Inpatient Glycemic ManagementBethany Klopfenstein MD

Director, Inpatient Glycemic ControlAssociate Professor, Division of Endocrinology,

Diabetes, and Clinical NutritionOregon Health & Science University

Disclosures

• None

Objectives – to discuss:

• Impact of hyperglycemia in the hospital

• Glycemic targets for hospitalized patients

• Strategies for management of hyperglycemia in the hospital

2014 National Diabetes Statistics Report• 29.1 million individuals in the US have diabetes (9.3% of the

population)– Diagnosed: 21.0 million – Undiagnosed: 8.1 million (28% of people with diabetes are

undiagnosed)• 86 million have prediabetes

– 35% of adults ≥ 20 yrs and 50% of adults >65 yrs

• High prevalence of hyperglycemia in the hospitalized patient– > 60% of ICU patients experience BG >180– > 46% of non-ICU patients experience BG >180– ~ 30% of inpatients have a (patient-day weighted) mean BG

>180 mg/dL

National Diabetes Statistics Report. 2014. http://www.cdc.gov/DIABETES/pubs/estimates14.htm#6Cook et al. A Glycemic Survey of 126 US Hospitals. Journal of Hospital Medicine 2009; 4:E7-E17.

Economic Burden of Diabetes

• In 2012, estimated diabetes related-costs totaled $245 billion

–Direct medical costs totaled $176 billion (52% increase from 2007)

–Hospital inpatient care accounts for 43% of total medical cost

– Higher rates of admission and readmission– Longer LOS per admission

American Diabetes Association. Diabetes Care. 2008;31(3):596-615, andDiabetes Care. 2012 http://care.diabetesjournals.org/content/early/2013/03/05/dc12-2625.full.pdf+html

Hyperglycemia in the Hospital

• Diabetes:– Previously diagnosed– Previously undiagnosed

• HbA1c ≥ 6.5% during admission

• Hyperglycemia without diabetes diagnosis– Diabetes diagnosed on follow-up– Prediabetes with overt hyperglycemia during

acute physiologic stress– Hyperglycemia due to physiologic stress without

underlying metabolic abnormality • normal follow-up testing

Identifying Hyperglycemia in the Hospital

Inhospital hyperglycemia is defined as an admission or inhospital BG > 140 mg/dl.

HbA1c testing can be useful to: assess glycemic control prior to admission assist with differentiation of newly diagnosed diabetes

from stress hyperglycemia designing an optimal regimen at the time of discharge

HbA1c > 6.5% can be identified as having diabetes, and HbA1C 5.7%-6.4% is consistent with prediabetes.

Impact of Hyperglycemia in Hospitalized Patients

Relationship of Postoperative Hyperglycemia and Risk of Postoperative Infection

Ramos, M., et al., Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg, 2008. 248(4): p. 585-91.

Every 40 mg/dL increase in post-op glucose is associated with a 30% increased risk of post-op infection

In-Hospital Complication Rates are Increased in Patients with Diabetes

02468

101214

%

Non-diabetesDiabetes

Frisch et al. Diabetes Care. 2010;133(8): 1783-1788.

†p=0.1; *p<0.001; ‡p<0.017

† ‡

*

** *

*

Hyperglycemia Increases the Risk of Adverse Events in Surgical Patients with and without Diabetes

0

2

4

6

8

10

12

14

Compositeinfections

Allreoperative

interventions

In-hospitaldeaths

Prop

ortio

n of

pat

ient

s (%

) Glucose ≤ 180 (n=1729)

Glucose > 180(n=2369)

0

2

4

6

8

10

12

14

Compositeinfections

Allreoperative

interventions

In-hospitaldeaths

Prop

ortio

n of

pat

ient

s (%

) Glucose ≤ 180 (n=6512)

Glucose > 180(n=1013)

Kwon, Steve; MD, MPH et al. Importance of Perioperative Glycemic Control in General Surgery: A Report From the Surgical Care and Outcomes Assessment Program. Annals of Surgery. 257(1):8‐14, January 2013.

AEs among patients with diabetes AEs among patients without diabetes

*

*

*

*

*P<0.01

†

†P<0.05

0

2

4

6

8

10

12

14

100 150 200 250 300

Odd

s R

atio

for 3

0-da

y M

orta

lity

Mean Glucose Before Surgery

Nondiabetic patients

Diabetic patients

Hyperglycemia Increases Risk of 30-Day Mortality in Patients without Prior

Diagnosis of Diabetes

05

101520253035404550

100 150 200 250 300

Odd

s R

atio

for 3

0-da

y M

orta

lity

Mean Glucose After Surgery

Nondiabetic patientsDiabetic patients

Frisch et al. Diabetes Care. 2010;133(8): 1783-1788.

Detrimental Physiologic Impact of Hyperglycemia

Deedwania P, et al. Circulation. 2008;117(12):1610-1619. Modified from Clement S, et al. Diabetes Care. 2004;27(2):553-591.

Metabolic stress response Stress hormones and peptides

Prolonged hospital stay Disability Death

Glucose Insulin

FFA Ketones Lactate

Immune dysfunction

Infection

Reactive O2 species

Transcription factors

InflammationImpaired healing

AcidosisElectrolyte fluxesVolume depletionTissue damage

Infarction/ischemia

Platelet aggregation

Thrombosis

Glycemic Targets for Hospitalized Patients

Strategies for Management of Inpatient Hyperglycemia

Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4). http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.

AACE/ADA Target Glucose Levels in Hospitalized Patients

• ICU setting:

• Non-ICU setting:

Recommended140-180

Acceptable110-140

Not recommended<110

Not recommended>180

Hypoglycemia = BG <70 mg/dLSevere hypoglycemia = BG <40 mg/dL

Random< 180

Pre-Meal< 140

Antihyperglycemic Therapy

InsulinNon-Insulin

Antihyperglycemic Drugs

Recommendations for Managing Hyperglycemia in the Inpatient Setting

Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4). http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.

AACE/ADA Consensus Statement

Non-insulin therapies in the hospital?

Sulfonylureas can cause hypoglycemiaMetformin contraindicated in setting of decreased renal

blood flow and with use of iodinated contrast dyeThiazolidinediones associated with edema and CHFα glucosidase inhibitors are weak glucose lowering agentsDPP-4 inhibitors not effective in the inpatient setting for

patients with CBG >180SGLT-2 inhibitors have potential risk of UTI and can

contribute to mild volume depletionPramlintide and GLP1-agonists can cause nausea and

have a greater effect on postprandial glucose

Moghissi ES, et al. AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009

Antihyperglycemic Therapy

InsulinRecommended

Non-Insulin DrugsNot Generally

Recommended

Recommendations for Managing Inpatient Hyperglycemia

Clement S, et al. Diabetes Care. 2004;27(2):553-591.Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4). http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.

What is the best approach?

Antihyperglycemic Therapy

InsulinRecommended

Non-Insulin DrugsNot Generally

Recommended

IV InsulinCritically ill patients

Perioperative

SC InsulinNon–critically ill

patients

Recommendations for Managing Inpatient Hyperglycemia

Clement S, et al. Diabetes Care. 2004;27(2):553-591.Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4). http://www.aace.com/pub/pdf/guidelines/InpatientGlycemicControlConsensusStatement.pdf.

Management of Hyperglycemia using Insulin Infusion

Intravenous Insulin

• Many different protocols published• Therapy of choice in the ICU• Best results in patients who are NPO• For best results in patients that are eating:

– Use IV insulin as basal insulin– Add SC mealtime insulin

B L D

IV Insulin

Overlap of IV / SCGlargine: 3 hoursNPH: 90 minutes

Rapid-acting Insulin based on

intake

Basal glargine

Basics of SC Insulin After IV

Management of Hyperglycemia using Subcutaneous Insulin

Sliding-Scale Insulin Alone Not Recommended

Adapted from :DeWitt DE, Dugdale DC. JAMA. 2003;289(17):2265-2269.Skyler JS. In: DeFronzo RA, ed. Current Therapy of Diabetes Mellitus. St Louis, MO: Mosby-Year Book, Inc;1998:36-49.

Concerns:Reactive approach:↑ Hyperglycemia

Insu

lin E

ffect

Time, h

BG = 220

0 2 4 6 8 10 12 14 16 18 20 22 24

BG = 280 BG = 247BG = 200

Sliding-Scale Insulin AloneNot Recommended

Adapted from :DeWitt DE, Dugdale DC. JAMA. 2003;289(17):2265-2269.Skyler JS. In: DeFronzo RA, ed. Current Therapy of Diabetes Mellitus. St Louis, MO: Mosby-Year Book, Inc;1998:36-49.

Concerns:Reactive approach:↑ Hyperglycemia

Insulin stacking:↑ Hypoglycemia

Insu

lin E

ffect

Time, h

BG = 380BG = 50

BG = 197BG = 289

0 2 4 6 8 10 12 14 16 18 20 22 24

Combined Effect

Rabbit 2 Trial: Improvement in Glucose Levels With Basal-Bolus vs. Sliding Scale Insulin

Mean overall BG difference between the groups during hospital stay was 27 mg/dL (P<.01) No difference in hypoglycemia

Adapted with permission from Umpierrez GE, et al. Diabetes Care. 2007;30(9):2181-2186.

Days of Therapy

BG

, mg/

dL

100

120

140

160

180

200

220

240

Admit 1

Sliding-scale

Basal-bolus

aP<.05.

aa a

a aa

a

2 3 4 5 6 7 8 9 10

0%

5%

10%

15%

20%

25%

30%

Sliding Scale Basal‐Bolus

Rabbit 2 Surgery Trial: Improved Outcomes with Basal-Bolus Insulin in Non-ICU Surgical Patients

% o

f Pat

ient

s w

ith C

ompl

icat

ions

Complications include:•Wound infection•Pneumonia•Acute respiratory failure•Acute renal failure•Bacteremia

n = 107

p = 0.003

Umpierrez et al. Diabetes 59:Suppl 1 Abstract 0033, 2010

n = 104

Mean BG POD1: 172 ± 47 (Sliding scale) vs. 145 ± 32 mg/dl (Basal-Bolus)

5 Step Approach to Inpatient Insulin Management

STEP 1: Estimate the Total Daily Insulin Requirement: Basal + Nutritional Insulin

= Total Daily Dose (TDD)• Weight-based estimate:

– TDD = 0.4-0.5 units/kg (for type 2 diabetes)– Adjust TDD down to 0.2-0.3 units/kg for those with hypoglycemia risk factors

• Elderly, renal failure, liver disease, low body weight, type 1 or no history of diabetes

– Adjust TDD up to 0.5-0.6 units (or more)/kg for those with hyperglycemia risk factors

• Obesity, glucocorticoids

• Insulin drip-based estimate (for patients treated with an insulin infusion)

• For patients on insulin prior to admission, consider the patient’s preadmission subcutaneous regimen TDD and glycemic control on that regimen

STEP 2: Assess the Patient’s Nutritional Situation

• Eating meals predictably• Eating meals but with unpredictable intake• Enteral feeding

– Continuous– Part of the day– Bolus

• TPN• Combinations of above• NPO

STEP 3: Divide the Total Daily Dose (TDD) into Basal and Nutritional Components

• Basal insulin can generally be estimated to be 50% of the TDD– Decrease to 40% if receiving AM corticosteroids

• Nutritional insulin can be estimated to be the remaining 50% of the TDD– Increase to 60% if receiving AM corticosteroids– If eating, divide boluses between meals

STEP 4: Decide Which Components of Insulin the Patient Will Require

• In the majority of cases, basal insulin should be provided

• When a patient is not receiving nutrition, nutritional insulin should not be given, however basal insulin should be continued

• Nutritional insulin needs must be matched to the actual nutritional intake (eating, tube feeds, TPN, etc.)• Patients with unpredictable PO intake: Bolus insulin can be given

immediately after the meal, in a ratio determined by amount eaten

• Generally, well-designed correction insulin regimens should also be provided in addition to scheduled bolus insulin

STEP 5: Assess Blood Glucose Pattern Daily (at a minimum) and Adjust Insulin Doses

• Adjust basal and bolus doses based on glucose patterns• If glucoses consistently >180-200, increase TDD by 20%• If any glucose < 70, decrease TDD by 20%

• Improvement of hyperglycemia and avoidance of hypoglycemia can only be achieved via continuous management of the insulin regimen

• There is no “autopilot” insulin regimen for a hospitalized patient

Inpatient Insulin Management:Tailor to the situation

• Patients that are eating (reliably or unreliably)

• Other nutrition (Tube feeds, TPN)• Corticosteroids • Procedures/surgery

Inpatient Insulin Management:Tailor to the situation

• Patients that are eating (reliably or unreliably)

Basal-Bolus Insulin Treatment With Glargine and Rapid-acting Analogs

Time4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Breakfast Lunch DinnerGlucoseGlargine, DetemirAspart/Lispro/ Glulisine

Glargine

Rapid acting insulin

Basal-Bolus Insulin Treatment With NPH BID and Rapid-acting Analogs

Time4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Breakfast Lunch DinnerGlucoseNPHAspart/Lispro/ Glulisine

NPH

Rapid acting insulin

NPH + Regular/Rapid Acting Analog or 70/30, 2 injections per day: Not recommended for

Inpatient management

Time4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Breakfast Lunch DinnerGlucoseNPHAspart/Lispro/ Glulisine/Regular

NPH

Short acting insulin

Inpatient Insulin Management:Tailor to the situation

• Patients that are eating (reliably or unreliably)

• Other nutrition (Tube feeds, TPN)

Insulin Requirement During Continuous Enteral Nutrition

04:00 08:00 12:00 16:00 20:00 00:00 04:00

NPH q8 hours During Continuous Enteral Nutrition or TPN

04:00 08:00 12:00 16:00 20:00 00:00 04:00

NPH q 8 hours During Continuous Enteral Feedings (or TPN)

BG q 2 hr, dextrose if < 100 Enteral Feeding stopped, hold next NPH dose

TF restarted

04:00 08:00 12:00 16:00 20:00 00:00 04:00

Glargine During Continuous Enteral Feedings or TPN

glargine

04:00 08:00 12:00 16:00 20:00 00:00 04:00

Glargine During Continuous Enteral Feedings (or TPN)

glargine

10% dextrose at same rate IV, BG q2hrTF stopped

TF restarted, stop 10% dextrose

04:00 08:00 12:00 16:00 20:00 00:00 04:00

04:00 08:00 12:00 16:00 20:00 00:00 04:00

Overnight Enteral Feedings with Daytime Grazing

04:00 08:00 12:00 16:00 20:00 00:00 04:00

Bolus Enteral Feedings

GlucoseRapid acting analogGlargine

TPN

• Parenteral nutrition often causes hyperglycemia and often requires insulin treatment, even in patients who would not require insulin otherwise

• Consider IV insulin for first 1-2 days to gauge the insulin requirements

• Then place about 80% of the insulin requirement in the TPN and use a supplemental insulin scale

• Redistribution strategy – add 2/3’s of yesterdays correction therapy to today’s bag

Inpatient Insulin Management:Tailor to the situation

• Patients that are eating (reliably or unreliably)

• Other nutrition (Tube feeds, TPN)• Corticosteroids

Typical Blood Glucose Pattern With Morning Steroid Therapy

Breakfast Lunch Dinner

Glucose Level

Inpatient Therapy of Patients on AM Corticosteroids

Breakfast Lunch Dinner

Glucose Level

Basal insulin

Prandial insulin

20-25%

20%

25%

15%

15-20%

Inpatient Therapy of Patients on AM Corticosteroids

Breakfast Lunch Dinner

Glucose Level

Basal insulin

Prandial insulin

40%

20%

25%

15%

Inpatient Insulin Management:Tailor to the situation

• Patients that are eating (reliably or unreliably)

• Other nutrition (Tube feeds, TPN)• Corticosteroids • Procedures/surgery: NPO

Management while NPO

8 12 6 10

lispro

glargine

• Insulin Infusion• Patients on established basal/bolus regimens

• Basal dose does not need to be reduced• Hold the bolus doses when NPO

Transition to Outpatient Care

Can Patients Go Back to Oral Agents at Discharge?

• If preadmission control acceptable, yes!

• Admission HbA1C helpful

• Hospital discharge is an opportunity to adjust therapy

AACE Discharge Recommendations For Patients with Type 2 Diabetes on Orals

HbA1c level Recommended Actions<7% Return to previous therapy7-8% Increase dose of previous oral agents, or

Add a third agent, orAdd bedtime basal insulin

>8% If already on 2 oral agents, add once daily basal insulin

10% Consider discharging on basal-bolus regimen, continuing doses as started in the hospital

Improved HbA1c with Discharge Regimen Based on Admission HbA1c in Patients with Type 2 Diabetes

Umpierrez et al. Diabetes Care. 2014 Nov;37(11):2934-9.

58

Hospital Discharge Transition of Inpatients with Hyperglycemia

• Stabilize blood glucose prior to discharge

• Provide inpatient education (survival skills)

• Refer patient for outpatient education

• Prepare for outpatient follow-up with PCP

Magee MF. Hosp Physician. 2006;2(4):17-28.Clement S, et al. Diabetes Care. 2004;27(2):553-591.Inzucchi SE. N Engl J Med. 2006;355(18):1903-1911.Hassan E. Am J Health Syst Pharm. 2007;64(10 suppl 6):S9-S14.

Post-discharge Outcomes for Hyperglycemic Patients With No

Prior History of Diabetes

• 60% of patients with no prior history of diabetes who are found to have hyperglycemia (random BG >125 mg/dL) during hospitalization are likely to have diabetes on follow-up testing1

• ADA recommends follow-up testing for diabetes in such patients within 1 month of hospital discharge2

1. Greci LS, et al. Diabetes Care. 2003;26(4):1064-1068.2. Clement S, et al. Diabetes Care. 2004;27(2):553-591.

Summary• Inpatient hyperglycemia is associated with increased

morbidity and mortality in patients with and without diabetes

• Hyperglycemia in the hospital is best managed via physiologic insulin therapy (basal/nutritional), with additional supplemental insulin used if needed

• Choice of regimen needs to be individualized and account for source of nutrition, changing medical status, and factors increasing risk of hypoglycemia and hyperglycemia

• Insulin regimen should be adjusted daily depending on prior day’s results