Evaluation of postprandial total triglycerides within the TIGG model for characterizing postprandial response of glucose, insulin, and GLP-1.

Autor: Leohr J; Department of Pharmacokinetics/Pharmacodynamics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA., Kjellsson MC; Pharmacometrics Research Group, Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2023 Oct; Vol. 12 (10), pp. 1529-1540. Date of Electronic Publication: 2023 Sep 04.
DOI: 10.1002/psp4.13030
Abstrakt: The TIGG model is the first model to integrate glucose and insulin regulation, incretin effect, and triglyceride (TG) response in the lipoprotein subclasses of chylomicrons and VLDL-V6. This model described the response following a high-fat meal in individuals who are lean, obese, and very obese and provided insights into the possible regulation of glucose homeostasis in the extended period following a meal. Often, total TGs are analyzed within clinical studies, instead of lipoprotein subclasses. We extended the existing TIGG model to capture the observed total TGs and determined if this model could be used to predict the postprandial TG response of chylomicron and VLDL-V6 when only total TGs are available. To assess if the lipoprotein distinction was important for the model, a second model (tTIGG) was developed using only the postprandial response in total TGs, instead of postprandial TG response in chylomicrons and VLDL-V6. The two models were compared on their predictability to characterize the postprandial response of glucose, insulin, and active GLP-1. Both models were able to characterize the postprandial TG response in individuals who are lean, obese, or very obese following a high-fat meal. The extended TIGG model resulted in a better model fit of the glucose data compared to the tTIGG model, indicating that chylomicron and VLDL-V6 provided additional information compared to total TGs. Furthermore, the expanded TIGG model was able to predict the postprandial TG response of chylomicrons and VLDL-V6 using the total TGs and could therefore be used in studies where only total TGs were collected.
(© 2023 Eli Lilly and Co and The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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