insulin-hospital 2009 -ne...the nice-sugar study investigators. nejm 360: 1283-1297, 2009 nice-sugar...

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




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


StudyStudyYearYear

YesYesThe Portland ProjectThe Portland ProjectOngoingOngoing

Yes*Yes*LeuvanLeuvan MICUMICU20062006

YesYesLazarLazar20042004YesYesKrinsleyKrinsley20042004

YesYesLeuvanLeuvan SICUSICU20012001

YesYesDIGAMI 1DIGAMI 119971997


StudyStudyYearYear

YesYesThe Portland ProjectThe Portland ProjectOngoingOngoingNoNoHIHI--5520062006

Yes*Yes*LeuvanLeuvan MICUMICU20062006NoNoCreate ECLACreate ECLA20052005NoNoDIGAM 2DIGAM 220052005YesYesLazarLazar20042004YesYesKrinsleyKrinsley20042004NoNoDutch GIKDutch GIK20032003YesYesLeuvanLeuvan SICUSICU20012001NoNoPolPol--GIKGIK19991999YesYesDIGAMI 1DIGAMI 119971997

GlycemicGlycemicSeparationSeparation


StudyStudyYearYear

YesYesYesYesThe Portland ProjectThe Portland ProjectOngoingOngoingNoNoNoNoHIHI--5520062006YesYesYes*Yes*LeuvanLeuvan MICUMICU20062006NoNoNoNoCreate ECLACreate ECLA20052005NoNoNoNoDIGAM 2DIGAM 220052005YesYesYesYesLazarLazar20042004YesYesYesYesKrinsleyKrinsley20042004NoNoNoNoDutch GIKDutch GIK20032003YesYesYesYesLeuvanLeuvan SICUSICU20012001NoNoNoNoPolPol--GIKGIK19991999YesYesYesYesDIGAMI 1DIGAMI 119971997



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


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



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




StudyStudyYearYear


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



StudyStudyYearYear


The The LeuvanLeuvan SICU StudySICU Study

Van den Berghe G. et al N Engl J Med 2001; 345:1359




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


6104 Patients From ICUs of 42 Hospitals in 6104 Patients From ICUs of 42 Hospitals in Australia, New Zealand, and North Australia, New Zealand, and North AmericaAmerica2 2 GlycemicGlycemic Treatment Groups:Treatment Groups:

Insulin Given For Glucose > 180 mg/dl and Insulin Given For Glucose > 180 mg/dl and Stopped For Glucose < 144 mg/dlStopped For Glucose < 144 mg/dlGlucose Target: 81 Glucose Target: 81 –– 108 mg/dl108 mg/dl

Median Duration of Treatment 4.2 Median Duration of Treatment 4.2 -- 4.3 4.3 DaysDays




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%



144144±± 23 mg/dl23 mg/dl

115 115 ±± 18 mg/dl18 mg/dl



OR 1.14 (CI, 1.02, 1.28)OR 1.14 (CI, 1.02, 1.28)

P = 0.02P = 0.02


CV Death More Common With CV Death More Common With Intensive Control, 42 vs. 36%, p = Intensive Control, 42 vs. 36%, p = 0.020.02Number Needed To Harm: 38Number Needed To Harm: 38Hypoglycemia ( < 40 mg/dl) More Hypoglycemia ( < 40 mg/dl) More Common With Intensive Control, 6% Common With Intensive Control, 6% vs. 0.5%, p < 0.001vs. 0.5%, p < 0.001



Intensive Intensive GlycemicGlycemic Control Led To Control Led To NoNoDifference InDifference In

Single or Multiple Organ FailureSingle or Multiple Organ FailureNumber Of Ventilator DaysNumber Of Ventilator DaysRenal Replacement TherapyRenal Replacement TherapyPositive Blood CulturesPositive Blood CulturesRBC TransfusionRBC Transfusion


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 PatientsNon 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

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






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






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

< 70 Off< 70 Off7070--109 0.2109 0.2

110110--119 0.5119 0.5120120--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

< 70 Off< 70 Off7070--109 0.2109 0.2

110110--119 0.5119 0.5120120--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/dlBut After 1 Hour The BG But After 1 Hour The BG Remains About The SameRemains About The Same

Insulin Drip AlgorithmInsulin Drip Algorithm

< 70 Off< 70 Off < 70 Off< 70 Off7070--109 0.2109 0.2 7070--109 0.5109 0.5

110110--119 0.5119 0.5 110110--119 1.0119 1.0120120--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 AlgorithmThe Initial Algorithm

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 Protamine Hagedorn Neutral Protamine Hagedorn (1946)(1946)

Insulin Glargine (2001)Insulin Glargine (2001)

Insuin Detemir (2006)Insuin Detemir (2006)

NPH/Reg Vs. Glargine Insulin After NPH/Reg Vs. Glargine 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 GlargineGive This Amount As Glargine

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 = 20 Units Of Glargine SQ; Give 1.0 X 20 = 20 Units Of Glargine 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 InsulinPrandial InsulinPrandial Insulin

Correction Factor InsulinCorrection Factor Insulin

Currently AvailableBolus Insulins

Regular (1921)Regular (1921)Insulin Lispro (1996)Insulin Lispro (1996)Insulin Aspart (2000)Insulin Aspart (2000)

Insuln Glulisine (2006)Insuln Glulisine (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 Prandial First, The Prandial DoseDose……

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% Prandial, Divided Over 3 Meals50% Prandial, Divided Over 3 Meals

ExampleExample: Patient Is On 20 Units : Patient Is On 20 Units Glargine Daily; Give 7 Units With Glargine Daily; Give 7 Units With Each Meal Of Lispro (Humalog) Or Each Meal Of Lispro (Humalog) Or Aspart (Novolog) Or Glulisine Aspart (Novolog) Or Glulisine (Apidra) (Apidra)

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 InsulinPrandial InsulinPrandial InsulinPrandial Insulin

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

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

What About Patients What About Patients Admitted With Admitted With

Hyperglycemia On The Hyperglycemia On The Floor?Floor?

A Word on InA Word on In--Patient Sliding Scale Patient Sliding Scale ManagementManagement……

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 Glargine And Bolus Regime With Glargine And Glulisine Compared To SSIGlulisine Compared To SSI

Umpierrez, G. et al Diabetes Care 30: 2181-2186, 2007






Glucose Difference Between Groups 27 Glucose Difference Between Groups 27 mg% (p < 0.01)mg% (p < 0.01)Percentage Of Patients At TargetPercentage Of Patients At Target

(< 140 mg%)(< 140 mg%)Basal Bolus SSIBasal Bolus SSI

66% 38%66% 38%No Difference In Hypoglcemia (<0.5%)No Difference In Hypoglcemia (<0.5%)





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

Starting BasalStarting Basal--Bolus From Bolus From ScratchScratch

Basal Insulin = Basal Insulin = ½½ TDDTDDGive All of Calculated Glargine Dose Q 24h Give All of Calculated Glargine Dose Q 24h Goal: FBS And PreGoal: FBS And Pre--Meal Glucose = 80Meal Glucose = 80--110 mg/dl110 mg/dl

Bolus Doses = Bolus Doses = ½½ TDDTDDPrandial Dose + Correction FactorPrandial Dose + Correction Factor

AFTER THE MEALAFTER THE MEALGoal: 2h PostGoal: 2h Post--Prandial <180 mg/dlPrandial <180 mg/dl

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

Not for Acute Illness Not for Acute Illness With Variable IntakeWith Variable IntakeSecretagoguesSecretagogues

Can Give or NotCan Give or NotGlitazonesGlitazones

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 RadiocontrastSurgery, or Radiocontrast

MetforminMetformin

Not for Acute Illness Not for Acute Illness With Variable IntakeWith Variable Intake

αα Glucosidase Glucosidase InhibitorsInhibitors

Have A Discharge PlanHave A Discharge Plan

If PreIf Pre--Admission Control Acceptable, Admission Control Acceptable, YES!!!YES!!!

Admission HbA1C HelpfulAdmission HbA1C HelpfulIf Not At Goal on Maximum Oral If Not At Goal on Maximum Oral Agents, Needs AdjustmentAgents, Needs Adjustment

Can A Patient Go Back To Oral Can A Patient Go Back To Oral Agents At Discharge?Agents At Discharge?

Glycemic ControlGlycemic Control





Floor PatientFloor Patient65 y/o male with DM2, hyperlipidemia, 65 y/o male with DM2, hyperlipidemia, HTN, and DJDHTN, and DJDAdmitted to General Medicine with chest Admitted to General Medicine with chest painpainMetformin 1000mg BID and glipizide 5mg Metformin 1000mg BID and glipizide 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 troponinsSerial troponinsPossible adenosine myoview Possible adenosine myoview

Floor PatientFloor Patient65 y/o male65 y/o maleDM2, hyperlipidemia, DM2, hyperlipidemia, HTN, and DJDHTN, and DJDMetformin 1000mg Metformin 1000mg BID and glipizide BID and glipizide 5mg BID5mg BIDHbA1c 6.4% HbA1c 6.4% Glucose 275 mg/dlGlucose 275 mg/dlAdmit ordersAdmit orders

Serial troponinsSerial troponinsPossible 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 y/o male (75kg)65 y/o male (75kg)DM2, hyperlipidemia, DM2, hyperlipidemia, HTN, and DJDHTN, and DJDMetformin 1000mg Metformin 1000mg BID and glipizide BID and glipizide 5mg BID5mg BIDHbA1c 6.4% HbA1c 6.4% Glucose 275 mg/dlGlucose 275 mg/dlAdmit ordersAdmit orders


Start glargine and Start glargine 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




Patient NPO after Patient NPO after midnight for midnight for adenosine myoviewadenosine myoview

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




Patient NPO after Patient NPO after midnight for midnight for adenosine myoviewadenosine myoview

Reversible defect Reversible defect on myoview led on myoview 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 y/o female with DM2, HTN, & 65 y/o female with DM2, HTN, & hyperlipidemiahyperlipidemiaAdmitted to the MICU with sepsisAdmitted to the MICU with sepsisMetformin 1000mg BID, glipizide 10mg Metformin 1000mg BID, glipizide 10mg BID, rosiglitazone 8mg qdayBID, rosiglitazone 8mg qdayHbA1c 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 metformin and glipizidea. Continue metformin and glipizideb. Start glargine and logb. Start glargine and logc. Start an insulin dripc. Start an insulin drip

ICU PatientICU Patient

65 y/o female with 65 y/o 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 y/o female with 65 y/o 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 y/o female with 65 y/o 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


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


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 Second morning on the floorSecond morning on the floor

Fasting glucose 138 mg/dlFasting glucose 138 mg/dl

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 PatientsNon 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


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 Second morning on the floorSecond morning on the floor

Fasting glucose 138 mg/dlFasting glucose 138 mg/dlIncrease next glargine dose to 34U Increase next glargine dose to 34U

Adjust Basal Insulin By FBS:

Decrease 4 U if FBS are below 60 mg/dLDecrease 4 U if FBS are below 60 mg/dLDecrease 2 U if FBS Is 60Decrease 2 U if FBS Is 60--80 mg/dL80 mg/dLIf FBS Is 80If FBS Is 80--100mg/dL, 100mg/dL, At GoalAt Goal--No Change is No Change is NeededNeededIncrease 2 U If FBS Is 100 to 120 mg/dLIncrease 2 U If FBS Is 100 to 120 mg/dLIncrease 4 U If FBS Is 121 to 140 mg/dLIncrease 4 U If FBS Is 121 to 140 mg/dLIncrease 6 U If FBS Is 141 to 160 mg/dLIncrease 6 U If FBS Is 141 to 160 mg/dLIncrease 8 U If FBS Is 161 to 180 mg/dLIncrease 8 U If FBS Is 161 to 180 mg/dLIncrease 10 U If FBS Is > 180 mg/dLIncrease 10 U If FBS Is > 180 mg/dL

Or Adjust Based On Previous Days Correction Factor DosesOr Adjust Based On Previous Days Correction Factor Doses

Former ICU, Now Floor, PatientFormer ICU, Now Floor, Patient65 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 Second morning on the floorSecond morning on the floor

Fasting glucose 138 mg/dlFasting glucose 138 mg/dlIncrease next glargine dose to 34 Increase next glargine dose to 34 unitsunits

Third morning on the floorThird morning on the floorFasting glucose 110mg/dlFasting glucose 110mg/dlContinue glargine 34 unitsContinue glargine 34 units


Patient going home!!Patient going home!!Glargine 34 units daily and log Glargine 34 units daily and log 1111units TIDunits TIDMedium dose correction factor Medium dose correction factor HbA1c 9%HbA1c 9%

How should her diabetes medication(s) be adjusted?a) Discontinue insulin and restart oral medicationsb) Reintroduce metformin and rosiglitazone to insulin c) Continue insulin only

Glycemic ControlGlycemic Control





insulin-hospital 2009 -ne...the nice-sugar study investigators. nejm 360: 1283-1297, 2009 nice-sugar...

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