The clinical impact of serum 1,5-anhydro-D-glucitol levels on coronary artery calcification and adverse outcomes assessed by coronary optical coherence tomography in diabetic patients

Abstract

Background: Serum 1,5-anhydro-D-glucitol (1,5-AG) is a novel biomarker for short-term glycemic status and postprandial hyperglycemia. The association between serum 1,5-AG levels and coronary artery calcification (CAC) through a quantitative assessment using optical coherence tomography (OCT) is unclear. We aimed to evaluate this association using OCT in patients with diabetes mellitus (DM).

Methods: From June 2016 to December 2019, we prospectively enrolled 256 patients who underwent OCT-guided percutaneous coronary intervention (PCI). Half of the patients had diabetes. Patients were followed up for a mean period of 1.8 ± 0.8 years (median: 2.2 years). The relative calcium index and relative lipid core index measured by quantitative OCT analysis were used to evaluate the intra-plaque calcium and lipid levels of culprit plaques. We also analyzed the correlation between serum 1,5-AG levels and long-term major adverse cardiovascular events.

Results: Serum 1,5-AG levels were significantly lower in diabetic patients than in non-diabetic patients (DM vs. non-DM: 55.6 ± 27.9 μg/mL vs. 63.7 ± 26.1 μg/mL, p = 0.016), and lower in fibrocalcified lesions than in fibrotic or fibrolipidic lesions (fibrocalcified vs. fibrotic or fibrolipidic: 42.8 ± 19.1 vs. 72.9 ± 25.2 or 66.4 ± 27.5 μg/mL, p < 0.001, respectively). In addition, we found a significant inverse correlation between serum 1,5-AG levels and relative calcium index (r = -0.729, p < 0.001). In multivariate Cox regression analysis, low serum 1,5-AG level was identified as an independent predictor for major adverse cardiovascular events in diabetic patients (p = 0.043), but not in non-diabetic patients (p = 0.748) after adjusting for age and sex.

Conclusion: This study revealed that low serum 1,5-AG levels were associated with an increased risk of CAC as assessed by OCT, especially in diabetic patients. Low serum 1,5-AG levels may predict future major adverse cardiovascular events in diabetic patients undergoing OCT-guided PCI.

Keywords: 1; 1,5-AG; 5-anhydro-D-glucitol; coronary artery calcification; diabetes mellitus; optical coherence tomography.

FIGURE 1

Study flow.

FIGURE 2

Serum 1,5-AG levels were stratified by DM and plaque characteristics. p-values by analysis of variance (ANOVA and Chi-square) were shown. Post hoc comparisons were performed by the Bonferroni test. (A) Serum 1,5-AG level was significantly lower in DM patients than in non-DM patients (DM vs. non-DM: 55.6 ± 27.9 μg/mL vs. 63.7 ± 26.1 μg/mL, p = 0.016). (B) Serum 1,5-AG levels were significantly lower in fibrocalcified lesions than in fibrotic or fibrolipidic lesions (fibrocalcified vs. fibrotic or fibrolipidic: 42.8 ± 19.1 vs. 72.9 ± 25.2 or 66.4 ± 27.5 μg/mL, p < 0.001). 1,5-AG, 1,5-anhydro-D-glucitol, DM, diabetes mellitus.

FIGURE 3

Correlations between serum 1,5-AG level and relative calcium index. 1,5-AG, 1,5-anhydro-D-glucitol.

FIGURE 4

Three representative cases with different correlations between OCT-detected plaque type and serum 1,5-AG levels. (A,B) A 68-year-old man with hypertension and stable angina is shown to have a lesion in the middle LAD on angiography. OCT examination shows a fibrotic lesion. The serum 1,5-AG level is 102.3 μg/mL. (C,D) A 72-year-old man with DM and NSTEMI is shown to have a severe lesion in the middle RCA on angiography. OCT examination shows a fibrolipidic lesion. The serum 1,5-AG level is 77.4 μg/mL. (E,F) A 68-year-old man with DM and stable angina is shown to have a diffuse lesion in the proximal LCX on angiography. OCT examination shows a fibrocalcified lesion. The serum 1,5-AG level is 35.2 μg/mL. 1,5-AG, 1,5-anhydro-D-glucitol; DM, diabetes mellitus; LAD, left anterior descending artery; LCX, left circumflex artery; NSTEMI, non ST-segment elevation myocardial infarction; OCT, optical coherence tomography; RCA, right coronary artery.