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Patofisiologi Diabetes

Achmad Rudijanto
PERKENI

2012

1

Diabetes Mellitus (kencing manis)
Merupakan kelainan metabolisme
karbohidrat akibat kekurangan absolut
atau relatif dari hormon insulin
Disertai pula dengan kelainan
metabolisme protein dan lemak
Inapatientwithclassicsymptomsofhyperglycemiaorhyperglycemiccrisis,
12/30/2015
Criteriaforthediagnosisofdiabetes
A1C6.5%.Thetestshouldbeperformedinalaboratoryusingamethod
thatisNGSPcertifiedandstandardizedtotheDCCTassay.*
OR
FPG126mg/dl(7.0mmol/l).Fastingisdefinedasnocaloricintakeforat
least8h.*
OR
Twohourplasmaglucose200mg/dl(11.1mmol/l)duringanOGTT.
ThetestshouldbeperformedasdescribedbytheWorldHealth
Organization,usingaglucoseloadcontainingtheequivalentof75g
anhydrousglucosedissolvedinwater.*
OR
arandomplasmaglucose200mg/dl(11.1mmol/l).
*In the absence of unequivocal hyperglycemia, criteria 13 should be
confirmed by repeat testing.
ADA, 2010
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Global Projections for the

Diabetes Epidemic: 2010-2030 IncreaseprevalenceofDMinIndonesia

NAC EUR
37.4 M
55.2 M SEA 11.1%
66.2 M
53.2 M
20% 58.7 M WP Maluku
42%
101.0 M
76.7 M Utara
MENA 72%
26.6 M 112.8 M
51.7 M 47%
94% 6.1%
World SACA Riskesdas, 2008: Manado
AFR
2010=285 M 18.0 M 12.1 M - Prevalence 5.7%
2030=438 M 29.6 M 23.9 M - Pre DM 11.0%
54% 65% 98%

0.8% 1.7%
Toraja Papua
2010
2030
1980 2007
M=million; AFR=Africa; MENA=Middle East and North Africa; EUR=Europe; NAC=North America and Caribbean;
SACA=South and Central America; SEA=South-East Asia; WP=Western Pacific. PERKENI, 2006
International Diabetes Federation. Diabetes Atlas. 4th ed. http://www.diabetesatlas.org/content/regional-overview.
Accessed November 29, 2010.
RISKESDAS, 2007

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KLISIFIAKSI DM (ADA, 2010) insulin secretion

Ca++
DMtipe1(akibat kerusakan sel betapankreas
VDCC
kekurangan insulin) KATPchannel
DMtipe2(akibat adanya resistensi insulinyangdisusul
Ca++
dengan kerusakan sel beta) ATP/ADP +
DMtipe lain(faktor genetik,akibat obat atau bahan nucleus
kimia yangmerusak pankreas) mitochondria Ca++
Islet
trancription insulin
DMsaat kehamilan (GDM=DMselama kehamilan) Pyruvate
factors

Glucose6phosphatase
Secretory
Glucokinase granules
Glucose

GLUT2
Glucose

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Pancreatic Islet Morphology: Structural Kelainan kadar glukosa darah pada berbagi tipe
Defects are Evident in T-1DM DM dan gangguan toleransi glukosa

Normal T1DM

Normoglycemia Hyperglycemia
Stages
-Cells Normal Glucose regulation Impaired Glucose Tolerance Diabetes Mellitus
or
(insulin) Types Impaired Fasting Glucose Not Insulin Insulin Requiring Insulin Requiring
(Pre-Diabetes) Requiring for control for survival

-Cells Tipe 1*
(glucagon)
Tipe 2
Tipe lain**
Disorganized and misshapen
Marked reduction in -cell number
DM kehamilan**

T2DM = type 2 diabetes mellitus

Adapted from Rhodes CJ. Science. 2005; 307:380384.

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Pancreatic Islet Morphology: Structural Organyangterlibat pada keseimbangan glukosa

Defects are Evident in T-2DM
Penyerapanmakanan
Normal T2DM Mengeluarkanhormoninkretinygikutmerangsangpelepasaninsulin

-Cells Amyloid
(insulin) plaque Produksiinsulinyangmendorongpenyerapanglukosa
Produksiglukagonyangberperanpdpembentukanglukosawaktupuasa

-Cells Menyimpanglukosadalambentukglikogen butuhinsulin

(glucagon) Memproduksiglukosadariglikogen butuhglukagon

Disorganized and misshapen Tempatutamametabolismeglukosa(7080%) perluinsulin

Marked reduction in -cell number
Amyloid plaques
Decreased insulin production Tempatdepositkelebihankalori perluinsulin

T2DM = type 2 diabetes mellitus

Adapted from Rhodes CJ. Science. 2005; 307:380384.

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Kerja Inkretin:di pankreas dan diluar pankreas Oral/Intravenous Glucose Infusion Study
OTAK Incretin Effect After Oral Glucose
Satiety
Appetite Was Diminished in Type 2 Diabetes
Healthy controls (n=8) Type 2 diabetes (n=14)
JANTUNG Oral glucose (50 g/400 ml) Isoglycemic intravenous glucose

Venous plasma glucose

Venous plasma glucose

20 20
cardiovascular protective
effects and improved 15 15
cardiac function

(mmol/L)

(mmol/L)
10 10
LIVER
5 5
Glucose production
0 0
PANKREAS 10 5 60 120 180 10 5 60 120 180
insulin secretion 80 Normal 80
insulin synthesis incretin effect

IR insulin (mU/L)

IR insulin (mU/L)
beta cell neogenesis 60 60 Diminished
beta cell proliferation incretin effect
beta cell mass 40 40
*
beta cell apoptosis * *
20 * * * * * * 20
glucagon secertion *

0 0
LAMBUNG 10 5 60 120 180 10 5 60 120 180
Gastric emptying Time (minutes) Time (minutes)
*p0.05 vs. respective value after oral load
Acid secretion
IR=immunoreactive 14
Adapted from Nauck M et al Diabetologia 1986;29:4652.

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Berbagai organ yang berperan pada Keseimbangan Glukosa Dalam Ke4adaan

keseimbangan glukosa Normal (berbagai organ yang terlibat
-Penyerapan
keseimbangan glukosa)
-Hormon incretin
Saluran
Pencernaan

-Glyconeogenesis -cell: insulin

-Glycogenesis
-cell: glukagon

-Hormon insulin Glucosa Darah Hati Pankreas

-Hormon glucagon
Glukose darah

-Penggunaan
glukosa

adipocytes
-Menyimpan enersi (lypogenesis)
-Melepaskan enersi (lypolysis)

Otot

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Keseimbangan Glukosa Dalam Keseimbangan Glukosa Dalam

Keadaan Setelah Makan Keadaan Setelah Makan

Saluran Saluran
Pencernaan glukosa Pencernaan glukosa
Pankreas Pankreas
-cell: insulin -cell: insulin

-cell: glukagon -cell: glukagon

glukosa glukosa
Hati Hati
glikogenesis
Glukose darah insulin Glukose darah insulin
normal

adipocytes adipocytes
Lipoogenesis
Otot Otot
Uptake glukosa

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Keseimbangan Glukosa Dalam Ke4adaan Keseimbangan Glukosa Dalam Ke4adaan

Puasa Puasa

Saluran Saluran
Pencernaan Pankreas Pencernaan Pankreas

-cell: insulin -cell: insulin

X -cell: glukagon X -cell: glukagon

Hati Hati
Glukone Glukoneo-
Glukose darah genesis
Glukose darah
o-genesis
Normal

Uptake lipolisis Uptake X lipolisis

adipocytes adipocytes

Otot Otot

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Organyangterlibat pada keseimbangan glukosa NATURAL HYSTORY of TYPE-2 DM

meal absorption
Incretin secreion
Over-
NORMAL weight OBESE DIABETES
Liver
gluconeogenesis lipolysis
Blood Glucose Adipocytes
glycogenesis Blood glucose
lipogenesis

Insulin resistance
-cell: insulin
Glucose uptake
-cell: glucagon

Pancreas
Muscle
Insulin secretion
Kidney

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Keseimbangan Enersi
Healthy food choices

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The Profile of Insulin Resistance and

Secretion During Progression of type-2 DM

250 Insulin resistance

Obesity, Beta-cell failure

200
Blood glucose

Beta-cell function (%)

150
- insulin resisten
100

Insulin secretion
50

0
-10 -5 0 5 10 15 20 25
Year

Bergenstal et al, 2001

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Timecourseofplasmaglucose(A),insulinconcentrations(B)andinsulinsecretionsrate
(C)innondiabeticpatient(NGT),impairedglucosetolerance(IGT)andtype2DM(DM)
Muscelli E. Diabetes 57:1340-1348, 2008

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Pancreatic Islet (a-cell and b-cell) Dysfunction Leads to

Hyperglycemia in T2DM
1stphase
Fewer -Cells
Normal -Cells Hypertrophy

Insufficient Excessive
Insulin Glucagon
- +
+
2ndphase

DM Glucose
patients Glucose HGO
uptake
Basal

0 5 minutes 100
HGO = hepatic glucose output
Insulinreleaseinvitroinresponsetoglucosestimulation Adapted from Ohneda A, et al. J Clin Endocrinol Metab.
1978;46:504510; Gomis R, et al. Diabetes Res Clin Pract. 1989;6:191198.

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Pemantauan Glukosa Darah

Mandiri Mengetahui profil glukosa darah harian:
Mengetahui keberhasilan terapi (sesuai target)
Menyesuaikan dosis /mengganti obat bila perlu

Carbohydratehasthemostsignificantaffectonbloodglucose

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Blood glucose fluctuation

Hyperglikemi

Hiperglikemi dan
Kehamilan:
- Kehamilan Hiperglikemi
-Hipertglikemi Kehamilan

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Hiperglikemi pada Kehamilan

Pada Kehamilan
Hati
-cell: insulin

Glukosa darah puasa cenderung rendah -cell: glukagon

X
oleh karena glukosa darah ibu waktu Pankreas
malam (puasa) dipergunakan oleh janin X
yang dikandung
X
Pada kehamilan sering disertai dengan
peningkatan hormon kontra insulin adipocytes
Terjadi resistensi insulin relatif uptake
glukosa oleh hati/otot/jar. lemak Otot Reseptor insulin Bila terjadi ggn kerja reseptor (resistensi
insulin)maka insulintidak berkerja
mengalami gangguan sehingga uptakeglukosa oleh
hati/otot/sel lemak tidak terjadi glukosa
tetap beredar dalam darah

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Association between hyperglycaemia and CVD

starts long before the onset of type 2 diabetes

Prediabetes Diabetes tipe-2

Plasma glucose (mmol/L)

Type 2
diabetes

Micro-
Undiagnosed vascular
diabetes disease

IGT
Normal

Macro-
vascular
Up to 10 years disease

NHANES: National Health and Nutrition Examination Survey

Thank you
www.cdc.gov/nchs/products/elec_prods/subject/nhanesii.htm
Janka HU. Fortschr Med 1992;110:63741

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