose monitoring before stenting. At the OCT follow-up, we evaluated the percentage of uncovered struts and three-dimensional uniformity of neointimal distribution by calculating the mean neointimal thickness (NIT) within 360 equally-spaced radial sectors for every 1-mm cross-sectional OCT analysis, and assessed the incidence of major adverse cardiovascular events (MACE).
  
  
  RESULTS
  We evaluated 60 lesions in 50 patients. Linear mixed effect models were used to explore the influence of different variables on variability in NIT and the percentage of uncovered struts and to adjust for covariates. Univariate analysis showed that MAGE was most strongly correlated with the previously mentioned OCT measurements (coefficient β ± standard error = 0.267 ± 0.073 and 0.016 ± 0.003, t = 3.668 and 6.092, both P < 0.001, respectively). In multivariate analysis, MAGE had the strongest effect on variability in NIT (coefficient β ± standard error = 0.239 ± 0.093, P = 0.014) and the percentage of uncovered struts (coefficient β ± standard error = 0.019 ± 0.004, P < 0.001). Five lesions in four patients required target lesion revascularization (10.0 %) at a mean duration of 9 months after EES implantation. Compared to non-MACE cases, cases of MACE exhibited a significantly higher MAGE (99 vs. 68; P = 0.004), maximum NIT (580 vs. 330 µm; P = 0.002), and variability in NIT (100 vs. 65; P = 0.007), although there was no significant difference in these groups' HbA1c levels.
  
  
  CONCLUSIONS
  Glucose fluctuation may affect vessel healing after EES implantation in patients with CAD who are receiving lipid-lowering therapy. Therefore, glucose fluctuations may be an important target for secondary prevention after coronary stenting, which is independent of dyslipidemia control.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan. shinke@med.kobe-u.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shinke
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Otake
authors.affiliation: Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Takaya
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Hachidai
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Terashita
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Uzu
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tahara
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Daiji
authors.initials: D
authors.lastname: Kashiwagi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Shinkura
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagasawa
authors.affiliation: Division of Diabetes and Metabolism, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sakaguchi
authors.affiliation: Division of Diabetes and Metabolism, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Division of Diabetes and Metabolism, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects; D054855:Drug-Eluting Stents; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000379:methods
chemical_list: D000068338:Everolimus; D005947:Glucose; D020123:Sirolimus
keywords: Continuous glucose monitoring; Glucose fluctuation; Mean amplitude of glycemic excursion; Optical coherence tomography