Beyond Glycemia in T1D: Insulin Resistance and Multiorgan Injury in Type 1 Diabetes-Part 2.

Insulin resistance (IR) in type 1 diabetes drives multiorgan injury that extends far beyond glycemic dysregulation. Subcutaneous insulin delivery reverses the portal-to-peripheral insulin gradient, downregulating peripheral insulin receptors and promoting ectopic lipogenesis. Excess insulin drives concurrent hepatorenal injury by promoting metabolic dysfunction-associated steatotic liver disease and IR in the liver while inducing hyperfiltration and increased vascular permeability in the kidneys. Visceral adiposity and atherogenic dyslipidemia accelerate vascular aging, with subclinical cardiac dysfunction occurring in adolescents. We advocate shifting from glucocentric care to a holistic Cardiovascular-Kidney-Metabolic framework incorporating insulin sensitivity estimation, steatosis and cardiovascular screening, and targeted adjunctive pharmacotherapy.