Ahmad Fadli Mohamad Dahlan, Gustaf J. Wellhagen, Mats O. Karlsson, Maria C. Kjellsson
Department of Pharmaceutical Biosciences, Uppsala University
Objectives: To investigate the impact of different carbohydrate intakes to HbA1c for well-controlled and uncontrolled patients with type 2 diabetes (T2D) through model-predicted mean plasma glucose (MPG).
Methods: Data was simulated with the IGI model (1) mimicking different populations, well-controlled or uncontrolled T2D, by varying fasting plasma glucose (FPG) and fasting serum insulin (FSI). Glucose and insulin time-profiles were simulated following four different meal regimens: (I) Low carbohydrate intake, with three standard meals of 62.5 g glucose each, (II) Medium, with three standard meals and three snacks of 12.5 g, (III) High, with three standard meals and three large snacks of 25 g and (IV) decreased frequency “FQ”, with the same carbohydrate intake as “Medium” but distributed on three large meals, 75 g each. MPG was calculated from the simulated profiles and used as input to the IGRH model (2) for simulation of HbA1c. The same individuals were tested with all dietary regimens and the difference in HbA1c was calculated relative to the Medium intake regimen.
Results: Predicted average HbA1c was 5.6% and 7.8% for well-controlled and uncontrolled patients following the Medium carbohydrate intake. For well-controlled patients, the mean difference relative to Medium was -0.04% (HbA1c units) for Low, -0.02% for FQ and +0.05% for High. For uncontrolled patients it was -0.01% for Low, -0.01% for FQ and +0.02% for High.
Conclusions: Our simulations show that carbohydrate intake has a small predicted impact on the HbA1c for uncontrolled patients (high FPG), while the impact is slightly larger for subjects with normal FPG (well-controlled T2D patients). Overall, the relatively small direct effect of carbohydrate intake on MPG and HbA1c as predicted by the combined IGI and IGRH models makes further investigation into indirect effects interesting to study. A primary indirect effect is the body weight changes associated with carbohydrate level intake and the impact this has on the glucose homeostasis.
References:
[1] Jauslin PM, Silber HE, Frey N, Gieschke R, Simonsson USH, Jorga K, et al. An Integrated Glucose-Insulin Model to Describe Oral Glucose Tolerance Test Data in Type 2 Diabetics. J Clin Pharmacol. 2007;47(10):1244–55.
[2] Lledó-García R, Mazer NA, Karlsson MO. A semi-mechanistic model of the relationship between average glucose and HbA1c in healthy and diabetic subjects. J Pharmacokinet Pharmacodyn. 2013 Apr;40(2):129–42.
Reference: PAGE 25 () Abstr 6012 [www.page-meeting.org/?abstract=6012]
Poster: Drug/Disease modeling - Endocrine