Manejo del Paciente Diabetico en la Unidad de Cuidados Intensivos y Sala General Guillermo E....

Manejo del Paciente Manejo del Paciente Diabetico en la Unidad de Diabetico en la Unidad de Cuidados Intensivos y Sala Cuidados Intensivos y Sala

GeneralGeneralGuillermo E. Umpierrez, MD, FACP, FACEGuillermo E. Umpierrez, MD, FACP, FACE

Professor of MedicineProfessor of Medicine

Director, Grady Hospital Clinical Research Director, Grady Hospital Clinical Research UnitUnit

Emory University School of MedicineEmory University School of Medicine

Director, Diabetes & Endocrinology SectionDirector, Diabetes & Endocrinology Section

Grady Hospital CIN (Research Unit)Grady Hospital CIN (Research Unit)

Grady Health SystemGrady Health System

Hiperglucemia en el Hospital: Hiperglucemia en el Hospital: AgendaAgenda

1.1. Magnitud del Problema:Magnitud del Problema: Cual es la frecuencia e impacto de Cual es la frecuencia e impacto de

hiperglucemia y diabetes en el hospital? hiperglucemia y diabetes en el hospital? Cuales criterios diagnosticos debemos de Cuales criterios diagnosticos debemos de

utilizar?utilizar? Que niveles de glucosa son recomendables?Que niveles de glucosa son recomendables?

Umpierrez et al. J Clin Endocrinol Metabol. 97(1):16-38, 2012Umpierrez et al. J Clin Endocrinol Metabol. 97(1):16-38, 2012

2.2. Como debemos de manejar la Como debemos de manejar la hiperglucemia en UCI y en en sala hiperglucemia en UCI y en en sala generales?generales? Insulina – Que tipo, regimen, y como Insulina – Que tipo, regimen, y como

comenzar?comenzar? Incretinas – debemos de utilizarlas en el Incretinas – debemos de utilizarlas en el

hospital?hospital? Alta hospitalaria– Cual es el papel de la HBA1c, Alta hospitalaria– Cual es el papel de la HBA1c,

que regimen utilizar? HbA1c?que regimen utilizar? HbA1c?

Distribution of patient-day-weighted Distribution of patient-day-weighted mean POC-BG values for ICU mean POC-BG values for ICU

Swanson et al. Endocrine Practice, October 2011

Data from ~12 million BG readings from 653,359 ICU patients - mean POC-BG: 167 mg/dL

Hyperglycemia: Scope of the ProblemHyperglycemia: Scope of the Problem

Kosiborod M, et al. J Am Coll Cardiol. 2007;49(9):1018-183:283A-284A.

No Diabetes

26%

Diabetes 50

40

30

20

10

0<110110-140

50

40

30

20

10

0<110110-140 140-170170-200>200

78%

140-170170-200>200

Mean BG, mg/dL

Pati

en

ts,

%

Perioperative Hyperglycemia in Patients Perioperative Hyperglycemia in Patients With and Without Diabetes Undergoing With and Without Diabetes Undergoing

CABG Surgery CABG Surgery No-DM DM P-value

# of pts 150 152 --

BMI 29±6 33±8 p<0.001

Admission BG 111±28 171±72 p<0.001

HbA1c 6.1±0.2 8.0±2 p<0.001

Pre-op BG 108±23 155±51 p<0.001

Intra-op BG 138±20 157±31 p<0.001

ICU BG 135±16 149±18 p<0.001

Periop BG >140 83% 98% P=0.48

Started CII 88% 94% P=0.06

Insulin dose, Units 61±84 161±229

Transition to basal insulin after CII

48% 98% P<0.001

Pasquel et al, Endocrine Society 2014, submitted. Unpublished

Hyperglycemia*: A Common Hyperglycemia*: A Common Comorbidity in Medical-Surgical Comorbidity in Medical-Surgical Patients in a Community HospitalPatients in a Community Hospital

62%62%

12%12%

26%26%

NormoglycemiaNormoglycemia

Known DiabetesKnown Diabetes

New HyperglycemiaNew Hyperglycemia

Umpierrez G et al, J Clin Endocrinol Metabol 87:978, 2002Umpierrez G et al, J Clin Endocrinol Metabol 87:978, 2002

n = 2,020n = 2,020

* Hyperglycemia: Fasting BG * Hyperglycemia: Fasting BG 126 mg/dl 126 mg/dl or Random BG or Random BG 200 mg/dl X 2 200 mg/dl X 2

Diagnosis & recognition of hyperglycemiaDiagnosis & recognition of hyperglycemiaand diabetes in the hospital settingand diabetes in the hospital setting

AdmissionAdmissionAssess all patients for a history of diabetes Assess all patients for a history of diabetes

Obtain laboratory BG testing on admissionObtain laboratory BG testing on admission


No history of diabetesBG<140 mg/dl (7.8 mmol/L)

Initiate POC BG monitoring according

to clinical status

History of diabetes

BG monitoring

No history of diabetes BG >140 mg/dl

Start POCBG monitoring x 24-48h

Check A1C

A1C ≥ 6.5%

A1C for Diagnosis of Diabetes in A1C for Diagnosis of Diabetes in the Hospitalthe Hospital

HbA1c should be measured in non-diabetic HbA1c should be measured in non-diabetic subjects with hyperglycemia (BG>140 mg/dl or subjects with hyperglycemia (BG>140 mg/dl or 7.8 mmol/L) and in subjects with diabetes if not 7.8 mmol/L) and in subjects with diabetes if not done within 2-3 months prior to admission. done within 2-3 months prior to admission.

In the presence of hyperglycemia, a patient In the presence of hyperglycemia, a patient with HbA1c > 6.5% can be identified as having with HbA1c > 6.5% can be identified as having diabetes. diabetes.

Implementation of A1C testing can be useful:Implementation of A1C testing can be useful: assess glycemic control prior to admissionassess glycemic control prior to admission assist with differentiation of newly diagnosed assist with differentiation of newly diagnosed

diabetes from stress hyperglycemiadiabetes from stress hyperglycemia designing an optimal regimen at the time of designing an optimal regimen at the time of

dischargedischargeUmpierrez et al, J Clin Endocrinol Metabol, 2012

Hyperglycemia in the ICU: Hyperglycemia in the ICU: Lecture AgendaLecture Agenda

1.1. Scope of the Problem:Scope of the Problem: What is the frequency of hyperglycemia and What is the frequency of hyperglycemia and

diabetes? diabetes? Why should we care about hyperglycemia in the Why should we care about hyperglycemia in the

ICU?ICU? Mechanisms for hyperglycemia in acute critical Mechanisms for hyperglycemia in acute critical

illness and ICU illness and ICU 2.2. How should we manage hyperglycemia in the How should we manage hyperglycemia in the ICU and non-ICU settings?ICU and non-ICU settings? Insulin regimens Insulin regimens Incretin-base regimentsIncretin-base regiments Other agents? Other agents?

N= 55,530 patients records in ICU and non-ICU, Emory University Hospital. Composite of complications: pneumonia, acute renal or respiratory failure, acute MI, bacteremia, and death.Patients with admission BG >400 mg/dL, DKA, and GFR <15 were excluded.

Hyperglycemia and Hospital Complications: Hyperglycemia and Hospital Complications: What glucose level predicts What glucose level predicts

complications?complications?

Thirty Day Mortality and Hospital Complications in Diabetic and Non-diabetic subjects Undergoing General Non-Cardiac Surgery

†p = 0.1 * p= 0.001 #p=0.017

†

*

**

*#

*

%

A Frisch et al. Diabetes Care, May 2010

Adverse Events Stratified by Adverse Events Stratified by Perioperative HyperglycemiaPerioperative Hyperglycemia

BG at any point on the day of surgery, post-op day 1 and 2N= 11,633, colorectal and bariatric surgery; 29.1% with hyperglycemia

Diabetes No Diabetes

*

*

*

*

§

§ p <0.05* P <0.01

Known et al. Ann Surg 2013

Proportion of Patients (%)

BG > 180 mg/dl BG < 180 mg/dl

Hyperglycemia: An Independent Marker of In-Hospital Mortality in Patients with Undiagnosed Diabetes

Total In-patient MortalityTotal In-patient Mortality

NormoglycemiaNormoglycemia Known Known New New DiabetesDiabetes Hyperglycemia Hyperglycemia

1.7%1.7% 3.0%3.0%

16.0% 16.0% **

Mort

alit

y (

%)

Mort

alit

y (

%)

* P < 0.01* P < 0.01

Umpierrez GE et al, J Clin Endocrinol Metabol 87:978, 2002Umpierrez GE et al, J Clin Endocrinol Metabol 87:978, 2002

Inpatient Hyperglycemia: ICU and non-Inpatient Hyperglycemia: ICU and non-ICUICULecture OutlineLecture Outline

1.1. What is the frequency of hyperglycemia and What is the frequency of hyperglycemia and diabetes? diabetes?

2.2. What is the association between What is the association between hyperglycemia and outcomes?hyperglycemia and outcomes?

3.3. Does treatment of hyperglycemia in ICU Does treatment of hyperglycemia in ICU and non-ICU matters?and non-ICU matters?

What is the evidence for intensive glycemic What is the evidence for intensive glycemic control?control?

4.4. How should we manage hyperglycemia in How should we manage hyperglycemia in non-ICU settingnon-ICU setting

Prospective study of 2,467 consecutive diabetics who underwent open heart surgery.Prospective study of 2,467 consecutive diabetics who underwent open heart surgery.DSWI, deep sternal wound infection; SCI, subcutaneous insulin; CII, continuous insulin infusion.

4.0

3.0

2.0

1.0

0.0

DSWI(%)

87 88 89 90 91 92 93 94 95 96 97Year

Furnary AP, et al. Ann Thorac Surg. 1999;67:352–362.

CIISCI

Portland Diabetes Project: Portland Diabetes Project: Insulin Infusion Reduces DSWI Insulin Infusion Reduces DSWI

SCI Group:Day of surgery: 241 mg/dL POD #1: 206 mg/dL

CII Group:Day of surgery: 199 mg/dL POD #1: 176 mg/dL

Hyperglycemia and surgical ICU Hyperglycemia and surgical ICU morbidity and mortalitymorbidity and mortality

Intensive Glucose Management in RCT

Trial N Setting Primary Outcome

ARR RRR Odds Ratio(95% CI)

P-value

Van den Berghe2006

1200 MICU Hospital mortality

2.7% 7.0% 0.94* (0.84-1.06)

N.S.

Glucontrol2007

1101 ICU ICU mortality

-1.5% -10% 1.10*(0.84-1.44)

N.S.

Ghandi2007

399 OR Composite 2% 4.3% 1.0*(0.8-1.2)

N.S.

VISEP2008

537 ICU 28-d mortality

1.3% 5.0% 0.89*(0.58-1.38)

N.S.

De La Rosa 2008

504 SICUMICU

28-d mortality

-4.2% * -13%* NR N.S.

NICE-SUGAR2009

6104 ICU 3-mo mortality

-2.6% -10.6 1.14(1.02-1.28)

< 0.05

*not significant

Griesdale DE, et al. CMAJ. 2009;180(8):821-827.

Griesdale DE, et al. CMAJ. 2009;180(8):821-827.

Favors IIT Favors Control

Hypoglycemic Events

Intensive Insulin Therapy and Hypoglycemic Events in Critically Ill Patients

No. Events/Total No. Patients

Study IIT Control Risk ratio (95% CI)

Van den Berghe et al 39/765 6/783 6.65 (2.83-15.62)

Henderson et al 7/32 1/35 7.66 (1.00-58.86)Bland et al 1/5 1/5 1.00 (0.08-11.93)Van den Berghe et al 111/595 19/605 5.94 (3.70-9.54)Mitchell et al 5/35 0/35 11.00 (0.63-191.69)Azevedo et al 27/168 6/169 4.53 (1.92-10.68)De La Rosa et al 21/254 2/250 10.33 (2.45-43.61)Devos et al 54/550 15/551 3.61(2.06-6.31)Oksanen et al 7/39 1/51 9.15 (1.17-71.35)Brunkhorst et al 42/247 12/290 4.11(2.2-7.63)Iapichino et al 8/45 3/45 2.67 (0.76-9.41)Arabi et al 76/266 8/257 9.18 (4.52-18.63)Mackenzie et al 50/121 9/119 5.46 (2.82-10.60)NICE-SUGAR 206/3016 15/3014 13.72 (8.15-23.12)

Overall 654/6138 98/6209 5.99 (4.47-8.03)

0.1 1 10

Risk Ratio (95% CI)

NICE-SUGAR Trial: Hypoglycemia and Mortality

The NICE-SUGAR Study Investigators. N Engl J Med 2012;367:1108-1118

Moghissi ES, et al; AACE/ADA Inpatient Glycemic Control Consensus Panel. Endocr Pract. 2009;15(4).

2009 AACE/ADA Recommended Target 2009 AACE/ADA Recommended Target Glucose Levels in ICU PatientsGlucose Levels in ICU Patients

Starting threshold of no higher than 180 mg/dLStarting threshold of no higher than 180 mg/dL

Recommended140-180

Acceptable110-140

Not recommended<110

Not recommended>180

2012 Critical Society Guidelines 2012 Critical Society Guidelines ICU Target Glucose Goal < 150 mg/dlStart Insulin Therapy when BG ≥ 150 mg/dLStart Insulin Therapy when BG ≥ 150 mg/dLMaintain BG values <180 mg/dL Jacobi, et al. Crit Care Med 2012;40:3251–3276 Jacobi, et al. Crit Care Med 2012;40:3251–3276

2012 American College of Physicians (ACP) ICU Target Glucose Goal < 200 mg/dl

Annals Intern Med 2012

Glycemic Targets in NON-ICU Glycemic Targets in NON-ICU SettingSetting

1.1. Premeal BG target of <140 mg/dl (7.8 mmol/L) Premeal BG target of <140 mg/dl (7.8 mmol/L) and random BG <180 mg/dl (10 mmol/L) for the and random BG <180 mg/dl (10 mmol/L) for the majority of patients.majority of patients.

2.2. Glycemic targets be modified according to clinical Glycemic targets be modified according to clinical status. status.

3.3. For avoidance of hypoglycemia, diabetic therapy For avoidance of hypoglycemia, diabetic therapy be reassessed when BG<100 mg/dl (5.5 mmol/L). be reassessed when BG<100 mg/dl (5.5 mmol/L).


American College of Physicians recommended a target BG <200 mg/dl (11.1 mmol/L), Ann Intern Med

2012

Hyperglycemia in the ICU: Hyperglycemia in the ICU: Lecture AgendaLecture Agenda

1.1. Scope of the Problem:Scope of the Problem: What is the frequency of hyperglycemia and What is the frequency of hyperglycemia and

diabetes? diabetes? Why should we care about hyperglycemia in the Why should we care about hyperglycemia in the

ICU?ICU?2.2. How should we manage hyperglycemia How should we manage hyperglycemia in the ICU and non-ICU settings?in the ICU and non-ICU settings?

Leuven SICU Study1 Yale Insulin Infusion Protocol2

MICU Insulin Infusion Protocol (N=69)

0

50

100

150

200

250

300

350

400

450

0 12 24 36 48 60 72

Hours

Blo

od

Glu

cose (

mg

/dL)

Glucommander3

0

50

100

150

200

250

300

350

400

450

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

Hours

Glu

cose (

mg

/dL)

1. Van den Berghe et al. N Engl J Med. 2001;345:1359-1367. 2. Goldberg PA et al. Diabetes Care. 2004;27:461-467.

3. Davidson et al. Diabetes Care. 2005;28:2418-2423. 4. Finfer S, et al. N Engl J Med. 2009;360(13):1283-1297.

Admission Day 1 Day 5 Day 15

Blo

od

Glu

cose (

mm

ol/L) Intensive - Mean BG 103 mg/dL

Conventional - Mean BG 153 mg/dL

0

2

4

6

8

10

12

14

Last day

Strategies for Achieving Glycemic Targets in the ICU

NICE-SUGAR4

BG

, m

g/d

L

180

160

140

120

100

800

1 2 3 4 5 86 7 9 10 11 12 13 14Base-line

Days After Randomization

CIT

IIT

108

ProtocolProtocol Hypo definitionHypo definition % patients% patients RRRR

Leuven SICULeuven SICU11 <40 mg/dL<40 mg/dL 5.1%5.1% 77

Leuven MICULeuven MICU22 <40 mg/dL<40 mg/dL 19%19% 66

GlucontrolGlucontrol33 <40 mg/dL<40 mg/dL 8.6% ----

VISEPVISEP44 <40 mg/dL<40 mg/dL 17.4%17.4% 4.114.11

NICE SUGARNICE SUGAR55 <40 mg/dL<40 mg/dL 6.5%6.5% 13.713.7

GLUCO-CABGGLUCO-CABG66 <40 mg/dl<40 mg/dl 0%0% ----

Van Den Berghe G, et al. N Engl J Med. 2001:345:1359; Van Den Berghe G, et al. N Engl J Med. 2006;354:449-461; Brunkhorst FM et al. N Engl J Med. 2008; 358:125-139; Preiser JC, SCCM, 2007; Finfer S, et al. N Engl J Med. 2009;360(13):1283-1297; Umpierrez , ADA 2014

Hypoglycemia Rates in Intensive IV Insulin Protocols

ProtocolProtocol IITIIT CITCITLeuven SICULeuven SICU 103103 153 153

Leuven MICULeuven MICU 111111 153 153

De la RosaDe la Rosa 120120 149 149

GlucontrolGlucontrol 118118 143143

VISEPVISEP 112112 151151

NICE SUGARNICE SUGAR 118118 145145

GLUCO-CABGGLUCO-CABG 132132 154154

Van Den Berghe G, et al. N Engl J Med. 2001; Van Den Berghe G, et al. N Engl J Med. 2006;De la Rosa,et al, Crit Care 2008; Brunkhorst et al. N Engl J Med. 2008; Preiser JC, SCCM, 2007; Nice Sugar, NEJM 2009; Umpierrez 2014 (ADA, unpublished)

Glycemic Values Achieved with IV Insulin Protocols

IIT: Intensive insulin therapy; CIT: Control, conventional/Conservative insulin therapyResults are expressed as mean BG during hospital stay, mg/dL

1.ACE/ADA Task Force on Inpatient Diabetes. Diabetes Care. 2006 & 20092.Diabetes Care. 2009;31(suppl 1):S1-S110..

Antihyperglycemic Therapy

Insulin Recommended

OADs Not Generally

Recommended

Recommendations for Managing Patients With Diabetes in the Hospital Setting

D/C oral antidiabetic drugs on admissionD/C oral antidiabetic drugs on admission

Insulin naïve: Insulin naïve: starting total daily dose starting total daily dose (TDD): (TDD): 0.3 U/kg to 0.5 U/kg 0.3 U/kg to 0.5 U/kg Lower doses in the elderly and renal Lower doses in the elderly and renal

insufficiencyinsufficiency

Previous insulin therapy: Previous insulin therapy: reduce reduce outpatient insulin dose by 20-25%outpatient insulin dose by 20-25%

Basal bolus regimen: Basal bolus regimen: Half of TDD as Half of TDD as basal and half as rapid-acting insulin basal and half as rapid-acting insulin before mealsbefore meals

Insulin Therapy in patients with T2DInsulin Therapy in patients with T2D

Umpierrez et al, Diabetes Care 30:2181–2186, 2007; Baldwin et al, Diabetes Care 10:1970-4, 2011; Rubin et al, Diabetes Care 34:1723-8, 2011

Inpatient Management in non-ICU Setting

Sliding Scale Regular Insulin

Basal Bolus Insulin Regimen

In insulin naïve patients with T2DM, does In insulin naïve patients with T2DM, does treatment with basal bolus regimen with glargine treatment with basal bolus regimen with glargine once daily and glulisine before meals is superior once daily and glulisine before meals is superior to sliding scale regular insulin? to sliding scale regular insulin?

RABBIT-2D TRIAL: RABBIT-2D TRIAL: - Research Question:- Research Question:

Umpierrez et al, Diabetes Care 30:2181–2186, 2007

D/C oral antidiabetic drugs on admissionD/C oral antidiabetic drugs on admission

Starting total daily dose (TDD): Starting total daily dose (TDD): 0.4 U/kg/d x BG between 140-200 mg/dL0.4 U/kg/d x BG between 140-200 mg/dL 0.5 U/kg/d x BG between 201-400 mg/dL 0.5 U/kg/d x BG between 201-400 mg/dL

Half of TDD as insulin glargine and half as Half of TDD as insulin glargine and half as rapid-acting insulin (glulisine)rapid-acting insulin (glulisine) Insulin glargine - once daily, at the same Insulin glargine - once daily, at the same

time/day. time/day. Glulisine- three equally divided doses (AC)Glulisine- three equally divided doses (AC)

RaRandomized ndomized BBasal asal BBolus versus Sliding Scale olus versus Sliding Scale Regular Regular IInsulin in patients with nsulin in patients with ttype ype 22 Diabetes Diabetes

MellitusMellitus(RABBIT-2 Trial)(RABBIT-2 Trial)

Umpierrez et al, Diabetes Care 30:2181–2186, 2007

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

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

Days of Therapy

BG

, m

g/d

L

100

120

140

160

180

200

220

240

Admit 1

Sliding-scale

Basal-bolus

bP<.05.

aa a

b bb

b

2 3 4 5 6 7 8 9 10

aP<.05.

• Sliding scale regular insulin (SSRI) was given 4 times daily • Basal-bolus regimen: glargine was given once daily; glulisine was given before meals.0.4 U/kg/d x BG between 140-200 mg/dL0.5 U/kg/d x BG between 201-400 mg/dL

Hypoglycemia Hypoglycemia rate:rate:

Basal Bolus Group: BG < 60 mg/dL: 3% BG < 40 mg/dL:

none

SSRI: BG < 60 mg/dL: 3% BG < 40 mg/dL: none

Inpatient Management in non-ICU Setting


NPH and Regular Insulin-

Spilt-Mixed Regimen

In patients with T2DM on diet, oral agents or In patients with T2DM on diet, oral agents or insulin treatment, does treatment with basal insulin treatment, does treatment with basal bolus regimen with detemir once daily and aspart bolus regimen with detemir once daily and aspart before meals is superior to NPH and Regular split-before meals is superior to NPH and Regular split-mixed insulin regimen? mixed insulin regimen?

DEAN TRIAL: DEAN TRIAL: - Research Question:- Research Question:

Umpierrez et al, J Clin Endocrinol Metab 94: 564–569, 2009

DEAN Trial: Changes in Mean Daily DEAN Trial: Changes in Mean Daily Blood Glucose ConcentrationBlood Glucose Concentration

BG

, m

g/d

L

Duration of Therapy, d

Data are means SEM.

Detemir + aspartNPH + regular

Basal-bolus regimen: detemir was given once daily; aspart was given before meals.NPH/regular regimen: NPH and regular insulin were given twice daily, two thirds in AM, one third in PM.Umpierrez GE, et al. J Clin Endocrinol Metab. 2009;94(2):564-569.

P=NS

100

120

140

160

180

200

220

240

Pre-RxBG

0 1 2 3 4 5 6-10

NPH/Regular BG < 40 mg/dl: 1.6% BG < 60 mg/dl: 25.4%

Detemir/Aspart BG < 40 mg/dl: 4.5% BG < 40 mg/dl: 32.8%

DEAN Trial: Hypoglycemia

Randomized Controlled Study Randomized Controlled Study Comparing Basal Bolus with Comparing Basal Bolus with

Insulin Analogs vs Human Insulins Insulin Analogs vs Human Insulins in General Medicine Patientsin General Medicine Patients

Bueno, Benitez eta al. 2012 ADA Scientific Meeting, New Orleans Bueno, Benitez eta al. 2012 ADA Scientific Meeting, New Orleans

Basal bolus with glargine QD + glulisine AC Basal bolus with glargine QD + glulisine AC versus NPH b.i.d. & regular AC. versus NPH b.i.d. & regular AC.

- 0.4 U/kg/d x BG: 140-200 mg/dL - 0.5 U/kg/d x BG: 201-400 mg/dL

Basal Bolus Regimen Basal Bolus Regimen Analogs vs. Human Insulins Analogs vs. Human Insulins


Hypoglucemias por brazo de Hypoglucemias por brazo de intervenciónintervención

ALLN= 134

AnalogsN=66

HumanN=68

p-value

Patients with Hypoglycemia, n (%)

49 (37) 23 (35) 26 (38)OR:1.16p: 0.68

Severe Hypoglucemia, n (%)

22 (16) 5 17OR:2.93P:0.04

Mild Hypoglucemia, n (%)

95 44 51

Patients withn ≥2 episodes, n (%)

26 (19) 10 16OR:2.08

P:0.2


Umpierrez et al, Diabetes Care 34 (2):1–6, 2011

Primary Outcomes:

•Differences between groups in mean daily BG

•Composite of hospital complications: wound infection, pneumonia, respiratory failure, acute renal failure, and bacteremia

In patients with T2DM on diet, oral agents or In patients with T2DM on diet, oral agents or insulin treatment, does treatment with basal insulin treatment, does treatment with basal bolus regimen with glargine and glulisine is bolus regimen with glargine and glulisine is superior to SSRI? superior to SSRI?

Research Question:Research Question:

Randomized study of basal bolus insulin therapy in the management of general surgery patients with T2DM (Rabbit Surgery)

**

**

****

Mean BG before meals and at Mean BG before meals and at bedtime during basal bolus and SSI bedtime during basal bolus and SSI

therapytherapy

BreakfastBreakfast Lunch Lunch Dinner Dinner Bedtime Bedtime

*p<0.001*p<0.001

Glargine+GlulisineGlargine+Glulisine

Sliding Scale InsulinSliding Scale Insulin

Umpierrez et al, Diabetes Care 34 (2):1–6, 2011Umpierrez et al, Diabetes Care 34 (2):1–6, 2011

Postoperative ComplicationsPostoperative Complications

P=0.003

P=NS

P=0.05 P=0.10

P=0.24

Glargine+Glulisine

Sliding Scale Insulin


23

50

5

10

15

20

25

Insulin Glargine + Insulin Glulisine

SSI

P<0.001

4 00

5

10

15

20

25


SSI

P=0.057

Percent of patients with Percent of patients with hypoglycemia during basal bolus hypoglycemia during basal bolus

and SSI therapyand SSI therapyBG <70 mg/dL BG <60 mg/dL BG <40 mg/dL

There were no differences in hypoglycemia between patients treated with insulin prior to admission compared to insulin-naïve patients.


12

20

5

10

15

20

25


SSI

P<0.001

Insulin Treatment in in Non-ICU Setting

Do you need basal bolus in ALL patients?

Do you need basal bolus in ALL patients?

T2DM with BG > 140 mg/dl (7.7 mmol/l)

Basal insulin - Start at 0.2-0.25 U/Kg/day*- Correction doses with rapid acting insulin AC- Adjust basal as needed

NPOUncertain oral intake

AdequateOral intake

Basal BolusTDD: 0.4-0.5 U/Kg/day-½ basal, ½ bolus-- adjust as needed

Basal Plus Correction vs. Basal BolusBasal Plus Correction vs. Basal Bolus

Basal plus supplementsBasal plus supplements Starting glargine*: 0.25 Starting glargine*: 0.25

units/kg units/kg Correction with glulisine Correction with glulisine

for BG >140 mg/dl per for BG >140 mg/dl per sliding scale sliding scale

Basal Bolus RegimenBasal Bolus Regimen Starting TDD*: 0.5 U/kgStarting TDD*: 0.5 U/kg

GGlargine: 0.25 U/kglargine: 0.25 U/kg Glulisine: 0.25 U/kg Glulisine: 0.25 U/kg

in three equally in three equally divided doses (AC)divided doses (AC)

Correction with glulisine Correction with glulisine for BG >140 mg/dl per for BG >140 mg/dl per sliding scale sliding scale

* * Reduce TDD to 0.15 U/kg in Reduce TDD to 0.15 U/kg in patients ≥70 yrs and/or serum patients ≥70 yrs and/or serum

creatinine ≥ 2.0 creatinine ≥ 2.0 mg/dLmg/dL

* * Reduce TDD to 0.3 U/kg in Reduce TDD to 0.3 U/kg in patients ≥70 yrs and/or serum patients ≥70 yrs and/or serum

creatinine ≥ 2.0 creatinine ≥ 2.0 mg/dLmg/dLUmpierrez et al, Diabetes Care 2013Umpierrez et al, Diabetes Care 2013

Duration of Treatment (days)

0 1 2 3 4 5 6 7 8 9 10

Blo

od G

luco

se (

mg/

dL)

120

140

160

180

200

220

240 Basal Plus Basal Bolus

Basal-PLUS vs Basal Bolus: Basal-PLUS vs Basal Bolus: 300 medical & surgical non-ICU 300 medical & surgical non-ICU

patients patients

Preliminary results: Basal bolus 51 patients, basal-plus: 49 patients

Basal Plus:glargine once daily0.25 U/kg plus glulisine supplements

Basal Bolus:TDD: 0.5 U/kg/dGlargine 50%glulisine 50%

Umpierrez et al, Diabetes Care 2013

Differences in glycemic control and frequency of treatment failures in patients treated with basal bolus, basal plus and sliding scale regular insulin

Umpierrez et al, Diabetes Care, 2013

Basal-PLUS vs Basal Bolus: Medicine and Basal-PLUS vs Basal Bolus: Medicine and Surgery PatientsSurgery Patients

Medicine Surgery

BG AC & HS

Daily BG Daily BG

BG AC & HS

Smiley et al, Diabetes Care 2013

Inpatient Management

in non-ICU

Basal Bolus or

Basal PlusRegimens

Management of Patients With Diabetes in Non-ICU Settings

What about Incretin-Based

Therapy?

DPP-4 Therapy in Hospitalized Patients

Study Type: Multicenter, prospective, open-label randomized clinical trial

Patient Population: Patients with T2D admitted to general medicine and surgery services at 3 hospitals: Emory University, Grady, and University of Michigan

Treatment Groups* Group 1. Sitagliptin once daily (n=30) Group 2. Sitagliptin plus glargine insulin once daily (n=30) Group 3. Basal bolus regimen with glargine once daily

and lispro before meals (n=30)

* All groups received supplemental doses of lispro for BG > 140 mg/dl before meals

Umpierrez et al. Care. 36(11):3430-5, 2013

Randomi-zation

Mean Daily BG During TreatmentMean Daily BG During Treatment


Mean BG before meals and at bedtime during Treatment

Data is mean ± SE

P=0.22 P=0.15 P=0.52 P=0.57


Mea

n D

aily

Blo

od G

luco

se (m

g/dL

)

Randomization Blood Glucose (<180 mg/dl Randomization Blood Glucose (<180 mg/dl and >180 mg/dl) and Mean Daily Glucose and >180 mg/dl) and Mean Daily Glucose

concentrationconcentration

p= 0.91

p= 0.08


Use admission A1C to adjust therapy at discharge

7%

8%

9%

10%

Adjust original therapy, ADD another agent or basal insulin

Return to original therapy

ADD basal insulin therapy

ADD basal or REPLACE with basal/bolus

Umpierrez G et al, J Clin Endocrinol Metabol, 2012Umpierrez G et al, J Clin Endocrinol Metabol, 2012

Recommendations for Managing Patients With Diabetes After Hospital Discharge

A1C < 7%

Re-start outpatient treatment regimen

(OAD and/or insulin)

A1C 7%-9%

Re-start outpatient oral agents and D/C

on glargine once daily at

50-80% of hospital dose

A1C >9%

D/C on basal bolus at same hospital

dose.

Alternative: re-start oral agents

and D/C on glargine once daily at 80% of hospital

dose

Discharge Insulin Algorithm

Discharge Treatment

Umpierrez et al, ADA Scientific Sessions, 2012

Hospital Discharge Algorithm Based on Hospital Discharge Algorithm Based on Admission HbA1C for the Management of Admission HbA1C for the Management of Patients with T2DMPatients with T2DM

8.75%

7.9%

7.35%%


Hospital Discharge Algorithm Based on Admission HbA1C for the Management of Patients with T2DM

Primary outcome: - change in A1C at 4 wks and 12 wks after discharge

All Patients

OAD OAD + Glargine

Glargine+

Glulisine

Glargine

# patients, n (%) 224 81 (36) 61 (27) 54 (24) 20 (9)

A1C Admission, % 8.7±2.5 6.9±1.5 9.2±1.9 11.1±2.3 8.2±2.2

A1C 4 Wks F/U, % 7.9±1.7* 7.0±1.4 8.0±1.4ψ 8.8±1.8ψ 7.7±1.7

A1C 12 Wks F/U, % 7.3±1.5* 6.6±1.1 7.5±1.6* 8.0±1.6* 6.7±0.8*

BG<70 mg/dl, n (%)

62 (29) 17 (22) 17 (30) 23 (44) 5 (25)

BG<40 mg/dl, n (%)

7 (3) 3 (4) 0 (0) 3 (6) 0 (0)* p< 0.001 vs. Admission A1C; ψp=0.08


Management of diabetes in Management of diabetes in non-critical care settingnon-critical care setting

So… What really have we So… What really have we learned?learned?

Guillermo E. Umpierrez, MDGuillermo E. Umpierrez, MD

[email protected]@emory.edu

Thank you!Thank you!

Inpatient Management of Inpatient Management of Medical and Surgical Patients Medical and Surgical Patients

with Type 2 diabetes- ICU with Type 2 diabetes- ICU and non-ICUand non-ICU

Guillermo E. Umpierrez, MD, FACP, FACEGuillermo E. Umpierrez, MD, FACP, FACE

Professor of MedicineProfessor of Medicine

Director, Grady Hospital Clinical Research Director, Grady Hospital Clinical Research UnitUnit

Emory University School of MedicineEmory University School of Medicine

Director, Diabetes & Endocrinology SectionDirector, Diabetes & Endocrinology Section

Grady Hospital CIN (Research Unit)Grady Hospital CIN (Research Unit)

Grady Health SystemGrady Health System

External Industry

Relationships *

Company Name(s)

Role

Equity, stock, or options in biomedical

industry companies or

publishers

None

Board of Directors or officer

None

Royalties from from external

entity

None

Industry funds to Emory for my

research

Sanofi-AventisMerck

Novo NordiskBoehringer Ingelhein

Investigator-Initiated Research Projects

Dr. Guillermo Umpierrez, Personal/Professional Financial Relationships with Industry

Hyperglycemia in non-critical care Hyperglycemia in non-critical care setting: Lecture Agendasetting: Lecture Agenda

1.1. Scope of the Problem:Scope of the Problem: What is the frequency and impact of What is the frequency and impact of

hyperglycemia and diabetes? hyperglycemia and diabetes? What diagnosis criteria should we use?What diagnosis criteria should we use? What target glucose should we aim?What target glucose should we aim?


2.2. How should we manage hyperglycemia in How should we manage hyperglycemia in ICU and non-ICU setting?ICU and non-ICU setting? Insulin regimens – Which and how to start?Insulin regimens – Which and how to start? Incretin-base regimens – are they safe & Incretin-base regimens – are they safe &

effective?effective? Discharge algorithm – What is the role of the Discharge algorithm – What is the role of the

admission HbA1c?admission HbA1c?

Blood Glucose (mg/dL)

<150 150- 175

200- 225

175- 200

>250225- 250

P<0.0001

*P<0.001

Postop

Mortality

BG <200

n=662

1.8%

BG >200

n=1369

5.0% *

Posto

p M

ort

ality

(%

)Adjusted for 19 clinical and operation variables

Furnary AP et al. Circulation. 1999:100 (Suppl I): I-591.

1.4 1.72.1

3.8

5.8

8.6

0

2

4

6

8

10

Hyperglycemia: A Predictor of Hyperglycemia: A Predictor of Mortality Following CABG in Mortality Following CABG in DiabeticsDiabetics

CABG, coronary artery bypass graft.

First Postop Glucose >200• 2x LOS• 3x Vent duration• 7x mortality !!!

Hyperglycemia and Pneumonia Hyperglycemia and Pneumonia OutcomesOutcomes

BG (mg/dl) < 110 110 - <198 198 - <250 ≥250

* *

* *

* p: < 0.05 vs BG < 198 mg/dl (11 mmol/L)

Admission glucose (mg/dl)

%

McAllister et al, Diabetes Crae 28:810-815, 2005McAllister et al, Diabetes Crae 28:810-815, 2005

N= 2,471 patients with CAP

Pharmacologic Therapy in Non-ICU Pharmacologic Therapy in Non-ICU SettingSetting

Patients treated with insulin at home require Patients treated with insulin at home require scheduled SQ insulin therapy in the hospital (1)scheduled SQ insulin therapy in the hospital (1)

Avoid prolonged use of sliding scale insulin as sole Avoid prolonged use of sliding scale insulin as sole method for glycemic management (2)method for glycemic management (2)

Scheduled SQ insulin consists of basal or intermediate Scheduled SQ insulin consists of basal or intermediate acting insulin in combination with RAI or Regular acting insulin in combination with RAI or Regular insulin administered before meals in patients who are insulin administered before meals in patients who are eating(1)eating(1)

Include correction insulin as a component of scheduled Include correction insulin as a component of scheduled SQ insulin for treatment of BG above desired range (2)SQ insulin for treatment of BG above desired range (2)

GE Umpierrez, R Hellman, MT Korytkowski, M Kosiborod, GA Maynard, VM Montori, JJ Seley, GV GE Umpierrez, R Hellman, MT Korytkowski, M Kosiborod, GA Maynard, VM Montori, JJ Seley, GV den Berghe. J Clin Endocrinol Metabol. 97(1):16-38, 2012den Berghe. J Clin Endocrinol Metabol. 97(1):16-38, 2012


D/C oral antidiabetic drugs on admission

Starting total daily dose (TDD): 0.5 U/kg/day

TDD reduced to 0.3 U/kg/day in patients ≥ 70 years of age or with a serum creatinine ≥ 2.0 mg/dL

*If a patient was not able to eat, insulin glargine was given but, insulin glulisine was held until meals were resumed.

Half of TDD as insulin glargine and half as insulin glulisine*– Glargine - once daily, at the same time of the

day – Glulisine- three equally divided doses (AC)


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