title: On the problem of patient-specific endogenous glucose production in neonates on stochastic targeted glycemic control.
abstract: BACKGROUND
  Both stress and prematurity can induce hyperglycemia in the neonatal intensive care unit, which, in turn, is associated with worsened outcomes. Endogenous glucose production (EGP) is the formation of glucose by the body from substrates and contributes to blood glucose (BG) levels. Due to the inherent fragility of the extremely low birth weight (ELBW) neonates, true fasting EGP cannot be explicitly determined, introducing uncertainty into glycemic models that rely on quantifying glucose sources. Stochastic targeting, or STAR, is one such glycemic control framework.
  
  
  METHODS
  A literature review was carried out to gather metabolic and EGP values on preterm infants with a gestational age (GA) &lt;32 weeks and a birth weight (BW) &lt;2 kg. The data were analyzed for EGP trends with BW, GA, BG, plasma insulin, and glucose infusion (GI) rates. Trends were modeled and compared with a literature-derived range of population constant EGP models using clinically validated virtual trials on retrospective clinical data.
  
  
  RESULTS
  No clear relationship was found for EGP and BW, GA, or plasma insulin. Some evidence of suppression of EGP with increasing GI or BG was seen. Virtual trial results showed that population-constant EGP models fit clinical data best and gave tighter control performance to a target band in virtual trials.
  
  
  CONCLUSIONS
  Variation in EGP cannot easily be quantified, and EGP is sufficiently modeled as a population constant in the neonatal intensive care insulin-nutrition-glucose model. Analysis of the clinical data and fitting error suggests that ELBW hyperglycemic preterm neonates have unsuppressed EGP in the higher range than that seen in literature.
authors.affiliation: Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand. jennifer.dickson@pg.canterbury.ac.nz
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dickson
authors.forename: James N
authors.initials: JN
authors.lastname: Hewett
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Gunn
authors.forename: Adrienne
authors.initials: A
authors.lastname: Lynn
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Shaw
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Chase
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy*; D007206:Individuality; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D007235:Infant, Premature, Diseases / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy; D007328:Insulin / Q000008:administration & dosage; D015931:Intensive Care, Neonatal / Q000379:methods / Q000706:statistics & numerical data; D008991:Monitoring, Physiologic / Q000379:methods* / Q000706:statistics & numerical data; D013269:Stochastic Processes
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
references.citation: J Clin Invest. 1993 Oct;92(4):1752-8
references.pmid: 8408627
references.citation: Mayo Clin Proc. 2003 Dec;78(12):1471-8
references.pmid: 14661676
references.citation: Pediatr Res. 1997 Jan;41(1):132-8
references.pmid: 8979302
references.citation: Ann Intensive Care. 2011 Sep 19;1:38
references.pmid: 21929821
references.citation: Pediatr Res. 1986 Jan;20(1):49-52
references.pmid: 3511440
references.citation: BMJ. 1988 Nov 19;297(6659):1304-8
references.pmid: 2462455
references.citation: IEEE Trans Biomed Eng. 2010 Mar;57(3):509-18
references.pmid: 19884072
references.citation: Clin Nutr. 2005 Oct;24(5):727-36
references.pmid: 16182036
references.citation: Am J Physiol Endocrinol Metab. 2001 Sep;281(3):E472-8
references.pmid: 11500302
references.citation: Arch Dis Child Fetal Neonatal Ed. 2010 Nov;95(6):F413-8
references.pmid: 20682577
references.citation: Diabetes. 1999 Apr;48(4):791-800
references.pmid: 10102696
references.citation: JPEN J Parenter Enteral Nutr. 2001 Jul-Aug;25(4):180-1
references.pmid: 11434647
references.citation: Pediatr Res. 2003 Oct;54(4):480-6
references.pmid: 12815113
references.citation: Metabolism. 2003 Aug;52(8):945-9
references.pmid: 12898456
references.citation: Comput Methods Programs Biomed. 2008 Feb;89(2):141-52
references.pmid: 17544541
references.citation: Acta Paediatr. 1996 Nov;85(11):1339-43
references.pmid: 8955462
references.citation: J Diabetes Sci Technol. 2009 Sep 01;3(5):1066-81
references.pmid: 20144420
references.citation: Pediatr Res. 1993 Feb;33(2):97-100
references.pmid: 8433898
references.citation: Pediatr Res. 1996 Oct;40(4):553-7
references.pmid: 8888282
references.citation: BMC Pediatr. 2012 Aug 07;12:117
references.pmid: 22871230
references.citation: J Clin Invest. 1983 Mar;71(3):467-75
references.pmid: 6338038
references.citation: Pediatrics. 2012 Apr;129(4):639-47
references.pmid: 22430450
references.citation: Pediatr Res. 2006 May;59(5):732-5
references.pmid: 16627891
references.citation: IEEE Trans Biomed Eng. 2012 Dec;59(12):3357-64
references.pmid: 22929365
references.citation: Lancet. 2000 Mar 4;355(9206):773-8
references.pmid: 10711923
references.citation: N Engl J Med. 2001 Nov 8;345(19):1359-67
references.pmid: 11794168
references.citation: J Pediatr. 2011 Jun;158(6):891-6
references.pmid: 21324479
references.citation: Pediatr Res. 1994 Oct;36(4):550-5
references.pmid: 7816531
references.citation: J Pediatr. 1994 Aug;125(2):283-7
references.pmid: 8040779
references.citation: Pediatr Res. 1993 Jun;33(6):583-9
references.pmid: 8378116
references.citation: Pediatr Res. 2003 Apr;53(4):635-41
references.pmid: 12612213
references.citation: Comput Methods Programs Biomed. 2006 Feb;81(2):181-92
references.pmid: 16413632
references.citation: Crit Care Clin. 2001 Jan;17(1):107-24
references.pmid: 11219223
references.citation: Am J Physiol Endocrinol Metab. 2002 May;282(5):E992-1007
references.pmid: 11934663
references.citation: Pediatr Res. 2003 Apr;53(4):628-34
references.pmid: 12612212
references.citation: Am J Physiol Endocrinol Metab. 2006 Apr;290(4):E723-30
references.pmid: 16291574
references.citation: Pediatr Res. 1999 May;45(5 Pt 1):674-9
references.pmid: 10231863
references.citation: Diabetes. 2002 Nov;51(11):3170-5
references.pmid: 12401707
references.citation: N Engl J Med. 2008 Oct 30;359(18):1873-84
references.pmid: 18971490
references.citation: Pediatr Res. 1997 Oct;42(4):492-7
references.pmid: 9380442
references.citation: Comput Methods Programs Biomed. 1997 Mar;52(3):147-56
references.pmid: 9051338
references.citation: Crit Care. 2008;12(2):R49
references.pmid: 18412978
references.citation: Biomed Eng Online. 2010 Dec 14;9:84
references.pmid: 21156053
references.citation: Crit Care. 2010;14(4):R154
references.pmid: 20704712