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

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