In-Hospital Management of Diabetes

هللا يحميك يا مصر

The frequency of hyperglycemia potential contribution to

morbidity and mortality in hospitalized patients make

measurement of blood glucose mandatory in all patients

admitted to the hospital whether or not known diabetes

Introduction

STANDARDS OF MEDICAL CARE IN DIABETES—2011

ADA Recommendations: Diabetes Care in the Hospital

All patients with diabetes admitted to the hospital should have

– Their diabetes clearly identified in the medical record

– An order for blood glucose monitoring, with results

available to the health care team

ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.

Diabetes increases the risk for disorders that predispose individuals to hospitalization ,including cardiovascular diseases, nephropathy, infection and lower-extremity amputations.

Hyperglycemia Adversely Affects Outcomes

Hyperglycemia Adversely Affects Outcomes

Hyperglycemia impacts

– Mortality

– Morbidity

– Rate of infections

– Length of hospital stay

Types Of Hyperglycemia in Hospitalized Patients

Hyperglycemia in Hospitalized Patients

• Pre-existing known diabetes

• Newly diagnosed diabetes

• Hospital related or stress hyperglycemia

Hospital related or stress hyperglycemia

Stress hormones cortisol, epinephrine Glucose Production

Lipolysis

FFAs

FFAs

+

Glucose Uptake

Illness

Illness leads to Stress Hyperglycemia

Glucose Fatty Acids

Glucose Production

Lipolysis

FFAs

FFAs

+

Glucose Uptake

Hemodynamic insult

Electrolyte losses

Oxidative stress

Myocardial injury

Hypercoagulability

Altered immunity

Wound healing

Inflammation

Endothelial function

Stress hormones cortisol, epinephrine

Illness Illness

“Stress Hyperglycemia” Exacerbates Illness

Glucose Fatty Acids

Traditionally acute hyperglycemia was defined as RBS more than 200 mg/dl*

* (mcCowen et-el 2001 crit care clin 2001:17:107-24)

Stress Hyperglycemia

On 2010 ADA proposed a threshold of blood sugar 140 mg/dl in patient not known to have diabetes

A1c eleveted should be measured above 6.5% indicate preexisting diabetes in need for long term follow up

Strategy of In-Hospital Management of Diabetes

Dose improving glycemic control improve clinical outcomes for inpatients with hyperglycemia ?

What glycemic target can be recommended in different patients ?

Strategy of In-Hospital Management of Diabetes

Strategy of In-Hospital Management of Diabetes

What treatment options are available for achieving

optimal glycemic targets safely and effectively in specific clinical situation?

Dose improving glycemic control improve clinical

outcomes for inpatients with hyperglycemia ?

Hyperglycemia and Hospital Mortality

0

5

10

15

20

25

30

35

Total Non-ICU ICU

Normoglycemia Known diabetes New hyperglycemia

*

*P<.01 compared with normoglycemia and known diabetes.

*

*

Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982.

Mo

rta

lity

(%

)

Umpierrez et al. J Clin Endocrinol Metab 87:978, 2002

30

20

10

0

Mort

alit

y (

%)

Normoglycemia Known New Diabetes Hyperglycemia

10% 11%

31%*

*P<0.01

ICU Mortality

Hyperglycemia: An Independent Marker of

ICU Mortality

• No doubt that hyperglycemia is associated with poor clinical outcomes

• However, it does not mean that treatment of hyperglycemia will improve clinical outcomes

Intervention Studies

DIGAMI Study Diabetes, Insulin Glucose Infusion in Acute Myocardial Infarction(1997)

Acute MI With BG > 200 mg/dl

Intensive Insulin Treatment

IV Insulin For > 24 Hours

Four Insulin Injections/Day For > 3 Months

Reduced Risk of Mortality By:

28% Over 3.4 Years

51% in Those Not Previous Diagnosed

Malmberg BMJ 1997;314:1512

DIGAMI Study: CVD Mortality Post-AMI

All Subjects (N = 620)

Standard treatment

0

.3

.2

.4

.7

.1

.5

.6

0 1

Years of Follow-up

2 3 4 5

Subjects at low CV risk and

w/ no prior insulin therapy

(N = 272)

Intensive management

0

.3

.2

.4

.7

.1

.5

.6

0 1

Years of Follow-up

2 3 4 5

RRR=28% P=.011

RRR=51% P=.0004

Malmberg K et al. BMJ 314: 1512-1515, 1997

Van Den Berghe et al: Intensive Insulin Therapy in Critically Ill Patients

------------------------------SICU---------------------------

Prospective randomized controlled study.

Enrolled 1548 SICU patients into 2 groups

Intensive therapy targeted glucose between 80-110 and

the conventional range was 180-200

Primary outcome was death in ICU which was 4.6

percent in the Intensive Glucose control group vs. 8.0

percent in Conventional glucose control group which

was statistically significant.

Van den Berghe et al 2 Intensive Insulin Therapy in the

Medical ICU

Prospective, randomized, controlled study of 1200

patients

Same authors and same conventional and intensive

parameters as the first study

Primary outcome was death in hospital which was

37.3% in the intensive group versus 40% in the

conventional group which was statistically

insignificant.

Wiener et al

Meta analysis of 34 randomized trials totaling 8432

patients.

Hospital mortality did not differ between tight vs.

conventional glucose control.

Tight glucose control was not associated with a

decreased risk for new dialysis, but was a associated

with a decreased risk of septicemia.

Tight glucose control was associated with an increased

risk of hypoglycemia.

GLUCONTROL

Prospective randomized control trial stopped early due to adverse events in the tight BG control group.

Tight (80-110 mg/dL) vs Conventional(140-180 mg/dL) glucose control.

Incidence of severe hypoglycemia (BG<40 mg/dL) was significantly more frequent in patients assigned to tighter control group. Risk of death was not increased by hypoglycemia.

No difference in mortality 17% vs. 15% and the conclusion of the authors was that there are no apparent benefits of tight glucose control.

Intensive versus Conventional Glucose Control in Critically Ill Patients

Randomized, prospective un-blinded clinical controlled trial

of 6104 patients.

NICE-SUGAR

Patients were randomized into one of 2 groups within 24

hours of admission to the ICU if they were expected to be

in the ICU for more than 3 days.

The 2 groups were intensive glucose control target (80-

108 mg/dL) or the conventional control target (180mg/dL

or less).

.

In the intensive control group, control of blood glucose was achieved with an insulin infusion.

In the conventional group, insulin was administered if the blood glucose level exceeded 180mgdL.

NICE-SUGAR

Results

.

829 patients(27.5%) died in the intensive control group

751(24.9%) in the conventional-control group which is

a difference of 2.6%.

There was no statistical difference between surgical vs. medical ICU patients

.

NICE-SUGAR

Results

Severe hypoglycemia(<40mg/dL) was recorded in 6.8%

of patients in the intensive control group, vs. 0.5%

in the conventional group.

NICE-SUGAR

These conflecting findinges have called to question the

benefit of tight control and highlight in the risk for severe

hyperglycemia

so

What glycemic target can be recommended in different patients ?

ADA/AACE Inpatient Task Force Endocrine Practice 2009;15;1-17

ADA/AACE Target Glucose Levels in ICU Patients

ICU setting:

– Insulin infusion should be used to control hyperglycemia

– Starting threshold of no higher than 180 mg/dl

– Once IV insulin is started, the glucose level should be maintained

between 140 and 180 mg/dl

– Lower glucose targets (110-140 mg/dl) may be appropriate in

selected patients

– Targets <110 mg/dL are not recommended

Recommended 140-180

Acceptable 110-140

Not recommended < 110

Not recommended >180

AACE-ADA Consensus Statement on Inpatient Glycemic Control: ICU

Glucose target

140-180mg/dl

Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et al., Endocrine Practice 2009;15:353

• Lower target acceptable

• ( 110-140 mg/dl )

AACE-ADA Consensus Statement on Inpatient Glycemic Control: ICU

Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et al., Endocrine Practice 2009;15:353

• Tighter targets ( <110 mg/dl ) not safe; • >180 mg/dl not acceptable.

AACE-ADA Consensus Statement on Inpatient Glycemic Control: ICU

Moghissi E et al., Diabetes Care 2009;32:1344; Moghissi E et al., Endocrine Practice 2009;15:353

ADA/AACE Inpatient Task Force Endocrine Practice 2009;15:1-17

ADA/AACE Target Glucose Levels in Non-ICU Patients

Non-ICU setting: – Pre-meal glucose targets <140 mg/dL

– Random BG <180 mg/dL

– To avoid hypoglycemia, reassess insulin regimen if BG levels fall

below 100 mg/dL

– Occasional patients may be maintained with a glucose range

below or above these cut-points

Hypoglycemia= BG < 70 mg/dl Severe hypoglycemia= BG < 40 mg/dl

Achieving Tight Glycemic Targets

. What treatment options are available for achieving optimal glycemic targets safely and effectively in specific clinical situation?

Insulin

Oral Antidiabetes Agents

OR

Achieving Tight Glycemic Targets

Oral Antidiabetes Agents in the Hospital

Oral agents can be continued in stable patients with

normal nutritional intake, normal blood glucose levels,

and stable renal and cardiac function.

However, there are several potential disadvantages to

using these medications in hospital patients:

Disadvantages of most oral agents: Slow-acting / difficult to titrate

Disadvantages of insulin secretagogues

(e.g. sulfonylureas and meglitinides such as glyburide,

glypizide, repaglinide, etc.):

• Hypoglycemia if caloric intake is reduced

• Some are long-acting (hypoglycemia may be prolonged)

Disadvantages of Metformin:

• Lactic acidosis can occur when used in the setting of

renal dysfunction, circulatory compromise, or hypoxemia

• Slow onset of action

• GI complications: Nausea, diarrhea

Insulin

The agent we have

to control blood glucose

only

most powerful powerful

Conclusions

Inhospital glycemic control is now recognized as a patient safety issue

BG target 140 mg/dL-180 mg/dL

Safe and Effective Protocols can be implemented institutionally to attain goals with acceptable hypoglycemia

American Diabetes Association. Diabetes Care. 2006;29:S4-S42.

Thank You

54

IV Insulin Therapy: Recommended Uses

Continuous Variable Rate IV Insulin Drip

Major Surgery, NPO, Unstable, MI, DKA,

Hyperglycemia, Steroids, Gastroparesis,

Delivery, etc

Basal / Bolus Therapy when eating

Best method to achieve quick glycemic control

Bode et al. Endocr Pract. 2004;10(suppl 2):71-80

Patient with an Acute MI

53 yo male with DM 2 on SU, Metformin and

Glitazone presents with an acute MI

BG random is 220 mg/dl

What do you recommend for glucose control?

1. Sliding scale rapid analog?

2. Basal Bolus insulin therapy?

3. IV insulin drip?

Patient with an Acute MI

For acute MI with elevated glucose, you can give in

type 2’s IV variable rate insulin infusion in all

persons with elevated glucose

If you order an IV insulin drip ;

1- What dilution of IV insulin?

2- How often do you check the glucose?

1U to 1cc or 0.5U to 1cc of drip mixture

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

Continuous Variable Rate IV Insulin Drip

Adjust Multiplier (initially 0.02) to obtain glucose in

target range 100 to 140 mg/dL

If BG > 140 mg/dL, increase by 0.01

If BG < 100 mg/dL, decrease by 0.01

If BG 100 to 140 mg/dL, no change in Multiplier

If BG is < 80 mg/dL, Give D50 cc = (100 – BG) x 0.4

Give continuous rate of Glucose in IVF’s

Once eating, continue drip till 2 hours post SQ insulin

< 100 off

100-109 0.5

110-129 1.0

130-149 1.5

150-169 2.0

170-189 2.5

190-209 3.0

210-254 4.0

255-299 5.0 etc.

Check BG every 1 hr and adjust

rate

The default insulin drip column

Converting to SC insulin

If More than 0.5 u/hr IV insulin required with

normal BG, start long-acting insulin (glargine)

Must start SC insulin at least 2 hours before

stopping IV insulin

Some centers start long-acting insulin on initiation

of IV insulin or the night before stopping the drip

How to Initiate

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

Starting dose = 0.45 x wgt. in kg

Wt. is 100 kg; 0.45 x 100 = 45 units

Bolus dose (aspart / lispro) = 20% of starting dose

at each meal; 0.2 x 45 = 9 units ac (tid)

Basal dose (glargine) = 40% of starting dose at HS;

0.4 x 45 = 18 units at HS

Correction bolus = (BG - 100)/ CF, where

CF = 1700/total daily dose; CF = 40 or 3000 / wgt kg

Correction Bolus Formula

Example:

–Current BG: 250 mg/dl

– Ideal BG: 100 mg/dl

–Glucose Correction Factor: 40 mg/dl

Current BG - Ideal BG

Glucose Correction factor

250 - 100

40 = ~4.0u

Calculating Initial MDI* Doses for Insulin-naïve Patients

*Give after meals as rapid-acting analog if food intake is in doubt

*MDI = Multiple daily injection

Thompson et al. Diabetes Spectrum. 2005;18:20-27.

Starting dose = 0.5 × weight in kg

Basal dose = 40%-50% of starting dose at bedtime

Total prandial dose = 50%-60% of starting dose, 1/3 at

each meal*

Do not skip correction dose even if

no food eaten

Adjust upwards daily by adding 50% of correction doses to basal and bolus

doses

Calculating Initial MDI* Dose: Example

*Give after meals as rapid-acting analog if food intake is in doubt

*MDI = Multiple daily injection

Thompson et al. Diabetes Spectrum. 2005;18:20-27.

Starting dose = 0.5 × 100 kg =50U

Basal dose =

0.4–0.5 x 50 U = 20-25 U at bedtime

Prandial doses = (0.5–0.6 x 50) = 25-30 U ÷ 3 or 8–

10 U at each meal*

Give correction dose

Assume 100-kg person with moderate insulin resistance

Non-ICU Hospital Management

Which is the outpatient regimen?

What is the current glucose

When is the patient to eat?

How well is it controlling glucose

Why is the patient admitted

What to do depends on several questions

Who is the patient?

Hyperglycemia & Patients on General Medical Wards

Absolute risk of adverse outcome (death or prolonged stay) increased

15% per 18-mg/dL increase in glucose levels

0

5

10

15

20

25

30

35

< 109

mg/dL

109-125

mg/dL

126-162

mg/dL

>163

mg/dLBaker EH et al. Thorax. 2006;61:284-289.

N=433 patients with COPD Exacerbations

Mo

rtality

(%

)

New AACE-ADA Consensus Statement on Inpatient Glycemic Control

- Most patients:

• pre-meal BG <140 mg/dL

• random BG <180 mg/dL

- More stringent targets may be appropriate in stable

patients

- Scheduled SQ insulin with basal- nutritional-

correction preferred

Moghissi E et al. Diabetes Care 2009, Endocrine Practice 2009

Non–ICU

Setting

RABBIT 2 Trial

Prospective randomized trial of 130 insulin naïve T2DM non-ICU inpatients

Admission blood glucose b/w 140-400 mg/dl

Basal- bolus insulin with glargine and glulisine vs Regular insulin SS

Does inpatient management of hyper-glycemia represent a safety concerns?

Hypoglycemia

Common Features Increasing Risk of Hypoglycemia

in an Inpatient Setting

• Advanced age

• Decreased oral intake

• Chronic renal failure

• Liver disease

• Changes in clinical status or

Beta-blockers ,Corticosteroids

medications

A person with diabetes on tube feedings

What is the best insulin treatment for a DM

patient on tube feedings? (BG 150 to 300 mg/dl)

If unstable, first give IV insulin and determine the

requirement over 24 hours and then change to

SC basal (glargine Q 12 hours) with supplemental

rapid acting every 4 to 6 hours.

Can also use NPH Q 8 hours or regular Q 6 hours

as the basal

A person with diabetes on TPN

What is the best insulin treatment for a DM

patient on TPN? (BG 150 to 300 mg/dl)

If unstable, first give IV insulin variable drip and

determine the requirement over 24 hours and

then add all the insulin to the TPN bag.

Continue to supplement every 4 to 6 hours with SC

rapid acting insulin using BG – 100 / CF where CF

is equal to 3000 divided by weight in kg. On

average, CF = ~ 30 to 40

DM 1 patient in DKA (ph 7.0; BG 400 mg/dl: weight 80 kg)

When do you start potassium and how much?

When do you start dextrose and how much?

preference is 2 liters saline followed by D50.45

saline with 40 meq KCL/liter at

250 ml/hour. Monitor electrolytes Q 4 to 8

hours.

Treat Any Patient With BG >140 mg/dl With Insulin

– Treat Any BG >140 mg/dl with Rapid-acting Insulin

(BG-100) / (3000 / wt kg) or 1700 / total daily insulin

– Treat Any Recurrent BG >180 mg/dl with IV Insulin if

failing SC therapy or >140 mg/dl if NPO, acute MI,

perioperative, ICU, or >100 mg/dl if pregnant

If More than 0.5 u/hr IV Insulin Required with Normal BG

Start Long Acting Insulin

Protocol for Insulin in Hospitalized Patient

Protocol for Insulin in Hospitalized Patient

Daily Total: Pre-Admission or Weight (#) x 0.2 u

– 40 % as (Basal)

– 60% as Rapid-acting insulin (Bolus)

• Give in Proportion to Meal’s CHO Eaten

BG >140 mg/dl: (BG-100) / CF

CF = 1700 / Total Daily Insulin or 3000 / wgt kg

Do Not Use Sliding Scale As Only Diabetes

Management

All hospital patients should

have control blood glucose

Recommendations: Diabetes Care in the Hospital (2)

Goals for blood glucose levels

– Critically ill patients: 140-180 mg/dl (10 mmol/l) (A)

– More stringent goals, such as 110-140 mg/dl (6.1-7.8 mmol/l) may be appropriate for selected patients, if achievable without significant hypoglycemia (C)

– Non-critically ill patients: base goals on glycemic control, severe comorbidities (E)

ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.

Recommendations: Diabetes Care in the Hospital (3)

Scheduled subcutaneous insulin with basal, nutritional, correction components (C)

Use correction dose or “supplemental insulin” to correct premeal hyperglycemia in addition to scheduled prandial and basal insulin (E)

Initiate glucose monitoring in any patients not known to be diabetic who receives therapy associated with high risk for hyperglycemia (B)

ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.

Recommendations: Diabetes Care in the Hospital (4)

A hypoglycemia management protocol should be adopted and implemented by each hospital or hospital system

– Establish a plan for treating hypoglycemia for each patient; document episodes of hypoglycemia in medical record and track (E)

Obtain A1C for all patients if results within previous 2-3 months unavailable (E)

Patients with hyperglycemia who do not have a diagnosis of diabetes should have appropriate plans for follow-up testing and care documented at discharge (E)

ADA. VIII. Diabetes Care in Specific Settings. Diabetes Care. 2011;34(suppl 1):S43.

When is the patient to

eat?

What to do depends on several questions

How well is it

controlling glucose? What is the

current glucose?

Why is the patient

admitted?

Who is the

patient?

Which is the

outpatient regimen?

• Type 1? • Type 2?

• Orals? • Insulin? • Combo?

• A1c 6.5%? • A1c 9.5%?

• BG=142? • BG=442?

• NPO? • Full diet?

• Sepsis? • A-Fib?

Intervention Studies

Showing Benefits

• Van den Bergh-SICU

• Van den Bergh-MICU

• DIGAMI-1

• Krinsley study

• Furnary data

Showing No Benefits

• DIGAMI-2

• CREATE-ECLA

• VISEP trial

• GIST-UK

• Intra-operative cardiac

surgery study