Hepatic Glucose Uptake During Euglycemic Hyperinsulinemia Associates With Glycemia During Oral Glucose Tolerance Test

Abstract

<p><strong>Context: </strong><br></p><p>Postprandial hepatic glycogen synthesis and glycolysis are reduced in hepatic insulin resistance. However, the physiologic interpretation of the reduction in hepatic glucose uptake (GU) during the gold-standard measurement of insulin sensitivity, hyperinsulinemic euglycemic clamp, in insulin resistance is unclear. This is because the peripheral route of glucose and insulin delivery during a clamp study differs greatly from the physiological route. <br></p><p><strong>Objective: </strong><br></p><p>We hypothesized that hepatic GU during hyperinsulinemic euglycemic clamp would predict glycemia during oral glucose tolerance test (OGTT). <br></p><p><strong>Design: </strong><br></p><p>We analyzed cross-sectional data of 120 individuals (70 men and 50 women) who did not have diabetes from the CMgene study cohort. Hepatic GU was measured with [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) and positron emission tomography. Results: In a multiple regression analysis, hepatic GU, endogenous glucose production, insulin secretion capacity, and serum triglycerides predicted OGTT glucose area under the curve (<em>P</em> for all <.05), whereas skeletal muscle GU, the antilipolytic insulin index, and insulin clearance were not statistically significant predictors (<em>P</em> > .05). <br></p><p><strong>Conclusions: </strong><br></p><p>Hepatic GU measured during hyperinsulinemic euglycemic clamp is an independent predictor of OGTT glucose area under the curves even when accounting for well-known other factors affecting glycemic control. This finding supports the idea that insulin-mediated hepatic GU, and more broadly, first-pass glucose extraction, have a meaningful contribution to glycemic control. Thus, this measurement provides useful information about hepatic insulin sensitivity in the more physiologic conditions of the OGTT which may be useful when studying the pathophysiology of impaired glucose tolerance and when evaluating potential treatments for impaired glycemic control.<br></p>