Increase in soluble RAGE following intensive insulin therapy is associated with β‐cell functional improvement and glycemic remission in newly diagnosed type 2 diabetes

AIMS: To investigate the dynamic changes of soluble receptor for advanced glycation end products (sRAGE) and its relationship with β-cell function and glycemic remission in newly diagnosed type 2 diabetes mellitus (T2DM) after short-term intensive insulin therapy (SIIT). METHODS: A total of 98 drug-naive patients with newly diagnosed T2DM underwent a two-week SIIT and were followed for 16 weeks. Serum sRAGE was measured at baseline, after SIIT, and at the 1-month follow-up. HOMA-β and HOMA-IR were used to reflect β-cell function and insulin resistance, respectively. Pearson or Spearman correlation coefficients were used to assess the correlations, and logistic regression was applied to evaluate associations between changes in sRAGE (ΔsRAGE) and 16-week glycemic remission, adjusting for potential confounders. RESULTS: sRAGE levels increased significantly after SIIT (P < 0.001) and remained higher at 1 month. The increase in sRAGE after SIIT was positively correlated with the changes in HOMA-β and negatively correlated with changes in HOMA-IR. Participants who achieved glycemic remission had greater ΔsRAGE after SIIT than those who did not (273.9 ± 268.2 vs 76.7 ± 257.7 pg/mL, P = 0.001). In multivariate analysis, ΔsRAGE was independently associated with remission (OR = 1.228 per 100 pg/mL, 95% CI 1.006-1.500, P = 0.044), and the AUC of this model was 0.783 (95% CI 0.690-0.876). CONCLUSIONS: Elevation of sRAGE after SIIT is independently associated with short-term glycemic remission in newly diagnosed T2DM. The increase in sRAGE accompanied by an improvement in β-cell function, suggests that increased sRAGE may reflect a compensatory response during metabolic recovery.