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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