Contributions of β-Cell Dysfunction and Insulin Resistance to the Pathogenesis of Impaired Glucose Tolerance and Impaired Fasting Glucose

TLDR

Impaired glucose tolerance and impaired fasting glucose are intermediate states between normal glucose tolerance and type 2 diabetes, characterized by distinct populations with partial overlap and differing patterns of insulin resistance and β‑cell dysfunction. The study aims to determine whether the differing metabolic profiles of IFG and IGT necessitate distinct therapeutic strategies to prevent progression to type 2 diabetes. Epidemiological and clinical studies show that IFG is associated with severe hepatic insulin resistance and preserved muscle sensitivity, whereas IGT exhibits marked muscle insulin resistance and mild hepatic resistance, with both conditions displaying reduced early‑phase insulin secretion and IGT additionally having impaired late‑phase secretion.

Abstract

Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are intermediate states in glucose metabolism that exist between normal glucose tolerance and overt diabetes. Epidemiological studies demonstrate that the two categories describe distinct populations with only partial overlap, suggesting that different metabolic abnormalities characterize IGT and IFG. Insulin resistance and impaired β-cell function, the primary defects observed in type 2 diabetes, both can be detected in subjects with IGT and IFG. However, clinical studies suggest that the site of insulin resistance varies between the two disorders. While subjects with IGT have marked muscle insulin resistance with only mild hepatic insulin resistance, subjects with IFG have severe hepatic insulin resistance with normal or near-normal muscle insulin sensitivity. Both IFG and IGT are characterized by a reduction in early-phase insulin secretion, while subjects with IGT also have impaired late-phase insulin secretion. The distinct metabolic features present in subjects with IFG and IGT may require different therapeutic interventions to prevent their progression to type 2 diabetes.