Sex-specific efficacy of curcumin-loaded nanoparticles and insulin for ocular-cardiac complications in type 2 diabetes mice.

Current Type 2 diabetes therapies inadequately address multi-organ complications. We evaluated bivalent nanoparticles encapsulating curcumin, combined with insulin, against diabetic complications. Our data indicate shared pathophysiological mechanisms driving the association between retinal and cardiac injury, specifically systemic inflammation and mitochondrial dysregulation across both organs. Retinal stress (HIF1α, REDD1, VEGF) preceded cardiac remodeling, characterized by lymphangiogenesis (LYVE1, VEGFR3) and impaired PPARα/ PGC1α signaling. Furthermore, we identified a strong pathological correlation between intraocular and systemic blood pressures as an in-vivo physiological readout of widespread vascular dysregulation. While males exhibited an earlier onset, females progressed more rapidly to complications. The combination therapy proved highly effective in both sexes. While females exhibited a more pronounced reduction in systemic inflammation and pathological pressure correlation, males demonstrated robust metabolic and structural preservation. These findings highlight ocular hemodynamics as an early physiological indicator of cardiac complications, supporting this sex-specific nanotherapeutic strategy, combined with insulin, to mitigate diabetic complications.