Quantifying the contribution of triglycerides to metabolic resilience through the mixed meal model

E-DES-PROT: A novel computational model to describe the effects of amino acids and protein on postprandial glucose and insulin dynamics in humans

“…A model based on E-DES that incorporates dietary fat has been developed in parallel and was recently published. 20 A next step would be to merge these two models into a model able to fully capture the effects of a complex meal, taking into account all three major macronutrient classes (i.e. carbohydrate, protein, and fat).…”

Quantifying the effect of nutritional interventions on metabolic resilience using personalized computational models

“…The Mixed Meal Model is a physiology-based computational model describing the systemic insulin mediated interplay between glucose and lipid species. 28 The model consists of a system of thirteen coupled ordinary differential equations accounting for the key reactions governing the postprandial changes in plasma glucose, insulin, triglyceride, and NEFA concentrations. The Mixed Meal Model describes the rate of appearance of meal derived glucose and triglyceride in the plasma via the gut and lymphatic system respectively.…”

“…In previous work, we have shown that the Mixed Meal Model could be reliably fit to population level meal response data by estimating a subset of nine model parameters from the data. 28 Here, we set about generating personalized Mixed Meal Models. To this end, the model individualisation pipeline proposed by Erdos et al.…”

“…Where the cost function is composed of the sum of squared error between the model simulation for a parameter set and the measures plasma concentration of metabolite and time point and a number of terms to penalised physiologically undesirable behaviors such as nutrient dumping or a failure to return to the measured fasting state following the meal. 28 These additional penalties have been dubbed physiology-informed learning. To tailor the model to an individual, basal glucose and insulin values are fixed to the measured fasting values as recommended in Maas et al.…”

“… 27 The Mixed Meal Model is a physiology-based computational model that explicitly accounts for the insulin-mediated interactions between glucose, triglyceride, and non-esterified fatty acids (NEFAs). 28 Application of the Mixed Meal Model to population data has shown that the model captures features from meal responses that are indicative of glucose homeostasis such as insulin resistance and β-cell functionality but also properties related to lipid metabolism such as hepatic fat accumulation. In this way, the multi-variate time series of meal response data can be reduced to a low-dimensional interpretable set of parameters allowing for the assessment of intervention effects on multiple features of metabolic health at once.…”