Sparse Reconstruction of Glucose Fluxes Using Continuous Glucose Monitors.

A new technique for estimating postprandial glucose flux profiles without the use of glucose tracers is proposed. A sparse vector space representation is first found for the space of plausible glucose flux profiles using sparse encoding. A Lasso formulation is then used to estimate the glucose fluxes that combines (1) known patient model parameters; (2) the vector space of plausible glucose flux profiles; (3) continuous glucose monitor measurements taken during the meal; (4) amount of insulin injected; (5) amount of meal carbohydrates; and (6) an estimate of the initial conditions. Three glucose fluxes are then estimated, namely; glucose rate of appearance from the intestine; endogenous glucose production from the liver; insulin dependent glucose utilization; and other important state variables. The simulation results show that the technique is capable of estimating the glucose fluxes with high accuracy, even for complex meal scenarios. The experimental results indicate that the technique is capable of reproducing the triple tracer measurements for three T1DM undergoing the triple tracer protocol while estimating the missing measurements for a certain model parameter selection.

Metabolic networks in a porcine model of trauma and hemorrhagic shock demonstrate different control mechanism with carbohydrate pre-feed.

BACKGROUND: Treatment with oral carbohydrate prior to trauma and hemorrhage confers a survival benefit in small animal models. The impact of fed states on survival in traumatically injured humans is unknown. This work uses regulatory networks to examine the effect of carbohydrate pre-feeding on metabolic response to polytrauma and hemorrhagic shock in a clinically-relevant large animal model. METHODS: Male Yorkshire pigs were fasted overnight (n = 64). Pre-fed animals (n = 32) received an oral bolus of Karo\textregistered\syrup before sedation. All animals underwent a standardized trauma, hemorrhage, and resuscitation protocol. Serum samples were obtained at set timepoints. Proton NMR was used to identify and quantify serum metabolites. Metabolic regulatory networks were constructed from metabolite concentrations and rates of change in those concentrations to identify controlled nodes and controlling nodes of the network. RESULTS: Oral carbohydrate pre-treatment was not associated with survival benefit. Six metabolites were identified as controlled nodes in both groups: adenosine, cytidine, glycerol, hypoxanthine, lactate, and uridine. Distinct groups of controlling nodes were associated with controlled nodes; however, the composition of these groups depended on feeding status. CONCLUSIONS: A common metabolic output, typically associated with injury and hypoxia, results from trauma and hemorrhagic shock. However, this output is directed by different metabolic inputs depending upon the feeding status of the subject. Nodes of the network that are related to mortality can potentially be manipulated for therapeutic effect; however, these nodes differ depending upon feeding status.