Reconsidering Glucocorticoid-Induced Hyperglycemia as a Distinct Pathophysiological Entity: Implications for Inpatient Glycemic Protocols in Non-Diabetic Critically Ill Patients

Abstract

Glucocorticoid-induced hyperglycemia (GIH) has historically been managed under frameworks designed for pre-existing diabetes mellitus, yet mounting evidence suggests this conflation carries significant clinical risk. This study examined the pathophysiological divergence of GIH from type 2 diabetes in 312 non-diabetic critically ill patients receiving systemic corticosteroid therapy across three tertiary care centers. Using continuous glucose monitoring, hyperinsulinemic-euglycemic clamp studies, and β-cell secretory profiling, we characterized unique postprandial glucose excursions and relative insulin resistance patterns specific to GIH. Multivariate regression identified corticosteroid dose, administration timing, and hepatic glucose output as primary modulators. Our findings challenge the universal applicability of standard inpatient glycemic targets and advocate for GIH-specific titration protocols, with observed reductions in hypoglycemic episodes and length-of-stay when tailored interventions were applied.