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Diabetes Management in the Hospital
Bruce W. Bode, MD, FACE Atlanta Diabetes
Associates Atlanta, Georgia
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Diabetes in Hospitalized Patients1997

• 3.5 Million US Hospitalizations
• 15 of Admissions
• 14 Million Hospital Days
• 20 of All Hospital Days
• 36 First Diagnosed in Hospital
  66 No Documentation by Physician
  27 Labeled Hyperglycemia
  2 Diagnosed on Chart

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Diabetes in Hospitalized Patients1997 Costs

• 23,500 Each Diabetes Patient vs.
• 12,200 for Non-Diabetes Patient
• 60 of All Diabetes-Related Costs
• Only 5 DKA, HHNKC
• 48 Diabetes Complications
• 52 Other Conditions

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Diabetes in Hospitalized PatientsReason for
Higher Costs

• Higher Rate of Hospitalization
• Longer Stays
• More Procedures, Medications
• Chronic Complications
• More Arteriosclerotic Disease
• More Infections
• Complicated Pregnancies

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Diabetes in Hospitalized Patients

• High-risk for Bacterial Infection
• Surgery
• Catheters
• Intravenous Access
• Anaesthesia

• Problems with wound healing

• Problems with tissue and organ perfusion

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Infections in Diabetes

• Unique
• Necrotizing Fasciitis
• Fourniers Gangrene
• Mucoromycosis
• Emphysematous GB
• Malignant External Otitis

• More Frequent
• Bacteremia
• Septic Shock
• Pyelonephritis
• Candida
• TPN

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Infections in Diabetes

• One BG gt220 mg/dl results in 5.8 times increase
  in nosocomial infection rate
• Two hours hyperglycemia results in impaired WBC
  function for weeks

Pomposelli, New England Deaconess, J
Parenteral and Enteral Nutrition 2277-81,1998
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TPN In DiabetesVA Cooperative Trial

• Benefit Negated
• Increased Infections
• Related to Hyperglycemia

Buzby et al. NEJM 325525-531, 1991
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Side Effects of BG gt200 mg/dl

• Reduced Intravascular Volume
• Dehydration
• Electrolyte Fluxes
• Impaired WBC Function
• Immunoglobulin Inactivation
• Complement Disabling
• Increased Collagenase, Decreased Wound Collagen

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Psychology of Diabetes in Hospital

• Patients expect good glycemic control as part of
  hospital care
• They strive for recommended goals at home
• Difficult to understand staffs casual approach
  to BGs gt150

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Evidence for Immediate Benefit of Normoglycemia
in Hospitalized Patients

• Numerous Publications on in Vitro Evidence
• Neutrophil Dysfunction
• Complement Inhibition
• Altered Redox State (Pseudohypoxia)
• Glucose Rich Edema as Culture Media
• Six Recent Clinical Publications supporting good
  glucose control in the hospital setting

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Open Heart Surgery in DiabetesPortland St.
Vincent Medical Center

• Control Group
• N968
• 1987-1991
• SubQ Insulin q 4 h
• Goal 200 mg/dl
• Standard Deviation 36
• All Mean BGs lt200 47

• Study Group
• N1499
• 1991-1997
• IV Insulin
• Goal 150-200 mg/dl
• Standard Deviation 26
• All Mean BGs lt200 84

Furnary et al, The 34th Meeting of The Society of
Thoracic Surgeons New Orleans, LA January 26, 1998
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Open Heart Surgery in DiabetesPortland CII
ProtocolDemographics

• Total Open Heart Surgery Patients 14,468
• Diabetes at Admission 2467 (17)
• Age 65 SD 10
• Males 62
• Insulin Rx 36
• OHA 48

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Open Heart Surgery in DiabetesPortland St.
Vincent Medical Center Perioperative Blood
Glucose
Furnary et al, The 34th Meeting of The Society of
Thoracic Surgeons New Orleans, LA January 26, 1998
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Incidence of DSWI 1987-1997
CII
Furnary, et al, The 34th
Meeting of The Society of Thoracic Surgeons New
Orleans, LA January 26, 1998
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Open Heart Surgery in DiabetesPortland CII
ProtocolInfectious Complications

• Diabetes
• 31/2467 (1.3) Deep Sternal Wound Infection
  (DSWI)
• 23/31 Required Second Admission
• 22 Micrococcus
• 0 Anaerobes, fungal, yeast
• Non-Diabetes
• 40/12,005 (0.3)

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Open Heart Surgery in DiabetesPortland CII
ProtocolMortality

• All (99/2467) 4.0
• SQI 6.1
• CII 3.0
• DSWI 19.0
• No DSWI 3.8
• Recent Experience
• 1994-1997 DSWI as in non-diabetics
• 1996-7 No DSWI in last 15 mo.

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Open Heart Surgery in DiabetesPortland CII
ProtocolComparison of GroupsHigher Risk
Patients in CII Group
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Open Heart Surgery in DiabetesPortland CII
ProtocolUnivariate Analysis of DSWI
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Estimated USA Socioeconomic Savings
Assumes 742K cases, 20 prevalence of DM 2
DSWI with SQI

Variable SQI CII Savings DSWI 2,968 1009 1,959
Additional LOS 47,488 16,416 31,342 Additional
78.4M 26.6M 51.7M Deaths 564 192 372
1998 Heart Stroke Statistical update, AHA
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Open Heart Surgery in DiabetesPortland CII
ProtocolWeakness of Study

• Not Randomized
• Temporal Sequential Nature
• Subtle Cumulative Improvements in Techniques

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Open Heart Surgery in DiabetesPortland CII
ProtocolConclusions

• Magnitude and Strength of Study is Compelling
• Ethics of Confirming Study Would be Questionable
• Application of CII is Simple and Safe
• Hyperglycemia Predicts DSWI
• CII Prevents DSWI

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Open Heart Surgery in DiabetesJohn Hopkins

• Prospective Cohort Study of 411 OHS pts with
  Diabetes 1990 1995
• Diabetes based on history (42 insulin treated,
  45 oral agents)
• SMBG 4x/day with sliding scale
• Measured relationship between peri-operative
  control and risk of all infections

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Open Heart Surgery in DiabetesJohn Hopkins

• 24.3 with infections
• BG divided into quartiles Relative
  Odds
• Q1 121-206 20.1
• Q2 207-229 21.6
  1.17
• Q3 230-252 29.8
  1.86
• Q4 252-352 25.7
  1.72

P lt 0.01
Golden SH Diabetes Care 22 1408, 1999
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DIGAMI StudyDiabetes, Insulin Glucose Infusion
in Acute Myocardial Infarction(1997)

• Acute MI With BG gt 200 mg/dl
• Intensive Insulin Treatment
• IV Insulin For gt 24 Hours
• Four Insulin Injections/Day For gt 3 Months
• Reduced Risk of Mortality By
• 28 Over 3.4 Years
• 51 in Those Not Previous Diagnosed

Malmberg BMJ 19973141512
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Cardiovascular RiskMortality After MI Reduced
by Insulin Therapy in the DIGAMI Study
IV Insulin 48 hours, then
4 injections daily
All Subjects
Low-risk and Not Previously on Insulin
.7
.7
(N 620)
(N 272)
.6
.6
Risk reduction (51)
Risk reduction (28)
.5
.5
P .011
P .0004
.4
.4
.3
.3
.2
.2
.1
.1
0
0
0
1
2
3
4
5
0
1
2
3
4
5
Years of Follow-up
Years of Follow-up
Malmberg, et al. BMJ. 19973141512-1515.
6-11
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ICU Survival

• 1548 Patients (mostly OHS pts.)
• All with BG gt200 mg/dl
• Randomized into two groups
• Maintained on IV insulin
• Conventional group (BG 180-200)
• Intensive group (BG 80-110)
• Conventional Group had 1.74 X mortality

Van den Berghe et al, NEJM 2001345(19)1359
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ICU IV Insulin Protocol

• If gt 100 mg/dl, 2 U/h If gt 200 mg/dl, 4 U/h
• If gt 140 mg/dl, increase by 1 2 U/h
• If 121 to 140 mg/dl, increase by 0.5 1 U/h
• If 111 to 120 mg/dl, increase by 0.1 0.5 U/h
• If 81 to 110 mg/dl, no change
• If 61 to 80 mg/dl, change back to prior rate

• Van den Berghe et al, NEJM 2001345(19)1359

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ICU Survival

• Blood glucose control
• Convetional
  Intensive
• Mean AM BG 153
  103
• Receiving Insulin 39
  100
• BG lt 40 mg/dl 6
  39

In no instance was hypoglycemia considered to be
a serious event
Van den Berghe et al, NEJM 2001345(19)1359
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ICU Survival

• Intensive Therapy (80 to 110 mg/dL) resulted in
• 34 reduction in mortality
• 46 reduction in sepsis
• 41 reduction in dialysis
• 50 reduction in blood transfusion
• 44 reduction in polyneuropathy

Van den Berghe et al, NEJM 2001345(19)1359
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Conclusion

• All hospital patients should have normal glucose

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Insulin

• only

powerful
powerful

• The agent we haveto
  control glucose

most
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Comparison of Human Insulins / Analogues

• Insulin Onset of Duration ofpreparations
  action Peak action

Regular 3060 min 24 h 610 h
NPH/Lente 12 h 48 h 1020 h
Ultralente 24 h Unpredictable 1620 h
Lispro/aspart 515 min 12 h 46 h
Glargine 12 h Flat 24 h
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Physiological Serum Insulin Secretion Profile
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Breakfast
Lunch
Dinner
50
Plasma insulin (µU/ml)
25
400
800
1200
1600
2000
2400
400
800
Time
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Basal/Bolus Treatment Program withRapid-acting
and Long-acting Analogs
Breakfast
Lunch
Dinner
Aspart Aspart Aspart
or
or
or
Lispro Lispro Lispro
Plasma insulin
Glargine or Detemir
400
1600
2000
2400
400
800
1200
800
Time
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Methods For Managing Hospitalized Persons with
Diabetes

• Continuous Variable Rate IV Insulin Drip
• Major Surgery, NPO, Unstable, MI, DKA,
  Hyperglycemia, Steroids, Gastroparesis, Delivery,
  etc
• Basal / Bolus Therapy (MDI) when eating

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Continuous Variable Rate IV Insulin Drip

• Mix Drip with 125 units Regular Insulin into
• 250 cc NS
• Starting Rate Units / hour (BG 60) x 0.02
• where BG is current Blood Glucose
• and 0.02 is the multiplier
• Check glucose every hour and adjust drip
• Adjust Multiplier to keep in desired glucose
• target range (100 to 140 mg/dl)

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Continuous Variable Rate IV Insulin Drip

• Adjust Multiplier (initially 0.02) to obtain
  glucose in target range 100 to 140 mg/dL
• If BG gt 140 mg/dL, increase by 0.01
• If BG lt 100 mg/dL, decrease by 0.01
• If BG 100 to 140 mg/dL, no change in
  Multiplier
• If BG is lt 80 mg/dL, Give D50 cc (100 BG) x
  0.3
• Give continuous rate of Glucose in IVFs
• Once eating, continue drip till 1 hour post SQ
  insulin

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Glucose Management System
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Glucommander

• Based on 15 Year Experience with a Computer Based
  Algorithm for the Administration of IV Insulin
• Developed for Marketing by MiniMed and Roche
• GMS System
• Shelved Pending FDA Approval of IV Use of Insulin
• Useful and Safe for Any Application of IV Insulin

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Glucommander Effectiveness

• Initial blood glucose
• Median 292 mg/dl
• Range 181-1,568
• Time to achieve glucose lt 180 mg/dl
• Median 3 hours
• Range 0.3 - 19.7
• Time to achieve three consecutive glucose results
  between 60 - 180 mg/dL
• Median 3. 1 hours
• Range 0.3 - 22.5

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Converting to SQ insulin

• Establish Daily Insulin Requirement
• IV Insulin First Night
• (BG - 60) x Multiplier Ins/hr Targeted to 120
• 60 x Multiplier x 24 Daily Insulin Requirement
• Give One-Half Amount As Basal
• Give p.c. Boluses Based on CHO Intake
• Start at CHO/Ins 1 CHO 1.5 units Rapid-acting
• Monitor a.c. tid, hs, and 3 am
• Supplement All BG gt150
• (BG-100)/(1700/Daily Insulin Requirement)

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Protocol for SQ Insulin in Hospitalized Patient

• Bedtime Wt (kg) x 0.2 Units of Glargine
• Meals Eaten 1.5 units per 15 Gm CHO eaten
• BG gt150 (BG-100) / CF
• CF 3000 / Wt (kg)
• Do Not Use Sliding Scale Only
• Any BG lt80 D50 (100-BG) x 0.3 ml
• Maintain INT
• Do Not Hold Insulin When BG Normal

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How to Initiate MDI

• Starting dose 0.4 to 0.5 x weight in kilograms
• Bolus dose (aspart/lispro) 20 of starting dose
  at each meal
• Basal dose (glargine) 40 of starting dose
  given at bedtime or anytime
• Correction bolus (BG - 100)/ Correction Factor,
  where CF 1700/total daily dose

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How to Initiate MDI

• starting dose 0.45 x wgt. in kg
• Wt. is 80 kg 0.45 x 80 36 units
• Bolus dose (aspart / lispro) 20 of starting
  dose at each meal 0.2 x 36 7 units ac (tid)
• Basal dose (glargine) 40 of starting dose at
  HS 0.4 x 36 14 units at HS
• Correction bolus (BG - 100)/ CF, where
  CF 1700/total daily dose CF 50

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Correction Bolus Formula
Current BG - Ideal BG Glucose Correction factor

• Example
• Current BG 250 mg/dl
• Ideal BG 100 mg/dl
• Glucose Correction Factor 50 mg/dl

250 - 100 50
3.0u
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Piedmont Diabetes PlanWhat Can We Do For
Patients Admitted To Hospital?

• NPO Pathway For All Diabetes Patients
• Finger Stick BG ac qid on ALL Admissions
• Check All Steroid Treated Patients
• Diagnose Diabetes
• FBG gt126 mg/dl
• Any BG gt200 mg/dl

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Piedmont Diabetes PlanWhat Can We Do For
Patients Admitted To Hospital?

• Document Diagnosis in Chart
• Hyperglycemia Is Diabetes Until Proven
• Bring to All Physicians Attention
• Note on Problem List and Face Sheet
• Check Hemoglobin A1C
• Hold Metformin Hold TZD with CHF, Liver
  Dysfunction
• Start Insulin in All Hospitalized Patients Not
  Already on Insulin

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Piedmont Diabetes PlanWhat Can We Do For
Patients Admitted To Hospital?

• Get Diabetes Education Consult
• Instruct Patient in Monitoring and Recording
• See That Patient Has Meter on Discharge
• Decide on Case Specific Program for Discharge
• Arrange Early F/U with PCP

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Piedmont Diabetes PlanWhat Can We Do For
Patients Admitted To Hospital?

• Follow Guidelines For Endocrinology Consult
• Any Hypoglycemia Requiring Intervention
• DKA or HHNC
• Patient on Insulin Pump
• Diabetes in Pregnancy
• Glucocorticoid Therapy in Diabetes
• Progressive Diabetes Complications
• A1C gt8, Microalbuminuria gt30 mg

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Protocol for Insulin in Hospitalized Patient

• Treat Any Patient With BG gt 150 With Insulin
• Treat Any BG gt150 with Rapid-acting Insulin
  (BG-100) / (5000 / wt ) or (3000 /
  wt kg)
• Treat Any Recurrent BG gt200 with IV Insulin
• If More than 0.5 u/hr IV Insulin Required with
  Normal BG Start Long Acting Insulin

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Protocol for Insulin in Hospitalized Patient

• Daily Total Pre-Admission or Weight () x 0.2 u
• 40 as Glargine (Basal)
• 60 as Rapid-acting insulin (Bolus)
• Give in Proportion to Meals CHO Eaten
• BG gt150 (BG-100) / CF
• CF 5000 / Wt() or 3000 / Wt(kg)
• Do Not Use Sliding Scale As Only Diabetes
  Management

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Protocol for Insulin in Hospitalized Patient

• Treatment of Hypoglycemia
• Any BG lt80 mg/dl D50 (100-BG) x 0.3 ml IV
• Do Not Hold Insulin When BG Normal

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Diabetes at Piedmont HospitalConclusions

• Any BG gt200 mg/dl Is Diabetes (Fasting gt126
  mg/dl)
• Most Diabetes Is Type 2
• All DM patients Must Self-Monitor BGs and Record
• No BG gt150 mg/dl Should Go Untreated
• Most Hospitalized DM atients Should Be on
  Insulin
• IV Insulin is Most Effective, Efficient, Safest
  Rx in Acute Illness (Glucommander)

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Diabetes at Piedmont HospitalConclusions 2

• Type 2 Diabetics Are Resistant to Insulin
  Reactions
• Treat Insulin Reactions in Hospital With IV
  Glucose
• Do Not Be Hold Insulin for Normal BG, i.e. 80-120
  mg/dl
• A1C Values gt7 Indicates Sub-optimal Care

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Diabetes at Piedmont HospitalConclusions 3

• Discharge Plan For BG Control
• You Are the Link Between the Best Diabetes Care
  and the Patient
• Use Your Diabetes Resources
• Diabetes Education Center Endocrinologists

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The Paradigm for the MilleniumHyperglycemia A
Mortal Sin

• A blood glucose over 200 in a hospitalized
  patient causes increased morbidity and mortality.
• In the 21st Century Neglecting a BG gt200 Will Be
  Malpractice

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Conclusion

• Intensive therapy is
• the best way to treat
• patients with diabetes

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QUESTIONS

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