Association of sRAGE with Inflammatory Markers and Insulin Resistance across A Spectrum of T2DM Mellitus, Prediabetes, and Healthy Controls

Background: Recent research on type 2 diabetes (T2DM) has linked the mediation of receptors for advanced glycation end products (RAGE) to underlying inflammation.However, studies regarding the role of soluble RAGE (sRAGE) in prediabetes and diabetes remain sparse.Aim: To compare serum sRAGE, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) levels in T2DM, prediabetes, and controls and to correlate sRAGE with inflammatory markers and insulin resistance.Materials and methods: Based on fasting plasma glucose and HbA1c values, 105 subjects aged 25-55 years were categorized into T2DM, prediabetes, and control groups.Serum sRAGE, IL-6, and hsCRP levels were estimated using sandwich enzyme-linked immunosorbent assay (ELISA), and insulin resistance was computed using the HOMA2-IR calculator.Statistical analysis was performed in SPSS version 20 employing ANOVA for intergroup mean comparisons and Pearson's correlation for correlation analysis.Results: Serum sRAGE levels were significantly decreased in T2DM (4.45 1.06 ng/mL; p < 0.001) as compared to controls (5.65 1.32 ng/mL).IL-6 and hsCRP were increased in the diabetes and prediabetes groups (p < 0.05).Soluble RAGE correlated inversely with inflammatory markers, insulin resistance, and glycemic indices in the diabetes and prediabetes groups (p < 0.05).Conclusion: Soluble RAGE is generally considered protective against diseases originating from RAGE activation.Thus, its decreased levels in diabetics could be associated with disease progression.Soluble RAGE levels correlated inversely with the inflammatory markers and IR suggesting its possible role as marker of vascular inflammation in diabetes.Elevated levels of cardiovascular disease (CVD) risk markers, like IL-6 and hsCRP, and their strong correlation of these inflammatory markers with glycemic indices and IR even at the preclinical stage predisposes them to an increased risk of CVD.Clinical significance: Elevated CVD risk markers highlight an increased risk of CVD even at the preclinical stage of diabetes.The strong correlation between sRAGE and inflammatory markers in our study highlights its role as a novel biomarker for vascular inflammation.