DIABETES MELLITUS-II

GARIS BESAR KULIAH UNTUK MAHASISWA SEMESTER-6

FAKULTAS KEDOKTERAN UNIVERSITAS AIRLANGGA, SURABAYA

2012
17-928-M
Kuliah I : SLIDE 1- 40; Kuliah II : SLIDE 41- 80

Prof. Dr. dr. Askandar Tjokroprawiro Sp.PD, K-EMD, FINASIM

dr. Sri Murtiwi Sp.PD, K-EMD, FINASIM
Division of Endocrinology and Metabolism Dept. of Internal Medicine
SURABAYA DIABETES AND NUTRITION CENTRE - Dr. SOETOMO TEACHING HOSPITAL
FACULTY OF MEDICINE AIRLANGGA UNIVERSITY, SURABAYA

SURABAYA, 5 MARCH 2012

ASK-SDNC

41

MAP OF ORAL ANTI DIABETES (OAD) IN DAILY PRACTICE

42

(Summarized : Tjokroprawiro 1996-2012)

I

INSULIN SECRETAGOGUES

- SUs : Gliquidone, Glipizide, Gliclazide, Glibenclamide, Glimepiride

- NON-SUs (Metaglinides : Nateglinide, Repaglinide)

II

INSULIN SENSITIZERS

(Rosi-*), Pio-, Neto-, Dar-glitazone)

1 THIAZOLIDINEDIONES (TZDs): Glitazone Class
2 NON-TZDs :
a Glitazar Class (Mura-*), Raga-, Ima-, Tesaglitazar) : MRIT
*) Withdrawn
b Non-Glitazar Class (Metaglidasen : Non Edema and Non Weight Gain)
3 BIGUANIDE : - Metformin , Metformin XR (Glucophage XR) , 3-Guanidinopropionic-Acid
4 DLBS-3233 (INLACIN)

III

INTESTINAL ENZYME INHIBITORS

IV

INCRETIN-ENHANCERS

V
VI

DPP-4 INHIBITORS

1 -Glucosidase Inhibitor: Acarbose

2 -Amylase Inhibitor: Tendamistase

Sita-, Vilda-, Saxa-, Lina-, Alo-, Dena-,

Duto-, Melo-, Teneli-gliptin, SYR-322, TA-666

FIXED DOSE COMBINATION (FDC) TYPES

Glucovance , Amaryl-M, Galvusmet, Janumet , ACTOplusmet, Duet act
OTHER SPECIFIC (OS) TYPES

1 Sodium GLucose co Transporter-2 (SGLT2)-Inhibitors:

ASP1941, BI 10773 , Canagliflozin, Dapagliflozin, Seragliflozin, Remogliflozin, AVE-2268,
KGT-1681, LX-4211, TS-033, YM-543 2 Glucokinase Activator (GKA): MTBL1, MK-0941.
3 Oxphos-Blocker
4 FBPase Inhibitor
5 INCB13739 (11HSD1inhibitor)
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43

PERSYARATAN OHO = OAD BERHASIL BAIK, bila :

POLA HIDUP (Terapi Nutrisi Medis = TNM atau DIET dan
LATIHAN FISIK TERJADWAL) sudah dilaksanakan DENGAN
BENAR (J1, J2, J3) (Tjokroprawiro, 1980-2012) :
1 UMUR > 40 th
2 LAMA DM KURANG DARI 5 th
3 BELUM PERNAH SUNTIK INSULIN, atau bila pernah
suntik insulin : kebutuhan insulin kurang dari 20 unit per hari
4 BELUM PERNAH MENGIDAP KETO ASIDOSIS DIABETIK

J1 = Jumlah
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J2 = Jadwal

J3 = Jenis

Macam Insulin dalam Praktek Sehari-hari

44

(Summarized : Tjokroprawiro, 2003-2012)

1 INSULIN KONVENSIONAL, mengandung komponen a, b, dan c,

misalnya : IR = Insulin Reguler ( Novo dan Organon), NPH (Novo),

PZI = Protamine Zinc Insulin (Novo dan Organon) dan juga campuran IR : PZI = 30 : 70.
2 INSULIN MONOKOMPONEN = Insulin MC (Insulin Mono-Component =

Highly Purified Insulin) = hanya mengandung Komponen c, misalnya

Actrapid (Short-Action = Kerja Pendek, identik dengan Insulin Reguler),
semua dari Novo Industries, ~ Humalog (Eli Lily)
Ada juga Insulatard (identik dengan NPH) dan Mixtard (campuran short
dan long acting insulin dengan perbandingan 30:70), keduanya dari Novo.
3 INSULIN MANUSIA = Human Insulin (HM = Human Monocomponent).
4 INSULIN ANALOGUES ( 3 macam ) :

A. Rapid-Acting (Kerja Cepat) Insulin Analogue :

Lis Pro (R/ Humalog), Glulisin (R/ Apidra), Aspart (R/ Novorapid)
B. Premixed Short 25-30% with Long Acting (70-75%) : Humalog Mix25, Novomix 30/70
C. Long-Acting Peakless Insulin Analogues : Insulin Glargine (R/Lantus), Detemir (R/ Levemir)
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PHARMACOKINETICS OF HUMAN INSULIN AND INSULIN ANALOGUES

45

(Summarized : Tjokroprawiro 2008-2012)

INSULIN PREPARATION
SHORT ACTING *)

ONSET OF
ACTION

PEAK OF ACTION
(HRS)

DURATION OF
ACTION (HRS)

30-60 mins
5-15 mins
5-15 mins
5-15 mins

2-4
1-2
1-2
1-2

6-8
3-4
3-4
3-4

RAPID ACTING **)

Regular Human Insulin = RHI*)

Insulin Glulisine : Apidra **)
Insulin Aspart : Novorapid **)
Insulin Lispro : Humalog **)

INTERMEDIATE-ACTING
1-3 hrs
5-7
13-16
NPH
1-3 hrs
4-8
13-20
Lente
LONG-ACTING
Insulin Glargine (lantus )
1-3 hrs
No Peak
24
1-3 hrs
No Peak
24
Detemir (Levemir )
Ultralente
2-4 hrs
8-14
22-24 hrs
Ultra-long-acting insulin DEGLUDEC : New Gen. Basal Ins. that forms Soloble Hexamers upon SC inj.
PREMIXED
Insulin Lispro 75/25 (Humalog Mix25 )
10 mins
1-4
10-20
Insulin Aspart 70/30 (NovoMix )
10 mins
1-4
16-20
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INDIKASI INJEKSI INSULIN

(KONSENSUS PERKENI 2011)

1
2
3
4
5
6
7
8

PENURUNAN BERAT BADAN YANG CEPAT

HIPERGLIKEMIA BERAT YANG DISERTAI KETOSIS
KETOASIDOSIS DIABETIK (KAD)
HIPERGLIKEMIA HIPEROSMOLAR NON KETOTIK (K-HONK)

HIPERGLIKEMIA DENGAN ASIDOSIS LAKTAT (KAAL)

Gagal dengan kombinasi OHO dosis optimal
Stres berat (infeksi sistemik, operasi besar, IMA, stroke)
Kehamilan dengan DM/Diabetes Mellitus Gestasional (GDM)
yang tidak terkendali dengan Perencanaan Makan
9 Gangguan Fungsi Ginjal dan atau Hati yang berat
10 Kontraindikasi dan atau alergi terhadap OHO
ASK-SDNC

Lihat Slide no 50 dan 51

46

INSULIN INJECTION SITES : CLOCK WISE ROTATION

Sites of SC Insulin Injection should be at the Healthy Areas
Distance between the Two SITES of Injection : Minimally 2.5 cm
(Clinical Experiences : Tjokroprawiro 1993-2012)

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76-90

1-15

61-75

16-30

46-60

31-45

47

48

PRACTICAL TOOL FOR INSULIN RESISTANCE AND -CELL FUNCTION

(Mathews et al 1985, Falutz et al 2002, Summarized : Tjokroprawiro 2005-2012)

HOMA-R : Fasting Insulin (U/ml) x FPG (mmol/l) (N: < 4.0)

22.5

Insulin Resistance

HOMA-B

:
-Cell Function

20 x Fasting Insulin (U/ml)

FPG (mmol/l) 3.5

HOMA-R and HOMA-B :

Useful in Daily Practice

ASK-SDNC

(N: 70150%)

1 RATIONALE TREATMENT
2 FOLLOW-UP OF TREATMENT

PREVALENCE OF IR IN SELECTED METABOLIC DISORDERS

(Bonora 1998, Summarized and Illustrated : Tjokroprawiro 2006-2012)
IFG = Impaired Fasting Glucose

1st Phase and IR in Liver

HYPER-CHOL

URIC ACID

T2DM
1

IGT = Impaired Glucose Tolerance

1st Phase and IR in Periphery

2 IFG & IGT

SEQUENTIAL
PREVALENCES OF IR
in

3 The MetS

METABOLIC
DISORDERS
LOW HDL-C

4 HYPERTENSION

5
IR = INSULIN RESISTANCE
ASK-SDNC

HYPERTRIGLYCERIDAEMIA

IR = INSULIN RESISTANCE

49

COMBINED THERAPY OF ORAL AGENT AND INSULIN (CTOI)

Terapi Kombinasi Tablet Oral dan Insulin (TKOI)

50

(Clinical Experiences : Tjokroprawiro 2003-2012)

I PRIMARY INDICATION
1 USE FORMULA 2-4-8 :
FORMULA 2 : FPG > 200 mg/dl
FORMULA 4 : 1h-PG > 400 mg/dl
FORMULA 8 : A1C > 8 %

2 HOMA-B < 35% (Normal : 70-150%)

3 EARLY INSULINATION, if :
- HOMA-B < 50%
- SEVERE UNCONTROLLED WEIGHT LOSS (> 10%)
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Continued

COMBINED THERAPY OF ORAL AGENT AND INSULIN

(KTT : KACANG, TAHU, TEMPE)

(Clinical Experiences : Tjokroprawiro 2003-2012)

II SECONDARY INDICATIONS FOR DIABETIC PATIENTS WITH :

1 BONE FRACTURES
2 MODERATE-SEVERE RENAL
FAILURE : LOW or NO-KTT

INSULIN SUPPRESSES
ARGINASE ACTIVITY
BUN
ARGININE

( N < 20)

ARGINASE

CKD : CHRONIC KIDNEY DISEASE

AVOID KTT if eGFR < 40 or S. CREATININE > 4.0 mg/dL

3
4
5
6

KTT & OTHER

PROTEIN

Lantus or Levemir
Apidra or Novorapid

CKD
ADVANCED PULMONARY TBC
DECOMPENSATED OR SPECIAL CASES OF LIVER CIRRHOSIS

UNCONTROLLED OR SEVERE WEIGHT-LOSS (> 10%)

OTHER SPECIFIC CASES : NON-INFECTIVE ULCER, ETC

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51

The 21 ENDOCARDIOMETABOLIC PROPERTIES OF INSULIN

52

(Summarized Illustrated : Tjokroprawiro 2009-2012)

19

RESTORE
LH, FSH, TESTOSTERON

1 GLYCEMIC CONTROL
A1C

LIPOLYSIS via HSL

(Hormone Sensitive Lipase)

21 HSP 70 / HSP 72
(For Wound Healing, Etc)

17 LIPOGENESIS via LPL

(Lipoprotein Lipase)

21 INSULIN
PROPERTIES

15 GLYCOGEN SYNTHESIS
14 ADMA IN PLASMA
AND IN ENDOTHELIUM

13 BONE ANABOLIC

( UREA ~ BUN)

ANTI-ATHEROSCLEROSIS
( ROS, NFB, CRP, etc)

4 PROFIBRINOLYSIS ( PAI-I)
5

16 PROTEIN SYNTHESIS

12 PLASMA ARGINASE

(ANIMALS, HUMAN)
HUMAN

18

( OSTEOGENESIS)

2 CARDIO-PROTECTION

VASODILATATION
( NO, eNOS)

6 ANTI-PLATELET ( c-AMP)
7

ANTI-THROMBOSIS
( TISSUE FACTOR)
ACTOR

ANTI-APOPTOSIS
(Heart, Brain, Cell)
Cell
ANTI-INFLAMMATION

11

GROWTH DEVELOPMENT

HYPOTHETICAL WAY TO TUMOR

VIA IGF1 RECEPTOR ?

9 IB, NFB, TNF,

ICAM-1, MCP-1,CRP

10 ANTI-OXIDANT ( ROS)

20 VASPIN mRNA IS INCREASED WITH INSULIN INJECTION IN SEVERE INSULIN RESISTANCE

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NUTRITION IN DIABETES MELLITUS

53

Clinical Experiences : Tjokroprawiro 1978-2012

ORAL NUTRITION
Since 1978

PAR ENTERAL NUTRITION = P.E.N.

Since 1993

ENTERAL NUTRITION
Since 1995

DIABETIC DIETS

PAR ENTERAL NUTRITION

( "SONDE" )

MEDICAL NUTRITION THERAPY

(MNT)

21 Types of Diabetic Diets

at Dr. Soetomo Hospital
From the B-Diet 1978
to
21 Types of Diabetic Diets
(2004)
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P.E.N.

P-P.E.N.

Ten Principles
of
P-P.E.N. in DM
PERIPHERAL
PAR
ENTERAL
NUTRITION

P
P
E
N

E1 , E 2 , E 3 , E 4 , E 5 , E 6

E1 :08.00 E2 :11.00
E3 :14.00 E4 :17.00
E5 :20.00 E6 :23.00
INSULIN NO INSULIN

NUTRITION IN DIABETES MELLITUS

Clinical Experiences : Tjokroprawiro 1978-2012

PAR ENTERAL NUTRITION = P.E.N.

Since 1993

PAR ENTERAL NUTRITION

P.E.N.

P-P.E.N.
TEN PRINCIPLES
of
P-P.E.N. in DM

PERIPHERAL
PAR
ENTERAL
NUTRITION
ASK-SDNC

P
P
E
N

54

SEPULUH PETUNJUK N.P.E. PERIFER-DIABETIK

55

(Pengalaman Klinik : Tjokroprawiro 1993-2012)

START SLOW - GO SLOW - STOP SLOW : S-G-S

1 LARUTAN NPE : OSMOLARITAS IDEAL< 600 Maksimal-1000 mOsm/L
Bila Osmol >1000
Infus Cabang : Cairan A dan Cairan B
Contoh : Cairan Cairan A > 1000 mOsm/l, Cairan B 275-600 mOsm/l
A (Misalnya Cairan A : 500ml NaCl 3% (1200 mOsm/l) 7 tt/mnt
di Cabang dengan Cairan B Isotonis (275-300 mOsm/l) atau
Hipertonis-Ringan (300-600 mOsm/l)
Contoh : Cairan B , Infus 500ml Martos 10% = B1 14 tt/mnt
disusul urut dengan Infus 500ml Potacol-R = B 2, dg tetesan 14 tt/mnt.
Jadi : Cairan A : 500 ml NaCl 3% 7 tt/mnt (500 ml/24 jam) dan Cairan
B : 500 ml Martos 10% = B1 (12 jam) dan 500 ml Potacol-R = B2 (12 jam)
dengan tetesan 14 tt/mnt. Kesimpulan :
Cairan A dan Cairan B1 , B2 akan habis bersamaan dalam 24 jam.
ASK-SDNC

(Continued)

SEPULUH PETUNJUK NPE PERIFER-DIABETIK

56

(Pengalaman Klinik : Tjokroprawiro 1993-2012)

START SLOW - GO SLOW - STOP SLOW : S-G-S

2 PEDOMAN JUMLAH CAIRAN : + 30 ml/kg BB; ENERGI : + 30 kcal/kg BB
Karbohidrat (Glukosa) minimal 100-150 g/hari
Tambahan : - 300 ml untuk kenaikan 1oC
- 300 ml untuk tambahan cairan Intra Seluler (Anabolik)
3A PERBAIKI HEMODINAMIK (RESUSCITATION)
3B BILA GLUKOSA >250 mg/dl

LALU : NPE

JANGAN LAKSANAKAN NPE

Laksanakan
Regulasi Cepat
Lebih Dahulu !!

4 BILA GLUKOSA <250 mg/dl (Syarat dimulainya NPE)

LAKSANAKAN NPE
TUJUAN : GLUKOSA < 200 mg/dl (Agar Fungsi Lekosit Normal)
(Continued)
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SEPULUH PETUNJUK NPE PERIFER-DIABETIK

57

(Pengalaman Klinik : Tjokroprawiro 1993-2012)

START SLOW - GO SLOW - STOP SLOW : S-G-S

5 KALORI HARI 1-3 : BASAL (400-800 Kcal)
Naik Pelan, Turun Pelan, Stop Pelan (Start Slow, Go Slow, Stop Slow : SGS)
6 GLUKOSA 5% atau MALTOSA 10%; usahakan minimal 100-150 g/hari
(atau 3-4 g/kg BB) : untuk OTAK , LEUKOSIT, ERITROSIT, MEDULLA RENALIS
Glukosa 5% atau Maltosa 10% " aman", Beri Insulin + 10 u dalam Botol Infus
1 unit Insulin Dalam Botol per 5g Maltosa; 1 unit untuk setiap 2.5g Glukosa
Dosis Martos 10% Maks 1 L/hari bila BB <60 kg dan 1.5 L untuk BB >60 kg
7

INFUS AA (Asam Amino) + 5% KAL. TOTAL : hari ke 2-3, minimal 12,5-25 g/h
Landasan : 25 Kcal/1 g AA atau Rasio Kal. KNP (Kalori Non Protein) : Protein (gram) > 25

(Continued)
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SEPULUH PETUNJUK NPE PERIFER-DIABETIK

58

(Pengalaman Klinik : Tjokroprawiro 1993-2012)

START SLOW - GO SLOW - STOP SLOW : S-G-S

8 Infus Lipid : 20 - 40% KNP (Kalori Non Protein) ALE : Asam Lemak Essensial
untuk Energi (dapat dimulai sejak awal) dan untuk kebutuhan ALE hari ke 4.
Dosis ALE : 2-4% Kalori Total 2x seminggu
9 Pemberian Emulsi Lipid secara Kontinu 500 ml/24 jam lebik baik d/p Intermiten
10 Bila no. 1 s/d no. 9 sudah dipenuhi, laksanakan NPE + FLUID THERAPY :
RATIONALE
MAINTENANCE FLUID THERAPY
SHOULD CONTAIN

Na+, K+, Cl Ca++, P, Mg++

GLUCOSE , EAA BCAA

Zn+

INFUS AA JANGAN DIPERHITUNGKAN SEBAGAI SUMBER ENERGI

MELAINKAN UNTUK REGENERASI DAN SINTESIS PROTEIN VISCERAL
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TEN GUIDELINES OF PERIPHERAL P.E.N.

59

(Clinical Experiences : Tjokroprawiro 1993-2012)

START SLOW

GO SLOW

STOP SLOW

1 CHECK OSMOL.: < 600-1000 mOsm/l

6 Maltose/Glucose: 100-150 g/day

2 FLUID & CALORIE (per kg BW) :

7 AA-INFUSION: CONTINUOUS INFUSION

Day 2-3; Backed up: 25 kcal/1g AA

FLUID : 30 ml & CALORIE : 30 kcal/kg BW

3 a. RESUSCITATION & HEMODYNAMIC!!

b. RAPID GLYCEMIC CONTROL
WITH TARGET : BS < 250 mg/dl

4 P-P.E.N. IF GLUCOSE < 250 mg/dl

8 Fat Emulsion : 20-40 % NPC,

20% Sol. is Recommended 500 ml/24 jam

9 FAT EMULSION : 10 ADVANTAGES

SHOULD BE CONTINUOUS INFUSION 500 ml/ 24 h

5 DAY 1-3 : SGS (400-800 Kcal/day)

10 P-P.E.N. & MAINTENANCE FLUID THER.

Insulin Dose : Formula 5-1 or 2.5-1

MAINTENANCE FLUID THERAPY

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TARGET PENGENDALIAN DIABETES MELLITUS

(KONSENSUS PERKENI-2011)
PARAMETER
IMT (kg/m2)

Risiko KV (-)

Risiko KV (+)

18.5 - <23

18.5 - <23

Tekanan Darah Sistolik (mmHg)

Tekanan Darah Diastolik (mmHg)

< 130
< 80

<130
< 80

Glukosa Darah Puasa (mg/dL)

Glukosa Darah 2 jam PP (mg/dL)

< 100
< 140

<100
<140

<7

<7

Kolesterol LDL (mg/dl)

< 100

< 70

Kolesterol HDL (mg/dl)

Pria > 40
Wanita > 50

Pria > 40
Wanita > 50

HbA1c (%)

Trigeliserida

< 150

Keterangan : KV = KARDIOVASKULAR, PP = POST PRANDIAL,

IMT = INDEX MASSA TUBUH
ASK-SDNC

< 150

60

METHOD-A : CTOI (TKOI) with MORNING LANTUS or LEVEMIR and AMARYL-M or GLUCOVANCE

61

(Clinical Experiences : Tjokroprawiro 2003-2012)

OAD : AMARYL-M or GLUCOVANCE, ADMINISTERED AFTER MEALS

Breakfast : 6.30 am
Fritsche et al 2003
Morning (Method A)
LANTUS or LEVEMIR
is
Better than Bedtime
(Method B)

LANTUS or LEVEMIR
6-30 u sc

AMARYL-M or GLUCOVANCE

Lunch : 0.30 pm

Dinner : 6.30 pm

PRANDIAL APIDRA or
NOVORAPID

PRANDIAL APIDRA or
NOVORAPID

9.30 am

3.30 pm

9.30 pm

Snack

Snack

Snack

OPTIONAL THERAPY
METFORMIN
GLIPTIN CLASS: DPP4-Is

AMARYL-M or GLUCOVANCE

METFORMIN DOSE : 1500 2000 mg/day

METHOD-A: LANTUS or LEVEMIR + AMARYL-M or GLUCOVANCE : SAFE FOR CANCER RISK

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METHOD-B : LANTUS or LEVEMIR in the EVENING or BEDTIME

62

OAD : AMARYL-M or GLUCOVANCE, ADMINISTERED AFTER MEALS

Breakfast : 6.30 am

Lunch : 0.30 pm

PRANDIAL APIDRA or
NOVORAPID

Fritsche et al 2003
Morning (Method A)
LANTUS or LEVEMIR
is
Better than Bedtime
(Method B)

PRANDIAL APIDRA or
NOVORAPID

3.30 pm

9.30 pm

9.30 am

Snack

Snack

Snack

OPTIONAL Tx
METFORMIN

OADS
AMARYL-M or
AMARYL-M

GLUCOVANCE

Dinner : 6.30 pm

GLIPTIN CLASS : DPP4-Is

METFORMIN DOSE : 1500 2000 mg/day

LANTUS or LEVEMIR

6-30 u sc
AMARYL-M or
GLUCOVANCE

METHOD-B : CTOI (TKOI) with EVENING LANTUS or LEVEMIR + AMARYL-M or GLUCOVANCE

(Clinical Experiences : Tjokroprawiro 2003-2012)

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KOMPLIKASI AKUT DIABETES MELLITUS

(Pengalaman Klinik : Tjokroprawiro 1993-2012)

1 HIPOGLIKEMIA : TRUE, REACTIVE

2 KETOASIDOSIS DIABETIK (KAD)
3

HHS / NKHC / HONK

HHS : Hyperosmolar Hyperglycemic State

NKHC : Non-Ketotic Hyperosmolar Coma
HONK : Hiperosmoler Non Ketotik

4 KOMA ASIDOSIS ASAM LAKTAT (KAAL)

No. 2 dan No. 3 DISEBUT KRISIS HIPERGLIKEMIA
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63

PETUNJUK PRAKTIS TERAPI HIPOGLIKEMIA

DENGAN FORMULA 3-2-1-1

64

(Pengalaman Klinik : Tjokroprawiro 1996-2012)

KADAR
GLUKOSA
(mg/dl)

TERAPI HIPOGLIKEMIA DENGAN

FORMULA 3-2-1-1

: I.V GLUKOSA 40%, BOLUS

30-50 mg/dl *) : I.V GLUKOSA 40%, BOLUS
50-70 mg/dl *) : I.V GLUKOSA 40%, BOLUS
70-90 mg/dl **) : I.V GLUKOSA 40%, BOLUS
< 30 mg/dl *)

GLUKOSA 40%
1 FLAKON : 25 ml

Isi 10 g Glukosa

3 FLAKON

FORMULA - 3

2 FLAKON
1 FLAKON
1 FLAKON

FORMULA - 2
FORMULA - 1
FORMULA - 1

GLUKOSA DARAH DIPERIKSA LAGI 30 MENIT SESUDAH I.V. GLUKOSA 40%

KEDUA TIPE HIPOGLIKEMI DIBAWAH INI (*) dan **)) HARUS DISERTAI GEJALA KLINIS KLASIK HIPOGLIKEMI

*) True Hypoglycemia : Bila kadar Glukosa Darah < 70 mg/dl. Dalam kondisi ini (<70 mg/dl) akan keluar hormon
CGCG (Catecholamine, Glucagon, Cortisol, Growth hormon). Hindarkan : HONEY MOON PHENOMENA
**) Reactive Hypoglycemia : Bila terjadi penurunan Kadar Glukosa Darah yang sangat cepat, sehingga nilai kadar
Glukosa darah turun menjadi sekitar 70 90 mg/dl, misal : kadar Glukosa Darah dari 400 mg/dl menjadi < 90
mg/dl. Pada kondisi ini kenaikan kadar hormon CGCG tidak terlalu nyata.
Gejala Klasik Hipoglikemia : gejala adrenergik (berdebar, banyak berkeringat, gemetar dan rasa lapar)
dan gejala neuro-glikopenik ( pusing, gelisah, kesadaran turun sampai koma)
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65

REGULASI CEPAT DENGAN INSULIN

(Pengalaman Klinik : Askandar Tjokroprawiro, 1993-2012)

Dapat dibagi menjadi : 1 R.C. INTRAVENA (RCI)

2 R.C. SUBKUTAN (RCS)
Perlu diketahui, bahwa pada pelaksanaan RCI (REGULASI CEPAT
INTRAVENA), perlu diingat beberapa rumus antara lain :
1 RUMUS MINUS-SATU : 1

2 RUMUS KALI-DUA : X2

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HIPERGLIKEMIA >200 mg/dl

(Contoh : Kasus Glukosa Darah 650 mg/dl)
REGULASI CEPAT INTRAVENA (RCI)
(Pengalaman Klinik : Tjokroprawiro 1987-2012)

GLUKOSA AWAL
Sebelum R-C (mg/dl)
2
3
4
5
6

ASK-SDNC

DOSIS INSULIN
Intravena 4 U/jam

00 - 300
00 - 400
00 - 500
00 - 600
00 - 700

1x
2x
3x
4x
5x

DOSIS RUMATAN
Insulin Subkutan (unit)
3x 4
3x 6
3x 8
3 x 10
3 x 12

RUMUS MINUS SATU

RUMUS KALI DUA

6 Minus 1 = 5

6 Kali 2 = 12

66

HIPERGLIKEMIA >200 mg/dl

(Contoh : Kasus Glukosa Darah 650 mg/dl)
REGULASI CEPAT SUBKUTAN (RCS)
(Pengalaman Klinik : Tjokroprawiro 1987-2012)

GLUKOSA AWAL
Sebelum R-C (mg/dl)
2
3
4
5
6

00 - 300
00 - 400
00 - 500
00 - 600
00 - 700

Rumus Kali Dua

6 Kali 2 = 12
ASK-SDNC

DOSIS INSULIN
Subkutan (unit)
4
6
8
10
12

DOSIS RUMATAN
Insulin Subkutan (unit)
3x 4
3x 6
3x 8
3 x 10
3 x 12

67

TERAPI KETOASIDOSIS DIABETIK (KAD) - REVISI 2010

68

(Clinical Experiences and Illustrated : Tjokroprawiro 1991-2012)

FASE-I

1 REHIDRASI
: NaCl 0.9% atau RL, 2 L / 2 jam pertama, lalu 80 tt/m
selama 4 jam, lalu 30 tt/m selama 18 jam (4-6 L/24 jam),
diteruskan sampai 24 jam berikutnya ( 20 tt/m) : FORMULA KAD : 2,4,18-24
2 IDRIV (NovoRapid) : 4 unit/jam i.v (FORMULA MINUS SATU)
3 INFUS KALIUM : 25 mEq (bila K+ = 3.0-3.5 mEq/l), 50 mEq (K+ = 2.5 - 3.0),
PER 24 JAM
75 mEq (bila K+ = 2.0-2.5), dan 100 mEq (bila K+ < 2.0 mEq)
4 INFUS
: bila pH < 7.2 atau BIK <12 mEq/l : 50-100 mEq / 500ml / 24 jam
Bolus BIK 50 mEq / 10 menit diberikan bila pH < 7.0
BIKARBONAT
dan sisanya (50 mEq) diberikan dengan drip selama 2 jam
5 ANTIBIOTIK
: HARUS RASIONAL dengan DOSIS ADEKUAT

Glukosa Darah + 250 mg/dl atau Reduksi Urine +

IDRIV : INSULIN DOSIS RENDAH INTRA VENA

1 MAINTENANCE

FASE-II

NaCl
: 0.9% atau Pot. R (INS 4-8u), Maltosa 10% (INS 6-12u)
bergantian : 20 tt/m (Start Slow, Go Slow, Stop Slow)
2 KALIUM
: p.e (bila K+ < 4 mEq/l), atau per os (air tomat/kaldu)
: 3 x 8-12 U sc (ingat : FORMULA KALI DUA)
3 NovoRapid
4 MAKANAN LUNAK : KARBOHIDRAT KOMPLEKS PER ORAL

FORMULA : 2,4,18,24Time ; FORMULA : 2,80,30,20Fluid

Koreksi HIPOKALEMIA gunakan FORMULA sbb :
HIPO K: F1, F2, F3, F4 (251005) *)
ASK-SDNC
Hati hati pada pasien CKD dan GAGAL JANTUNG

*)

F4 : 25 meq K+, dlm 100 ml RL, drip 5 jam

FORMULA KAD :

2
2

4 18 24 TIME
80 30 20 FLUID

IDRIV AMAN pada kasus HIPOKALEMIA

PROTOCOL FOR DIAGNOSIS AND THERAPY OF HONK or HHS

(Clinical Experiences and Illustrated : Tjokroprawiro 1991-2012)

CLINICAL DIAGNOSIS : 1 YES & 3 NO

PATHOGENESIS
PRECIPITATING FACTORS

1
2
3
4
5
6
7
8

Thiazide
Glucose Drinks
Infection
Corticosteroid
Beta Blocker
Phenytoin
Cimetidine
Chlorpromazine

1
2
3
4

TETRALOGY HONK :
1 YES & 3 NO

YES: Glycemia >600 mg/dl

NO: History of DM NO: Kussmauls Breathing NO: Ketonuria - or +

Grossly Elevated Glucagon

Relative Insulin Deficiency
Sufficient Insulin to inhibit lipolysis

THERAPY
SIMILAR WITH DKA THERAPY

pH > 7.30
a PLASMA Na <150 mEq/l
Neurological Sign
Prerenal Uremia
NORMAL SALINE
Mental Impairment
Severe Dehydration
b PLASMA Na >150 mEq/l
Age : More than 60 Years Old

Osm/l = 2x (Na) +

SOLUTION NaCL 0.45%

Glucose (mg/dl)
> 325
18

PENTALOGY HONK : 1 YES, 3 NO, Osmol/l > 325

HHS : HYPERGLYCEMIC HYPEROSMOLAR STATE

ASK-SDNC

1
2
3
4
5
6

TETRALOGY HHS (1 YES & 3 NO) : 1 H + 3 NO

PATHOPHYSIOLOGY

SUPPORTING FINDINGS

69

HONK : HYPEROSMOLAR NON KETOTIK

70

KAAL - Tipe A
(PRIMER : HIPOKSIA)
1. Semua jenis shock
2. Decomp. Cordis
3. Asfiksia
4. Intoksikasi CO

KOMA ASIDOSIS ASAM LAKTAT (KAAL)

(Tipe A dan Tipe B )

(Pengalaman Klinik : Tjokroprawiro 1991-2012)

ASAM LAKTAT + H2 O + O2

BIKARBONAT

KAAL - Tipe B
KELAINAN SISTEMIK
1. DM
2. Neoplasia
3. RFT/LFT terganggu
4. Konvulsi

OBAT

1. Biguanide
2. Salisilat
3. Alkohol (Metanol, Etanol)
4. Glukosa-Alkohol (Sorbitol, dll)
ASK-SDNC

ISKHEMIA
Infeksi, Shock, Peny. Kardiovaskuler/Angiopati, Gangguan

LFT-RFT , DM + Biguanide, Gg. Oksigenasi : PPOK, dll

Dx : Hiperglikemia plus Anion Gap > 20 mEq
(K + Na) - (Cl + CO2 ) > 20 mEq atau
(Na) - (Cl + CO2 ) > 15 mEq
Tx : Kausal (Tipe A atau B, dan Regulasi DM)

KOMPLIKASI KRONIK DM

71

(Summarized : Tjokroprawiro 1991-2012)

1 INFEKSI

: SELULITIS/GANGRENE, ISK, CHOLECYSTITIS, PARU

(TBC), ORAL INFECTION, SEPSIS (GANGREN: 3.8%)

2 MATA

: RETINA, LENSA, CILIARY BODY (RETINOPATI: 27.2%)

3 MULUT

: XEROSTOMIA, PERIODONTITIS (10-75%)

4 JANTUNG : PIK, IMA (Makrovaskuler), KARDIOMIOPATI (Mikrovaskuler)

5 TRACTUS UROGENETALIS :
NEFROPATI DIABETIK (5.7%)
6 DISFUNGSI EREKSI (DE) : 50.9%
7 SARAF (Lihat slide no. 5) : 51.4%
8 KULIT
ASK-SDNC

: NECROBIOSIS LIPOIDICA DIABETICORUM,

DIABETIC DERMOPATHY, SELULITIS/ GANGRENE

72

KLASFIKASI IMPOTENSI DIABETIK

Sekarang disebut : Disfungsi Ereksi Diabetik = DE-D
(Pengalaman Klinik 1991 2012)

1 DE-D PSIKOGENIK (Test Ereksi Pagi Positif)

2 DE-D ORGANIK (Test Ereksi Pagi Negatif)
- Apabila lama <6 bulan "REVERSIBLE"
- 6 bulan - 24 bulan meragukan sembuh
- > 2 th biasanya IREVERSIBLE
3 DE-D PSIKOGENIK dan ORGANIK (prognosis lebih parah).
- Terapi Disfungsi Ereksi
ASK-SDNC

FORMULA-5: FIVE GUIDELINES (FOR ED) PRIOR TO SEXUAL INTERCOURSE

73

FIVE (5) TIPS for DIABETIC PATIENTS : Tjokroprawiro 1998 2012

1 BLOOD SUGAR < 200mg/dl and TESTOSTERONE > 400ng/dl (Median 426)

SUPPORTING FINDINGS (mmHg/mg/dl) : BP < 130/80, LDL < 100, TG <150

2 PATIENT SHOULD be PHYSICALLY and MENTALLY FIT

3 DURING the D-day of S.I, : DAILY-MEAL SHOULD be LOW-FAT CONSUMPTION
4 AVOID DRUG INDUCED ERECTILE DYSFUNCTION (ED) : SMOKING, Etc
5 SEXUAL INTERCOURSE CAN BE STARTED 2-3 HOURS AFTER MEAL

AFTER ALL 5 (FIVE) REQUIREMENTS ABOVE MENTIONED HAVE BEEN MET,

DRUGS WHICH CAN BE USED are : ONE of the FOLLOWING TRIBULUS in mg
(FITOGRA-50, PROLIBI-250, EREMED-250, Etc), LEVITRA & Etc, THESE
DRUGS CAN BE SWALLOWED (EMPTY STOMACH) 2-3 HOURS BEFORE S.I.
USE LUBRICANT (if needed) FOR PENETRATION S.I. = SEXUAL INTERCOURSE
ASK-SDNC

SEPULUH PETUNJUK POLA HIDUP SEHAT

74

GULOH-SISAR = SINDROMA-10
(Askandar Tjokroprawiro 1995-2012)
Pusat Diabetes dan Nutrisi Surabaya, RSUD Dr. Soetomo FK Universitas Airlangga

(LAKSANAKAN HIDUP SEHAT GULOH-SISAR dengan PEDOMAN BNI : BATASI, NIKMATI, IMBANGI)
BAGI PASIEN DIABETES (DM) : HINDARKAN SEMUA YANG MANIS, atau SANGAT BATASILAH YANG MANIS TERSEBUT

1 G (GULA) : Pantang Gula bagi DM. Bagi

Non-DM Kurangilah Konsumsi Gula
2 U (asam URAT) : Batasi JAS-BUKKET

6 S (SIGARET) : Stop Merokok

7 I

(INAKTIVITAS): Hindarkan Inaktivitas, dan Rutinkanlah Latihan

Fisik 300 kcal/hr atau Jalan 3 km/hari, atau SIT-UP 50-100 X/hr

3 L (LEMAK) : Batasi TEK-KUK-CS2

8 S (STRESS) : Usahakan Tidur 6-7 Jam Sehari untuk meredakan Stress

4 O (OBESITAS): Target LP Pria < 90 cm

9 A (ALKOHOL) : Stop Alkohol

5 H (HIPERTENSI): Untuk Pasien Hipertensi,

10 R

LP = Lingkar Pinggang

Wanita < 80 cm

Batasi Garam, Ikan Asin, Kacang Asin, dll

(REGULAR CHECK UP) : Usahakan check up Teratur dan

Konsultasi Ahli, bagi umur > 40 th, setiap 3, 6,12 Bulan

JAS-BUKKET : Jerohan, Alkohol, Sarden - Burung Dara, Unggas, Kaldu, Kacang, Emping,
Tape
TeK-KUK-CS2 : Telor, Keju - Kepiting, Udang, Kerang - Cumi, Susu, Santen
"MABUK" (Mengandung banyak Chromium) : Mrica, Apel, Brokoli, Udang, Kacang-kacangan
Chromium (Cr) Dapat Memperbaiki Kerja Insulin. Ini berarti Cr bermanfaat bagi Penderita Diabetes

BNI
BNI
BNI

Makanan Suplemen yang Dianjurkan : Buncis, Bawang Putih, Teh Hijau, Merica, dan TKW-PJKA-BK
TKW PJKA BK : Banyak Mengandung Antioksidan Tomat, Kacang-kacangan, Wortel - Pepaya, Jeruk, Kurma, Apel - Brokoli, Kobis

HABIBIE-AWARD
CEREMONY Jakarta, 30 November 2006. TVRI Surabaya : TALK SHOW Acara SEMANGGI. 21 September 2011
ASK-SDNC

75

Short and Long Sleep Durations as Risk Factor for T2DM

(Yaggi et al 2006; Summarized : Tjokroprawiro 2006-2012)

Men with Short Sleep Duration (5 h Sleep per Night)

TWICE AS LIKELY TO DEVELOP DIABETES

Men with Long Sleep Duration (> 8 h Sleep per Night)

MORE THAN THREE TIMES AS LIKELY TO DEVELOP DIABETES

THE EFFECTS OF SLEEP ON DM COULD BE MEDIATED VIA

ENDOGENOUS TESTOSTERON LEVELS
ASK-SDNC

LIFESTYLE RELATED DISEASES AND THE STAGING OF OBESITY

76

(Clinical Experiences and Illustrated : Tjokroprawiro 2005-2012)

LRDS**RISKS: OBESITY, INSULIN RESISTANCE, the METS, CMR as TIME BOMB PRECLINICAL DISEASES

STAGE 0

STAGE 1

STAGE 2

STAGE 3

STAGE 4

Westernized Abdominal Obesity Preclinical : the MetS, CMR Clinical CMDS : CAD,
Indonesian
T2DM**** (Adult & Adol.)
Healthy Lifestyle Unhealthy Lifestyle (Adult & Adolescent) Pre-DM : Adult & Adol.*) STROKE, T2DM****
*ADOLESCENT MetS/T2DM
**LRDS : Lifestyle Related Diseases
****Adult & Adolescent T2DM

1 WAIST CIRCUMFERENCE = WC
INDONESIA : > 90; > 80

JAPAN : > 85; > 90

***TLCS : Therapeutic Lifestyle Changes

*ELDERLY MetS/T2DM
CMR: Cardio Metabolic Risk
CMD: Cardio Metabolic Disease

5 FASTING PLASMA GLUCOSE

2 TRIGLYCERIDE

> 100 mg/dl

> 150 mg/dl

ATP-III 2001 - Criteria

3 from 5

GULOH***

4 BLOOD PRESSURE
> 130/85 mmHg

CISAR***

METFORMIN

IDF 2005 - Criteria

3 HDL-CHOL
o < 40 mg/dl
o
+ < 50 mg/dl

WC >90 or >80
plus
2 from no. 25

STAGE - 3 (the MetS & CMR ) will be the "TIME-BOMB PRECLINICAL DISEASES by 2020?
ASK-SDNC

THE STAGING of OBESITY and the PREVALENCE of METS in SURABAYA

(Tjokroprawiro 2005-2012)

77

SURABAYA DIABETES AND NUTRITION CENTER, Dr. SOETOMO TEACHING HOSPITAL - FACULTY OF MEDICINE AIRLANGGA UNIVERSITY

STAGE 0

STAGE 1

STAGE 2

STAGE 3

Westernized Abdominal Obesity Preclinical : Adult & Adol.*)

Indonesian
Healthy Lifestyle Unhealthy Lifestyle (Adult & Adolescent) Pre-DM - the MetS*, CMR
The Prevalence of the MetS in Surabaya 2005
( Preliminary Survey )
Non DM : 32.0%
DM After Treatment : 43.3%
DM Obesity
: 81.7%
Nave DM : 59.0%
MALE PREVALENCE : 45 x Fold than FEMALE

STAGE 4
Clinical CMDS: CAD,

STROKE,
TROKE, T2DM****
T2DM**** (Adult & Adol.)

WAIST CIRCUMFERENCE : WC
INDONESIA : >90; >80

JAPAN : > 85; > 90

11 FEATURES OF
THE METABOLIC SYNDROME
1 VISCERAL FAT
2 INSULIN RESISTANCE, PRE-DM, T2DM

4 FASTING GLUCOSE

1 TRIGLYCERIDE

> 100 mg/dl

> 150 mg/dl

3 ATHEROGENIC DYSLIPIDEMIA
4 RAISED BLOOD PRESSURE
5 PROINFLAMMATORY STATE
6 HYPERURICEMIA
7 PROTHROMBOTIC STATE
8 VASCULAR ABNORMALITIES
9 ADRENAL INCIDENTALOMA
10 FATTY ACID DEPOSITION (FATTY LIVER)

3 BLOOD PRESSURE

> 130/85 mmHg

2 HDL-CHOL
o < 40 mg/dl
o+ < 50 mg/dl

METABOLIC SYNDROME
WC (INA) : > 90 cm () and > 80 cm ()
:
(IDF 2005)
Plus 2 from the 4 above mentioned Factors

11 HYPOGONADISM (TESTOSTERONE)

IDF = International Diabetes Federation, INA = Indonesia, AMI = Acute Miocardial Infarction, CHD = Coronary Heart Disease
ASK-SDNC

MYSTERY OF FAT CELL : 67 BIOLOGIC SUBSTANCES

78

(Illustrated : Tjokroprawiro 1997-2012)

31 Lactate, Lysophospholipid, Adenosine, Glutamine

FIAF 30

33 Galectin-12

Aquaporins 29
PC-1 28
38 UCP, P450, ZAG

ApoE,LPL,ICAL,CETP,PLTP 26

40 Macrophage CSF

RBP4 25
Metallothionein 24
11 HSD-1 22
ACTH, Cortisol 21
Eicosanoids, 20
PGE2, PGI2

41 Macrophage Inflammatory Protein 1

VCAM-1
4 TNF

MIF 18

5
IL-1, IL-6

17

Ob Protein (LEPTIN)

Perilipsins 16

AII

LPL & FFA

Lipotransin 15

HSL, DGAT 14

ASP, Adipsin, Factors : B, C3

VISFATIN 13

8 Adhesive Proteins

Adiponectin 12

9 PAI-1
(Esp. Omental Fat)

Resistin 11

ASK-SDNC

10 TF

OMENTIN VISFATIN
A-FABP ADMA

39 Complement System Products

3 Agouti Related
Protein (AgRP)

FAT CELL

TGF, VEGF,
19
IGF-1, IGF BP
FFAs

42

37 aP2

43 VASPIN
44 Chemerin
1 Estrogen
45 LCN2 STAMP2
2 Ob Protein (LEPTIN)
1 Renal Renin (AII)

Aromatase 23

34 ESM-1

35 Apelin

36 FATPI

NO 27

32 Monobutyrin

Hyperuricemia
2
3

Predictor of the MetS

Necrosis
Apoptosis
Proliferative Effect
Hypertension
Body Weight

NPY, AGRP
Inhibits Bone Formation
(Central Relay)

IRS-1
IRTK
TG
HDL
LDL3
Fribrinogen
PAI-1
F VII

INSULIN
RESISTANCE

Cell
STAT-3

GLUT-4
EXPRESSION

INSULIN
SECRETION

IGT - T2DM

OBESITY and Its CONSEQUENCES : IR, the METS, CMR to CMDs

79

(Wellen et al 2003, Takahashi et al 2008, Provided : Tjokroprawiro 2006-2012)

MACROPHAGE INFLAMMATORY PATHWAY

FROM NORMAL (STAGE-0) TO OBESITY STAGE-3
LRDS = Lifestyle Related Diseases
ADIPOCYTE

WEIGHT GAIN

TNF-

DIO

CHRONIC LOW GRADE INFLAMMATION

IR, the METS & CMR the CMDs L

E
HSP70 / HSP72
P
WEIGHT GAIN
T
STAMP2

Apn
IR
I

OMENTIN
JNK1
N
Leptin
NFB
VEGF

VASPIN

R
RESISTIN
E
TNF-
Physical Stress/Oxidative
A-FABP
S
Damage to Endothelium?
MCP-1
PREADIPOCYTE
CHEMERIN
I
LCN-2 : Lipocalin-2
MCP-1
LEPTIN
FFA
S
BAFF
Apn = Adiponectin
TNF, IL-6,
IL-1, CRP
DIO : Diet Induced Obesity
T
MACROPHAGE RECRUITMENT
ATM
*)
MACROPHAGE

FETUIN-A
CMR : Cardio Metabolic Risk
PREADIPOCYTE MACROPHAGE
RECRUITMENT
A
CERAMIDE
ATM : Adipose Tissue Macrophage CMDs : Cardio Metabolic Diseases NAFLD NASH / CIRRHOSIS
ADMA
N
MCP-1,
STAMP2 : Six TrAns Membrane Protein of prostate 2
FETUIN-A = Hepatic Secretory Protein
VISFATIN LCN-2
PAI-1, FFA
VASPIN = Visceral Adipose tissuederived Serine Protease INhibitor BAFF = B-cell Activating Factor
C
NORMAL ADIPOCYTE ADIPOCYTE DYSFUNCTION INFLAMMED ADIPOSE TISSUE E
EndothelialAngiogenesis
Cell

*)

ASK-SDNC

IL-6
IL-1

I M
NE
ST
UA
L B
I O
NL
I
RC
E
SS
I Y
SN
TD
AR
NO
CM
EE

N
O
N
A
L
C
O
H
O
L
I
C
F
A
T
T
Y
L
I
V
E
R

80

Alm.
Soeharjono

Askandar Tj.

Alm.
Hendromartono

Ari Sutjahjo

Agung Pranoto

Sri Murtiwi

Soebagijo Adi

Sony Wibisono

The 8 CORE STAFFS of SDNC 1986 - 2012

PLUS 52 EXPERT MEMBERS FROM MULTIPLE DISCIPLINES
SDU 22

SDW
PEPIC
DIAPIC

NOS 2
SUMETSU 8
MECARSU 8
SOBU 4
OBELAR

Jongky Hendro

Hermina Novida

SUMETSU-8 MECARSU-8 SOBU-4

18-19 FEBRUARY 2012

* EDUCATION
* HEALTH SERVICE
* INVESTIGATION:
WDF, GIANT, Etc

SURABAYA DIABETES AND NUTRITION CENTER (SDNC)

Dr. SOETOMO TEACHING HOSPITAL
FACULTY OF MEDICINE AIRLANGGA UNIVERSITY SURABAYA
ASK-SDNC