Impact of renal function on the underlying pathophysiology of coronary plaque composition in patients with type 2 diabetes mellitus

BACKGROUND Both the progression of diabetic kidney disease and increased glycemic variability play important roles in the pathogenesis of coronary plaque formation via inflammatory pathways in patients with type 2 diabetes mellitus (T2DM). Therefore we evaluated the role of renal function in the contributory effects of blood glucose fluctuations and blood levels of inflammatory cytokine concentrations on the tissue characteristics of coronary plaques in patients with T2DM. METHODS We prospectively enrolled 71 T2DM patients (mean age: 68 ± 9, male 79%) with 153 coronary artery lesions. Patients were divided into 2 groups according to their estimated glomerular filtration rate (eGFR) levels: Group 1 (≥ 60 mL/min/1.73 m2, n = 40) and Group 2 (< 60 mL/min/1.73 m2, n = 31). All patients underwent continuous glucose monitoring (CGM) for 120 h and the mean amplitude of glycemic excursions (MAGE) was calculated. Serum tumor necrosis factor (TNF)-α was also measured. In addition, gray-scale coronary intravascular ultrasound (IVUS) and iMap-IVUS were performed in the coronary lesions with < 50% luminal reduction. RESULTS In Group 1, MAGE correlated with percent lipidic volume (%LV) (r = 0.477, p = 0.002). In this group, stepwise multivariate linear regression analyses showed that only MAGE was independently associated with %LV (β = 0.477, p = 0.002). In contrast, in Group 2, only serum TNF-α correlated with percent fibrotic volume (%FV) (r = - 0.471, p = 0.007), %LV (r = 0.496, p = 0.005) and percent necrotic volume (%NV) (r = 0.426, p = 0.017). In this group, stepwise multivariate linear regression analyses showed that only serum TNF-α was independently associated with each tissue characteristic (%FV β = - 0.471 and p = 0.007, %LV β = 0.496 and p = 0.005, %NV: β = 0.426 and p = 0.017). CONCLUSIONS In T2DM patients, the tissue characteristics of coronary plaques were associated with MAGE in patients with eGFR ≥ 60 mL/min/1.73 m2 and with serum TNF-α in those with eGFR < 60 mL/min/1.73 m2.