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Management of Diabetes and Hyperglycemia in

the Hospital Patient:


non-critically ill, adult patient

Dr. Nanang Miftah Fajari, SpPD


SMF Ilmu Penyakit Dalam Ratu Zaleha Martapura
Reason for Admission Patients With
Diabetes
66.6 % (the majority) of patients were admitted
for medical reasons other than diabetes
9.0 % of patients admitted specifically for the
management of their diabetes; 47.0 % of patients
were admitted with active foot disease
People with diabetes are more likely to be
admitted as an emergency compared to the
general population (84.5% vs 80.8%)
Summary Findings from the National Diabetes Inpatient Audit (NaDIA) 2010
(England).www.diabetes.nhs.uk. Downloaded 8November 2013
Hyperglycemia Is Prevalent
at Hospital Admission
38% of all patients at admission have hyperglycemia
Of those patients, nearly one-third have no history of diabetes

31%
History of diabetes
No history of diabetes
69%

Single-center, retrospective chart review of 1886 patients hospitalized over 15 weeks in a


community teaching hospital. Hyperglycemia defined as BG 126 mg/dL on admission or while
fasting, or random BG 200 mg/dL on 2 occasions.
Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:978-982.
Hyperglycemia: Scope of the Problem

50 Diabetes 50 No Diabetes

40 40 26%
78%
Patients,

30 30
%

20 20

10 10

0 0
<110 110-140 140-170 170-200 >200 <110 110-140 140-170 170-200 >200

Mean BG, mg/dL


Kosiborod M, et al. J Am Coll Cardiol. 2007;49(9):1018-183:283A-284A.
Hyperglycemia and Mortality
in the MICU

~4x
45 ~3x
40
~2x
Mortality Rate (%)

35
30
25
20
15
10
5
0
80-99 100-119 120-139 140-159 160-179 180-199 200-249 250-299 >300

Mean Glucose Value (mg/dL)


N=1826 ICU patients.
Krinsley JS. Mayo Clin Proc. 2003;78:1471-1478.
Diabetes Care in Hospital

Patient Patient
Centered Safety

TEAM WORK
Managing Diabetes in the Hospital Presents Different
Challenges than Managing Diabetes in the Outpatient.

Inpatient management is associated


with:
- Nutritional and clinical instability
- The need for changes from the home diabetes
medical regimen
- Acute illness, stress-related hyperglycemia
- Use of medications that impact glycemic control
Why Should We Care?

Hyperglycemia occurs frequently in hospital


patients, and is associated with poor outcomes

Hypoglycemia occurs frequently in hospital


patients, and is unpleasant and dangerous

Adequate metabolic control is an attainable goal


for hospital patients
Hyperglycemia is Undesirable!

Hyperglycemia in the hospital is associated with adverse


outcomes
Hyperglycemia can occur in patients without a known
diagnosis of diabetes
Undiagnosed diabetes
Illness-related hyperglycemia
Patients with hyperglycemia without a known diagnosis
of diabetes experienced worse outcomes than the
known diabetes patients in this study

Umpierrez et al. Journal of Clinical Endocrinology and Metabolism 2002; 87: 978-82.
Hyperglycemia is Undesirable!

Improved glycemic control is associated with


improved outcomes in several different patient
populations, including those with:
Acute myocardial infarction
Cardiac surgery
Critical illness

(Diabetes Care 2004; 27: 553-91, Endocrine Practice 2004; 10: 77-82, and
Diabetes Care 2006; 29: 1955-62)
Hyperglycemia and Poor Hospital Outcome
Metabolic stress response

stress hormones and peptides

Glucose
Insulin
Reactive O2 species
Immune dysfunction
FFA
Transcription factors
Ketones
Lactate
Infection dissemination Secondary mediators

Cellular injury/apoptosis
Inflammation
Tissue damage
Altered tissue wound repair

Clement et al, Prolonged hospital stay


Diabetes Care 27:553-591, 2004
Disability / Death
How Can Diabetes and Hyperglycemia be
Controlled in the Hospital?

Oral agents = often inappropriate for hospital


patients
IV insulin = most often used in the intensive care
unit setting (or in other defined populations)
Subcutaneous insulin = the drug of choice for
controlling hyperglycemia in the majority of non-
critically ill patients
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.
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
Oral Antidiabetes Agents in the Hospital,
continued

Disadvantages of thiazoladinediones (e.g. rosiglitazone,


pioglitazone):
Slow onset of action (2-3 weeks)
Can cause fluid retention (particularly when used with insulin), and
increase risk for CHF
Disadvantages of alpha-glucosidase inhibitors (e.g. acarbose,
miglitol)
Abdominal bloating and flatus
Need pure glucose to treat hypoglycemia
Disadvantages of GLP-1 mimetics (e.g. exenatide)
Newer agents without data to support use in the hospital
Abdominal bloating and nausea secondary to delayed gastric emptying
Diabetes and Hyperglycemia Require Proactive
Management

Diabetes requires proactive management in all


hospital patients. There are no autopilot
insulin regimens
Insulin is a high alert medication that is
frequently associated with medication errors in
the hospital
insulin to be one of the highest risk
medications in the hospital
(JCAHO Website, 2006)
The Issue of Hypoglycemia
Fear of hypoglycemia often results in the use of non-
physiologic insulin regimens (e.g. sliding scale insulin,
alone)
Hypoglycemia in the hospital can be reduced by using
standardized, physiologic insulin regimens

Treat to Target without


Hypoglycemia
What is the Appropriate Glycemic Control Target
for Inpatients?

Controversial!

ICU Non-ICU, Non-ICU,


Preprandial Maximum

ACCE/ACE 110 mg/dl 110 mg/dl 180 mg/dl

ADA 110 mg/dl 90-130 mg/dl 180 mg/dl


AACE/ADA Target Glucose Levels
in NonICU Patients

NonICU setting:
Premeal 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 and/or above these cut-points

Hypoglycemia = BG <70 mg/dL


Severe hypoglycemia = BG <40 mg/dL

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
Selecting a Non-ICU Glycemic Target For Your
Practice/Institution

Examples of target ranges set by some institutions:

90-150 mg/dL
Pre-prandial target 90-130 mg/dL; Random glucose < 180 mg/dL
Pre-prandial target 80-130 mg/dL for most patients; pre-prandial
target 90-150 mg/dL for patients with hypoglycemia risk factors
Current Practice Best Practice
Dependence on non-physiologic insulin prescribing (as
opposed to insulin that mimics physiologic insulin
secretion)
Dependence on reactive strategies (e.g. sliding-scale
insulin)
Overemphasis on simplicity (particularly simplicity
from the perspective of the ordering physician)
Overemphasis on avoidance of hypoglycemia
Lack of standardization of insulin use in the hospital
What is the Best Practice for Managing Diabetes and
Hyperglycemia in the Hospital?

anticipatory
physiologic insulin dosing
prescribed as a basal/bolus insulin regimen

giving the right type of insulin


at the right time
in the right amount
The Components of a
Physiologic Insulin Regimen

Nutritional Correctional
Basal insulin
insulin insulin
Physiologic Insulin Secretion:
Basal/Bolus Concept
Nutritional (Prandial) Insulin
50
(U/mL)
Insulin

25 Suppresses Glucose
Production Between
0 Basal Insulin Meals & Overnight
Breakfast Lunch Supper

150 Nutritional Glucose


Glucose
(mg/dL)

100 The 50/50 Rule


50
Basal Glucose
0
7 8 9 101112 1 2 3 4 5 6 7 8 9
A.M. P.M.
Time of Day
Providing Exogenous Basal Insulin
Long-acting, non-peaking insulin is preferred as it provides
continuous insulin action, even when the patient is fasting

Required in ALL patients with type 1 diabetes

Many patients with type 2 diabetes will require basal insulin in


the hospital

Can be estimated to be about 1/2 of the total daily dose of insulin


(TDD)
Which Insulins are Best for
Basal Coverage?
NPH
Detemir (Levemir)
Glargine (Lantus)
Insulin Effect

Regular
Lispro (Humalog)
Aspart (Novolog)
Glulisine (Apidra)
Inhaled insulin

0 6 12 18 24
Time (hours)
Providing Exogenous Nutritional Insulin

Usually given as rapid-acting analogue (preferred in


most cases) or regular insulin, for those patients who
are eating meals
Must be matched to the patients nutrition
Should not be given to patients who are not receiving
nutrition (e.g. NPO)
Can be estimated to be about of the total daily dose
of insulin (TDD)
Which Insulins are Best for
Nutritional Coverage?
NPH
Detemir (Levemir)
Glargine (Lantus)
Insulin Effect

Regular
Lispro (Humalog)
Aspart (Novolog)
Glulisine (Apidra)
Inhaled insulin

0 6 12 18 24
Time (hours)
Providing Exogenous Correctional Insulin
Correctional insulin is extra insulin that is given to correct
hyperglycemia

Usually rapid-acting or regular insulin (usually the same as the


nutritional insulin)

Often written in a stepped format that is used in addition to basal


and nutritional insulin

Customized to the patient using an estimate of the patients insulin


sensitivity

If correctional insulin is required consistently, or in high doses, it


suggests a need to modify the basal and/or nutritional insulin doses
Using Exogenous Insulin to Imitate
Physiologic Insulin Secretion: Summary
Basal insulin: Use non-peaking, longer acting
insulins
Glargine or detemir are preferred
NPH also possible
Nutritional insulin: Depends on the type of
nutrition
Rapid-acting insulin is preferred when patients are eating
meals
Regular insulin also possible
Correctional insulin: Use rapid-acting (or regular)
insulin
Usually the same as the nutritional insulin
Which Patients Should be Treated with a
Physiologic Insulin Regimen?
During hospitalization
Any patient with blood glucose levels consistently above the target
range

Immediately at the time of admission


All patients with type 1 diabetes
Patients with type 2 diabetes if
They are known to be insulin-requiring
They are known to be poorly controlled despite treatment with
significant doses of oral agents
They are known to require high doses of oral agents that will be held
in the hospital
A Stepwise Approach to Physiologic Insulin Dosing
in the Hospital

1. Estimate the amount of insulin the patient would need


over one day, if getting adequate nutrition = Total
Daily Dose (TDD)
2. Assess the patients nutritional situation
3. Decide which components of insulin the patient will
require, and which percentage of the TDD each should
represent
4. Assess blood glucoses at least daily, adjusting insulin
doses as appropriate
STEP 1: Estimate the Amount of Insulin the Patient Would
Need Over One Day, If Getting Adequate Nutrition = Total
Daily Dose (TDD)
Insulin drip-based estimate (for patients treated with an insulin
infusion- see below)

For patients already treated with insulin, consider the patients


preadmission subcutaneous regimen and glycemic control on that
regimen

Weight-based estimate:
TDD = 0.4 units x Wt in Kg

Adjust down to 0.3 units x Wt in Kg for those with hypoglycemia risk


factors, including kidney failure, type 1 diabetes (especially if lean),
frail/low body weight/ malnourished elderly, or insulin nave patients

Adjust up to 0.5-0.6 units (or more) x Wt in Kg for those with


hyperglycemia risk factors, including obesity and high-dose glucocorticoid
treatment
Conditions Associated with Hypoglycemia in
Hospitalized Patients
Known sensitivity to insulin recognized as low TDD of insulin (e.g.
type 1 diabetes) or lean body habitus
Malnutrition or low body weight
Specific medical conditions, including renal failure (ESRD), liver
disease, heart failure, malignancy, circulatory failure (shock),
adrenal insufficiency, burns, alcoholism
Prior hypoglycemia or labile blood glucose control
Medications: sulfonylureas, pentamidine, quinine, or lowering of
the doses of glucocorticoids
Decreases in nutritional intake (e.g. those related to physician
orders, delays in food delivery, sudden discontinuation of
parenteral or enteral nutrition, or patient-specific factors such as
nausea, etc)
Advanced age
Conditions Associated with Hyperglycemia in
Hospitalized Patients

Known insulin resistance recognized by high TDD of insulin or


obesity

Medications: glucocorticoids, catecholamines, tacrolimus,


cyclosporine

Significant illness: Stress response related to the release of


counter-regulatory hormones

Increases in nutritional intake (e.g. restarting a diet, starting


enteral or parenteral nutrition)
STEP 2: Assess the Patients Nutritional Situation

Eating meals or receiving bolus tube feeds

Eating meals but with unpredictable intake

Getting continuous tube feeds

Getting tube feeds for only part of the day

Getting parenteral nutrition

NPO
STEP 3: Decide Which Components of
Insulin the Patient Will Require, and Which Percentage of
the TDD Each Should Represent

Basal insulin can generally be estimated to be 1/2 of the TDD

Nutritional insulin makes up the remaining 1/2 of the TDD


STEP 3: Decide Which Components of
Insulin the Patient Will Require, and Which Percentage of
the TDD Each Should Represent, Continued

In most cases, basal insulin should be provided

In most cases, well-designed corrective insulin regimens should


be provided

When a patient is not receiving nutrition, nutritional insulin


should not be given

Nutritional insulin needs must be matched to the actual


nutritional intake
STEP 4: Assess Blood Glucoses at Least Daily, Adjusting
Insulin Doses as Appropriate

Blood glucose targets can only be achieved via


continuous management of the insulin program
Example Cases
Introduction to the Cases
Case 1
56 year old woman with DM2 admitted with a diabetes-related foot
infection which may require surgical debridement in the near future,
eating regular meals.

- Weight: 100 kg
- Home medical regimen: Glipizide 10 mg po qd, Metformin
1000 mg po bid, and 20 units of NPH q HS
- Control: A recent HbA1c is 10%, POC glucose in ED 240 mg/dL

What are your initial orders for basal and nutritional insulin?
How would you manage the oral agents?
Case 1: Solution
Bedside glucose testing AC and HS
Discontinue oral agents
Total daily dose 100 kg x 0.6 units/kg/day = 60

Basal: Glargine /Detemir 30 units q HS

Nutritional: Rapid-acting analogue 10 units q ac at the


first bite of each meal

Correction: Rapid-acting analogue per scale q ac and HS


(Note: Use correctional insulin with caution at HS,
reduce the daytime correction by up to 50% to avoid
nocturnal hypoglycemia)
Case 1 Continued
The patient is made NPO after midnight for a test, but is expected to
be able to resume her diet at lunch or dinner the next day. What
changes would you make to her management program regarding
glucose monitoring and her insulin program? Would you provide
dextrose in her IV fluids?
Case 1 continued: Solution
Change bedside glucose checks to q 6 hours, as the
patient will not be eating meals
Continue basal insulin: If using glargine/detemir,
continue as is. If using NPH, continue in equal twice
daily doses with a dose reduction of 1/3-1/2 while NPO.

Hold nutritional insulin while NPO

Provide a low level of intravenous dextrose (e.g. 75-125


cc/hr of a D5 containing solution)

Continue appropriate correctional insulin for


hyperglycemia
Transitioning to the Outpatient Arena
Deciding on a home regimen
HbA1c
Anticipating clinical improvement
Patient factors: Financial, social, abilities, wishes

Patient education
Changes made in the hospital
Diabetes/insulin survival skills

Communication with outpatient physicians


Systems for Improving the Quality of Insulin Use
in Inpatients

Protocols

Standardized order sets

Physician, midlevel provider, and nurse education


Summary
Understanding these basic principles of physiologic, anticipatory
insulin will allow clinicians to formulate rational insulin regimens in
virtually any clinical situation.
The componen of Physiologic insulin regimen in hospital setting :
Basal Insulin
Nutritional Insulin
Correctional Insulin
There is no autopilot insulin regimen for a hospitalized
patient!
Giving insulin in the right type, at the right time, and in the right
dose
Treat to target and avoid hypoglycemia
Thank You