Consequences of Iatrogenic Insulin Resistance and How to Mitigate These Risks

Wood M, Bando H and Ebe K

Published on: 2024-11-29

Abstract

Understanding of diabetes pathophysiology has progressed tremendously since insulin was first administered in 1922. Currently there is a plethora of known acute and chronic adverse effects associated with insulin use in type 1 diabetes (T1D) patients. Iatrogenic insulin resistance (IIR) is an inescapable consequence of peripheral insulin delivery (PID). Endogenous insulin is normally secreted into the portal vein at a concentration that is more than 3 times the systemic concentration. About half of the insulin excreted by the pancreas is extracted by the liver where it plays an important role in hepatic glucose regulation. The liver is bypassed in PID, disrupting the normal portal vein to systemic insulin ratio. Subsequently, supraphysiologic levels of insulin are required for glucose disappearance which is shifted more to the peripheral tissue. Despite over six decades of research suggesting that PID induced hyperinsulinemia results in insulin resistance (IR) in T1D, IIR is still underappreciated among clinicians. Understanding IIR is imperative to clinical judgment when designing diabetes therapeutic plans.