ppt presentation - stritch school of medicine
TRANSCRIPT
GlycemicGlycemic ControlControlInsulin In The Hospital Insulin In The Hospital
SettingSetting
GlycemicGlycemic ControlControl
The Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
The Mechanism of InsulinThe Mechanism of Insulin’’s Benefits Benefit
The Achievement of InsulinThe Achievement of Insulin’’s Benefits Benefit
A Few CasesA Few Cases……
Hyperglycemia In The Setting Of Hyperglycemia In The Setting Of Acute Coronary SyndromesAcute Coronary Syndromes
The Evidence For Tight The Evidence For Tight GlycemicGlycemicControl In The Critically SickControl In The Critically Sick
The Early StoryThe Early StoryThe Rest Of The StoryThe Rest Of The Story
Hyperglycemia In The Setting Of Hyperglycemia In The Setting Of Acute Coronary SyndromesAcute Coronary SyndromesThe Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
Many Observational Many Observational StudiesStudies
Major Prospective Major Prospective StudiesStudies
Hyperglycemia In Critical IllnessHyperglycemia In Critical IllnessFrom The VA Inpatient Evaluation CenterFrom The VA Inpatient Evaluation Center
From 177 ICUs In 73 VA HospitalsFrom 177 ICUs In 73 VA Hospitals216,000 Patients216,000 PatientsGlycemiaGlycemia Independent Predictor Of Independent Predictor Of Mortality Starting At 1 mg% Above Mortality Starting At 1 mg% Above Normal (Normal = 70Normal (Normal = 70--110 mg%)110 mg%)True In Medical, Surgical & Cardiac True In Medical, Surgical & Cardiac ICUsICUs
Falciglia, M. et al Annual Meeting of the American Diabetes Association, 2006
Hyperglycemia In The Setting Of Hyperglycemia In The Setting Of Acute Coronary SyndromesAcute Coronary SyndromesThe Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
Many Observational Many Observational StudiesStudies
Major Prospective Major Prospective StudiesStudies
DIGAMI StudyDIGAMI Study
620 Randomized to 2 Groups At 19 Swedish 620 Randomized to 2 Groups At 19 Swedish HospitalsHospitals
Control: Standard Coronary Care for Their CenterControl: Standard Coronary Care for Their CenterIntensive: InsulinIntensive: Insulin--Glucose Infusion for >24 HrsGlucose Infusion for >24 Hrs
Target Serum Glucose 126 Target Serum Glucose 126 –– 180 mg/dl180 mg/dlMultidoseMultidose (4/day) Insulin for Minimum of 3 Months (4/day) Insulin for Minimum of 3 Months Following DischargeFollowing Discharge
BMJ 314: 1512-1515, 1997
Glucose Achieved:Glucose Achieved:
Control 211 mg/dlControl 211 mg/dl
Intensive 173 mg/dlIntensive 173 mg/dl
Cardiovascular RiskMortality After MI Reduced by Insulin Therapy in the
DIGAMI Study
All Subjects(N = 620)Risk reduction (28%)P = .011
Standard treatment
0
.3
.2
.4
.7
.1
.5
.6
0 1Years of Follow-up
2 3 4 5
Low-risk and Not Previously on Insulin(N = 272)Risk reduction (51%)P = .0004
IV Insulin 48 hours, then 4 injections daily
0
.3
.2
.4
.7
.1
.5
.6
0 1Years of Follow-up
2 3 4 5
Lazar, H. et al Circulation 109:1997-1502,2004
Lazar, H. et al Circulation 109:1997-1502,2004
Glucose Achieved:Glucose Achieved:
Control 267 mg/dlControl 267 mg/dl
Intensive 134 mg/dlIntensive 134 mg/dl
The Effect of GIK Infusion For The Effect of GIK Infusion For CABG in Type 2 DiabetesCABG in Type 2 Diabetes
Lazar, et al: Circulation 109:1497, 2004
05
1015202530354045
Pacing A. Fib Infection Time onVent (h)
ICU Stay(h)
Hospital Stay(Days)
GIK n=72No GIK n=69
Other Other Important Important StudiesStudies
Other Important StudiesOther Important StudiesFurnaryFurnary et alet al11
Prospective Observational Study Of 3554 Prospective Observational Study Of 3554 Diabetic Patients Showing Decreased Diabetic Patients Showing Decreased Mortality After CABG With Better Mortality After CABG With Better GlycemicGlycemicControlControl
KrinsleyKrinsley 22
Prospective Observational Study Of 800 Prospective Observational Study Of 800 Patients Before And 800 Patients After Patients Before And 800 Patients After Institution Of Tight Institution Of Tight GlycemicGlycemic Control, Showing Control, Showing Reduced Mortality And Morbidity In Mixed Reduced Mortality And Morbidity In Mixed MedMed--SurgSurg ICU With Better ICU With Better GlycemicGlycemic ControlControl
1 Furnary et al J Thoracic Cardiovasc Surg 125:10073, 2003
2 Krinsley J Mayo Clin Proc 79: 992-1000, 2004
Hyperglycemia In The Setting Of Hyperglycemia In The Setting Of Acute Coronary SyndromesAcute Coronary Syndromes
The Evidence For Tight The Evidence For Tight GlycemicGlycemicControl In The Critically SickControl In The Critically Sick
The Early StoryThe Early StoryThe Rest Of The StoryThe Rest Of The Story
Clinical Clinical BenefitBenefit
StudyStudyYearYear
YesYesThe Portland ProjectThe Portland ProjectOngoingOngoing
YesYesLazarLazar20042004YesYesKrinsleyKrinsley20042004
YesYesDIGAMI 1DIGAMI 119971997
Clinical Clinical BenefitBenefit
StudyStudyYearYear
YesYesThe Portland ProjectThe Portland ProjectOngoingOngoing
Yes*Yes*LeuvanLeuvan MICUMICU20062006
YesYesLazarLazar20042004YesYesKrinsleyKrinsley20042004
YesYesLeuvanLeuvan SICUSICU20012001
YesYesDIGAMI 1DIGAMI 119971997
Clinical Clinical BenefitBenefit
StudyStudyYearYear
YesYesThe Portland ProjectThe Portland ProjectOngoingOngoingNoNoHIHI--5520062006
Yes*Yes*LeuvanLeuvan MICUMICU20062006NoNoCreate ECLACreate ECLA20052005NoNoDIGAM 2DIGAM 220052005YesYesLazarLazar20042004YesYesKrinsleyKrinsley20042004NoNoDutch GIKDutch GIK20032003YesYesLeuvanLeuvan SICUSICU20012001NoNoPolPol--GIKGIK19991999YesYesDIGAMI 1DIGAMI 119971997
GlycemicGlycemicSeparationSeparation
Clinical Clinical BenefitBenefit
StudyStudyYearYear
YesYesYesYesThe Portland ProjectThe Portland ProjectOngoingOngoingNoNoNoNoHIHI--5520062006YesYesYes*Yes*LeuvanLeuvan MICUMICU20062006NoNoNoNoCreate ECLACreate ECLA20052005NoNoNoNoDIGAM 2DIGAM 220052005YesYesYesYesLazarLazar20042004YesYesYesYesKrinsleyKrinsley20042004NoNoNoNoDutch GIKDutch GIK20032003YesYesYesYesLeuvanLeuvan SICUSICU20012001NoNoNoNoPolPol--GIKGIK19991999YesYesYesYesDIGAMI 1DIGAMI 119971997
GlycemicGlycemicSeparationSeparation
Clinical Clinical BenefitBenefit
StudyStudyYearYear
NoNoNoNoHIHI--5520062006NoNoNoNoCreate ECLACreate ECLA20052005NoNoNoNoDIGAMI 2DIGAMI 220052005NoNoNoNoDutch GIKDutch GIK20032003NoNoNoNoPolPol--GIKGIK19991999YesYesYesYesThe Portland ProjectThe Portland ProjectOngoingOngoingYesYesYes*Yes*LeuvanLeuvan MICUMICU20062006YesYesYesYesLazarLazar20042004YesYesYesYesKrinsleyKrinsley20042004YesYesYesYesLeuvanLeuvan SICUSICU20012001YesYesYesYesDIGAMI 1DIGAMI 119971997
GlucoseGlucose--InsulinInsulin--Potassium Potassium TherapyTherapy
Pittas, A. et al Arch Intern Med 164: 2005-11, 2004
GlucoseGlucose--InsulinInsulin--Potassium Potassium TherapyTherapy
MetaMeta--Analysis of 35 StudiesAnalysis of 35 Studies
8,478 Patients8,478 Patients
Overall, A 15% Reduction In Overall, A 15% Reduction In Mortality With GIKMortality With GIK
Pittas, A. et al Arch Intern Med 164: 2005-11, 2004
GlucoseGlucose--InsulinInsulin--Potassium Potassium TherapyTherapy
Control Of Control Of GlycemiaGlycemia
In Trials That Targeted Glucose, In Trials That Targeted Glucose, 29% Reduction In Mortality With 29% Reduction In Mortality With InsulinInsulin
No Benefit When Insulin Was No Benefit When Insulin Was Administered Without Regard To Administered Without Regard To Glucose LevelsGlucose Levels
Pittas, A. et al Arch Intern Med 164: 2005-11, 2004
GlycemicGlycemicSeparationSeparation
Clinical Clinical BenefitBenefit
StudyStudyYearYear
NoNoNoNoHIHI--5520062006NoNoNoNoCreate ECLACreate ECLA20052005NoNoNoNoDIGAMI 2DIGAMI 220052005NoNoNoNoDutch GIKDutch GIK20032003NoNoNoNoPolPol--GIKGIK19991999YesYesYesYesThe Portland ProjectThe Portland ProjectOngoingOngoingYesYesYes*Yes*LeuvanLeuvan MICUMICU20062006YesYesYesYesLazarLazar20042004YesYesYesYesKrinsleyKrinsley20042004YesYesYesYesLeuvanLeuvan SICUSICU20012001YesYesYesYesDIGAMI 1DIGAMI 119971997
Arch Intern MedArch Intern Med 164: 2005164: 2005--11, 200411, 2004
Mayo Clinic Proceedings 83: 418Mayo Clinic Proceedings 83: 418--430, 2008430, 2008
JAMA 300: 933JAMA 300: 933--944, 2008944, 2008
Characteristics Of Negative Characteristics Of Negative TrialsTrials
Lack Of Lack Of GlycemicGlycemic SeparationSeparation
The Issue Of Statistical PowerThe Issue Of Statistical Power
More Recent TrialsMore Recent Trials
GIST GIST -- UKUKVISEPVISEP
GlucontrolGlucontrol
The Issue Of Statistical PowerThe Issue Of Statistical Power
Characteristics Of Negative Characteristics Of Negative TrialsTrials
Lack Of Lack Of GlycemicGlycemic SeparationSeparation
UnderpoweredUnderpowered
Insulin In The Hospital Setting
The days of casual The days of casual glycemicglycemic control for control for critically ill patients critically ill patients
should be over!should be over!
So, Reducing Glucose Is So, Reducing Glucose Is Good!!Good!!
But how low should we goBut how low should we go……
AACE Position Statement 12/16/03: AACE Position Statement 12/16/03: Hospital Hospital GlycemicGlycemic GoalsGoals
Intensive Care Units: Intensive Care Units: 110 mg/110 mg/dLdL
NonNon--Critical Care Units:Critical Care Units:PrePre--PrandialPrandial 110 mg/110 mg/dLdLMax. Glucose Max. Glucose 180 mg/180 mg/dLdL
GlycemicGlycemicSeparationSeparation
Clinical Clinical BenefitBenefit
StudyStudyYearYear
NoNoNoNoHIHI--5520062006NoNoNoNoCreate ECLACreate ECLA20052005NoNoNoNoDIGAMI 2DIGAMI 220052005NoNoNoNoDutch GIKDutch GIK20032003NoNoNoNoPolPol--GIKGIK19991999YesYesYesYesThe Portland ProjectThe Portland ProjectOngoingOngoingYesYesYes*Yes*LeuvanLeuvan MICUMICU20062006YesYesYesYesLazarLazar20042004YesYesYesYesKrinsleyKrinsley20042004YesYesYesYesLeuvanLeuvan SICUSICU20012001YesYesYesYesDIGAMI 1DIGAMI 119971997
The The LeuvanLeuvan SICU StudySICU Study
Van den Berghe G. et al N Engl J Med 2001; 345:1359
Glucose Achieved:Glucose Achieved:
Control 153 mg/dlControl 153 mg/dl
Intensive 103 mg/dlIntensive 103 mg/dl
NICENICE--SUGARSUGARNormoglycemiaNormoglycemia in Intensive Care Evaluationin Intensive Care Evaluation--Survival Using Glucose Algorithm RegulationSurvival Using Glucose Algorithm Regulation
The NICE-SUGAR Study Investigators. NEJM 360: 1283-1297, 2009
NICENICE--SUGARSUGARNormoglycemiaNormoglycemia in Intensive Care Evaluationin Intensive Care Evaluation--Survival Using Glucose Algorithm RegulationSurvival Using Glucose Algorithm Regulation
6104 Patients From ICUs of 42 6104 Patients From ICUs of 42 Hospitals in Australia, New Zealand, Hospitals in Australia, New Zealand, and North Americaand North AmericaConventionalConventional
Insulin Given For Glucose > 180 mg/dl Insulin Given For Glucose > 180 mg/dl and Stopped For Glucose < 144 mg/dland Stopped For Glucose < 144 mg/dl
IntensiveIntensiveGlucose Target: 81 Glucose Target: 81 –– 108 mg/dl108 mg/dl
The NICE-SUGAR Study Investigators. NEJM 360: 1283-1297, 2009
NICENICE--SUGARSUGARNormoglycemiaNormoglycemia in Intensive Care Evaluationin Intensive Care Evaluation--Survival Using Glucose Algorithm RegulationSurvival Using Glucose Algorithm Regulation
The NICE-SUGAR Study Investigators. NEJM 360: 1283-1297, 2009
Primary OutcomePrimary Outcome
Death from Any Cause Within Death from Any Cause Within 90 Days After Randomization90 Days After Randomization
90% Power To Detect Absolute Mortality 90% Power To Detect Absolute Mortality Difference of 3.8% Assuming Baseline Difference of 3.8% Assuming Baseline
Mortality of 30%Mortality of 30%
NICENICE--SUGARSUGARNormoglycemiaNormoglycemia in Intensive Care Evaluationin Intensive Care Evaluation--Survival Using Glucose Algorithm RegulationSurvival Using Glucose Algorithm Regulation
The NICE-SUGAR Study Investigators. NEJM 360: 1283-1297, 2009
144144±± 23 mg/dl23 mg/dl
115 115 ±± 18 mg/dl18 mg/dl
NICENICE--SUGARSUGARNormoglycemiaNormoglycemia in Intensive Care Evaluationin Intensive Care Evaluation--Survival Using Glucose Algorithm RegulationSurvival Using Glucose Algorithm Regulation
The NICE-SUGAR Study Investigators. NEJM 360: 1283-1297, 2009
OR 1.14 (CI, 1.02, 1.28)OR 1.14 (CI, 1.02, 1.28)
P = 0.02P = 0.02
Insulin In The Hospital Setting
The days of casual The days of casual glycemicglycemic control for control for critically ill patients critically ill patients
should be over!should be over!
AACE Position Statement 12/16/03: AACE Position Statement 12/16/03: Hospital Hospital GlycemicGlycemic GoalsGoals
Intensive Care Units: Intensive Care Units: 110 mg/110 mg/dLdL
NonNon--Critical Care Units:Critical Care Units:PrePre--PrandialPrandial 110 mg/110 mg/dLdLMax. Glucose Max. Glucose 180 mg/180 mg/dLdL
ADA/AACE Consensus Statement on ADA/AACE Consensus Statement on Inpatient Inpatient GlycemicGlycemic ControlControl
20092009Critically Sick PatientsCritically Sick Patients
--Threshold to Start Insulin Therapy No Threshold to Start Insulin Therapy No Greater Than 180 mg%Greater Than 180 mg%-- On Therapy Goal Is 140On Therapy Goal Is 140--180 mg%180 mg%
Non Critically Sick Patients*Non Critically Sick Patients*-- PrePre--Meal < 140 mg%Meal < 140 mg%-- Random < 180 mg%Random < 180 mg%
Moghissi, E et al Endocrine Practice May/June, 2009*Reaffirmed by the Endocrine Society, 2012
Insulin In The Hospital SettingInsulin In The Hospital SettingThe Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
Question:Question:Does Hyperglycemia,Does Hyperglycemia,New Or Established, New Or Established,
Predict MortalityPredict Mortality
Hyperglycemia: An Independent Marker Hyperglycemia: An Independent Marker of Inof In--Hospital Mortality in Patients with Hospital Mortality in Patients with
UndiagnosedUndiagnosed DiabetesDiabetes
Question: Does Hyperglycemia, New or Question: Does Hyperglycemia, New or Established, Predict Mortality? Established, Predict Mortality?
2030 Consecutive Records of Adults 2030 Consecutive Records of Adults Admitted to Georgia Baptist Hospital Admitted to Georgia Baptist Hospital
Hyperglycemia: FBG Hyperglycemia: FBG ≥≥ 126 mg/dl or 126 mg/dl or Random Random Glucose Glucose ≥≥ 200 mg/dl 200 mg/dl
New Hyperglycemia 223 Pts. (12%)New Hyperglycemia 223 Pts. (12%)Umpierrez GR et al. J Clin Endocrinol Metab 2002; 87:978
Hyperglycemia: An Independent Marker of InHyperglycemia: An Independent Marker of In--Hospital Hospital Mortality in Patients with Mortality in Patients with UndiagnosedUndiagnosed DiabetesDiabetes
1.7%3.8%
16.0%
0%
5%
10%
15%
20%
Normoglycemia Known Diabetes New Hyperglycemia
Umpierrez GR et al. J Clin Endocrinol Metab 2002; 87:978
Total MortalityTotal Mortality
A Marker of InA Marker of In--Hospital Mortality in Patients Hospital Mortality in Patients with with Undiagnosed Undiagnosed DiabetesDiabetes
New Hyperglycemia Patients ~3 New Hyperglycemia Patients ~3 xx’’ss As As Likely to Be Admitted to ICULikely to Be Admitted to ICU
New Hyperglycemia Patients Had New Hyperglycemia Patients Had Twice the Length of StayTwice the Length of Stay
Umpierrez GR et al. J Clin Endocrinol Metab 2002; 87:978
GlycemicGlycemic ControlControl
The Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
The Mechanism of InsulinThe Mechanism of Insulin’’s Benefits Benefit
The Achievement of InsulinThe Achievement of Insulin’’s Benefits Benefit
A Few CasesA Few Cases……
Beneficial Effects Of Insulin In The Beneficial Effects Of Insulin In The Critical Care SettingCritical Care Setting
Hyperglycemia Is BadHyperglycemia Is BadSince Insulin Reduces Since Insulin Reduces Glucose, It Is GoodGlucose, It Is Good……But Beyond GlucoseBut Beyond Glucose……
InsulinInsulinIn The Critical Care SettingIn The Critical Care Setting
VasodilatesVasodilatesActs As Metabolic ModulatorActs As Metabolic Modulator
Enhances Cell SurvivalEnhances Cell SurvivalRestrains PlateletsRestrains Platelets
Promotes Promotes FibrinolysisFibrinolysisEnhances Granulocyte FunctionEnhances Granulocyte Function
Is A Potent AntiIs A Potent Anti--Inflammatory AgentInflammatory Agent
GlycemicGlycemic ControlControl
The Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
The Mechanism of InsulinThe Mechanism of Insulin’’s Benefits Benefit
The Achievement of InsulinThe Achievement of Insulin’’s Benefits Benefit
A Few CasesA Few Cases……
IV Insulin Infusion IV Insulin Infusion ProtocolsProtocols
IV Insulin Protocol Based On Insulin Protocol Based On Insulin SensitivityInsulin Sensitivity
BG Units/hr BG Units/hr BG Units/hr BG Units/hr< 60 = Hypoglycemia
<80 Off <80 Off <80 Off <80 Off80-109 0.2 80-109 0.5 80-109 1 80-109 1.5
110-119 0.5 110-119 1 110-119 2 110-119 3120-149 1 120-149 1.5 120-149 3 120-149 5150-179 1.5 150-179 2 150-179 5 150-179 7180-209 2 180-209 3 180-209 6 180-209 9210-239 2 210-239 4 210-239 7 210-239 12240-269 3 240-269 5 240-269 8 240-269 16270-299 3 270-299 6 270-299 10 270-299 20300-329 4 300-329 7 300-329 12 300-329 24330-359 4 330-359 8 330-359 14 >330 28
>360 6 >360 12 >360 16
Algorithm 1 Algorithm 2 Algorithm 3 Algorithm 4
IV Insulin Protocol Based On Insulin Sensitivity
≥ 320 40≥ 310 26≥ 390 24≥ 310 13≥ 320 10≥ 390 6
250–319 32260–309 22320–389 20260–309 11250–319 8320–389 5
215–249 24210–259 18250–319 16210–259 9180–249 6250–319 4
180–214 20185–209 14215–249 12160–209 7163–179 4180–249 3
163–179 16160–184 12180–214 10148–159 5145–162 3.5163–179 2
145–162 14135–159 10145–179 8135–147 4.5134–144 3145–162 1.7
128–144 12123–134 8128–144 6123–134 4122–133 2.6128–144 1.5
110–127 10110–122 7110–127 5110–122 3.5110–121 2.3110–127 1.2
105–109 8105–109 6105–109 4105–109 3105–109 2105–109 1
100–104 4.3100–104 3.3100–104 2.4100–104 1.8100–104 1.3100–104 0.7
95– 99 2.395–99 1.995–99 1.495–99 1.195–99 0.895–99 0.5
90–94 1.290–94 1.090–94 0.890–94 0.790–94 0.690–94 0.4
85–89 0.685–89 0.685–89 0.585–89 0.485–89 0.485–89 0.3
80–84 0.380–84 0.380–84 0.380–84 0.380–84 0.280–84 0.2
75–79 0.275–79 0.275–79 0.275–79 0.275–79 0.1
70–74 0.170–74 0.170–74 0.170–74 0.170–74 0.1
< 70 0.05< 70 0.05< 70 0.05< 70 0.05< 70 0.05
BG units/hBG units/hBG units/hBG units/hBG units/hBG units/hAlgorithm 6Algorithm 5Algorithm 4Algorithm 3Algorithm 2Algorithm 1
Drip On @ Drip On @ 160 mg/dl160 mg/dl
Drip Off @ Drip Off @ 120 mg/dl120 mg/dl
Aim For Aim For 140 mg/dl140 mg/dl
< 120 Off< 120 Off120120--149 1.0149 1.0150150--179 1.5179 1.5180180--209 2.0209 2.0210210--239 2.0 239 2.0 240240--269 3.0269 3.0270270--299 3.0299 3.0300300--329 4.0329 4.0
Etc.Etc.
Suppose The PatientSuppose The PatientStarts With BG = 254 mg/dlStarts With BG = 254 mg/dl
Insulin Drip AlgorithmInsulin Drip Algorithm
< 120 Off< 120 Off120120--149 1.0149 1.0150150--179 1.5179 1.5180180--209 2.0209 2.0210210--239 2.0 239 2.0 240240--269 3.0269 3.0270270--299 3.0299 3.0300300--329 4.0329 4.0
Etc.Etc.
Suppose The PatientSuppose The PatientStarts With BG = 254Starts With BG = 254But After One Hour The But After One Hour The Glucose Remains About The Glucose Remains About The SameSame
Insulin Drip AlgorithmInsulin Drip Algorithm
< 120 Off < 120 Off< 120 Off < 120 Off120120--149 1.0149 1.0 120120--149 1.5149 1.5150150--179 1.5179 1.5 150150--179 2.0179 2.0180180--209 2.0209 2.0 180180--209 3.0209 3.0210210--239 2.0 239 2.0 210210--239 4.0239 4.0240240--269 3.0269 3.0 240240--269 5.0269 5.0270270--299 3.0299 3.0 270270--299 6.0299 6.0300300--329 4.0 300329 4.0 300--329 7.0329 7.0
Etc. Etc.Etc. Etc.
The Next AlgorithmThe Next AlgorithmThe Initial Algorithm
ComputerComputer--based Insulin Infusion based Insulin Infusion ProtocolsProtocols
GlucommanderGlucommanderPractical Alternative to IV Insulin ProtocolsPractical Alternative to IV Insulin Protocols
Recommended IV FluidsRecommended IV FluidsTo Prevent Hypoglycemia, To Prevent Hypoglycemia,
HypokalemiaHypokalemia & Ketosis:& Ketosis:
Glucose: 5Glucose: 5--10 10 gmsgms/hour/hourPotassium: 20 Potassium: 20 meqmeq/L/LThe Primary Service Should Choose The Primary Service Should Choose the Type and the Rate of the Fluid the Type and the Rate of the Fluid Depending on the Underlying DiseaseDepending on the Underlying Disease
Life After The Life After The DripDrip……..
Transition From IV to SQ Insulin Transition From IV to SQ Insulin In The Adult PatienIn The Adult Patientt
Insu
lin(µ
U/m
L)G
luco
se(m
g/dL
)
Basal Basal -- BolusBolus
150
100
50
07 8 91011121 2 3 4 5 6 7 8 9
A.M. P.M.
Basal Glucose
Time of Day
50
25
0 Basal InsulinBreakfast Lunch Supper
Prandial Glucose
Bolus Insulin
Currently Available Basal Insulins
Neutral Neutral ProtamineProtamine HagedornHagedorn(1946)(1946)
Insulin Insulin GlargineGlargine (2001)(2001)
InsuinInsuin DetemirDetemir (2006)(2006)
NPH/NPH/RegReg Vs. Vs. GlargineGlargine Insulin After Insulin After Cardiovascular SurgeryCardiovascular Surgery
Yeldandi, R et al Diabetes Technology & Therapeutics 8: 609-616, 2006
Transition to SQ: An ApproachTransition to SQ: An Approach
To Transition A Patient From An IV To Transition A Patient From An IV Insulin Infusion To SQ InsulinInsulin Infusion To SQ Insulin
Multiply Last Drip Dose By 20, And Multiply Last Drip Dose By 20, And Give This Amount As Give This Amount As GlargineGlargine
Turn The IV Drip Off 2 Hours LaterTurn The IV Drip Off 2 Hours Later
ExampleExample: Last Drip Dose Is 1.0 Unit/Hour; : Last Drip Dose Is 1.0 Unit/Hour; Give 1.0 X 20 = Give 1.0 X 20 = 2020 Units Of Units Of GlargineGlargine SQ; SQ; Discontinue Drip Two Hours LaterDiscontinue Drip Two Hours Later
This Is This Is BasalBasal InsulinInsulin
Insu
lin(µ
U/m
L)G
luco
se(m
g/dL
)Basal Basal -- BolusBolus
150
100
50
07 8 91011121 2 3 4 5 6 7 8 9
A.M. P.M.
Basal Glucose
Time of Day
50
25
0 Basal InsulinBreakfast Lunch Supper
Prandial Glucose
Bolus Insulin
Transition From IV to SQ Transition From IV to SQ Insulin In The Adult PatienInsulin In The Adult Patientt
Basal InsulinBasal InsulinBolus InsulinBolus InsulinPrandialPrandial InsulinInsulin
Correction Factor InsulinCorrection Factor Insulin
Currently AvailableBolus Insulins
Regular (1921)Regular (1921)Insulin Insulin LisproLispro (1996)(1996)Insulin Insulin AspartAspart (2000)(2000)
InsulnInsuln GlulisineGlulisine (2006)(2006)
Insulin Profiles
0 2 4 6 8 10 12 14 16 18 20 22 24
Pla
sma I
nsu
lin
Levels
Regular
Time (hr)
Aspart, Lispro, Glulisine
Rosenstock J. Clin Cornerstone. 2001;4:50
First, The First, The PrandialPrandialDoseDose……
When Patient Is Able To Eat, When Patient Is Able To Eat,
Add Rapid Acting Insulin For Add Rapid Acting Insulin For Mealtime CoverageMealtime Coverage
Rule Of ThumbRule Of Thumb50% Basal 50% Basal
50% 50% PrandialPrandial, Divided Over 3 Meals, Divided Over 3 Meals
ExampleExample: Patient Is On 20 Units : Patient Is On 20 Units GlargineGlargine Daily; Give 7 Units With Daily; Give 7 Units With Each Meal Of Each Meal Of LisproLispro ((HumalogHumalog) Or ) Or AspartAspart ((NovologNovolog) Or ) Or GlulisineGlulisine((ApidraApidra) )
This Is This Is PrandialPrandial InsulinInsulin
Basal-Bolus Insulin Therapy: Glargine at HS and Mealtime Insulin Lispro, Aspart, Or
Glulisine
SLB B
Lispro/Aspart/Glulisine
HS
Glargine
Insu
lin E
ffec
t
20 units
7units
Transition From IV to SQ Transition From IV to SQ Insulin In The Adult PatienInsulin In The Adult Patientt
Basal InsulinBasal InsulinBasal InsulinBolus InsulinBolus InsulinPrandialPrandialPrandial InsulinInsulinInsulin
Correction Factor InsulinCorrection Factor Insulin
Correction Factor Dose, Added To Prandial Dose
Low DoseTotal Insulin Dose <40 units/day
Medium DoseTotal Insulin Dose 40-80 units/day
High DoseTotal Insulin Dose >80 units/day
11 units
9 units
7 units
5 units
3 units
Additional Insulin
5 units>320
4 units271-320
3 units221-270
2 units171-220
1 unit120-170
Additional Insulin
PremealBG
9 units>320
7 units271-320
5 units221-270
3 units171-220
1 units120-170
Additional Insulin
PremealBG
>320
271-320
221-270
171-220
120-170
Premeal BG
What About Patients What About Patients Admitted With Admitted With
Hyperglycemia On The Hyperglycemia On The Floor?Floor?
Sliding ScaleSliding Scale
Episodic Bolus Episodic Bolus InsulinInsulin
WITHOUTWITHOUTBasal InsulinBasal Insulin
Basal Bolus Versus SSIBasal Bolus Versus SSIRandomized Study Of BasalRandomized Study Of Basal--Bolus Insulin Therapy In The Bolus Insulin Therapy In The Inpatient Management Of Patients With Type 2 Diabetes Inpatient Management Of Patients With Type 2 Diabetes
The RABBIT 2 TrialThe RABBIT 2 Trial
130 Type 2 Diabetic Patients Admitted to 130 Type 2 Diabetic Patients Admitted to General Medicine ServicesGeneral Medicine ServicesManaged By Internal Medicine Residents Managed By Internal Medicine Residents Who Received A Copy Of Assigned Who Received A Copy Of Assigned Treatment ProtocolTreatment ProtocolBasalBasal--Bolus Regime With Bolus Regime With GlargineGlargine And And GlulisineGlulisine Compared To SSICompared To SSI
Umpierrez, G. et al Diabetes Care 30: 2181-2186, 2007
Basal Bolus Versus SSIBasal Bolus Versus SSIRandomized Study Of BasalRandomized Study Of Basal--Bolus Insulin Therapy In The Bolus Insulin Therapy In The Inpatient Management Of Patients With Type 2 Diabetes Inpatient Management Of Patients With Type 2 Diabetes
The RABBIT 2 TrialThe RABBIT 2 Trial
Umpierrez, G. et al Diabetes Care 30: 2181-2186, 2007
Basal Bolus Versus SSIBasal Bolus Versus SSIRandomized Study Of BasalRandomized Study Of Basal--Bolus Insulin Therapy In The Bolus Insulin Therapy In The Inpatient Management Of Patients With Type 2 Diabetes Inpatient Management Of Patients With Type 2 Diabetes
The RABBIT 2 TrialThe RABBIT 2 Trial
Glucose Difference Between Groups 27 Glucose Difference Between Groups 27 mg% (p < 0.01)mg% (p < 0.01)
No Difference In Hypoglycemia (<0.5%)No Difference In Hypoglycemia (<0.5%)
Umpierrez, G. et al Diabetes Care 30: 2181-2186, 2007
Percentage of Patients at Target ( < 140 mg/dL)
Basal - Bolus Sliding Scale Insulin
66% 38%
Basal Bolus Versus SSIBasal Bolus Versus SSIRandomized Study Of BasalRandomized Study Of Basal--Bolus Insulin Therapy In The Bolus Insulin Therapy In The Inpatient Management Of Patients With Type 2 Diabetes Inpatient Management Of Patients With Type 2 Diabetes
The RABBIT 2 TrialThe RABBIT 2 Trial
Umpierrez, G. et al Diabetes Care 30: 2181-2186, 2007
Basal Bolus Versus SSIBasal Bolus Versus SSIThe RABBIT 2 Surgery StudyThe RABBIT 2 Surgery Study
211 Type 2 Diabetic Surgical Patients on 211 Type 2 Diabetic Surgical Patients on Surgical Wards, NOT ICUSurgical Wards, NOT ICUAge 58 Age 58 ±± 11 Years11 YearsAdmission Glucose 190 Admission Glucose 190 ±± 92 mg/dl92 mg/dlHbA1c 7.7 HbA1c 7.7 ±± 2.2 %2.2 %BasalBasal--Bolus Regime With Bolus Regime With GlargineGlargine And And GlulisineGlulisine Compared To SSICompared To SSI
Umpierrez, G. et al Diabetes Care 34: 256-261, 2011
Basal Bolus Versus SSIBasal Bolus Versus SSIThe RABBIT 2 Surgery StudyThe RABBIT 2 Surgery Study
Umpierrez, G. et al Diabetes Care 34: 256-261, 2011
* % of patients, but no difference in severe hypoglycemia (< 40 mg/dl
SSI Basal Bolus pGlucose 176 ± 44 157 ± 32 < 0.001
Hypoglycemia 4.7%* 23% < 0.001
Basal Bolus Versus SSIBasal Bolus Versus SSIThe RABBIT 2 Surgery StudyThe RABBIT 2 Surgery Study
Umpierrez, G. et al Diabetes Care 34: 256-261, 2011
* % of patients, but no difference in severe hypoglycemia (< 40 mg/dl
SSI Basal Bolus pGlucose 176 ± 44 157 ± 32 < 0.001
Hypoglycemia 4.7%* 23% < 0.001Composite AE 24.3% 8.6% = 0.003
Basal Bolus Versus SSIBasal Bolus Versus SSIThe RABBIT 2 Surgery StudyThe RABBIT 2 Surgery Study
Umpierrez, G. et al Diabetes Care 34: 256-261, 2011
Calculate Starting Total Daily Dose (TDD)Calculate Starting Total Daily Dose (TDD)Previous Total Daily Insulin Units Used orPrevious Total Daily Insulin Units Used or0.4 units/kg (Type 1 DM)0.4 units/kg (Type 1 DM)0.6 units/kg (New Onset Or Lean Type 2)0.6 units/kg (New Onset Or Lean Type 2)0.8 units/kg (Type 2 DM)0.8 units/kg (Type 2 DM)
This Is Very Conservative and Actual Needs This Is Very Conservative and Actual Needs May Turn Out to Be Substantially MoreMay Turn Out to Be Substantially More
Starting BasalStarting Basal--Bolus From Bolus From ScratchScratch
Glu
cose
(mg/
dL)
Median inpatient glucose levels
These data are confidential and to be used for quality improvement purposes only.Month (number of results)
02/20
03 (n
=939
6)
03/20
03 (n
=112
36)
04/20
03 (n
=831
3)
05/20
03 (n
=974
8)
06/20
03 (n
=105
39)
07/20
03 (n
=110
56)
08/20
03 (n
=109
03)
09/20
03 (n
=898
7)
10/20
03 (n
=106
26)
11/20
03 (n
=887
9)
12/20
03 (n
=890
6)
01/20
04 (n
=107
62)
02/20
04 (n
=103
92)
03/20
04 (n
=111
38)
04/20
04 (n
=108
80)
05/20
04 (n
=125
15)
06/20
04 (n
=113
14)
07/20
04 (n
=112
40)
08/20
04 (n
=116
71)
09/20
04 (n
=127
07)
10/20
04 (n
=124
24)
11/20
04 (n
=123
44)
12/20
04 (n
=133
47)
01/20
05 (n
=130
36)
02/20
05 (n
=101
10)
03/20
05 (n
=128
84)
04/20
05 (n
=105
37)
05/20
05 (n
=116
38)
06/20
05 (n
=101
89)
07/20
05 (n
=984
1)
08/20
05 (n
=140
18)
09/20
05 (n
=119
12)
10/20
05 (n
=453
7)
135
140
145
150
155
160
165
UCL = 166.82
Mean = 157.00
LCL = 147.18
UCL = 153.22
Mean = 144.68
LCL = 136.15
Definition: Median inpatient glucose levels in patients with diabetes. Glucose readings below 40mg/dL and above 400mg/dL were excluded. Data Source: Clarity database, FORCE database.
Analysis: The median inpatient glucose value, which was previously stable with a median of 157mg/dL, has decreased, and continues to decrease, with the implementation of inpatient insulin protocols.
Transition From IV To Subq Protocol And ICU Insulin Infusion Released
Non-ICU Hyperglycemia Management Protocol Released
A Word About Oral A Word About Oral AgentsAgents……..
Therapy of Type 2 Diabetes Mellitus:Hospital Use of Oral Agents
Illness Decreases Illness Decreases Endogenous InsulinEndogenous InsulinSecretagoguesSecretagogues
Can Give or NotCan Give or NotGlitazone(sGlitazone(s))
Hold for Acute Illness If Hold for Acute Illness If Renal, Cardiac, or Liver Renal, Cardiac, or Liver Function Unstable, or Function Unstable, or Surgery, or Surgery, or RadiocontrastRadiocontrast
MetforminMetformin
Not for Acute Illness Not for Acute Illness With Variable IntakeWith Variable Intake
αα GlucosidaseGlucosidaseInhibitorsInhibitors
Have A Discharge PlanHave A Discharge Plan
If PreIf Pre--Admission Control Acceptable, Admission Control Acceptable, YES!!!YES!!!
Admission HbA1C HelpfulAdmission HbA1C HelpfulIf PreIf Pre--Admission Control Admission Control NotNot Acceptable, Acceptable, Medication Adjustment NeededMedication Adjustment Needed
Can A Patient Go Back To Oral Can A Patient Go Back To Oral Agents At Discharge?Agents At Discharge?
GlycemicGlycemic ControlControl
The Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
The Mechanism of InsulinThe Mechanism of Insulin’’s Benefits Benefit
The Achievement of InsulinThe Achievement of Insulin’’s Benefits Benefit
A Few CasesA Few Cases……
Floor PatientFloor Patient65 65 y/oy/o male with DM2, male with DM2, hyperlipidemiahyperlipidemia, , HTN, and DJDHTN, and DJDAdmitted to General Medicine with chest Admitted to General Medicine with chest painpainMetformin 1000mg BID and Metformin 1000mg BID and glipizideglipizide 5mg 5mg BID; HbA1c 6.4% 2 weeks agoBID; HbA1c 6.4% 2 weeks agoGlucose on floor arrival 275 mg/dlGlucose on floor arrival 275 mg/dlAdmit ordersAdmit orders
Serial Serial troponinstroponinsPossible adenosine Possible adenosine myoviewmyoview
Floor PatientFloor Patient65 65 y/oy/o malemaleDM2, DM2, hyperlipidemiahyperlipidemia, , HTN, and DJDHTN, and DJDMetformin 1000mg Metformin 1000mg BID and BID and glipizideglipizide5mg BID5mg BIDHbA1c 6.4% HbA1c 6.4% Glucose 275 mg/dlGlucose 275 mg/dlAdmit ordersAdmit orders
Serial Serial troponinstroponinsPossible adenosine Possible adenosine myoviewmyoview
What should be started to control glucose?
a) Metformin onlyb) Glipizide onlyc) Metformin and glipizided) Glargine and loge) Insulin and metforminf) Insulin and glipizide
Floor Patient65 65 y/oy/o male (75kg)male (75kg)DM2, DM2, hyperlipidemiahyperlipidemia, , HTN, and DJDHTN, and DJDMetformin 1000mg Metformin 1000mg BID and BID and glipizideglipizide5mg BID5mg BIDHbA1c 6.4% HbA1c 6.4% Glucose 275 mg/dlGlucose 275 mg/dlAdmit ordersAdmit orders
Serial Serial troponinstroponinsPossible adenosine Possible adenosine myoviewmyoview
Start Start glargineglargine and and loglog
What would be the insulin doses?
1)75 kg patient2)75 x 0.8 = 60 units insulin
total3)60 / 2 = 30 units4)30 units basal (glargine)5)30 units prandial (log) --
10 units after each meal6)Medium dose correction
factor
Floor Patient65 65 y/oy/o male (75kg)male (75kg)DM2, DM2, hyperlipidemiahyperlipidemia, , HTN, and DJDHTN, and DJDMetformin 1000mg Metformin 1000mg BID and BID and glipizideglipizide5mg BID5mg BIDHbA1c 6.4% HbA1c 6.4% Glucose 275 mg/dlGlucose 275 mg/dlAdmit ordersAdmit orders
Serial Serial troponinstroponinsPossible adenosine Possible adenosine myoviewmyoview
Start Start glargineglargine and and loglog
Patient NPO after Patient NPO after midnight for midnight for adenosine adenosine myoviewmyoview
How should insulin orders be changed once he is NPO?a) Stop all of the insulinb) Hold the prandial log only, continue glargine and
correction scalec) Hold the glargine only, continue log and correction scale
Floor Patient65 65 y/oy/o male (75kg)male (75kg)DM2, DM2, hyperlipidemiahyperlipidemia, , HTN, and DJDHTN, and DJDMetformin 1000mg Metformin 1000mg BID and BID and glipizideglipizide5mg BID5mg BIDHbA1c 6.4% HbA1c 6.4% Glucose 275 mg/dlGlucose 275 mg/dlAdmit ordersAdmit orders
Serial Serial troponinstroponinsPossible adenosine Possible adenosine myoviewmyoview
Start Start glargineglargine and and loglog
Patient NPO after Patient NPO after midnight for midnight for adenosine adenosine myoviewmyoview
Reversible defect Reversible defect on on myoviewmyoview led led to stentto stent
With which diabetes medication(s) should the patient be sent home?
a) Glargine and logb) Metformin 1000mg BID and glipizide 5mg BIDc) Insulin pump
ICU PatientICU Patient65 65 y/oy/o female with DM2, HTN, & female with DM2, HTN, & hyperlipidemiahyperlipidemiaAdmitted to the MICU with sepsisAdmitted to the MICU with sepsisMetformin 1000mg BID, Metformin 1000mg BID, glipizideglipizide 10mg 10mg BID q dayBID q dayHbA1c 8% 3 months agoHbA1c 8% 3 months agoGlucose on MICU arrival 230 mg/dlGlucose on MICU arrival 230 mg/dlWhat therapy should be started for What therapy should be started for glucose control?glucose control?
a. Continue a. Continue metforminmetformin and and glipizideglipizideb. Start b. Start glargineglargine and logand logc. Start an insulin dripc. Start an insulin drip
ICU PatientICU Patient
65 65 y/oy/o female with female with DM2, HTN, & DM2, HTN, & hyperlipidemiahyperlipidemiaAdmitted to the Admitted to the MICU with sepsisMICU with sepsisGlucose on MICU Glucose on MICU arrival 230 mg/dlarrival 230 mg/dlInsulin drip startedInsulin drip started
What diabetes lab should be ordered?a) Urine microalbuminb) Hemoglobin A1cc) Nothing
ICU PatientICU Patient65 65 y/oy/o female with female with DM2, HTN, & DM2, HTN, & hyperlipidemiahyperlipidemiaAdmitted to the MICU Admitted to the MICU with sepsiswith sepsisGlucose on MICU Glucose on MICU arrival 230 mg/dlarrival 230 mg/dlInsulin drip startedInsulin drip startedClear liquids startedClear liquids started
How should new diet be covered?
a) Adjust the insulin dripb) Continue the drip, start
SC log with carbohydrate counting
c) Continue the drip, restart glipizide
ICU PatientICU Patient65 65 y/oy/o female with female with DM2, HTN, & DM2, HTN, & hyperlipidemiahyperlipidemiaAdmitted to the MICU Admitted to the MICU with sepsiswith sepsisGlucose on MICU Glucose on MICU arrival 230 mg/dlarrival 230 mg/dlInsulin drip startedInsulin drip startedClear liquids startedClear liquids startedTransferring to Gen Transferring to Gen MedMed
What about insulin orders?a) Continue the insulin dripb) Stop the drip, start sliding
scale log c) Stop drip, start glargine/log
ICU PatientICU Patient65 65 y/oy/o female with female with DM2, HTN, & DM2, HTN, & hyperlipidemiahyperlipidemiaAdmitted to the MICU Admitted to the MICU with sepsiswith sepsisGlucose on MICU Glucose on MICU arrival 230 mg/dlarrival 230 mg/dlInsulin drip startedInsulin drip startedClear liquids startedClear liquids startedTransferring to Gen Transferring to Gen MedMed
What are the insulin doses, assuming last drip dose was
1.5 units/hour?
Glargine (1.5 units x 20 = 30 units)Log (30 units / 3 = 10 units)
10 units after each mealMedium dose correction factor
ICU PatientICU Patient65 65 y/oy/o female with female with DM2, HTN, & DM2, HTN, & hyperlipidemiahyperlipidemiaAdmitted to the MICU Admitted to the MICU with sepsiswith sepsisGlucose on MICU Glucose on MICU arrival 230 mg/dlarrival 230 mg/dlInsulin drip startedInsulin drip startedClear liquids startedClear liquids startedTransferring to Gen Transferring to Gen MedMed
What happens to the insulin drip?
Discontinue the insulin drip 2 hours after glargine injected
Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient
65 y/o female with DM2 and sepsis65 y/o female with DM2 and sepsisGlargine 30 units daily and log 10 units Glargine 30 units daily and log 10 units TIDTIDMedium dose correction factor Medium dose correction factor Daily insulin dose adjustmentsDaily insulin dose adjustments
Take the previous dayTake the previous day’’s correction s correction factor insulin dosefactor insulin doseAdd to todayAdd to today’’s insulin doses insulin dose
ADA/AACE Consensus Statement on ADA/AACE Consensus Statement on Inpatient Glycemic ControlInpatient Glycemic Control
20092009Critically Sick PatientsCritically Sick Patients
--Threshold to Start Insulin Therapy No Threshold to Start Insulin Therapy No Greater Than 180 mg%Greater Than 180 mg%-- On Therapy Goal Is 140On Therapy Goal Is 140--180 mg%180 mg%
Non Critically Sick Patients*Non Critically Sick Patients*-- PrePre--Meal < 140 mg%Meal < 140 mg%-- Random < 180 mg%Random < 180 mg%
Moghissi, E et al Endocrine Practice May/June, 2009*Reaffirmed by the Endocrine Society, 2012
Correction Factor Dose, Added To Prandial Dose
Low DoseTotal Insulin Dose <40 units/day
Medium DoseTotal Insulin Dose 40-80 units/day
High DoseTotal Insulin Dose >80 units/day
11 units
9 units
7 units
5 units
3 units
Additional Insulin
5 units>320
4 units271-320
3 units221-270
2 units171-220
1 unit120-170
Additional Insulin
Premeal BG
9 units>320
7 units271-320
5 units221-270
3 units171-220
1 units120-170
Additional Insulin
Premeal BG
>320
271-320
221-270
171-220
120-170
Premeal BG
Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient
65 y/o female with DM2 and sepsis65 y/o female with DM2 and sepsisGlargine 30 units daily and log 10 units Glargine 30 units daily and log 10 units TIDTIDMedium dose correction factor Medium dose correction factor YesterdayYesterday’’s Glucose values:s Glucose values:
Fasting 175 mg/dl 3 units Fasting 175 mg/dl 3 units PrePre--lunch 190 mg/dl 3 units lunch 190 mg/dl 3 units PrePre--dinner 225 mg/dl 5 unitsdinner 225 mg/dl 5 unitsHS 190 mg/dlHS 190 mg/dl
11 units of correction factor (CF) 11 units of correction factor (CF) aspart givenaspart given
Former ICU, Now Floor, PatientFormer ICU, Now Floor, PatientHow would you adjust today’s insulin dose?
Since all readings are above target, you could
add ~½ of CF to glargine and the remainder divided equally with
each meal.
Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient
65 65 y/oy/o female with DM2 and sepsisfemale with DM2 and sepsisGlargineGlargine 30 units daily and log 10 units 30 units daily and log 10 units TIDTIDMedium dose correction factor Medium dose correction factor
Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient
65 65 y/oy/o female with DM2 and sepsisfemale with DM2 and sepsisGlargineGlargine 3535 units daily and log units daily and log 1212 units units TIDTIDMedium dose correction factor Medium dose correction factor YesterdayYesterday’’s Glucose values:s Glucose values:
Fasting 120 mg/dl 1 unit Fasting 120 mg/dl 1 unit PrePre--lunch 150 mg/dl 1 unitlunch 150 mg/dl 1 unitPrePre--dinner 150 mg/dl 1 unitdinner 150 mg/dl 1 unitHS 180 mg/dlHS 180 mg/dl
3 units of correction factor (CF) 3 units of correction factor (CF) aspartaspart givengiven
Former ICU, Now Floor, PatientFormer ICU, Now Floor, PatientHow would you adjust today’s insulin dose?Fasting glucose is at target, but the rest of
the day is above target. So, you could
add the 1/3 of the entire CF with each
meal
Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient
65 65 y/oy/o female with DM2 and sepsisfemale with DM2 and sepsisGlargineGlargine 3535 units daily and log units daily and log 1212 units units TIDTIDMedium dose correction factor Medium dose correction factor
Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient
65 65 y/oy/o female with DM2 and sepsisfemale with DM2 and sepsisGlargineGlargine 3535 units daily and log units daily and log 1313 units units TIDTIDMedium dose correction factor Medium dose correction factor YesterdayYesterday’’s Glucose values:s Glucose values:
Fasting 115 mg/dl Fasting 115 mg/dl PrePre--lunch 118 mg/dllunch 118 mg/dlPrePre--dinner 119 mg/dldinner 119 mg/dlHS 170 mg/dlHS 170 mg/dl
No correction factor (CF) No correction factor (CF) aspartaspartgivengiven
Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient
Patient going home!!Patient going home!!On On GlargineGlargine and and aspartaspartHbA1c 9%HbA1c 9%
How should her diabetes medication(s) be adjusted?a) Discontinue insulin and restart oral medicationsb) Reintroduce metformin to insulin c) Continue insulin only
Special SituationsSpecial Situations
Patients Receiving CorticosteroidsPatients Receiving Corticosteroids
Patients Receiving Tube FeedsPatients Receiving Tube Feeds
Patients With Renal FailurePatients With Renal Failure
Patient on Patient on GlucocorticoidsGlucocorticoidsGlucocorticoid Effects on Glucose Glucocorticoid Effects on Glucose
MetabolismMetabolismIncreased hepatic gluconeogenesis Increased hepatic gluconeogenesis increases fasting glucoseincreases fasting glucoseInhibition of glucose uptake especially in Inhibition of glucose uptake especially in adipose tissue increases postadipose tissue increases post--prandial prandial glucoseglucosePredominant effect is postPredominant effect is post--prandial, so prandial, so glucose rises during the dayglucose rises during the day
InsulinInsulin
BreakfastBreakfast LunchLunch DinnerDinner
Basal/Bolus In Treating HyperglycemiaBasal/Bolus In Treating Hyperglycemia
GlucoseGlucose
InsulinInsulin
BreakfastBreakfast LunchLunch DinnerDinner
BasalBasal
BolusBolus
Basal/Bolus In Treating HyperglycemiaBasal/Bolus In Treating Hyperglycemia
50%50%
50%50%
GlucoseGlucose
InsulinInsulin
BreakfastBreakfast LunchLunch DinnerDinner
Basal/Bolus In Treating HyperglycemiaBasal/Bolus In Treating Hyperglycemia
GlucoseGlucose
InsulinInsulin
BreakfastBreakfast LunchLunch DinnerDinner
Patients On Once A Day Patients On Once A Day CorticosteroidsCorticosteroids
GlucoseGlucose
InsulinInsulin
BreakfastBreakfast LunchLunch DinnerDinner
Patients On Once A Day Patients On Once A Day CorticosteroidsCorticosteroids
GlucoseGlucose
>50%>50% BolusBolus
BasalBasal<50%<50%
InsulinInsulin
BreakfastBreakfast LunchLunch DinnerDinner
With CorticosteriodsWith Corticosteriods
Or Add Morning NPH Or Add Morning NPH …………
NPHNPH
GlucoseGlucose
Add Rapid Acting Insulin With DinnerAdd Rapid Acting Insulin With Dinner
NPH May Not Be EnoughNPH May Not Be Enough……..
GlucocorticoidGlucocorticoid Treated PatientTreated Patient
43 year old female with type 1 diabetes 43 year old female with type 1 diabetes on basal bolus regime with almost all on basal bolus regime with almost all glucose values at target in the glucose values at target in the outpatient settingoutpatient settingAdmitted to hospital for a worsening of Admitted to hospital for a worsening of asthma and put on a high dose asthma and put on a high dose morning morning glucocorticoidglucocorticoid regimeregime
GlucocorticoidGlucocorticoid Treated PatientTreated Patient
Outpatient basal bolus regime Outpatient basal bolus regime consisted of consisted of
Insulin Insulin glargineglargine 20 units at HS20 units at HSInsulin Insulin aspartaspart 7 units with each meal 7 units with each meal Medium dose correction factorMedium dose correction factor
ADA/AACE Consensus Statement on ADA/AACE Consensus Statement on Inpatient Inpatient GlycemicGlycemic ControlControl
20092009Critically Sick PatientsCritically Sick Patients
--Threshold to Start Insulin Therapy No Threshold to Start Insulin Therapy No Greater Than 180 mg%Greater Than 180 mg%-- On Therapy Goal Is 140On Therapy Goal Is 140--180 mg%180 mg%
Non Critically Sick Patients*Non Critically Sick Patients*-- PrePre--Meal < 140 mg%Meal < 140 mg%-- Random < 180 mg%Random < 180 mg%
Moghissi, E et al Endocrine Practice May/June, 2009*Reaffirmed by the Endocrine Society, 2012
Correction Factor Dose, Added To Prandial Dose
Low DoseTotal Insulin Dose <40 units/day
Medium DoseTotal Insulin Dose 40-80 units/day
High DoseTotal Insulin Dose >80 units/day
11 units
9 units
7 units
5 units
3 units
Additional Insulin
5 units>320
4 units271-320
3 units221-270
2 units171-220
1 unit120-170
Additional Insulin
Premeal BG
9 units>320
7 units271-320
5 units221-270
3 units171-220
1 units120-170
Additional Insulin
Premeal BG
>320
271-320
221-270
171-220
120-170
Premeal BG
Glucocorticoid Treated PatientGlucocorticoid Treated PatientYesterdayYesterday’’s insulin regime:s insulin regime:
Insulin glargine 20 units at HSInsulin glargine 20 units at HSInsulin aspart 7 units with each meal Insulin aspart 7 units with each meal Medium dose correction factorMedium dose correction factor
YesterdayYesterday’’s Glucose values:s Glucose values:Fasting 180 mg/dl 3 units Fasting 180 mg/dl 3 units PrePre--lunch 225 mg/dl 5 unitslunch 225 mg/dl 5 unitsPrePre--dinner 250 mg/dl 5 unitsdinner 250 mg/dl 5 unitsHS 195 mg/dlHS 195 mg/dl
13 units of correction factor (CF) 13 units of correction factor (CF) aspartaspart
GlucocorticoidGlucocorticoid Treated PatientTreated PatientHow would you adjust today’s insulin dose?
Since all readings are above target, you should
add CF to today’s regime, but rather than 50%/50% split, consider 40% addition to basal
and 60% to bolus.
Glucocorticoid Treated PatientGlucocorticoid Treated PatientYesterdayYesterday’’s insulin regime:s insulin regime:
Insulin glargine 20 units at HSInsulin glargine 20 units at HSInsulin aspart 7 units with each meal Insulin aspart 7 units with each meal Medium dose correction factorMedium dose correction factor
13 units X 0.4 = 5.2, so add about 5 units 13 units X 0.4 = 5.2, so add about 5 units to basalto basal13 units X 0.6 = 7.8, so add about 813 units X 0.6 = 7.8, so add about 8--9 units 9 units to bolusto bolus
Glucocorticoid Treated PatientGlucocorticoid Treated PatientYesterdayYesterday’’s insulin regime:s insulin regime:
Insulin glargine Insulin glargine 25 25 units at HSunits at HSInsulin aspart Insulin aspart 1010 units with each meal units with each meal Medium dose correction factorMedium dose correction factor
YesterdayYesterday’’s Glucose values:s Glucose values:Fasting 110 mg/dl 0 unit Fasting 110 mg/dl 0 unit PrePre--lunch 118 mg/dl 0 unitlunch 118 mg/dl 0 unitPrePre--dinner 115 mg/dl 0 unitdinner 115 mg/dl 0 unitHS 165 mg/dlHS 165 mg/dl
0 units of correction factor (CF) 0 units of correction factor (CF) aspartaspart
Special SituationsSpecial Situations
Patients Receiving CorticosteroidsPatients Receiving Corticosteroids
Patients Receiving Tube FeedsPatients Receiving Tube Feeds
Patients With Renal FailurePatients With Renal Failure
The Impact of Tube Feed on InThe Impact of Tube Feed on In--Patient HyperglycemiaPatient Hyperglycemia
Continuous And Persistent Carbohydrate Continuous And Persistent Carbohydrate AbsorptionAbsorption
Continuous And Persistent HyperglycemiaContinuous And Persistent Hyperglycemia
The Basal/Bolus Rule Is DifferentThe Basal/Bolus Rule Is Different……....
Glucose Glucose No TubeNo TubeFeedFeed
BreakfastBreakfast LunchLunch DinnerDinner
The Impact of Tube Feeding onThe Impact of Tube Feeding onInIn--Patient HyperglycemiaPatient Hyperglycemia
Tube Tube FeedFeed
Tube Feeding And InTube Feeding And In--Patient Patient HyperglycemiaHyperglycemia
InsulinInsulin
Continuous Tube FeedContinuous Tube Feed
GlucoseGlucose
Basal InsulinBasal Insulin == Total Daily DoseTotal Daily Dose
Patients on Continuous Tube FeedPatients on Continuous Tube Feed
Check Blood Glucose Every 6 Check Blood Glucose Every 6 HoursHours
Give Correction Factor Rapid Acting Give Correction Factor Rapid Acting Insulin Based On Algorithms Insulin Based On Algorithms
Patients on Continuous Tube FeedPatients on Continuous Tube Feed
Decrease Total DoseDecrease Total Dose10% If Glucose Level < 120 mg/dl 10% If Glucose Level < 120 mg/dl 20% Glucose Level < 80 mg/dl20% Glucose Level < 80 mg/dl
Increase Total DoseIncrease Total DoseBy Adding The Total Dose Of Correction By Adding The Total Dose Of Correction Factor Insulin The Previous DayFactor Insulin The Previous Day
Patients On Continuous Patients On Continuous Tube Feed And Liquid/Clear Tube Feed And Liquid/Clear
Diet Diet CarbohydrateCarbohydrate--Containing Liquid: Containing Liquid:
Give 1 unit For Each 15 Gram Give 1 unit For Each 15 Gram CarbohydrateCarbohydrate
BEWARE of BEWARE of HYPOGLYCEMIAHYPOGLYCEMIA
High Risk Of Hypoglycemia If Tube High Risk Of Hypoglycemia If Tube Feed Temporarily Stopped Feed Temporarily Stopped
Immediately Initiate IV Fluids To Immediately Initiate IV Fluids To Provide The Amount Of Glucose Provide The Amount Of Glucose That Was In The Tube FeedingThat Was In The Tube Feeding
GlucoseGlucose
BreakfastBreakfast LunchLunch DinnerDinner
Tube Feed at BedtimeTube Feed at Bedtime
NPH InsulinNPH Insulin
Patient on Continuous Tube Patient on Continuous Tube FeedingFeeding
71 year old male with type 2 diabetes 71 year old male with type 2 diabetes recovering from massive CVA leaving recovering from massive CVA leaving him unable to swallowhim unable to swallowHis outpatient glycemic regime His outpatient glycemic regime consisted of oral agents only, no insulinconsisted of oral agents only, no insulinHe is receiving continuous tube feedingHe is receiving continuous tube feedingHe weighs 180 lbs (82 kg)He weighs 180 lbs (82 kg)
How would you begin to develop his insulin regime?
Calculate Starting Total Daily Dose (TDD)Calculate Starting Total Daily Dose (TDD)Previous Total Daily Insulin Units Used orPrevious Total Daily Insulin Units Used or0.4 units/kg (Type 1 DM)0.4 units/kg (Type 1 DM)0.6 units/kg (New Onset Or Lean Type 2)0.6 units/kg (New Onset Or Lean Type 2)0.8 units/kg (Type 2 DM)0.8 units/kg (Type 2 DM)
Starting BasalStarting Basal--Bolus From Bolus From ScratchScratch
Calculate Starting Total Daily Dose (TDD)Calculate Starting Total Daily Dose (TDD)Previous Total Daily Insulin Units Used orPrevious Total Daily Insulin Units Used or0.50.5 units/kg (Type 1 DM)units/kg (Type 1 DM)0.80.8 units/kg (New Onset Or Lean Type 2)units/kg (New Onset Or Lean Type 2)1.01.0 units/kg (Type 2 DM)units/kg (Type 2 DM)
Starting BasalStarting Basal--Bolus From Bolus From ScratchScratch
Patient on Continuous Tube Patient on Continuous Tube FeedingFeeding
Weight based total daily dose of insulin Weight based total daily dose of insulin would be 1.0 units/kg X 82 kg = 82 unitswould be 1.0 units/kg X 82 kg = 82 unitsSo, give 82 units glargine as basalSo, give 82 units glargine as basalThere is no bolusThere is no bolusThere is, however, correction factor; There is, however, correction factor; high dose correction factorhigh dose correction factor
Correction Factor Dose, Added To Prandial Dose
Low DoseTotal Insulin Dose <40 units/day
Medium DoseTotal Insulin Dose 40-80 units/day
High DoseTotal Insulin Dose >80 units/day
11 units
9 units
7 units
5 units
3 units
Additional Insulin
5 units>320
4 units271-320
3 units221-270
2 units171-220
1 unit120-170
Additional Insulin
Premeal BG
9 units>320
7 units271-320
5 units221-270
3 units171-220
1 units120-170
Additional Insulin
Premeal BG
>320
271-320
221-270
171-220
120-170
Premeal BG
Patient on Continuous Tube Patient on Continuous Tube FeedingFeeding
Patient on 82 units glarginePatient on 82 units glargineYesterdayYesterday’’s Sugars CF Asparts Sugars CF Aspart
6 AM 210 mg/dl 5 units6 AM 210 mg/dl 5 unitsNoon 280 mg/dl 9 units Noon 280 mg/dl 9 units 6 PM 290 mg/dl 9 units 6 PM 290 mg/dl 9 units Midnight 310 mg/dl 9 unitsMidnight 310 mg/dl 9 units
32 units correction factor aspart 32 units correction factor aspart How would you adjust today’s insulin dose?
Patient on Continuous Tube Patient on Continuous Tube FeedingFeeding
Patient on Patient on 114114 units glargine (may split)units glargine (may split)YesterdayYesterday’’s Sugars CF Asparts Sugars CF Aspart
6 AM 180 mg/dl 5 units6 AM 180 mg/dl 5 unitsNoon 250 mg/dl 7 units Noon 250 mg/dl 7 units 6 PM 270 mg/dl 7 units 6 PM 270 mg/dl 7 units Midnight 280 mg/dl 9 unitsMidnight 280 mg/dl 9 units
28 units correction factor aspart 28 units correction factor aspart How would you adjust today’s insulin dose?
Patient on Continuous Tube Patient on Continuous Tube FeedingFeeding
Patient on Patient on 142142 units glargine (may split)units glargine (may split)YesterdayYesterday’’s Sugars CF Asparts Sugars CF Aspart
6 AM 135 mg/dl 3 units6 AM 135 mg/dl 3 unitsNoon 155 mg/dl 3 units Noon 155 mg/dl 3 units 6 PM 160 mg/dl 3 units 6 PM 160 mg/dl 3 units Midnight 170 mg/dl 3 unitsMidnight 170 mg/dl 3 units
12 units correction factor aspart 12 units correction factor aspart How would you adjust today’s insulin dose?
Patient on Continuous Tube Patient on Continuous Tube FeedingFeeding
Patient on Patient on 154154 units glargine (may split)units glargine (may split)YesterdayYesterday’’s Sugars CF Asparts Sugars CF Aspart
6 AM 110 mg/dl 0 units6 AM 110 mg/dl 0 unitsNoon 115 mg/dl 0 units Noon 115 mg/dl 0 units 6 PM 119 mg/dl 0 units 6 PM 119 mg/dl 0 units Midnight 119 mg/dl 0 unitsMidnight 119 mg/dl 0 units
0 units correction factor aspart 0 units correction factor aspart How would you adjust today’s insulin dose?
Special SituationsSpecial Situations
Patients Receiving CorticosteroidsPatients Receiving Corticosteroids
Patients Receiving Tube FeedsPatients Receiving Tube Feeds
Patients With Renal FailurePatients With Renal Failure
The Impact Of Renal Failure On InThe Impact Of Renal Failure On In--Patient HyperglycemiaPatient Hyperglycemia
Decreased Insulin ClearanceDecreased Insulin Clearance
Decreased GluconeogenesisDecreased Gluconeogenesis
Both Increase The Risk Of HypoglycemiaBoth Increase The Risk Of Hypoglycemia
Reduce Dose For Renal Reduce Dose For Renal InsufficiencyInsufficiency
ReduceReduce to 50%
ReduceReduce to 70%1515--2929
No ChangeNo Change>30 >30
Total Insulin DoseTotal Insulin DoseGFR GFR cc/mincc/min
<15 or Dialysis
Special SituationsSpecial Situations
Patients Receiving CorticosteroidsPatients Receiving Corticosteroids
Patients Receiving Tube FeedsPatients Receiving Tube Feeds
Patients With Renal FailurePatients With Renal Failure
GlycemicGlycemic ControlControl
The Evidence For InsulinThe Evidence For Insulin’’s Benefits Benefit
The Mechanism of InsulinThe Mechanism of Insulin’’s Benefits Benefit
The Achievement of InsulinThe Achievement of Insulin’’s Benefits Benefit
A Few CasesA Few Cases……