Diabetes MelitusDM

MUHAMMMAD UMAR FERDIANSAH Amd.Kep

SMF Ilmu Penyakit DalamPoli Spesialis RS AL-Irsyad Surabaya

2014

Aetiological Classification of Disorders of Glycaemia

Type 1 (beta–cell destruction, usually leading to absolute insulin deficiency) : Autoimmune: Idiopathic

Type 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance)

Other specific types

Genetic defects of beta–cell function

Genetic defects in insulin action

Diseases of the exocrine pancreas Endocrinopathies

Drug– or chemical–induced Infections Uncommon forms of

immune–mediated diabetes

Other genetic syndromes sometimes associated with diabetes

Gestational diabetes

Other types of Diabetes

Genetic defects of beta–cell function

Chr’me 20, HNF4_ (MODY1)

Chr’me 7, glucokinase (MODY2)

Chr’me 12, HNF1_ (MODY3)

Chr’me 13, IPF–1 (MODY4)

Mitochondrial DNA 3243 mutation

Genetic defects in insulin action

Type A insulin resistance

Leprechaunism

Rabson–Mendenhall syndrome

Lipoatrophic diabetes & Others

Diseases of the exocrine pancreas

Fibrocalculous pancreatopathy

Pancreatitis

Trauma / pancreatectomy

Neoplasia

Cystic fibrosis

Haemochromatosis & Others

Endocrinopathies

Cushing’s syndrome

Acromegaly

Phaeochromocytoma

Glucagonoma

Hyperthyroidism

Somatostatinoma & Others

Diabetes Melitus

Diabetes melitus ----- Penyakit metabolik yang paling sering, yang ditandai hiperglikemia dan glukosuria disertai komplikasi pendek atau jangka panjang pada mata, ginjal, saraf dan beberapa vaskuler.Sebagai akibat kurangnya insulin efektif dalam tubuh

Klasifikasi DM (ADA 1997)

1. DM tipe 11. Autoimun2. idiopatik

2. DM tipe 21. Resistensi insulin/ def insulin relatif

3. DM tipe lain1. Defek genetik (MODY,DNA mitokondria)2. Defek genetik kerja insulin 3. P eksokrin pankreas (pankreatitis, tumor, pankreopati

fibrocalculus)4. Endokrinopati ( akromegali, S Cushing, feokromositoma,

hipertoroidism)5. Karena obat ( vacor, petamidin, glukorkortikoid, hormon tirod,

dinlatin dll)6. Infeksi (rubella kongenital, CMV)7. Imunologi ( antibodi anti insulin)8. Sindrom genetik lain (S Down,S Klinefelter,S Turner dll)

4. DM gestational

Types-continued

InfectionsCongenital rubellaCytomegalovirusOthers  Uncommon forms of

immune–mediated diabetes

Insulin autoimmune syndrome (antibodies to insulin)

Anti–insulin receptor antibodies

“Stiff Man” syndromeOthers

Drug– or Chemical–induced Diabetes  

Nicotinic acid Glucocorticoids Thyroid hormone Alpha–adrenergic agonists Beta–adrenergic agonists Thiazides Dilantin Pentamidine Vacor Interferon–alpha therapy Others

ADA diagnostic criteria (1997) Symptoms of diabetes & a casual glucose concentration

more than or equal to 200 mg/dl(11.1 mmol/l); Casual is defined as any time of day without regards to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia and unexplained weight loss

or FPG more than or equal to 126 mg/dl (7.0 mmol/l).

Fasting is defined as no caloric intake for at least 8 hours

or 2 hour PG more than or equal to 200mg/dl(11.1 mmol/l)

during an OGTT. The test should be performed as described by WHO, using a glucose load containing the equivalent of 75 gm anhydrous glucose dissolved in water

WHO diagnostic criteria

whole bloodplasma

Diabetes mellitus (fasting) > 6.1mmol/l > 7.0mmol/l

2 hour post glucose load > 10.0 mmol/l > 11.1mmol/l

IGT (fasting) < 6.1mmol/l < 7.0mmol/l

& &2 hr post glucose load > 6.7 mmol/l > 7.8

mmol/l IFG (fasting) > 5.6 mmol/l >

6.1mmol/l

& <6.1 mmol/l & <7.0mmol/l

2hr post glucose load <6.7 mmol/l <7.8 mmol/l

Type 1 diabetes

Previously known as IDDM(Insulin dependent diabetes)

Ketosis prone:Usually diagnosed in younger age group(<30 years) (Peak incidence 11-13 yr)

Prevalence highly variable but approximately 0.20% with an incidence of 15-20 per 100000 population aged less than 21

Highest rate in Finland and Sicily( 30 new cases per 100000) to lowest in Japan and Korea (1 new case per 100000)

Seasonal variation- with lowest rate in spring and summer

Type 1 diabetes Presentation of type 1 is acute with symptoms

of polyuria, polydipsia, lethargy weight loss, nausea, vomiting,abdominal cramps,blurred vision and superficial infection

This presentation is the end point of recent and continuing beta cell function resulting in near total loss of Insulin production

Hyperglycaemia itself begets further beta cell destruction as treatment with insulin often results in a “honeymoon” period where the patient can often manage without insulin

Type 2 diabetes Previously known as NIDDM Non ketosis prone: , diagnosis > 30 years Prevalence highly variable1-2%, with a slight

male excess 1 in 1000 population as new cases each year Rates in relation to age ; 15- 44 yrs 0.5%,45-

64-1.8%,>65- 4.0% Rural population <1%

(Papua,Solomon,Bantu)Euro/N Americans 1-10%( Urban Bantu)Indo Asians abroad 10-20%(Australia, Aborigines)Pima Indians >20% (Nauru)

What is type 2 diabetes?

A progressive metabolic disordercharacterised by:

Insulin resistance

-cell dysfunction

Type 2diabetes

1. Beck-Nielsen H, Groop LC. J Clin Invest 1994;94:1714–17212. Saltiel AR, Olefsky JM. Diabetes 1996;45:1661–1669

Treatment of Diabetes

Non Pharmacological Diet, Low in fat, low refined sugars,high

carbohydrate,high fibre, low calories if obese, spacing of meals (Healthy eating)

Low cholesterol and triglyceride diet if hyperlipidemia

Exercise and Education All Type 1 patients will require Insulin

and type 2 can be on diet only, tablets or insulin treated

Treatment of diabetes- Tablets

Sulphonylureas: Glibenclamide, gliclazide, Tolbutamide,Glimiperide, Repaglanide etc.

Biguanides:Metformin Alpha glucosidase inhibitor:Acarbose Thiazolidinedione derivatives:

Troglitazone, Rosiglitazone,Pioglitazone.

Three main profiles: human bio-engineered,pork or Bovine.Various regimens: twice daily soluble and isophane, thrice daily soluble (pre-meal) and evening isophane, rarely once daily

Diabetic Complications

Acute Complication:

hypoglycaemia,ketoacidosis often with coma (DKA),

Hyperosmolar state often with coma (HONK)

Micro vascular complications

Diabetic retinopathy,nephropathy and neuropathy

Macro vascular complication

cerebrovascular accidents, coronary artery disease,hypertension, peripheral vascular disease

Pregnancy with increased maternal and foetal morbidity

Patogenesis

DM tipe I ( kerusakan sel Beta Pankreas, Reseptor perifer cukup. )Sintesis dan sekresi insulin kualitas maupun kuantitas kurang.Predisposisi genetik ---- lingkungan ----- kerusakan sel ß autoimun ---- DM Genetik HLA DR 4 Lingkungan

DM tipe 2 ( kelainan sekresi insulin dan reseptor insulin ) Sekresi insulin terlambat Reseptor insulin kurang ( < 30.000) Kualitas reseptor jelek Kelainan post reseptor ( glikolisis terganggu) Campuran

MRDM Sel beta rusak ok HCN Defisiensi protein dan kalori Sebab lain.

Gejala klinis :

fase kompensasi : polifagi, polidipsi, BB naik

fase dekompensasi : polidipsi, poliuri, BB turun. Mual

kronik : lemah badan, semutan, difungsi seks,

Laboratorium : GDP < 110 mg/dl, 2JPP < 140 mg/dl metode : Hagedorn- Jensen,

Somogyi Nelson, Autoanalyser, Ensimatik

Urine : Reduksi 3 x sebelum makan (Fehling, Benidict, Stick) keton : (Gerhard/Rothera) atau ketostik

Diagnosis

Kriteria DM (Perkeni 1998)

Poliuri, Polidipsi, BB sebab tidak jelas plus :1. GDA > 200 mg/dl atau2. GDP (vena) ≥ 126 mg/dla atau3. TTGO 2 JPP ≥200 mg/dl

Kriteria Diagnosis MRDM Surabaya – Kobe 1989

Kriteria dugaan MRDM

Didapatkan 1,2,3,4 atau lebih :

1. DM usia 15 – 40 tahun ( dapat kurang atau lebih)

2. Ax atau ada tanda malnutrisi-undernutrisi : BBR < 80 % atau BMI < 19

3. Tx perlu Insulin dan ada resistensi insulin ( 1,5-2 /Kg BB/hari)

4. Resistensi ketoasidosis

5. Nyeri perut berulang

6. Tanda malabsrbsi

7. Kalsifikasi pankreas

Kriteria definitif1. Fibrocalculus Pancreatic DM

(FCPD)1. DM umur 15 – 40 th, tanda

malnutrisi (BBR< 80 %), Tx insulin, resistensi insulin, resistensi ketoasidosis, kalsifikasi pankreas dengan atau tidak disertai tanda malnutrisi.

2. Tes fungsi pankreas menurun :1. BT- PABA urine < 60 % dan

atau2. Isoenzyme amylase positif

2. Protein Deficient Pancreatic DM (PDPD)

1. DM umur 15-40 tah, BBR< 80 %, Tx insulin, resistensi insulin, R ketoasidosi, tanpa kalsifikasi Pankreas

2. Tes fungsi pankreas menurun

Keluhan klinis

Positit Negatif

GDPGDS

³ 126³ 200

< 126 200

Ulang GDS atau GDP

110 < 126

110 - 190

< 110

TTGO2J PP

GDPGDS

³ 126³ 200

< 126< 200

> 126 200

GDPGDS

200 140 - 190 < 140

GDPTD I A B E T E S M E L L I T U S Normal TGT

EVALUASI: GIZI, PENYULIT, PERENCANAAN MAKANNasihat umum, makanan, olahraga, BB idaman, obat -

Langkah Dx Diabetes Melitus

PENATALAKSANAAN

TERAPI PRIMER

1. Diit (21 macam). Diit B, B1, B puasa, B1 puasa, B2, B3, Be, M, M puasa, G, KV, H dan GL.

Mengikuti 3 J ( Jumlah kalori dihabiskan, Jadwal ditepati,Jenis gula pantang)Diit tepat diberikan. Kumur setelah makan.Diit B2 untuk px ND stad IIDiit B3 untuk px ND stad IIIDiit Be untuk px ND stad IV

2. Latihan fisik : primer dan sekunder1. Latihan primer : latihan 1 atau 1,5 jam setelah makan2. Latihan sekunder : terutama px obesitas, latihan setiap pagi, siang sore.

3. Penyuluhan kesehatan masyarakatPerorangan , TV, Kaset video, Disko, Poster, Leaflet dll.

TERAPI SEKUNDER

4. Obat hipoglikemia (OHO dan insulin)

5. Cangkok Pankreass

Penatalaksaan gizi dan kalori Kebutuhan kolori/hari :

1. BB normal (BBR 90-100%) = 30 kal/KG BB/hari2. BB lebih (BBR.110 %) = 20 kal/KGBB/hari3. BB kurang (BBR< 90 %) = 40-60 kal/KGBB/hari4. Gemuk (BBR> 120 %) = 15 kal/KGBB/hari

Indikasi DIIT B (68 % kal KH, 20 % kal lemak, 12 % kal protein)5. Kurang tahan lapar6. Hiperkolesterolemia7. Makroangiopati 8. Mikroangiopati 9. DM >15 tahun

Indikasi DIIT B1 (60 % kal KH, 20 % kal Lemak, 20 % kal protein)1. Makan biasa tinggi protein lemak normal2. Kurus 3. Patah tulang4. Hamil atau menyusui5. Hepatitis kronis atau SH6. Tb paru7. Gangren8. Morbus basedowi9. Kanker10. Infeksi dll

Obat Hipoglikemik(OHO)

Indikasi : DM tipe 2, MRDM teregulasi baik; MRDM belum teregulasi baik dengan TKOI

Klasifikasi Rasional

Kelas A. hipoglkemik kuat ( glibenklamide, klorpropamide, glipisid). Kelas B. kel hepar dan atau ginjal ( glukoidon glimepiride, glipizide GITS) Kelas C. angiopati (glikazide dan glimepiride) Kelas D. DM ringan atau gg post reseptor ( glipizide) Kelas E. DM dgn kel hepar/ginjal ( glimepiride) Kelas BG. Absorbsi glukose menurun dan uptake perifer meningkat ( metformin) Kelas SP. Spesifik (Acarbose, Troglitazone, Rosiglitazone, Proglitazone, Repaglinide,

Nataglinide) Cara kerja

Sulfonilurea1. Tolbutamide, Acetahesamide, Tolazamid, Carbutamide, glycodiazin, klorpropamide2. Glibornurid, Glipizid, Glipizide GITS, Glisoxepid, Glibenclamide, Gliclazid, Gliquidon3. Glimepiride Biguanide

Phenformin, Metformin, Buformin

Syarat OHO berhasil baik: diit dan latihan sesuai 3 J, diberikan pada px umur > 40 th, lama DM < 5 th, Tx insulin belum pernah, KAD belum pernah.

INSULIN Indikasi

1. DMTI2. MRDM3. DM-tipe X4. Koma diabetik5. DM tipe 2 : gagal sek OHO,hamil, gangren, kurus, fraktur,

hepatitis/sirosis hati, operasi

Cara pemberian Dosis rumatan.3 x (2 x n)/ subkutan. n=angka awal GDS. Regulasi cepat.

Indikasi : DM-sepsis pro op; GPDO; IMA; rawat inap RC intravena (rumus 1,2,3,4,5 dan rumus 4,6,8,10,12)

Rumus minus 1 (rumus1,2,3,4,5) Rumus kali 2 (rumus 4,6,8,10,12)

RC subkutan. Rumus kali 2/sub kutan/1 x (dosis awal ekstra) dilanjutkan dosis rumatan.

Insulin pada NPE-Diabetik Rumus 5 –1. 5 gr glukosa alkohol (maltose dll) diperlukan 1 U IR Rumus 2,5 – 1. 2,5 gr glukosa diperlukan 1 U IR

TKOI. PPS (pagi OHO, sore insulin) & PPP (pagi OHO & insulin)

Penanganan komplikasi akut Hipoglikemia Gejala : lapar, gemetar, keringat dingin, berdebar,pusing –

koma. Diagnosis : Gejala + glukosa darah < 30 – 60 mg/dl Terapi :

1. Pisang/roti/kh lain, bila gagal ---no 22. The gula, bila gagal --- no 33. Glukosa 40% i.v 25 ml ---- dilanutkan M 10 % atau D 10 %. Dapat

diulang sampai 6 kali selang 0,5 jamrumus 3 – 2 - 1

4. Efedrin 25 – 30 mg atau glukagon 1 mg i.m

Koma lakto asidosis (KLA) Patogensesa. Gagal merubah laktat menjadi bikarbonat. Faktor predisposisi

Infeksi, shok/gg vaksuler lainnya, gg hepar & ginjal, DM+pherformin,gg oksigenasi (PPOM, mikroangiopati dll)

Gejala Stupor – koma, hiperglikemia ringan Bikarbonat < 15 mEq/l. A laktat > 7 mMol/l Anion gap.( K+ Na) – (Cl+CO2) >20mEq atau Na – (Cl+CO2) >15

mEq Terapi: kausal

Penanganan KHONK ( Askandar 1991-1998,1999,2000)

Diagnosis Klinik. Tetralogi KHONK

1. Rw DM tidak ada; Dehidrasi berat, hipotensi – syok, tidak ada Kussmaul, gejala nerolgi, reduksi +++, tidak bau aseton, tidak ada ketonuria

2. Gukosa dasar >600 mg/dl; BIK > 15 mEq/l; pH normal, tidak ada ketonemia, glukosa darah relatif rendah bl ada nefropati

3. Faktor peunjang : pH>7,3; prerenal azoemia; hipernatremia; gg kesadaran; nerologi (kejang)

Pasti. Pentalogi KHONK ( 1 + 2 ) plus OSM darah > 325 – 350 mOSM/ L

Patogenesa Faktor presipitasi : Thiazide, glukose, infeksi, steroid, B

bolcker,phenotoin, cimitidine, clorpromazine Glukagon meningkat Relatif defisiensi insulin Hambatan lipolisis oleh insulin cukup

Terapimirip terapi KAD, tanpa BIK

1. NaCl 0,9 % bila Na < 150 mEq/l; NaCl 0.45 % bila Na >150 mEq/l2. IR seperti KAD3. Antibiotika sesuai indikasi

Penanganan Ketoasidosis Diabetik

KRITERIA KAD1. Klinik : poliuri, polidipsi, mual/muntah, Kussmaaul, lemah

dehidrasi, hipotensi – syok dan kesadaran terganggu.2. Darah : glukosa darah > 300 mg/dl (biasanya > 500);

bikarbonat < 20 mEq/l (dan pH< 7,35)3. Urine ; glukosuria dan ketonuria

KLASIFIKASI KADI. Ringan. pH 7,30 – 7,35 ; BIK 15 – 20 mEq/lII. Sedang. pH 7,20 – 7, 30 ; BIK 12 – 15 mEq/lIII. Berat. pH 6,90 – 7,20 ; BIK 8 – 12 mEq/lIV. Sangat berat. pH < 6,90 ; BIK < 8 mEq/l

PATOGENESA1. Hiperglikemia 2. hiperketogenesis

TERAPI3. Fase I (gawat)4. Fase II (fase rehabilitasi) Dengan batas kedua fase glukosa darah 250 mg/dl

ADA Recommendations for Glycemic Control

Goal Take ActionPreprandial glucose mg/dl

80-120 <80>140

Bedtime glucose mg/dl

100-140 <100>160HbA1c % <7 >8

ADA Diabetes Care 2000

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