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ALI SANTOSA.
Definisi
12,0
10,0 10,2
(percentage)
8,0
6,0 5,7
4,0 4,2
2,0
1,5
0,0
IGT New-onset DM DM Total DM
5 5 s.@di
(Indonesia Ministry of Health Affair– 2007)
T2DM Is Characterised by Decreased Insulin
Secretion and Increased Insulin Resistance
Insulin Insulin
secretion resistance
Liver glucose
production
PRE-RESEPTOR
- insulin abnormal
RESPTOR
- jumlah reseptor menurun
- afinitas reseptor menurun
POST-RESEPTOR
- GLUT-4 menurun
- transduksi signal terganggu
- fosforilasi abnormal
Faktor penyebab RI
Hormon strees :
- katekolamin
- kortisol
- glukagon
- hormon pertumbuhan
Sitokin :
- interleukin-6
- TNF-alfa
Normal insulin
secretion Insulin
resistance
Normoglycaemia
β-cell
exhaustion
Insulin resistance
Normal insulin
secretion Insulin
resistance
Normoglycaemia
β-cell
exhaustion
Insulin resistance
330
Meal
Glucose
300
270
240
110
80
150 Depressed/delayed insulin response
120
(µU/ml)
Insulin
90
60
30
0
140
130
Glucagon
(µµg/ml)
Time (minutes)
*Insulin measured in five patients
Adapted from Müller WA et al N Engl J Med 1970;283:109–115.
15
Model of underlying factors in type 2 diabetes:
insulin resistance and -cell dysfunction
Diabetes genes
Adipokines
-CELL Inflammation
DYSFUNCTION Hyperglycaemia
Free fatty acids
Other factors
Insulin
secretion INSULIN
RESISTANC
E
Lipolysis Glucose Glucose
production uptake
Asupan makanan
Produksi gula hati (glikogenolisis dan glukoneogenesis)
penurunan up take glukosa oleh adiposit dan otot
Insulin
Pengendalian Reseptor
incretin
glukosa insulin
Post reseptor
PPAR gama
Pathogenesis of Type 2 Diabetes
Diabetic
dyslipidaemia PAI-1
Endothelial dysfunction
Hyperglycaemia
Type 2 diabetes
4.0 Control
production (mg/kg • min)
T2DM
Hepatic glucose
3.5
3.0
2.5
r = 0.847
P<0.001
2.0
0
1.5
0 100 200 300
Fasting plasma glucose (mg/dL)
Adapted from DeFronzo RA. Diabetes. 1988;37:667-687.
Impaired Insulin Effect at the Liver Causes
Fasting Hyperglycaemia
Production 2 mg/kg/min
Normal
Type 2 diabetes
Production
2.5 mg/kg/min
98 98
100 100
75 75 18 Urine
Glucose
from oral 80
g/5 h
glucose*
50 50
Other
20 tissues
Hepatic
glucose
production
0 0
Normal Diabetes Normal Diabetes
P<0.01 P<0.01
*Not significant.
Data from Mitrakou A et al. Diabetes. 1990;39:1381-1390.
Pathogenesis of Type 2 Diabetes
Glucose
Production of glucose
and TG in the liver In blood vessels Platelets, fibrinolysis
uptake
Dyslipidaemia PAI-1
Endothelial dysfunction
Hyperglycaemia
Type 2 diabetes
600
*
400
Before treatment
After treatment
200
N = 15; T2DM
22 24 2 4 6 8
Time of day (h)
*P<0.05, except for first 3 measurements.
Adapted from Taskinen MR et al. Diabetes. 1989;38:580-588.
Pathogenesis of Type 2 Diabetes
Glucose
Production of glucose
and TG in the liver In blood vessels Platelets, fibrinolysis
uptake
Dyslipidaemia PAI-1
Endothelial dysfunction
Hyperglycaemia
Type 2 diabetes
Glucose
Production of glucose
and TG in the liver In blood vessels Platelets, fibrinolysis
uptake
Dyslipidaemia PAI-1
Endothelial dysfunction
Hyperglycaemia
Type 2 diabetes
Normal TG
Normal
Normal
insulin
action
Glucose
Production of glucose
and TG in the liver In blood vessels Platelets, fibrinolysis
uptake
Dyslipidaemia PAI-1
Endothelial dysfunction
Hyperglycaemia
Type 2 diabetes
?
80
60
Pancreatic function
40 = 50% of normal
20
0
–10 –9 –8 –7 –6 –5 –4 –3 –2 –1 0 1 2 3 4 5 6
Time (y)
50
* *
* * * *
* *
* *
* *
25 * *
* *
0
0 1 2 3 0 1 2 3 0 1 2 3
Time (h)
*P<0.05.
Adapted from Kosaka K et al. Diabetologia. 1980;18:23-28.
Pathogenesis of Type 2 Diabetes
Glucose
Production of glucose
and TG in the liver In blood vessels Platelets, fibrinolysis
uptake
Dyslipidaemia PAI-1
Endothelial dysfunction
Hyperglycaemia
Type 2 diabetes
ACh=acetylcholine; M=muscarinic receptor; eNOS=endothelial nitric oxide synthase; NADPH=nicotinamide adenine dinucleotide
phosphate; GTP=guanosine triphosphate; cGMP=cyclic guanosine monophosphate; NO=nitric oxide.
1. Perticone F et al. Circulation. 2001;104:191-196.
2. Heitzer T et al. Circulation. 2001;104:2673-2678.
Faktor Risiko
Akut :
Hipoglikemi
Koma Lakto-Asidosis
Ketoasidosis Diabetik–Koma Diabetik
Koma Hiperosmoler Non-Ketotik
Kronis :
Mikroangiopati (nefropati DM, retinopati DM)
Makroangiopati (PJK, diabetic feet, stroke)
Mikro-makroangiopati (neuropati, mudah infeksi)
Lain-lain (artropati, kardiomiopati)
Hiperglikemia dikenal sebagai penyebab timbulnya radikal
bebas
Mata Stroke
Ginjal Penyakit
jantung koroner
1.Mengatur makan
4. Penyuluhan
Tujuan :
Bila harapan hidup tidak terlalu panjang
• Menghilangkan gejala
• Perbaikan kualitas hidup
• Atur kadar glukosa darah
• Cegah hipoglikemia
30 menit : 3 - 4 kali/minggu
(tiap hari lebih baik)
Olah raga Meningkatkan Uptake Glukosa di Sel Otot
dan Lemak
Cinnulin PF®
Cinnulin PF®
Cinnulin PF®
(B.Mang, et al., Effects of a Cinnamon Extract on Plasma Glucose, HbA1C, and serup lipids in diabetes mellitus Type 2,
(B.Mang, et al., Effects of a Cinnamon
EuropeanExtract
Journalon
of Plasma
Clinical Glucose, HbA1C,
Investigation and
(2006) serup
36, lipids in diabetes mellitus Type 2,
340-344
European Journal of Clinical Investigation (2006) 36, 340-344
Manfaat Gerak Badan
GLP-1 analogue
Thiazolidinedione
(exenatide
s
injectable)/DPP-4 Increase glucose uptake in
inhibitors skeletal muscle and
Improves glucose-dependent insulin decrease lipolysis in
secretion from pancreatic β-cells, adipose tissue
suppresses glucagon secretion from
Meglitinides
-cells, slows gastric emptying
Increase insulin secretion
from pancreatic -cells
Sulfonylureas
Increase insulin secretion
from pancreatic -cells
-Glucosidase
inhibitors
GLP = glucagon-like peptide. Delay intestinal carbohydrate
Adapted from Cheng and Fantus. CMAJ. 2005;172:213–226.
absorption
Schematic Representation of DPP IV - modulated
Incretin Action
Meal
DPP IV
Liver Stomach
Pancreas
GIP GLP-1 Minutes
-
- cells
cells
Insulin Glucagon
Small intestine
Glucose
DPP IV = diphenylpeptidase IV
Adapted from Demuth HU et al 2005
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