Escolar Documentos
Profissional Documentos
Cultura Documentos
350
300
300
250
221
200
150
150
100
2000
Diabetes care.2004;27:1047-1053
2010
2025
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
Ultralente
Lente
NPH
Regular
Lispro
Aspart
2
Onset
Peak
10
12
14
Duration
16
18
20
22
24
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
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
Insulin dependency
Pain during injection
life
Lack of knowledge
Willing of using insulin
Hypoglycemic effect of insulin
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
Period of unwanted
hyperglycemia
Baseline
level
Time (h)
SC injection
(mU/l)
(pmol/l)
500
Serum insulin
75
Human Actrapid
(0.2 U/kg)
400
50
NovoRapid
300
200
25
100
0
-60
60
Slide No. 25
Education
Physician
Patient/family
Population
Modify insulin and its delivery
Quality of Life
By patients
Quality of Life
Perspective in Life
Expectation of Life
1
Dreyer,1997
INSULIN ANALOGS
Modified structure of the human insulin
resulting altered physicochemical,
biological, and pharmacological
properties
Syringe
Pen insulin ( painless,
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
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
years
COMBO
(SU + Metformin)
Titrate dose
Begin Insulin
months
Begin Insulin
(Continue 1 OHA)
Titrate dose
1 OHA
Titrate dose
Insulin secretion
30%
Type 2 diabetes
50%
50%
IGT
70-100%
70%
100%
150%
100%
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?
Detemir+ glinide
Detemir + SU
Detemir + Metformin
Detemir + TZD
Detemir + AGI
Detemir + Incr
Fasting
glucose
Prandial
glucose
Less hypoglycemia
Better controlled A1C than non analog
insulin
Less weight gain
Flexible delivery
Rapid insulin can be delivered
intravenously
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