Inflammation and Insulin Resistance in Diabetic Chronic Coronary Syndrome Patients

Abstract

Limited evidence exists on the combined and mediating effects of systemic inflammation on the association between insulin resistance and cardiovascular events in patients with diabetes and chronic coronary syndrome (CCS). This secondary analysis of a multicenter prospective cohort included 4419 diabetic CCS patients. Triglyceride-glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) were applied to evaluate insulin resistance and systemic inflammation, respectively. The primary endpoint was major adverse cardiac event (MACE). Associations of TyG and hsCRP with cardiovascular events were estimated using Cox regression. A mediation analysis was performed to assess whether hsCRP mediates the relationship between TyG and cardiovascular events. Within a median 2.1-year follow-up period, 405 MACEs occurred. Patients with high levels of TyG and hsCRP experienced the highest MACE risk (hazard ratio = 1.82, 95% confidence interval: 1.24-2.70, p = 0.002) compared to individuals with low levels of both markers. HsCRP significantly mediated 14.37% of the relationship between TyG and MACE (p < 0.001). In diabetic CCS patients, insulin resistance and systemic inflammation synergically increased the risk of cardiovascular events, and systemic inflammation partially mediated the association between insulin resistance and clinical outcomes. Combining TyG and hsCRP can help identify high-risk patients. Controlling inflammation in patients with insulin resistance may bring added benefits.

Keywords: cardiac event; chronic coronary syndrome; diabetes; high-sensitivity C-reactive protein; inflammation; insulin resistance; mediation analysis; triglyceride–glucose index.

Figure 1

Study flowchart. Abbreviations: FBG, fasting blood glucose; H, high; hsCRP, high-sensitivity C-reactive protein; L, low; PROMISE, the PRospective Observational Multi-center cohort for ISchemic and hEmorrhage risk in coronary artery disease patients; TyG, triglyceride–glucose index.

Figure 2

Kaplan–Meier analysis of patients grouped by TyG and hsCRP levels. Survival curves for MACE (A), all-cause death (B), cardiac death (C), myocardial infarction (D), and any revascularization (E). Abbreviations: H, high; hsCRP, high-sensitivity C-reactive protein; L, low; MACE, major adverse cardiac event; TyG, triglyceride–glucose index.

Figure 3

Subgroup analysis for the association of TyG and hsCRP with MACE. Red indicates statistical significance, while black indicates statistical non-significance. Adjusted for age (continuous), sex, BMI (continuous), smoking history, peripheral artery disease, chronic kidney disease, prior myocardial infarction, prior stroke, prior revascularization, low-density lipoprotein cholesterol ≤ 1.8 mmol/L, left ventricular ejection fraction < 40%, left main stem/three-vessel disease, synergy between percutaneous coronary intervention with Taxus and cardiac surgery score (categorical), percutaneous coronary intervention status, aspirin adherence, statin adherence. Abbreviations: BMI, body mass index; CI, confidence interval; H, high; HR, hazard ratio; hsCRP, high-sensitivity C-reactive protein; L, low; MACE, major adverse cardiac event; PCI, percutaneous coronary intervention; TyG, triglyceride–glucose index.

Figure 4

Mediation effect of hsCRP on the association between TyG and cardiovascular events. (A) Directed acyclic graph; (B) mediation analysis for MACE; (C) mediation analysis for all-cause death; (D) mediation analysis for cardiac death. Abbreviations: ACME, average causal mediation effect; ADE, average direct effect; hsCRP, high-sensitivity C-reactive protein; MACE, major adverse cardiac event; TyG, triglyceride–glucose index.