title: Coordinated basal-bolus infusion for tighter postprandial glucose control in insulin pump therapy.
abstract: BACKGROUND
  Basal and bolus insulin determination in intensive insulin therapy for type 1 diabetes mellitus (T1DM) are currently considered independently of each other. A new strategy that coordinates basal and bolus insulin infusion to cope with postprandial glycemia in pump therapy is proposed. Superior performance of this new strategy is demonstrated through a formal analysis of attainable performances in an in silico study.
  
  
  METHODS
  The set inversion via interval analysis algorithm has been applied to obtain the feasible set of basal and bolus doses that, for a given meal, mathematically guarantee a postprandial response fulfilling the International Diabetes Federation (IDF) guidelines (i.e., no hypoglycemia and 2 h postprandial glucose below 140 mg/dl). Hypoglycemia has been defined as a glucose value below 70 mg/dl. A 5 h time horizon has been considered for a 70 kg in silico T1DM subject consuming meals in the range of 30 to 80 g of carbohydrates.
  
  
  RESULTS
  The computed feasible sets demonstrate that current separated basal/bolus strategy dramatically limits the attainable performance. For a nominal basal of 0.8 IU/h leading to a basal glucose of approximately 100 mg/dl, IDF guidelines cannot be fulfilled for meals greater than 50 g of carbohydrates, independent of the bolus insulin computed. However, coordinating the basal and bolus insulin delivery can achieve this. A decrement of basal insulin during the postprandial period is required together with an increase in bolus insulin, in appropriate percentages, which is meal dependent. After 3 h, basal insulin can be restored to its nominal value.
  
  
  CONCLUSIONS
  The new strategy meets IDF guidelines in a typical day, contrary to the standard basal/bolus strategy, yielding a mean 2 h postprandial glucose reduction of 36.4 mg/dl without late hypoglycemia. The application of interval analysis for the computation of feasible sets is demonstrated to be a powerful tool for the analysis of attainable performance in glucose control.
authors.affiliation: Instituto Universitario de Automática e Informática Industrial, Universidad Politécnica de Valencia, Camino de Vera s/n, Valencia, Spain. jbondia@isa.upv.es
authors.forename: Jorge
authors.initials: J
authors.lastname: Bondia
authors.forename: Eyal
authors.initials: E
authors.lastname: Dassau
authors.forename: Howard
authors.initials: H
authors.lastname: Zisser
authors.forename: Remei
authors.initials: R
authors.lastname: Calm
authors.forename: Josep
authors.initials: J
authors.lastname: Vehí
authors.forename: Lois
authors.initials: L
authors.lastname: Jovanovič
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Doyle
mesh_terms: D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D007332:Insulin Infusion Systems; D008962:Models, Theoretical
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin