dmt2 lecture ukrida
TRANSCRIPT
DIABETES MELLITUS DIABETES MELLITUS
Oleh :
DR. Dr. MARDI SANTOSO DTMH SpPD-KEMD
BAG.ILMU PENYAKIT DALAM
FK UKRIDA
DIABETES MELLITUSDIABETES MELLITUS
Penyakit metabolik endokrin yang kronik progesif, ditandai dengan adanya hiperglikemia kronik dan melibatkan semua organ tubuh yang disebabkan oleh karena defisiensi produksi insulin di dalam tubuh baik relatif/absolut atau produksi insulin kwantitasnya normal tetapi kualitasnya abnormal/kurang sensitif
Faktor-faktor yang mempengaruhi Faktor-faktor yang mempengaruhi timbulnya DMtimbulnya DM
Keturunan Suku bangsa Aktivitas fisik Infeksi Kegemukan Jenis Kelamin Bahn-bahan Kimia
Pekerjaaan Sosial Ekonomi Nutrisi Geografi Obat-obatan Penyakit tertentu
(endokrin) Dll
No Negara % Prevalensi
Tahun Keterangan
1
2
3
4
5
6
7
8
Vietnam
Indonesia
Malaysia
Singapore
Thailand
Hongkong
Jepang
China
2,5 %
5,7 %
> 8 %
10,9 %
11,9 %
7,7 %
9,7 %
2,5 %
1992
1992
1997
1992
1995
1990
1993
1994
Ho Chi Minh City (Urban)
Jakarta Urban
National Survey
Chinese Group
Provinsi Kaen
(30-74 th)
-
Yamagata Perfecture(>40 th)
19 propinsi(25-64 th)
Tabel 1. Prevalensi Penderita DM di Asia Tenggara
Tabel 1a : Prevalensi Penderita DM di Tabel 1a : Prevalensi Penderita DM di Indonesia (Perkeni)Indonesia (Perkeni)
1. Menado 6,1 % (1986)
2. Ujung Pandang (Urban) 2,9 % (1998)
3. Jakarta (Urban) 5,7 % (1993)
4. Tasikmalaya (Rural) 1,1 % (1996)
5. Surabaya(Urban-Rural) 1,43 – 1,47 % (1991)
6. Sesean (Toraja-Rural) 0,8 % (1995)
7. Semarang (Urban) 1,46 % (1975)
8. Padang (Urban) 1,5 % (1984)
Klasifikasi DM (PERKENI Klasifikasi DM (PERKENI 2006/ADA 1997)2006/ADA 1997)
1. DM Tipe 1
2. DM Tipe 2
3. DM Tipe lain
4. Gestational DM/Kehamilan
Phenotypic Type 2 DiabetesPhenotypic Type 2 Diabetes
5-10% are late-onset Type 1 diabetes5% MODY1% rare genetic defects85% ‘garden variety’ Type 2 diabetes
– non-obese ~10%– obese ~90%
PREDIABETES: IGT & FGT
PATHOGENESIS DM/ PATHOGENESIS DM/ TERJADINYA DM?TERJADINYA DM?
Makanan DI USUS
Glukosa darah
Glikogen
Otot Skeletal/otot Hepar/Hati
Insulin Islet/Sel b Pankreas
Tipe 1 DMTipe 1 DM
Defiensi Insulin Absolut Glukosa
Dekstruksi pankreas severe
Auto imun diseases(+HLA, Environment, Virus)
Tipe 1
Tipe 2 DMTipe 2 DM
Resistensi Insulin/?( Glut 4, FFA, Amylin)
Defisiensi/kurang InsulinRelatif/Mild
Probability Causes of Insulin Probability Causes of Insulin ResistanceResistance
IAAPGLUT 1 – 7TNF alfaPPAR gama
* Ob – Gen *GLUKOTOKSISITAS *LIPOTOKSISITAS*LEPTIN*ADIPONECTIN
Tipe 3 DM/akibat peny2 lainTipe 3 DM/akibat peny2 lain1. Defek Genetik Sel Beta
2. Defek Genetik Insulin
4. Penyakit Endokrin
3. Penyakit exocrin Pankreas
Glut 2, Glukokinase, Mitochondria
Insulin Gen, Reseptor Insulin
Pankreatitis, fibrosis, calculus, operasi
Akromegali,Cushing, hipertiroid/gondok, dll
Tipe 3 DM cont..Tipe 3 DM cont..
1. Obat2an/kimia
2. Infeksi virus
4. Penyakit genetik
3. Imulolagi jarang
Glukokartikoid, hormonTiroid, dilantin, tiazidInterferonalta, streptozotocin
Coxacky, Rubella, CMV
Ab anti insulin
Down sindrom, Klinefelter, turner,dll
Vacor, Alloxan, as.nicotinat, nitrosamin
4.GESTATIONAL DM/DM Hamil4.GESTATIONAL DM/DM Hamil
• Human Placental Lactogen• Cortisol
Resisten Insulin
Underlying causes of type 2 Underlying causes of type 2 diabetesdiabetes
Obesity
Insulinresistance
-celldefect
Impairedglucose tolerance
Earlydiabetes
Latediabetes
Hyperinsulinaemia
Decreased insulinsecretion
-cell failure
Adapted from Saltiel AR. J Clin Invest 2000;106:163–164.
Normal
The progressive nature of The progressive nature of type 2 diabetestype 2 diabetesImpaired
glucose tolerance
Type 2 diabetes
Fasting plasma glucoseInsulin sensitivityInsulin secretion
Insulin sensitive
Normal insulin secretion
Normoglycaemia
Hyperglycaemia
β-cell exhaustion
Insulin resistance
Late type 2 diabetes
complications
Adapted from Bailey CJ et al. Int J Clin Pract 2004;58:867–876. Groop LC. Diabetes Obes Metab 1999;1 (Suppl. 1):S1–S7.
Insulin resistance
Adapted from Stumvoll M et al. Lancet 2005;365:1333–1346.
Model of underlying factors in type 2 Model of underlying factors in type 2 diabetes: diabetes:
insulin resistance and insulin resistance and -cell -cell dysfunction dysfunction
-CELL DYSFUNCTION
INSULINRESISTANCE
Glucose uptake
Blood glucose Free fatty acids
Glucose production
Diabetes genesAdipokines
InflammationHyperglycaemiaFree fatty acidsOther factors
Insulin secretion
Lipolysis
What is insulin resistance?What is insulin resistance?
An impaired biological response to insulin1
An underlying defect in, and a strong predictor of, type 2 diabetes2
Genetic and environmental pathogenesis2
Links type 2 diabetes with cardiovascular disease (CVD)3
Associated with a range of CVD risk factors3
1Groop LC. Diabetes Obes Metab 1999;1(Suppl. 1):S1–S7. 2Del Prato S et al, Diabetes Technol Ther
2004; 6:719–731. 3Bonora E, et al. Diabetes Care 2002;25:1135–1141.
ADA (US)1
HbA1c < 7% IDF (Global)3
HbA1c 6.5%
CDA (Canada)4
HbA1c 7%
NICE (UK)5
HbA1c 6.5–7.5%
AACE (US)2
HbA1c 6.5% ALAD (Latin America)6
HbA1c < 6–7%
Australia9
HbA1c 7%
Diabetes management guidelines: Diabetes management guidelines: HbAHbA1c1c
IDF (Western Pacific Region)8
HbA1c 6.5%
IDF (Europe)7
HbA1c 6.5%
1American Diabetes Association. Diabetes Care 2004;27 (Suppl. 1):S15–S34. 2American Association of Clinical Endocrinologists. Endocr Pract 2005; in press.
3http://www.idf.org/webdata/docs/IDF%20GGT2D.pdf. 4Canadian Diabetes Association. Can J Diabetes 2003;27 (Suppl. 2):S1–S152.5National Institute for Clinical Excellence. 2002. Available at: http://www.nice.org.uk. 6ALAD. Rev Asoc Lat Diab 2000;Suppl. 1.
7European Diabetes Policy Group. Diabet Med 1999;16:716–730. 8Asian-Pacific Policy Group. Practical Targets and Treatments (4th Edition). www.idf.org/webdata/docs/T2D_practical_tt.pdf
9NSW Health Department. 1996.
Primary sites of action of Primary sites of action of traditional oral anti-diabetic traditional oral anti-diabetic
agentsagents
Adapted from Kobayashi M. Diabetes Obes Metab 1999;1(Suppl. 1):S32–S40.
Glucose
Adipose tissue
Gut
Stomach
Liver
Sulphonylureas and meglitinides
Biguanides
Muscle
PancreasInsulin
-glucosidase inhibitors
Gejala Klinis Diabetes MelitusGejala Klinis Diabetes Melitus
Berat badan Asthenia/lemas2 Poliphagi/makan banyak Poliuria/banyak kencing Polidipsi/banyak minum Gejala-gejala komplikasi DM
Komplikasi2 DM AkutKomplikasi2 DM Akut Infeksi : - Paru : Pneumonia, Bronkhitis
- Ginjal/TU : PNA, Cystitis, Uretritis
- Kulit/Mukosa : Dermatitis, Vaginitis
- Soft Tissue/Muscle : Selulitis, Abses, Ulkus, Gangren
• Koma diabetik Ketoasidosis
• Koma Diabetik Hiperosmolar
• Koma Hipoglikemia
Gejala-gejala komplikasi DM KronikGejala-gejala komplikasi DM Kronik
Matagejala katarak, kabur, silau, retinopati, buta
Ginjal
Saraf
Nefropati-renal failure
Neuropati perifer
Mual, udem, anemia, BAK sedikit
Kesemutan, Baal, Pegal, Nyeri
Neuropati viseral Diare, gangguan BAK, Impoten
Dimensia Gangguan Memori
Hati
Sirosis Hepatis Hati Fibrosis, odem, asites,Hematemesis, melena
Jantung PJK / PJI, ASHD
Arteriosklerosis, Hipertensi
Pembuluh Darah
Paru TuberkulosisKulit : gatal2 dll
Batuk, Sesak
2,2
4,6
6,2
8,4
9
14,3
18,9
19,6
19,8
22,6
27,8
34,4
58,6
64,6
0 10 20 30 40 50 60 70 80 90 100
Ulkus Gangren
Nefropati
Serebral
TBC
UTI
NPRD
Katarak
Dermatits
Disfungsi Ereksi
Frigiditas
CAD
Hipertensi
Dislipidemia
Neuropati
Tabel 2. Komplikasi-komplikasi DM 1238 penderita rawat jalan poli Diabetes RS Koja 2000-2001 ( Mardi Santoso 2001)
Terapi Diabetes MelitusTerapi Diabetes Melitus
Diet/PerencanaanmakanExercise/olah ragaOHO/Obat tab.DM/
TKOI/Insulin
Education/Penyuluhan
LABORATORY CRITERIALABORATORY CRITERIAADA/WHO 1998/PERKENIADA/WHO 1998/PERKENI
concensus 2006concensus 2006GTT 75 GramDM : 1. FASTING =/> 126Mg%
2. 2Hour GTT 200/> 200 Mg%
3. Ad Random 200/>200 Mg%
* IGT : BG 2 Hours 140 – 199 Mg%
* IFG : Fasting BG 100 – 125 Mg %
Hyperglycemia
3 Metabolic Defects in Diabetes3 Metabolic Defects in Diabetes
PancreasPancreas
LiverLiver MuscleMuscle
Hepatic Glucose Production (III)
GlucoseUptake
InsulinResistance(II)=
Progressive Insulin Secretory Defect ( I )
OBAT HIPOGLIKEMIK ORAL [ OHO ]OBAT HIPOGLIKEMIK ORAL [ OHO ]
A.A. SULFONIL UREASULFONIL UREAB.B. BIGUANIDBIGUANIDC.C. INHIBITOR ALFA GLUKOSIDASEINHIBITOR ALFA GLUKOSIDASED.D. THIAZOLIDINEDIONETHIAZOLIDINEDIONEE.E. GLINIDEGLINIDEF.F. DPP4 INHIBITORDPP4 INHIBITORG.G. INCRETIN MIMETICINCRETIN MIMETIC
Oral Hypoglycemic AgentsOral Hypoglycemic Agents
A. Sulphonylureas:– Chlorpropamide– Glibenclamide– Gliclazide/G-MR– Gliquidone– Glipizide– Glipizide GITS– Glimepiride
B.Biguanide
* Metformine
C.Alfa Glucosidase inhibibitor
* Acarbose
Oral Hypoglycemic AgentsOral Hypoglycemic Agents
D. Thiazolidinediones- Pioglitazone- Rosiglitazone
E. DPP 4-I:Sitagliptin,
vidaglptin
E. Glinite– Repaglinide– Nateglinide
G.Kombinasi- Glucovance- Glugoryl- Amaryl M
DeFronzo RA et al. J Clin Endocrinol Metab. 1991;73:1294-1301.
Insulinresistance
Blood glucose
Insulin resistance
1 Intestine: glucose absorption
3 Pancreas: insulin secretion
4 Liver: hepaticglucose outputMetformin HGO
2 Muscle and adipose tissue:glucose uptakeMetformin glucose utilization
Metformin: Mechanism of Action
©1997 PPS
C
DeFronzo RA. Diabetes. 1988;37:667-687.Lebovitz HE. In Joslin's Diabetes Mellitus. 1994:508-529.
Blood glucose
Insulin resistance
1 Intestine: glucose absorption 2 Muscle and adipose tissue:glucose uptake
4 Liver: hepaticglucose output
3 Pancreas: insulin secretionSulfonylureas
insulin secretion
Insulinresistance
Sulfonylureas: Mechanism of Action
©1997 PPS
C
INSULININSULIN
*Short action: RI, Humulin R, Actrapid
*Intermediate action: NPH, Insulatard, Monotard and Humulin N
*Long acting: PZI , Lantus*
*Mixed insulin: Mixtard, Humulin 30/70,
Novo Mix.
* Fast : Humalog, Novo Rapid,Apidra
Algoritma terapi untuk diabetes Algoritma terapi untuk diabetes tipe 2tipe 2
Tujuan
Perbaikan kontrol
Diet, exercise, edukasi kesehatan
Kombinasi oral
+Insulin
Insulin + OAD
metformin/sulfonil ureaGlucosidase InhibitorsGlitinidesThiazolidinediones
ALGORITME PENGELOLAAN DM TIPE 2 BB LEBIHALGORITME PENGELOLAAN DM TIPE 2 BB LEBIH
DM Tipe 2 BB lebih
Penyuluhan DMST
STT
Penekanan kembali OR, diet
EVALUASI 2 - 4 mg
+ 1 macam obat: Biguanid (B)/(PG)/((T)
STT
EVALUASI 2 - 4 mg
ST
ST STT EVALUASI 2 - 4 mg
Kombinasi 2 macam OHO: antara B/PG/T
STT
3 OHO: antara B + PG + T TKOI STT Insulin
Kombinasi 4 OHO: B + PG + Glitazon + IS TKOI STT Insulin
STT
ST
ST
EVALUASI 2 - 4 mg
EVALUASI 2 - 4 mg
STT
ST
Insulin TKOI STT Insulin
T ERUSKAN
EVALUASI 2 - 4 mg
ALGORITME PENGELOLAAN DM TIPE 2 BB TIDAK LEBIHALGORITME PENGELOLAAN DM TIPE 2 BB TIDAK LEBIH
DM Tipe 2 BB Tidak lebih
Penyuluhan DMST
STT
Perencanaan Makan, OR + IS
EVALUASI 2 - 4 mgSTT
EVALUASI 2 - 4 mg
ST
2 macam OHO: IS + PG/B/T
STT
Kombinasi 3 OHO: IS + PG + B/T TKOI STT Insulin
Kombinasi 4 OHO: IS + PG + B + T TKOI STT Insulin
STT
ST
ST
EVALUASI 2 - 4 mg
EVALUASI 2 - 4 mg
STT
ST
Insulin TKOI STT Insulin
T ERUSKAN
EVALUASI 2 - 4 mg
Baik Sedang
GLUKOSA DARAH PUASA (mg/dl) 80 – 100 110 – 125
GLUKOSA DARAH 2 JAM (mg/dl) 80 – 144 145 – 179
A1c (%) < 6,5 6,5 – 8
KOLESTEROL TOTAL (mg/dl) < 200 200 – 239
KOLESTEROL LDL (mg/dl) < 100 100 – 129
KOLESTEROL HDL (mg/dl) > 45
TRIGLISERIDA < 150 150 – 199
IMT (kg/m2) 18,5 – 22,9 23 – 25
TEKANAN DARAH =/< 130/80 130 – 140 / 80 – 90
KRITERIA PENGENDALIAN DM
(KONSENSUS PERKENI 2006)
ADA (USA)1
IDF (Europe)2
AACE (USA)3
FPG (mmol/L)
< 6.7 (120)*
< 6.0 (110)*
< 6.0 (110)*
HbA1C (%)
< 7
< 6.5
< 6.5
*mg/dL
Targets for glycaemic controlTargets for glycaemic control
1American Diabetes Association. Diabetes Care 1999; 22(Suppl 1):S1-S114; 2European Diabetes Policy Group. Diabetic Medicine 1999;16:716-30; 3American Association of Clinical Endocrinologists. Endocrine Pract (2002) 8(Suppl. 1):40-82
AGRESSIF TREATMENTAGRESSIF TREATMENT
A1C 7-8 % OHA COMBINATIONA1C 8-9 % OHA COMBINE INSULIN/TKOIA1C 9-10% “ “ “ A1C > 10% INSULIN COMBINATION
Konsensus PERKENI 2006
Terapi kombinasi Rasional 2 defek Terapi kombinasi Rasional 2 defek endokrin pada type 2 diabetesendokrin pada type 2 diabetes
Insulinresistance
β-celldeficiency
Metformin + Sulphonylurea 1
Metformin + TZD
Metformin + AGI
Sulphonylurea + TZD
Sulphonylurea + AGI
TZDs + AGI1 Sulphonylurea or meglitinideTZD: thiazolidinedione AGI: -glucosidase inhibitor
Target Target TerapiTerapi
Kualitas Hidup Morbiditas
Kuantitas Hidup Mortalitas
STANDAR DIETSTANDAR DIET
1. 1100 KALORI2. 1300 KALORI3. 1500 KALORI
4. 1700 KALORI5. 1900 KALORI6. 2100 KALORI7. 2300 KALORI8. 2500 KALORI
OVER WEIGHT
IDEAL WEIGHT
UNDER WEIGHT
Diet SeimbangDiet Seimbang
Jumlah kalori basal : umur, BBTambahan Kalori tetap : Aktivitas OR,
pekerjaanTambahan/Pengurangan Kalori karena
Penyakit-penyakit lain: Diet Jantung, diet Rendah protein
Kebutuhan / Jumlah Kalori :Kebutuhan / Jumlah Kalori :
Target BB Ideal
Perhitungan KaloriPerhitungan Kalori
Kalori Basal 25-30 Kalori/kg BBKerja - Ringan +20 % Basal
- Sedang +30 % Basal
- Berat + 40 % Basal
- Sangat berat + 50 % BasalFebris Tiap 1oC 13 % Basal
Kehamilan •Trimester 1•Trimester 2•Trimester 3
+ 150 kalori+ 350 kalori+ 350 kalori
Laktasi : Basal + 550 kalori
Obesitas / kurus : + / - : 20 - 30 %
Usia Lanjut : Kebutuhan kalori menurun
PENYULUHAN
1. PENGENALAN DM
2. PERENCANAAN MAKAN
3. LATIHAN JASMANI
4. MENGENAL OBAT2 AN
5. PEMANTAUAN LABORAT URINE/GD
LATIHAN JASMANI
SARAT2 : 1. CONTINOUS 2. RHYTMICAL 3. INTERVAL 4. PROGRESSIVE 5. ENDURANCE TARGET NADI LATIHAN 72 – 87 % NADI MAX [ 220 - UMUR ]
* SENAM DIABETES INDONESIA* SENAM DIABETES INDONESIA
Mengenai Pengobatan DM kiniMengenai Pengobatan DM kini
Gula darah harus cepat terkontrolMengapa ?: agar komplikasi2 dapat dicegahTarget GD sebaik mungkin Puasa<
125 ,2jam 140 mg persenObat tab.bisa langsung kombinasi Bila Gula
darah telalu tinggiAtau bisa langsung insulin bila GD terlalu
tinggi dan ada komplikasi2 akut
KESIMPULANKESIMPULANPatogenesis DM melibatkan faktor-faktor
Genetik, Biomolekuler, Imunologi &Environment
Komplikasi DM akut dan kronik frekwensinya masih sangat tinggi di Indonesia, karena kesadaran/kepatuhan penderita masih rendah, tenaga medis yang belum memadai dalam pencegahan primer, sekunder dan tersier, dan fasilitas RS belum memadai dan merata
SEKIANSEKIAN
SELAMAT BELAJAR