Berbagai macam insulin
dan cara kerjanya
THE WORLDWIDE PANDEMIC OF
TYPE 2 DIABETES
Indonesia 2030: 21.3 Mil
World wide diabetes
prevalence (millions)
350
300
300
Indonesia: 8.4 Mil
250
221
200
150
150
100
2000
Diabetes care.2004;27:1047-1053
2010
2025
International Diabetes Federation Diabetes Atlas 2000;
Amos et al. Diabet Med 1997;14 (Suppl 5):S1-S85.
Patho-mechanism of type-2 DM
Genetics
Insulin resistance
Environment
Excess energy
intake
Sedentary lifestyle
Obesity
FFA
Glucose
Impaired glucose tolerance
-cell failure
-cell failure
Type 2 diabetes
Liver
Muscle
Adipose
FFA release
Circulation
FFA
Glucose
Pancreas
FFA absorption
Glucose
absorption
Fat
MAJOR METABOLIC
DEFECT IN TYPE-2 DM
Carbohydrates
Intestines
Pharmacologic treatment
of DM
OAD
Liver
Muscle
Adipose
TZD
Biguanide
FFA release
Circulation
Glucose
FFA
Pancreas
Glucose
absorption
AGI
Biguanide
TZD
FFA absorption
Intestinal lipase inhibitor
Fat
Insulin secretagogues
Carbohydrates
Blocks
Promotes
Intestines
INSULIN
Liver
Muscle
Adipose
FFA release
Circulation
Glucose
FFA
Pancreas
Glucose
absorption
AGI
FFA absorption
Intestinal lipase inhibitor
Fat
Carbohydrates
INSULIN
Intestines
The action of human insulin
(onset, peak, and usual effective duration of action)
Glargine/
Detemir
Ultralente
Lente
NPH
Regular
Lispro
Aspart
2
Onset
Peak
10
12
14
Duration
16
18
20
22
24
PROFIL INSULIN SUBKUTAN
Aspart
(very fast)
7 am
Regular
(fast)
12 pm
NPH/Lente
(slow)
7 pm
Insulin
Detemir
(slow)
12 am
Ultralente
(very slow)
7 am
INSULIN
14
The problems related to immunogenicity have been relatively rare since
the use of highly (monocomponent) insulins
ANTI-INFLAMMATORY EFFECTS OF
INSULIN
Decrease CRP
Cell culture: reduce oxidative stress and its associated
apoptosis in cardiomyocytes
Induced endothelial-derived nitric oxide
Human aorta cell and human mononuclear cell culture:
dose-dependent reductions in ROS, proinflammatory
transcription factor NF-kB, ICAM-1, chemokine
monocyte chemoattractant protein (MCP-1)
Inhibit TNF-a and proinflammatory transcription factor
early growth response gene
Clement et al. Diabetes Care 27: 553-591, 2004
Cultural problems
Patients problems
Tool and delivery
problem
Physician problem
If
you use insulin every day by
injection, that means you are
unhealthy
Insulin dependency
Pain during injection
Using insulin is the end of your
life
Lack of knowledge
Willing of using insulin
Hypoglycemic effect of insulin
Subcutaneous insulin injection drain
into the peripheral, not portal
circulation
Insulin preparation are a poor match
for the finely tuned cell
Subcutaneous insulin absorption is
highly variable (intra-individual and
inter-individual)
50
Non-diabetic insulin
response to mixed meal
40
Plasma insulin (mU/L)
Comparison of change
in the plasma insulin
concentration in
response to a mixed
meal in non-diabetic
subjects, with changes
in free insulin
concentration after a
typical subcutaneous
(SC) dose of shortacting insulin in a type
1 diabetic patient
30
SC short-acting
insulin in
type 1 diabetes
20
10
0
0
1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0
Time (min)
Biotechnology of Insulin Therapy. Oxford: Blackwell Scientific Publications, 1991;1-23
Human Insulin Time-action Pattern
Change in serum insulin
Period of unwanted
hyperglycemia
Normal insulin secretion
at mealtime
Human insulin
Period of unwanted
hypoglycemia
Baseline
level
Time (h)
SC injection
Nonphysiologic Insulin (RI) Replacement
Does Not Mimic -cell Insulin Secretion
Twice daily, intermediate-acting NPH are commonly used as basal insulin
DeWitt DE and Hirsh IB, 2003
Twice as Rapid onset & as High peak
Doubleblind, cross-over, single dose study in healthy volunteers, N=24
(mU/l)
(pmol/l)
500
48 min/ 414 pmol/l
Serum insulin
75
Human Actrapid
(0.2 U/kg)
400
50
NovoRapid
123 min/ 239 pmol/l
300
200
25
100
0
-60
60
120 180 240 300 360 420 480 540 600
Time (minutes)
Heinemann L et al. Diabetes Med 1996;13:683-84
Slide No. 25
Education
Physician
Patient/family
Population
Modify insulin and its delivery
VALUATIONS OF THERAPEUTIC GOALS
By professionals
Quality of Life
By patients
Quality of Life
Perspective in Life
(Secondary and tertiary prevention)
Expectation of Life
1
Dreyer,1997
INSULIN ANALOGS
Modified structure of the human insulin
resulting altered physicochemical,
biological, and pharmacological
properties
Properties of ideal insulin analogues
Rapid-acting insulin analogues
Onset of action < 0.5 after SC injection
High peak activity
Duration of action < 4 h
Long-acting insulin analogues
Onset of action > 4 h after SC injection
Duration of action 24 h (one injection per day)
No pronounced peak activity
Almost constant action over time
General
Small intra-individual variability of insulin action
Metabolic effect greater than mitogenic effects
No significant immunogenic effects
Chemically stable
No problem with miscibility
The use of insulin analogues
may decrease the risk of
hypoglycemia
Syringe
Pen insulin ( painless,
easier, more accurate, less
complication)
Insulin pump
Subcutaneous
Intravenous
Intramuscular
Intraperitoneal
Intranasal
Oral
Treatment Modalities
Combination of basal (bed-time) insulin
with oral hypoglycemic agents
Basal plus
- Basal + 1
- Basal + 2
- Basal + 3 (Basal bolus)
Sliding scale
How to use insulin?
Prediabetes
Overt Diabetes
Normal
Metformin
INSULIN
Glucose
mg/dL
SU
Post-prandial
Fasting glucose
350
300
250
200
150
100
Relative to normal
(%)
Insulin resistance
250
200
150
100
50
0
Insulin level
-10
-5
10
Years
15
20
25
30
Algorhytm of Type 2 Diabetes Treatment
Lifestyle (dietary and activity)
Add 1st OHA
(SU or Metformin)
Titrate dose
years
Add 2nd OHA
(Combo)
Titrate dose
COMBO
(SU + Metformin)
Titrate dose
Begin Insulin
months
Add 3rd OHA
(Combo)
Begin Insulin
(Continue 1 OHA)
Titrate dose
Begin Insulin
(Continue 1 OHA)
Titrate dose
1 OHA
Titrate dose
Natural History of Type 2 Diabetes
Insulin sensitivity
Insulin secretion
30%
Type 2 diabetes
50%
50%
IGT
70-100%
70%
100%
Impaired glucose metabolism
Normal glucose metabolism
150%
100%
Diabetes Obes Metab 1999; 1(1): S1
Glucose profiles
Fasting
2 hr post prandial
GLUCOSE
Fasting glucose Normal
2-hr post prandial increase
Fasting glucose increase
2-hr post prandial normal
Fasting glucose increase
2-hr post prandial increase
Glinide,SU,
Metformin,Glitazone,
Prandial insulin
Metformin,
Glitazone, Fasting
insulin
Metformin,
Glitazone,Glinide,SU,
Fasting and
prandial insulin
Less injection
Able to control fasting and prandial
blood glucose
Decrease the amount of insulin needed
More simple than multiple daily
injection
Increase adherence to insulin
Less hypoglycemic episodes?
Targeting the dual glucose profile in diabetic
Detemir+ glinide
Detemir + SU
Detemir + Metformin
Detemir + TZD
Detemir + AGI
Detemir + Incr
* Not yet recommended
Fasting
glucose
Prandial
glucose
Can be given once, twice or three time
daily
Able to control fasting and prandial
glucose
Can be combined with OAD ( some times
glinide or AGI to control prandial glucose
in lunch time if given twice daily)
More adherence
Less hypoglycemia
Better controlled A1C than non analog
insulin
Less weight gain
Flexible delivery
Rapid insulin can be delivered
intravenously
Kendali HbA1c NovoMix lebih baik vs Mixtard
Tingkat keamanan :
Risiko kejadian nokturnal
dan hipoglikemia major
NovoMix30 lebih rendah
dibanding human premix
NovoMix vs.
Humalog Mix 25 and Mixtard 30
p < 0.001
Blood glucose excursion0 5h
(mmol/l h)
21
20
19
p < 0.05
17%
10%
18
17
16
15
14
13
0
Humalog Mix25
NovoMix 30
Mixtard 30
Hermansen K et al. Diabetes Care 2002;25:883888
TAKE HOME MASSAGE
Ingat IPTEk :
I : Indikasi
P : Perlu atau Tidak
T : Tehnik (cara pemberian,dosis)
Ek : Efek samping
