Insulin Usage in

Hospitalized patient
By dr. Olly Renaldi SpPD KEMD

HYPERGLYCEMIA

HYPERGLYCEMIA POOR
OUTCOMES
Hiperglyce
mia

Immune function
The cardiovascular
system
Thrombosis
Inflammation
Endothelial
dysfunction
The brain
Oxidative stress

Metabolic Stress Response

HOSPITALIZED PATIENTS
LINK BETWEEN HIGH BLOOD
GLUCOSE AND POOR OUTCOMES

Mortality
Hyperglycemia

Complications
Length of
stay

Pengelolaan Hiperglikemia
Pasien Rawat Jalan:
Umumnya tidak perlu tergesa-gesa menurunkan kadar
glukosa darah. Tidak harus segera dengan insulin
Moto: Start Low GO Slow, walaupun harus tetap agresif:
early diagnosis
early treatment
early combination
early insulin

Pasien Rawat Inap:

Umumnya memerlukan penurunan kadar glukosa darah
segera. Sasaran kadar glukosa darah lebih agresif.
Umumnya memerlukan insulin
Untuk yang dirawat karena hal lain, dan kadar glukosanya
sudah baik, modalitas pengelolaan hiperglikemia tidak
harus diubah

Hyperglycemia is linked to mortality,

regardless of diabetes status
60

% of patients

50
40

30
20

Euglycemic
patients without
diabetes
Euglycemic
patients with
diabetes
Hyperglycemic
patients with
diabetes
Hyperglycemic
patients without
diabetes

10
0
180-Day Mortality in Patients Admitted for MI
* 11.1 mmol/l (200 mg/dl)
Rady 2005; Ainla 2005

Causes of hyperglycemia in the hospital

setting
Hyperglycemia relates to three issues:
Patients with a known history of diabetes
Patients who have diabetes but are unaware of their
condition
Hyperglycemia as a result of physiological stress:
Infection, treatment (e.g. steroids), enteral or parenteral
feeding

There is a need for consistent and appropriate

treatment policies

Pengelolaan Rawat Inap DM tipe 2

Prinsip dasar pengelolaan kendali glukosa
tetap berlaku:
Mencapai keadaan kendali glukosa maksimal,
Menghindari hipoglikemia
Cermat, Hati-hati, Individualisasi
Pengelolaan DM seiring dan mengikuti
pengelolaan penyakit lain yang ada

Pada keadaan rawat inap, dalam keadaan

kritis, apalagi dekompensasi, tercapainya
sasaran harus lebih cepat-lebih agresif

Blood Glucose Target

Critically ill surgical patients: as normal as possible
(110 140 mg/dL)*
Insulin is needed, IV protocol
Close to 110 mg/dL (A)
Critically ill non surgical pts: as normal as possible
(110 140 mg/dL)*
Insulin is needed, IV protocol
Keep BG < 140 mg/dL (C)
Non critically ill: as normal as possible, no specific goals
Insulin is preferred
FBG <126 mg/dL, Random BG<180-200 mg/dL (E)
* Some institutions might considered this blood glucose target as
over aggressive due to their cautious attitude toward hypoglycemia
A D A Clinical Practice Recommendation
Diabetes Care. 2009;32(suppl 1): S 32-33

INSULIN

Strategies for attaining inpatient

glycemic targets
Continuous intravenous insulin infusions (critically ill
patients, nil by mouth for surgery)
Subcutaneous insulin therapy (non-critically ill patients):
Basal insulin
Nutritional (prandial) insulin (not always necessary; OAD
might be appropriate)
Correction (supplemental) insulin
Continuous subcutanous insulin infusion (CSII) pumps - for
patients using this device pre-admission

Oral medications: introducing new agents, amending doses

of current treatments
May need to change treatment several times during admission
or on discharge
Patients needs and condition may change over time

Indikasi Insulin
Dekompensasi Metabolik Berat
Ketoasidosis, hiperosmolar non-ketotik dan
asidosis laktat
BB turun cepat tanpa penyebab lain yang jelas
Stres berat (infeksi sistemik, operasi > 3 jam)

Indikasi Insulin selain Dekompensasi

Metabolik Berat
Gagal dengan OHO dosis (hampir) maksimal
Terdapat kontraindikasi OHO
DM gestasional yang tidak terkontrol dengan diet
Keadaan-2 lain (HbA1c , GD akibat steroid )
Tipe 1

Cara Menurunkan Hiperglikemia

Dengan Insulin
Intravena/ Drip: Dapat lebih cepat mencapai
sasaran. Pada pasien kritis penting
Perlu pemantauan yang ketat
(prasyarat)
Subkutan: pada pasien rawat inap umumnya dapat
dipakai untuk mencapai kendali glukosa
Kerja cepat
Kombinasi kerja cepat dan panjang
Kombinasi kerja panjang dan
dosis koreksi dengan cara sliding scale
Cara sliding scale konvensional tersendiri tidak dianjurkan

Managing hyperglycemia in the

hospital setting

Antihyperglycemic therapy

Non-insulin agents

Insulin
Generally recommended

IV Insulin
(Intra Vena Insulin)

Moghisis 2009

Stable patients
No contraindication to
non-insulin agents

SC Insulin
(Subcutan Insulin)

Relative proportion of insulin

requirements (%)*

Insulin requirements vary in health and

illness in patients with diabetes

140

Correction

120

Nutritional

100
80

Prandial/Bolus

60

Basal

40
20
0

Healthy

Sick/Eating

Sick/NPO

*Estimations for illustrative purposes: requirements may vary widely

Clement 2004

IV insulin

Antihyperglycemic therapy

Non-insulin agents

Insulin
Recommended

IV Insulin
(Intra Vena Insulin)

Moghisis 2009

Stable patients
No contraindication to
non-insulin agents

SC Insulin
(Subcutan Insulin)

Indikasi Terapi Insulin Intravena

1.
.
.
.
.
.

Indikasi kuat (evidence based medicine)

Ketoasidosis Diabetikum
HyperOsmolar Nonketotic Coma (HONC)
Penyakit Berat / Kritis
Infark miokard atau syok kardiogenik
Periode pasca operasi kardiak

Indikasi Terapi Insulin Intravena

2. Indikasi relatif (evidence belum banyak bila
dilihat dari data-data outcome)
. DM tipe 1 atau 2 yang perlu total parenteral
nutrition (TPN)
. Persiapan operasi (perioperative care)
. GD akibat terapi steroid dosis tinggi
. Stroke
. Strategi penentuan dosis insulin
. Kehamilan dan persalinan
. Infeksi, atau keadaan lain yang perlu GD ketat

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

Not recommended
< 110
22

Acceptable
110-140

Recommended
140-180

Not recommended
>180

ADA/AACE Inpatient Task Force

Endocrine Practice 2009;15;1-17

A.Petunjuk Umum
1.Target glukosa darah (GD)

150

110-

mg/dl
2.Drip Insulin dihentikan bila pasien
makan & menerima dosis pertama
insulin subkutan

B.Prosedur Drip Insulin dgn Syringe

pump : campurkan 50 U RI (Novorapid)
+ 50 cc NaCl 0,9% (1 : 1) dalam spuit
50cc
Mulai pada level 1 kecuali pasien
kriteria Level 2 Pasien yang
menggunakan glucocorticoids

<110
110119

<110
110119

Rapid Acting Insulin- NovoRapid

Soluble
Clear
Buffered
Onset : within 10-20 min
Peak : 1-3 hours
Duration: 3-5 hours

Treatment of Hypoglycemia (<80mg/dL)

Discontinued insulin drip And

Give D40% i.v.: -pts awake 25ml
-pts not awake 50ml
Recheck BG every 20 minutes and repeat 25 ml
D40% i.v. if <80mg/dL
Restart drip if BG >110mg/dL x2 checks
Restart drip with lower algorithm (moving down)

Considerations when converting

from IV to SC insulin
Initial doses of SC insulin are based on previously established
dose requirements1
75%-80% of the total daily IV infusion dose is
proportionally divided into basal and bolus components2
SC insulin must be given before discontinuation of IV insulin
to prevent hyperglycemia2
Intermediate- or long-acting insulin must be injected SC
2-3 h before discontinuing the IV insulin infusion 1
A short- or rapid-acting insulin should be given SC 1-2 h
before discontinuation of the IV insulin infusion 1

Clement 2004; 2 Moghissi 2009

Example of transition from

IV to SC insulin therapy
An estimation of the 24-h IV insulin requirement can be
extrapolated from the average amount of insulin infused
during the previous 6-8 h
Only if the patient is not receiving pressor agents and BG level
is stable in the target range

Patient has received an

average of 1 U/h IV during
previous 6 h

How do you dose this patient with an SC

injection?
Konsensus Perkeni 2011,
ADA, Diabetes Care 2010; 33: S11- S61
Bode 2004

Example of transition from IV to SC

insulin therapy

Calculate SC total daily dose (TDD)

SC TDD is 80% of 24-h insulin requirement:

1 Unit/h x 24 h =
24 Units

Konsensus Perkeni 2011,

ADA, Diabetes Care 2010; 33: S11- S61
Bode 2004

80% x 24 Units
= 19 Units

Example of transition from IV to SC

insulin therapy
Calculate basal and bolus dose from SC TDD
Basal dose is 50% of SC TDD:
50% of 19 Units = 10 Units of long-acting insulin
Give 2-3 h before discontinuing IV insulin
Bolus total dose is 50% of SC TDD:
50% of 19 Units = 10 Units
Give as ~3 Units with each meal

Konsensus Perkeni 2011,

ADA, Diabetes Care 2010; 33: S11- S61
Bode 2004

Correction factor (insulin sensitivity

factor)
CF (ISF) is the glucose lowering effect of 1 unit of insulin
over 2-4 hours
CF = 1700 if mg/dL
TDD
Correction dose = (actual BG - target BG)
CF

Bode 2004

Correction dose: example in mg/dl

The 1700 rule to calculate correction factor (CF)
CF (insulin sensitivity) = 1700/TDD
If TDD = 19 units, CF = 1700/19 = 89
Therefore, 1 unit reduced BG by 89 mg/dl
Therefore to reduce BG from (e.g.) 360 to 89 mg/dl,
give 3 units

Bode 2004

Intravenous insulin infusion (drip insulin) Vs.

subcutan (sliding scale)

SLIDING SCALE

DRIP INSULIN

Simple
Insulin Physiologic

simple
no

difficult
close to

Hyperglycemia
Hypoglycemia
Dose (3-4 hours)
Target

3X
more
fixed

rare
rare
modifiable

(Soewondo, 2005)

no

close to

SC insulin

Antihyperglycemic therapy

Non-insulin agents

Insulin
Usually recommended

IV Insulin
(Intra Vena Insulin)

Moghisis 2009

Stable patients
No contraindication to
non-insulin agents

SC Insulin
(Subcutan Insulin)

Strategy of insulin treatment

Kebutuhan Insulin Harian Pasien

di Rumah Sakit

Insulin Basal: mengatasi hiperglikemia puasa akibat

glukoneogenesis (intermediate-acting insulin long-acting
insulin)
Insulin Prandial/ Nutrisional/Bolus: mengatai glukosa
yang diberikan lewat intravena, TPN, lewat sonde
lambung, nutrisi tambahan dan makanan bebas (rapidacting insulin short-acting insulin)

Insulin suplemen/koreksi: memenuhi kebutuhan insulin

yang meningkat akibat penyakit akut / stres (rapid-acting
insulin atau short-acting insulin)

Jika
Jika gula
gula darah
darah puasa
puasa
meningkat
meningkat

Gunakan
Gunakan insulin
insulin
basal
basal

Jika
Jika gula
gula darah
darah sesudah
sesudah
makan
meningkat
makan meningkat

Gunakan
Gunakan insulin
insulin
bolus
bolus

Jika
Jika gula
gula darah
darah puasa
puasa
dan
sesudah
makan
dan sesudah makan
meningkat
meningkat

Gunakan
Gunakan insulin
insulin
premix
premix
Atau
Atau tambahkan
tambahkan
insulin
insulin basal
basal pada
pada
terapi
terapi OAD
OAD
Atau
Atau mulai
mulai terapi
terapi
basal
bolus
basal bolus

Perkeni, Petunjuk praktis terapi insulin pada pasien diabetes, 2011

Konsep Basal - Bolus

Hyperglycemia
Prandial
Prandial /Bolus
/Bolus

Basal
Basal

Perbaiki gula darah

puasa dahulu
Lanjutkan OAD
SMBG penting

Insulin
Insulin Prandial
Prandial

Insulin
Insulin Basal
Basal

Untuk memudahkan terapi gunakan insulin

premix (30% insulin prandial & 70% insulin
basal)

43

RECOMENDATION

44

Kontribusi kadar glukosa puasa dan glukosa prandial

terhadap HbA1c

Kontribusi terhadap
HbA1c

Kontribusi kadar glukosa prandial

40%

30%

45%
50%
70%

70%
60%

FIX THE FASTING

FIRST
55%
START
50% WITH BASAL INSULIN
30%
< 7.3

Kontribusi kadar glukosa puasa

7.4-8.4

8.5-9.2

9.3-10.2

>10,3

HbA1c
Monnier L et al. Diabetes Care 2003

Macam-macam Insulin di Indonesia

Bolus/prandi
al Insulin
Basal
Insulin

INSULIN CHOICES
BASAL
Detemir
Glargine

RAPID-ACTING
Aspart
Lispro
Glulisine

PRE-MIXED
Human or Analog
70/30
50/50

NPH

Regular

Other mixes

Levemir

NovoRapid

NovoMix 70/30

24/7 insulin for patients with

type 2 diabetes.
24-hour action at a once-daily
dose
Consistent insulin absorption
and action, day after day
Less weight gain
Low rate of hypoglycemia

Quick meal.
Quick insulin.
Mimics the bodys normal
mealtime insulin response
Provides significantly better
mean PPG levels than regular
human insulin
Offers convenient mealtime
dosing

One insulin. Two actions.

One simple way to help
control diabetes.
One insulin with both fasting
(FPG) and mealtime (PPG)
control
Efficacy that helped the
majority of patients with type
2 diabetes get
to goal
Low rate of hypoglycemia

Regimen Basal Bolus

---- Insulin endogen

----

Makan
Pagi

Makan
Siang

Makan
Malam

Levemir
NovoRapid

Sebelum tidur

Basal Bolus Concept dengan Levemir - NovoRapid

Tambahkan
NovoRapid
di sebelum
setiap makan
4 iu
(atur
dosis
Suntikkan
10Injeksi
iu Levemir
sekali
tidur.
Atur
dosisnya
tiap 3
hari)
untuk
Gula darahtarget
2 jam GDP
PP
(+3 atau
-3)
setiap
3 mengendalikan
hari sd. GDP mencapai
mencapai
target
< 140 mg/dL (Perkeni 2011)
<100 mg/dL
(Perkeni
2011)
400

T2DM

300

15

Plasma glucose (mmol/l)

Plasma glucose (mg/dl)

20

Profile T2DM

200

Hyperglycaemia due to an increase in fasting glucose

10

100

5
Normal

0
06.00

Meal

Meal

Meal

0
10.00

14.00

18.00

22.00

Time of day (hours)

02.00

06.00

Terapi Intensive Insulin dng Insulin Pump

Continuous Subcutaneous Insulin Injections
Insulin Secretion (pmol/min)

800

Bolus Bolus

Bolus
Normal
Type 2 gemuk

700
600

Type 2 non
gemuk
Type

500
1

400
300

Basal

200
100
0600

1000

1400

1800

2200

0200

0600Time

Polonsky et al. New Eng. J.Med.

Unit/me
Unit/24hr
al Insulin Dose
Bolus
Breakfast

Basal

BreakfastP

Blood Glucose
Lunch

Dinner Bed Time

LunchDinnerDayNightbeforeafter before after before after

Target GDS : 100-140 mg/dL

HbA1C (%)
Glukosa rata-rata
6-7

135 - 170

before

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
ADA/AACE Inpatient Task Force
Endocrine Practice 2009;15:1-17
51

Kesimpulan
Pada keadaan rawat inap:
sasaran harus dicapai lebih cepat, terutama
keadaan kritis. Obat oral jarang dipakai
Berbagai cara pemberian insulin dapat dilakukan
Intravena/Drip
- KAD
- Perlu penurunan cepat
Perlu pemantauan ketat, setting intensif

Subkutan dengan berbagai cara

Kerja pendek /cepat
Kerja menengah/panjang
Insulin kerja campuran
Kombinasi Basal + Bolus prandial

pada

Thank for your attention