Model-Based Assessment of Hepatic and Extrahepatic Insulin Clearance from Short Insulin-Modified IVGTT in Women with a History of Gestational Diabetes.

Abstract

Insulin clearance is an integral component of insulin metabolism. Yet, little is known about separate contribution of hepatic and extrahepatic insulin clearance in type 2 diabetes and in high-risk populations, such as women who experienced gestational diabetes mellitus (pGDM). A model-based method was recently proposed to assess both contributions from 3-hour insulin-modified intravenous glucose tolerance test (IM-IVGTT); the aim of this study was to assess the reliability of short (1 hour) IM-IVGTT in the application of such model-based method and to evaluate the role of the two contributions in determining insulin clearance in pGDM. A total of 115 pGDM women and 41 who remained healthy during pregnancy (CNT) were analyzed early postpartum and underwent a 3-hour IMIVGTT. Peripheral insulin clearance (CLP), hepatic fractional extraction (FEL) and extrahepatic distribution volume (VP) were estimated by performing a best-fit procedure on insulin IMIVGTT data considering firstly the overall 3-hour duration and then limiting data to 1 hour. Results showed no significant difference in parameter values between the 3-hour and the 1-hour IM-IVGTT. Comparison between pGDM and CNT (1-hour) showed no significant difference in CLp (0.23 [0.29] vs. 0.27 [0.43] L·min-1; p=0.64), FEL (50.2 [15.1] vs. 50.9 [11.7] %; p=0.63) and VP (2.01 [2.99] vs. 2.70 [4.00] L; p=0.92). In conclusion, short IM-IVGTT provides a reliable assessment of hepatic and extrahepatic insulin clearance through such model-based method. Its application to the study of pGDM women showed no alteration in hepatic and extrahepatic contributions with respect to women who had a healthy pregnancy.Clinical Relevance- This study proves the reliability of short (1 hour) IM-IVGTT to assess hepatic and extrahepatic insulin clearance in women who experienced gestational diabetes.