Essential Elements of the Native Glucoregulatory System,Which,If Appreciated,May Help Improve the Function of Glucose Controllers in the Intensive Care Unit Setting
Free accessResearch articleFirst published online January, 2010
Essential Elements of the Native Glucoregulatory System,Which,If Appreciated,May Help Improve the Function of Glucose Controllers in the Intensive Care Unit Setting
In 2001, Van den Berghe and colleagues were able to show that tight glucose control decreases morbidity and mortality rates in the intensive care unit (ICU) setting. Several large, prospective, randomized controlled trials have failed to confirm these results. All of these studies attempted tight glucose control using expert-designed algorithms to adjust the rate of intravenous insulin. Unfortunately, these studies each had high rates of hypoglycemia, a high percentage of glucose values outside of the target range, and increased glucose variability. These three measurements have been shown to increase mortality rates in ICU patients. In order to achieve a high rate of success with regards to tight glucose control, a closed-loop system will need to be created. The two main elements of such a system are a continuous glucose sensor and a recursive glucose control algorithm. This review highlights the important elements of the native glucoregulatory system, which, if utilized, may help create a successful glucose control algorithm for a closed-loop system.
FurnaryAPZerrKJGrunkemeierGLStarrA.Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg.1999;67 (2): 352–60.
2.
Van den BergheGWoutersPWeekersFVerwaestCBruyninckxFSchetzMVlasselaersDFerdinandePLauwersPBouillonR.Intensive insulin therapy in the critically ill patients. N Engl J Med.2001;345 (19): 1359–67.
3.
Van den BergheGWilmerAHermansGMeerssemanWWoutersPJMilantsIVan WijngaerdenEBobbaersHBouillonR.Intensive insulin therapy in the medical ICU. N Engl J Med.2006;354 (5): 449–61.
4.
LazarHLChipkinSRFitzgeraldCABaoYCabralHApsteinCS.Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events. Circulation.2004;109 (12): 1497–502.
5.
SchmeltzLRDeSantisAJThiyagarajanVSchmidtKO'Shea-MahlerEJohnsonDHenskeJMcCarthyPMGleasonTGMcGeeECMolitchME.Reduction of surgical mortality and morbidity in diabetic patients undergoing cardiac surgery with a combined intravenous and subcutaneous insulin glucose management strategy. Diabetes Care.2007;30 (4): 823–8.
6.
KrinsleyJS.Glycemic control, diabetic status, and mortality in a heterogeneous population of critically ill patients before and during the era of intensive glycemic management: six and one-half years experience at a university-affiliated community hospital. Semin Thorac Cardiovasc Surg.2006;18 (4): 317–25.
7.
Malmberg K, the DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. Prospective randomized study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ.1997;314 (7093): 1512–5.
8.
FalcigliaM.Hyperglycemia and mortality in 252,000 critically ill patients. American Diabetes Association 2006 Scientific Sessions, June 9–13, 2006, Washington, DC.
9.
The NICE-SUGAR Study Investigators, FinferSChittockDRSuSYBlairDFosterDDhingraVBellomoRCookDDodekPHendersonWRHébertPCHeritierSHeylandDKMcArthurCMcDonaldEMitchellIMyburghJANortonRPotterJRobinsonBGRoncoJJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med.2009;360 (13): 1283–97.
10.
GandhiGYNuttallGAAbelMDMullanyCJSchaffHVO'BrienPCJohnsonMGWilliamsARCutshallSMMundyLMRizzaRAMcMahonMM.Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Ann Intern Med.2007;146 (4): 233–43.
11.
De La RosaGDDonadoJHRestrepoAHQuinteroAMGonzalezLGSaldarriagaNEBedoyaMToroJMVelasquezJBValenciaJCArangoCMAlemanPHVasquezEMChavarriagaJCYepesAPulidoWCadavidCA, Grupo de Investigacion en Cuidado intensivo: GICI-HPTU. Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial. Crit Care.2008;12 (5): R120.
12.
WienerRSWienerDCLarsonRJ.Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA.2008;300 (8): 933–44.
13.
MoghissiESKorytkowskiMTDiNardoMEinhornDHellmanRHirschIBInzucchiSEIsmail-BeigiFKirkmanMSUmpierrezGE, American Association of Clinical Endocrinologists, American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract.2009;15 (4): 353–69.
14.
BrunkhorstFMEngelCBloosFMeier-HellmannARagallerMWeilerNMoererOGruendlingMOppertMGrondSOlthoffDJaschinskiUJohnSRossaintRWelteTSchaeferMKernPKuhntEKiehntopfMHartogCNatansonCLoefflerMReinhartK, German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med.2008;358 (2): 125–39.
15.
DevosPPreiserJMelotC.Impact of tight glucose control by intensive insulin therapy on ICU mortality and the rate of hypoglycemia: final results of the glucontrol study. Intensive Care Med.2007;33 (Suppl 2): S189.
16.
KrinsleyJSGroverA.Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med.2007;35 (10): 2262–7.
17.
BagshawSMBellomoRJackaMJEgiMHartGKGeorgeC, ANZICS CORE Management Committee. The impact of early hypoglycemia and blood glucose variability on outcome in critical illness. Crit Care.2009;13 (3): R91.
18.
TurchinAMathenyMEShubinaMScanlonJVGreenwoodBPendergrassML.Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care.2009;32 (7): 1153–7.
19.
DossettLACaoHMoweryNTDortchMJMorrisJMJrMayAK.Blood glucose variability is associated with mortality in the surgical intensive care unit. Am Surg.2008;74 (8): 679–85.
20.
EgiMBellomoRStachowskiEFrenchCJHartG.Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology.2006;105 (2): 244–52.
21.
OuattaraAGrimaldiARiouB.Blood glucose variability: a new paradigm in critical care?Anesthesiology.2006;105 (2): 233–4.
22.
KrinsleyJS.Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med.2008;36 (11): 3008–13.
23.
GerichJE.Physiology of glucose homeostasis. Diabetes Obes Metab.2000;2 (6): 345–50.
24.
TironeTABrunicardiFC.Overview of glucose regulation. World J Surg.2001;25 (4): 461–7.
25.
MizockBA.Alterations in carbohydrate metabolism during stress: a review of the literature. Am J Med.1995;98 (1): 75–84.
26.
McCowenKCMalhotraABistrianBR.Stress induced hyperglycemia. Crit Care Clin.2001;17 (1): 107–24.
27.
GoughDAKreutz-DelgadoKBremerTM.Frequency characterization of blood glucose dynamics. Ann Biomed Eng.2003;31 (1): 91–7.
28.
Trujillo-ArriagaHMRomán-RamosR.Fitting and evaluating the glucose curve during a quasi continuous sampled oral glucose tolerance test. Comput Biol Med.2008;38 (2): 185–95.
29.
SmithSW.The scientist and engineer's guide to digital signal processing. Chapter 15. San Diego: California Technical Publishing; 1997.
30.
Diabetes Research in Children Network (DirecNet) Study Group. The accuracy of the Guardian RT continuous glucose monitor in children with type 1 diabetes. Diabetes Technol Ther.2008;10 (4): 266–72.
31.
ZisserH.Accuracy of a novel intravascular fluorescent continuous glucose sensor. American Diabetes Association Meeting, June 5–9, 2009, New Orleans, LA. Abstract 1-LB.
32.
OliverNSToumazouCCassAEJohnstonDG.Glucose sensors: a review of current and emerging technology. Diabet Med.2009;26 (3): 197–210.
33.
GoldbergPASiegelMDRussellRRSherwinRSHalickmanJICooperDADziuraJDInzucchiSE.Experience with the continuous glucose monitoring system in a medical intensive care unit. Diabetes Technol Ther.2004;6 (3): 339–47.
34.
HendeeSVanslykeSStoutFBorrelloMWelshDRossAFettigAMarthaSTruongARobinsonRThompsonR.Evaluation of a near-infrared automated blood glucose monitor for use in critical care settings. Crit Care.2008;12 (Suppl 2): 165.
35.
BochicchioGBochicchioKLettichKLambertPHerreraALumpkinsKMagarianPScaleaT.Mid infrared spectroscopy (MIS) is highly accurate in measuring glucose in ICU patients. SCCM 38th Critical care Congress, February 2009. Poster 262.
36.
KovatchevBClarkeW.Peculiarities of the continuous glucose monitoring data stream and their impact on developing closed-loop control technology. J Diabetes Sci Technol.2008;2 (1): 158–63.
37.
RitzelRAVeldhuisJDButlerPC.Glucose stimulates pulsatile insulin secretion from human pancreatic islets by increasing secretory burst mass: dose-response relationships. J Clin Endocrinol Metab.2003;88 (2): 742–7.
38.
LangDAMatthewsDRPetoJTurnerRC.Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. N Engl J Med.1979;301 (19): 1023–7.
39.
JaspanJBLeverEPolonskyKSVan CauterE.In vivo pulsatility of pancreatic islet peptides. Am J Physiol.1986;251 (2Pt 1):E215–26.
40.
BalksHJSchmidtAPrankKHemmerFvon zur MühlenABrabantG.Temporal pattern of pancreatic insulin and C-peptide secretion and of plasma glucose levels after nutritional stimulation. J Clin Endocrinol Metab.1992;75 (5): 1198–203.
41.
PørksenNNyholmBVeldhuisJDButlerPCSchmitzO.In humans at least 75% of insulin secretion arises from punctuated insulin secretory bursts. Am J Physiol.1997;273 (5Pt 1):E908–14.
42.
SongSHMcIntyreSSShahHVeldhuisJDHayesPCButlerPC.Direct measurement of pulsatile insulin secretion from the portal vein in human subjects. J Clin Endocrinol Metab.2000;85 (12): 4491–9.
43.
PaolissoGSgambatoSPassarielloNScheenAD'OnofrioFLefebvrePJ.Greater efficacy of pulsatile insulin in type 1 diabetics critically depends on plasma glucagon levels. Diabetes.1987;36 (5): 566–70.
44.
PaolissoGSgambatoSTorellaRVarricchioMScheenAD'OnofrioFLefèbvrePJ.Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes. J Clin Endocrinol Metab.1988;66 (6): 1220–6.
45.
PaolissoGScheenAJAlbertALefebvrePJ.Effects of pulsatile delivery of insulin and glucagon in humans. Am J Physiol.1989;257 (5Pt 1):E686–96.
46.
SturisJScheenAJLeproultRPolonskyKSVan CauterE.24-hour glucose profiles during continuous or oscillatory insulin infusion. Demonstration of the functional significance of ultradian insulin oscillations. J Clin Invest.1995;95 (4): 1464–71.
47.
PørksenN.The in vivo regulation of pulsatile insulin secretion. Diabetologia.2002;45 (1): 3–20.
48.
PaolissoGSgambatoSGentileSMemoliPGiuglianoDVarricchioMD'OnofrioF.Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients. J Clin Endocrinol Metab.1988;67 (5): 1005–10.
49.
SchmitzOPedersenSBMengelAPørksenNBakJMøllerNRichelsenBAlbertiKGButlerPCOrskovH.Augmented effect of short-term pulsatile versus continuous insulin delivery on lipid metabolism but similar effect on whole-body glucose metabolism in obese subjects. Metabolism.1994;43 (7): 842–6.
50.
FerranniniEPiloA.Pattern of insulin delivery after intravenous glucose injection in man and its relation to plasma glucose disappearance. J Clin Invest.1979;64 (1): 243–54.
51.
DeFronzoRATobinJDAndresR.Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol.1979;237 (3): E214–23.
52.
ToschiECamastraSSironiAMMasoniAGastaldelliAMariAFerranniniENataliA.Effect of acute hyperglycemia on insulin secretion in humans. Diabetes.2002;51Suppl 1: S130–3.
53.
TurnerRCGrayburnJANewmanGBNabarroJD.Measurement of the insulin delivery rate in man. J Clin Endocrinol Metab.1971;33 (2): 279–86.
54.
WaldhäuslWKBratusch-MarrainPRVierhapperHNowotnyP.Insulin pharmacokinetics following continuous infusion and bolus injection of regular porcine and human insulin in healthy man. Metabolism.1983;32 (5): 478–86.
55.
HipszerBJosephJKamM.Pharmacokinetics of intravenous insulin delivery in humans with type 1 diabetes. Diabetes Technol Ther.2005;7 (1): 83–93.
NuttallFQNgoAGannonMC.Regulation of hepatic glucose production and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant?Diabetes Metab Res Rev.2008;24 (6): 438–58.
PlankLDHillGL.Energy balance in critical illness. Proc Nutr Soc.2003;62 (2): 545–52.
60.
LecavalierLBolliGCryerPGerichJ.Contributions of gluconeogenesis and glycogenolysis during glucose counterregulation in normal humans. Am J Physiol.1989;256 (6Pt 1):E844–51.
61.
CaprioSSaccàLTamborlaneWVSherwinRS.Relationship between changes in glucose production and gluconeogenesis during mild hypoglycemia in humans. Metabolism.1988;37 (8): 707–10.
62.
MitrakouARyanCVenemanTMokanMJenssenTKissIDurrantJCryerPGerichJ.Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. Am J Physiol.1991;260 (1Pt 1):E67–74.
63.
MizockBA.Alterations in carbohydrate metabolism during stress: a review of the literature. Am J Med.1995;98 (1): 75–84.
64.
MizockBA.Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract Res Clin Endocrinol Metab.2001;15 (4): 533–51.
65.
CaprioSNapoliRSaccaLTamborlaneWVSherwinRS.Impaired stimulation of gluconeogenesis during prolonged hypoglycemia in intensively treated insulin-dependent diabetic subjects. J Clin Endocrinol Metab.1992;75 (4): 1076–80.
66.
O'ConnorMDLandahlHDGrodskyGM.Role of rate of change of glucose concentration as a signal for insulin release. Endocrinology.1977;101 (1): 85–8.
67.
ChantCWilsonGFriedrichJO.Validation of an insulin infusion nomogram for intensive glucose control in critically ill patients. Pharmacotherapy.2005;25 (3): 352–9.
DunnTCEastmanRCTamadaJA.Rates of glucose change measured by blood glucose meter and the GlucoWatch Biographer during day, night, and around mealtimes. Diabetes Care.2004;27 (9): 2161–5.
70.
BaronJH.Dose response relationships of insulin hypoglycaemia and gastric acid in man. Gut.1970;11 (10): 826–36.
71.
LuttermanJAAdriaansenAAvan 't LaarA. Treatment of severe diabetic ketoacidosis. A comparative study of two methods. Diabetologia.1979;17 (1): 17–21.
72.
KrishnanRKEvansWJKirwanJP.Glucose clearance is delayed after hyperglycemia in healthy elderly men. J Nutr.2003;133 (7): 2363–6.
73.
ViciniPZachwiejaJJYarasheskiKEBierDMCaumoACobelliC.Glucose production during IVGTT by deconvolution: validation with the tracer-to-trace clamp technique. Am J Physiol.1999;276 (2Pt 1):E285–94.
74.
RabieeAAndreasikVAbu-HamdahRGaliatsatosPKhouriZGibsonBRAndersenDKElahiD.Numerical and clinical accuracy of a continuous glucose monitoring system during intravenous insulin therapy in the surgical and burn intensive care units. J Diabetes Sci Technol.2009;3 (4): 951–9.
75.
CheeFFernandoTvan HeerdenPV.Closed-loop glucose control in critically ill patients using continuous glucose monitoring system (CGMS) in real time. IEEE Trans Inf Technol Biomed.2003;7 (1): 43–53.
76.
MurakamiAGutierrezMALageSHRebeloMFGuiraldelliRHRamiresJA.A continuous glucose monitoring system in critical cardiac patients in the intensive care unit. Comput Cardiol.2006;33: 233–6.
77.
GoldbergPASiegelMDRussellRRSherwinRSHalickmanJICooperDADziuraJDInzucchiSE.Experience with the continuous glucose monitoring system in a medical intensive care unit. Diabetes Technol Ther.2004;6 (3): 339–47.
78.
BraithwaiteSSEdkinsRMacgregorKLSredzienskiESHoustonMZarzaurBRichPBBenedettoBRutherfordEJ.Performance of a dose-defining insulin infusion protocol among trauma service intensive care unit admissions. Diabetes Technol Ther.2006;8 (4): 476–88.
79.
ChaseJGShawGMLinJDoranCVHannCRobertsonMBBrownePMLotzTWakeGCBroughtonB.Adaptive bolus-based targeted glucose regulation of hyperglycaemia in critical care. Med Eng Phys.2005;27 (1): 1–11.
80.
DoyleDJNebbiaSP.Intravenous dead space and patient safety in patient-controlled analgesia. Can J Anaesth.1995;42 (7): 658.
81.
LovichMAKinnealleyMESimsNMPeterfreundRA.The delivery of drugs to patients by continuous intravenous infusion: modeling predicts potential dose fluctuations depending on flow rates and infusion system dead volume. Anesth Analg.2006;102 (4): 1147–53.
82.
GeggieDMooreD.Peripheral line dead space: an unrecognised phenomenon?Emerg Med J.2007;24 (8): 558–9.
83.
LovichMAPeterfreundGLSimsNMPeterfreundRA.Central venous catheter infusions: a laboratory model shows large differences in drug delivery dynamics related to catheter dead volume. Crit Care Med.2007;35 (12): 2792–8.
84.
GoldbergPAKedvesAWalterKGroszmannABelousAInzucchiSE.“Waste not, want not”: determining the optimal priming volume for intravenous insulin infusions. Diabetes Technol Ther.2006;8 (5): 598–601.
85.
DavidsonPCSteedRDBodeBW.Glucommander: a computer-directed intravenous insulin system shown to be safe, simple, and effective in 120,618 h of operation. Diabetes Care.2005;28 (10): 2418–23.
86.
WintergerstKADeissDBuckinghamBCantwellMKacheSAgarwalSWilsonDMSteilG.Glucose control in pediatric intensive care unit patients using an insulin-glucose algorithm. Diabetes Technol Ther.2007;9 (3): 211–22.
87.
CheeFFernandoTLSavkinAVvan HeedenV.Expert PID control system for blood glucose control in critically ill patients. IEEE Trans Inf Technol Biomed.2003;7 (4): 419–25.
88.
QinSJBadgwellTA.A survey of industrial model predictive control technology. Control Engineering Practice.2003;11 (7): 733–64.
89.
HovorkaRCanonicoVChassinLJHaueterUMassi-BenedettiMFedericiM OrsiniPieberTRSchallerHCSchauppLVeringTWilinskaME.Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes. Physiol Meas.2004;25 (4): 905–20.
90.
PlankJBlahaJCordingleyJWilinskaMEChassinLJMorganCSquireSHaluzikMKremenJSvacinaSTollerWPlasnikAEllmererMHovorkaRPieberTR.Multicentric, randomized, controlled trial to evaluate blood glucose control by the model predictive control algorithm versus routine glucose management protocols in intensive care unit patients. Diabetes Care.2006;29 (2): 271–6.
91.
HovorkaRKremenJBlahaJMatiasMAnderlovaKBosanskaLRoubicekTWilinskaMEChassinLJSvacinaSHaluzikM.Blood glucose control by a model predictive control algorithm with variable sampling rate versus a routine glucose management protocol in cardiac surgery patients: a randomized controlled trial. J Clin Endocrinol Metab.2007;92 (8): 2960–4.
92.
SaagerLCollinsGLBurnsideBTymkewHZhangLJacobsohnEAvidanM.A randomized study in diabetic patients undergoing cardiac surgery comparing computer-guided glucose management with a standard sliding scale protocol. J Cardiothor Vasc Anesth.2008;22 (3): 377–82.
93.
ZadehLA.Fuzzy sets. Inform Contr.1965;8: 338–53.
94.
BatesJHYoungMP.Applying fuzzy logic to medical decision making in the intensive care unit. Am J Respir Crit Care Med.2003;167 (7): 948–52.
95.
DazziDTaddeiFGavariniAUggeriENegroRPezzarossaA.The control of blood glucose in the critical diabetic patient: a neuro-fuzzy method. J Diabetes Complications.2001;15 (2): 80–7.
96.
MerouaniMGuignardBVincentFBorronSWKaroubiPFosseJPCohenYClec'hCVicautEMarbeuf-GueyeCLapostolleFAdnetF.Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic. Crit Care.2008;12 (6): R155.
97.
IbbiniM.A PI-fuzzy logic controller for the regulation of blood glucose level in diabetic patients. J Med Eng Technol.2006;30 (2): 83–92.
98.
GrantP.A new approach to diabetic control: fuzzy logic and insulin pump technology. Med Eng Phys.2007;29 (7): 824–7.
99.
Campos-DelgadoDUHernàndez-OrdoñezMFematRGordillo-MoscoscoA.Fuzzy-based controller for glucose regulation in type-1 diabetic patients by subcutaneous route. IEEE Trans Biomed Eng.2006;53 (11): 2201–10.
