High glucose fluctuation levels modulate monocyte cytokine expression via oxidative stress mechanism

This study investigated the impact of glycemic variability on cytokine expression (MCP-1, IL-6, TNF-α) and oxidative stress in monocytes, and explored the protective effect of the antioxidant α-lipoic acid (ALA). ‌Human THP-1 monocytes were cultured under four conditions: stable normoglycemia (5 mmol/L), persistent hyperglycemia (20 mmol/L), low-amplitude glucose fluctuation (alternating between 5 and 20 mmol/L), and high-amplitude fluctuation (alternating between 5 and 30 mmol/L). The effects of ALA supplementation were assessed in parallel. ‌Compared to the normoglycemic control, intracellular oxidative stress was significantly elevated in all hyperglycemic groups (p < 0.05), with the highest levels observed in the high-amplitude fluctuation group (p < 0.05 vs. low-amplitude fluctuation). Both sustained and fluctuating hyperglycemia upregulated the mRNA and protein expression of MCP-1, IL-6, and TNF-α (p < 0.05 vs. normal control). ALA treatment markedly suppressed this cytokine overexpression (p < 0.05). Furthermore, ALA significantly attenuated oxidative stress (p < 0.05) and restored antioxidant enzyme activity across all hyperglycemic groups. ‌In this monocyte model, high-amplitude glucose fluctuations induced greater oxidative stress and inflammatory cytokine dysregulation than sustained hyperglycemia, with the severity correlating with the fluctuation magnitude. The antioxidant α-lipoic acid attenuated these effects, suggesting a potential role for oxidative stress in this process. Further research is needed to elucidate the precise causal mechanisms linking glucose fluctuations to monocyte dysfunction.