Mild Physiologic Hyperglycemia Induces Hepatic Insulin Resistance in Healthy Normal Glucose-Tolerant Participants

Chronic hyperglycemia worsens skeletal muscle insulin resistance and b-cell function. However, the effect of sustained physiologic hyperglycemia on hepatic insulin sensitivity is not clear. Objective: To examine the effect of sustained physiologic hyperglycemia (similar to that observed in patients with type 2 diabetes) on endogenous (primarily reflecting hepatic) glucose production (EGP) in healthy individuals. Design: Volunteers participated in a three-step hyperinsulinemic (10, 20, 40 mU/m2 per minute) euglycemic clamp before and after a 48-hour glucose infusion to increase plasma glucose concentration by ;40 mg/dL above baseline. EGP was measured with 3-3H-glucose before and after chronic glucose infusion. Participants: Sixteen persons with normal glucose tolerance [eight with and eight without a family history (FH) of diabetes] participated in the study.