title: Prandial insulin dosing using run-to-run control: application of clinical data and medical expertise to define a suitable performance metric.
abstract: OBJECTIVE
  We propose a novel algorithm to adjust prandial insulin dose using sparse blood glucose measurements. The dose is adjusted on the basis of a performance measure for the same meal on the previous day. We determine the best performance measure and tune the algorithm to match the recommendations of experienced physicians.
  
  
  METHODS
  Eleven subjects with type 1 diabetes, using continuous subcutaneous insulin infusion, were recruited (seven women and four men, aged 21-65 years with A1C of 7.1 +/- 1.3%). Basal insulin infusion rates were optimized. Target carbohydrate content for the lunch meal was calculated on the basis of a weight-maintenance diet. Over a period of 2-4 days, subjects were asked to measure their blood glucose according to the algorithm's protocol. Starting with their usual insulin-to-carbohydrate ratio, the insulin bolus dose was titrated downward until postprandial glucose levels were high (180-250 mg/dl [10-14 mmol/l]). Subsequently, physicians made insulin bolus recommendations to normalize postprandial glucose concentrations. Graphical methods were then used to determine the most appropriate performance measure for the algorithm to match the physician's decisions. For the best performance measure, the gain of the controller was determined to be the best match to the dose recommendations of the physicians.
  
  
  RESULTS
  The correlation between the clinically determined dose adjustments and those of the algorithm is R2 = 0.95, P < 1e - 18.
  
  
  CONCLUSIONS
  We have shown how engineering methods can be melded with medical expertise to develop and refine a dosing algorithm. This algorithm has the potential of drastically simplifying the determination of correct insulin-to-carbohydrate ratios.
authors.affiliation: Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106-5080, USA.
authors.forename: Cesar C
authors.initials: CC
authors.lastname: Palerm
authors.forename: Howard
authors.initials: H
authors.lastname: Zisser
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Bevier
authors.forename: Lois
authors.initials: L
authors.lastname: Jovanovic
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Doyle
mesh_terms: D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004435:Eating / Q000502:physiology*; D006801:Humans; D007332:Insulin Infusion Systems; D019518:Postprandial Period / Q000502:physiology; D013997:Time Factors
chemical_list: D001786:Blood Glucose