title: Insulin kinetics and the Neonatal Intensive Care Insulin-Nutrition-Glucose (NICING) model.
abstract: Models of human glucose-insulin physiology have been developed for a range of uses, with similarly different levels of complexity and accuracy. STAR (Stochastic Targeted) is a model-based approach to glycaemic control. Elevated blood glucose concentrations (hyperglycaemia) are a common complication of stress and prematurity in very premature infants, and have been associated with worsened outcomes and higher mortality. This research identifies and validates the model parameters for model-based glycaemic control in neonatal intensive care.
  
  
  
  C-peptide, plasma insulin, and BG from a cohort of 41 extremely pre-term (median age 27.2 [26.2-28.7] weeks) and very low birth weight infants (median birth weight 839 [735-1000] g) are used alongside C-peptide kinetic models to identify model parameters associated with insulin kinetics in the NICING (Neonatal Intensive Care Insulin-Nutrition-Glucose) model. A literature analysis is used to determine models of kidney clearance and body fluid compartment volumes. The full, final NICING model is validated by fitting the model to a cohort of 160 glucose, insulin, and nutrition data records from extremely premature infants from two different NICUs (neonatal intensive care units).
  
  
  
  Six model parameters related to insulin kinetics were identified. The resulting NICING model is more physiologically descriptive than prior model iterations, including clearance pathways of insulin via the liver and kidney, rather than a lumped parameter. In addition, insulin diffusion between plasma and interstitial spaces is evaluated, with differences in distribution volume taken into consideration for each of these spaces. The NICING model was shown to fit clinical data well, with a low model fit error similar to that of previous model iterations.
  
  
  
  Insulin kinetic parameters have been identified, and the NICING model is presented for glycaemic control neonatal intensive care. The resulting NICING model is more complex and physiologically relevant, with no loss in bedside-identifiability or ability to capture and predict metabolic dynamics.
authors: Department of Mechanical Engineering, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand. Electronic address: jennifer.dickson@canterbury.ac.nz.
authors: J L
authors: JL
authors: Dickson
authors: Department of Mechanical Engineering, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand. Electronic address: chris.pretty@canterbury.ac.nz.
authors: C G
authors: CG
authors: Pretty
authors: Department of Paediatrics: Child and Youth Health, Auckland, New Zealand; Liggins Institute, University of Auckland, Auckland, New Zealand. Electronic address: j.alsweiler@auckland.ac.nz.
authors: J
authors: J
authors: Alsweiler
authors: Christchurch Women's Hospital Neonatal Intensive Care Unit, Christchurch, New Zealand. Electronic address: Adrienne.Lynn@cdhb.health.nz.
authors: A
authors: A
authors: Lynn
authors: Department of Mechanical Engineering, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand. Electronic address: geoff.chase@canterbury.ac.nz.
authors: J G
authors: JG
authors: Chase
mesh_terms: D001786:Blood Glucose; D006801:Humans; D062071:Infant, Extremely Premature / Q000097:blood*; D007230:Infant, Low Birth Weight / Q000097:blood*; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood*; D015931:Intensive Care, Neonatal; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: Glucose; Glycaemic control; Insulin; Physiological modelling; Premature infant