ASK-SDNC

2012
17-928-M
SURABAYA, 5 MARCH 2012
GARIS BESAR KULIAH UNTUK MAHASISWA SEMESTER-6
DIABETES MELLITUS-II

FAKULTAS KEDOKTERAN UNIVERSITAS AIRLANGGA, SURABAYA
41
Prof. Dr. dr. Askandar Tjokroprawiro Sp.PD, K-EMD, FINASIM
Kuliah I : SLIDE 1- 40; Kuliah II : SLIDE 41- 80
dr. Sri Murtiwi Sp.PD, K-EMD, FINASIM
SURABAYA DIABETES AND NUTRITION CENTRE - Dr. SOETOMO TEACHING HOSPITAL
FACULTY OF MEDICINE AIRLANGGA UNIVERSITY, SURABAYA
Division of Endocrinology and Metabolism Dept. of Internal Medicine
ASK-SDNC
(Summarized : Tjokroprawiro 1996-2012)
MAP OF ORAL ANTI DIABETES (OAD) IN DAILY PRACTICE
III INTESTINAL ENZYME INHIBITORS
o-Glucosidase Inhibitor: Acarbose
o-Amylase Inhibitor: Tendamistase
1
2
V FIXED DOSE COMBINATION (FDC) TYPES
Glucovance

, Amaryl-M

, Galvusmet

, Janumet

, ACTOplusmet

, Duet act

4
II
- Metformin , Metformin XR (Glucophage

XR) , 3-Guanidinopropionic-Acid
1
3 BIGUANIDE :
a
b
Glitazar Class (Mura-
*)
, Raga-, Ima-, Tesaglitazar) : MRIT
Non-Glitazar Class (Metaglidasen : Non Edema and Non Weight Gain)
2 NON-TZDs :
THIAZOLIDINEDIONES (TZDs): Glitazone Class
*
)
Withdrawn
INSULIN SENSITIZERS
(Rosi-
*)
, Pio-, Neto-, Dar-glitazone)
DLBS-3233 (INLACIN

)
42
I INSULIN SECRETAGOGUES
- NON-SUs (Metaglinides : Nateglinide, Repaglinide)
- SUs : Gliquidone, Glipizide, Gliclazide, Glibenclamide, Glimepiride
IV INCRETIN-ENHANCERS DPP-4 INHIBITORS
Sita-, Vilda-, Saxa-, Lina-, Alo-, Dena-,
Duto-, Melo-, Teneli-gliptin, SYR-322, TA-666
VI OTHER SPECIFIC (OS) TYPES
ASP1941, BI 10773 , Canagliflozin, Dapagliflozin, Seragliflozin, Remogliflozin, AVE-2268,
KGT-1681, LX-4211, TS-033, YM-543
3 Oxphos-Blocker FBPase Inhibitor 4
INCB13739 (11|HSD1inhibitor) 5
Sodium GLucose co Transporter-2 (SGLT2)-Inhibitors: 1
2
Glucokinase Activator (GKA): MTBL1, MK-0941.
ASK-SDNC
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 J2 = Jadwal J3 = Jenis
43
ASK-SDNC
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).
(Summarized : Tjokroprawiro, 2003-2012)
Macam Insulin dalam Praktek Sehari-hari
4 INSULIN ANALOGUES ( 3 macam ) :
A. Rapid-Acting (Kerja Cepat) Insulin Analogue :
Lis Pro (R/ Humalog), Glulisin (R/ Apidra), Aspart (R/ Novorapid)
C. Long-Acting Peakless Insulin Analogues : Insulin Glargine (R/Lantus), Detemir (R/ Levemir)
B. Premixed Short 25-30% with Long Acting (70-75%) : Humalog Mix25, Novomix 30/70
44
ASK-SDNC
PHARMACOKINETICS OF HUMAN INSULIN AND INSULIN ANALOGUES
(Summarized : Tjokroprawiro 2008-2012)
INTERMEDIATE-ACTING
NPH
Lente

1-3 hrs
1-3 hrs

5-7
4-8

13-16
13-20
INSULIN PREPARATION
ONSET OF
ACTION
PEAK OF ACTION
(HRS)
DURATION OF
ACTION (HRS)
45
RAPID ACTING **
)
SHORT ACTING *)

Regular Human Insulin = RHI*
)
Insulin Glulisine : Apidra

**)
Insulin Aspart : Novorapid

**)
Insulin Lispro : Humalog

**)

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
LONG-ACTING
Insulin Glargine (lantus

)
Detemir (Levemir

)
Ultralente
Ultra-long-acting insulin DEGLUDEC

1-3 hrs
1-3 hrs
2-4 hrs


24
24
22-24 hrs


No Peak
No Peak
8-14


10 mins
10 mins

1-4
1-4

10-20
16-20
PREMIXED
Insulin Lispro 75/25 (Humalog Mix25

)
Insulin Aspart 70/30 (NovoMix

)
: New Gen. Basal Ins. that forms Soloble Hexamers upon SC inj.
ASK-SDNC
INDIKASI INJEKSI INSULIN
(KONSENSUS PERKENI 2011)
1 PENURUNAN BERAT BADAN YANG CEPAT
2 HIPERGLIKEMIA BERAT YANG DISERTAI KETOSIS
3 KETOASIDOSIS DIABETIK (KAD)
4
HIPERGLIKEMIA HIPEROSMOLAR NON KETOTIK (K-HONK)
5 HIPERGLIKEMIA DENGAN ASIDOSIS LAKTAT (KAAL)
6 Gagal dengan kombinasi OHO dosis optimal
7 Stres berat (infeksi sistemik, operasi besar, IMA, stroke)
8 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
46
Lihat Slide no 50 dan 51
ASK-SDNC
(Clinical Experiences : Tjokroprawiro 1993-2012)
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
46-60 31-45
61-75 16-30
76-90
1-15
47
ASK-SDNC
PRACTICAL TOOL FOR INSULIN RESISTANCE AND |-CELL FUNCTION
(Mathews et al 1985, Falutz et al 2002, Summarized : Tjokroprawiro 2005-2012)
HOMA-R and HOMA-B
Useful in Daily Practice
:
1
2 FOLLOW-UP OF TREATMENT
RATIONALE TREATMENT
HOMA-B
|-Cell Function
:
(N: 70150%)
20 x Fasting Insulin ( U/ml)
FPG (mmol/l) 3.5
HOMA-R
Insulin Resistance
:
(N: < 4.0)
Fasting Insulin (U/ml) x FPG (mmol/l)
22.5
48
ASK-SDNC
PREVALENCE OF IR IN SELECTED METABOLIC DISORDERS
(Bonora 1998, Summarized and Illustrated : Tjokroprawiro 2006-2012)
4 HYPERTENSION
IFG & IGT 2
| URIC ACID
7
LOW HDL-C 6
3
The MetS
HYPER-CHOL
8
+ 1
st
Phase and | IR in Liver
IFG = Impaired Fasting Glucose
+ 1
st
Phase and | IR in Periphery
IGT = Impaired Glucose Tolerance
IR = INSULIN RESISTANCE IR = INSULIN RESISTANCE
DISORDERS
METABOLIC
SEQUENTIAL
PREVALENCES OF IR
in
49
HYPERTRIGLYCERIDAEMIA
5
T2DM
1
ASK-SDNC
COMBINED THERAPY OF ORAL AGENT AND INSULIN (CTOI)
Terapi Kombinasi Tablet Oral dan Insulin (TKOI)
(Clinical Experiences : Tjokroprawiro 2003-2012)
HOMA-B < 35% (Normal : 70-150%) 2
3 EARLY INSULINATION, if :
- HOMA-B < 50%
- SEVERE UNCONTROLLED WEIGHT LOSS (> 10%)
I PRIMARY INDICATION
Continued
1 USE FORMULA 2-4-8 :
: FPG > 200 mg/dl
: 1h-PG > 400 mg/dl
: A1C > 8 %
2
4
8
FORMULA
FORMULA
FORMULA
50
ASK-SDNC
II SECONDARY INDICATIONS FOR DIABETIC PATIENTS WITH :
1
BONE FRACTURES
INSULIN SUPPRESSES
ARGINASE ACTIVITY
2 MODERATE-SEVERE RENAL
FAILURE : LOW or NO-KTT
3
ADVANCED PULMONARY TBC
4
DECOMPENSATED OR SPECIAL CASES OF LIVER CIRRHOSIS
5
UNCONTROLLED OR SEVERE WEIGHT-LOSS (> 10%)
AVOID KTT if eGFR < 40 or S. CREATININE > 4.0 mg/dL
CKD : CHRONIC KIDNEY DISEASE
6
OTHER SPECIFIC CASES : NON-INFECTIVE ULCER, ETC
COMBINED THERAPY OF ORAL AGENT AND INSULIN
(KTT : KACANG, TAHU, TEMPE)
(Clinical Experiences : Tjokroprawiro 2003-2012)
51
ARGININE
BUN
( N < 20)
ARGINASE
KTT & OTHER
PROTEIN
CKD
Lantus

or Levemir

Apidra

or Novorapid

ASK-SDNC

(Summarized Illustrated : Tjokroprawiro 2009-2012)
The 21 ENDOCARDIOMETABOLIC PROPERTIES OF INSULIN
GLYCEMIC CONTROL
+ A1C
1
+ LIPOLYSIS via HSL
(Hormone Sensitive Lipase)
18
+ ADMA IN PLASMA
AND IN ENDOTHELIUM
14
BONE ANABOLIC
(| OSTEOGENESIS)
13
+ PLASMA ARGINASE
(+ UREA ~ + BUN)
12
RESTORE
LH, FSH, TESTOSTERON
19
VASPIN mRNA IS INCREASED WITH INSULIN INJECTION IN SEVERE INSULIN RESISTANCE 20
52
| GLYCOGEN SYNTHESIS 15
| PROTEIN SYNTHESIS 16
ANTI-ATHEROSCLEROSIS
(+ ROS, + NFkB, + CRP, etc)
3
PROFIBRINOLYSIS (+ PAI-I) 4
ANTI-APOPTOSIS
(Heart, Brain, | Cell)
8
ANTI-PLATELET (| c-AMP) 6
VASODILATATION
(| NO, | eNOS)
5
ANTI-THROMBOSIS
(+ TISSUE FACTOR)
7
CARDIO-PROTECTION
(ANIMALS, HUMAN)
2
ANTI-INFLAMMATION
|IkB, +NFkB, +TNFo,
+ICAM-1, +MCP-1,+CRP
9
ANTI-OXIDANT (+ ROS) 10
GROWTH DEVELOPMENT
HYPOTHETICAL WAY TO TUMOR
VIA IGF
1
RECEPTOR ?
11
| LIPOGENESIS via | LPL
(Lipoprotein Lipase)
17
21 INSULIN
PROPERTIES
| HSP 70 / HSP 72
(For Wound Healing, Etc)
21
ASK-SDNC
NUTRITION IN DIABETES MELLITUS
Clinical Experiences : Tjokroprawiro 1978-2012
DIABETIC DIETS

MEDICAL NUTRITION THERAPY
(MNT)
P.E.N. P-P.E.N.
PAR ENTERAL NUTRITION
( "SONDE" )

E
1
, E
2
, E
3
, E
4
, E
5
, E
6

:08.00
:14.00
:20.00
INSULIN
E
1

E
3

E
5

:11.00
:17.00
:23.00
NO INSULIN
E
2

E
4

E
6

ORAL NUTRITION
Since 1978
ENTERAL NUTRITION
Since 1995
PAR ENTERAL NUTRITION = P.E.N.
Since 1993
PERIPHERAL P
PAR P
ENTERAL E
NUTRITION N
Ten Principles
of
P-P.E.N. in DM
53
21 Types of Diabetic Diets
at Dr. Soetomo Hospital
From the B-Diet 1978
to
21 Types of Diabetic Diets
(2004)
ASK-SDNC
NUTRITION IN DIABETES MELLITUS
Clinical Experiences : Tjokroprawiro 1978-2012
PAR ENTERAL NUTRITION = P.E.N.
Since 1993
P.E.N. P-P.E.N.
PAR ENTERAL NUTRITION
PERIPHERAL P
PAR P
ENTERAL E
NUTRITION N
TEN PRINCIPLES
of
P-P.E.N. in DM
54
ASK-SDNC
SEPULUH PETUNJUK N.P.E. PERIFER-DIABETIK
(Pengalaman Klinik : Tjokroprawiro 1993-2012)
(Continued)
START SLOW - GO SLOW - STOP SLOW : S-G-S
disusul urut dengan Infus 500ml Potacol-R = B
2
, dg tetesan 14 tt/mnt.
Contoh : Cairan B , Infus 500ml Martos 10% = B
1
14 tt/mnt
Jadi : Cairan A : 500 ml NaCl 3% 7 tt/mnt (500 ml/24 jam) dan Cairan
B : 500 ml Martos 10% = B
1
(12 jam) dan 500 ml Potacol-R = B
2
(12 jam)
dengan tetesan 14 tt/mnt. Kesimpulan :
Cairan A dan Cairan B
1
, B
2
akan habis bersamaan dalam 24 jam.
Bila Osmol >1000
di Cabang dengan Cairan B Isotonis (275-300 mOsm/l) atau
Hipertonis-Ringan (300-600 mOsm/l)
A (Misalnya Cairan A : 500ml NaCl 3% (1200 mOsm/l) 7 tt/mnt
Infus Cabang : Cairan A dan Cairan B
Contoh : Cairan Cairan A > 1000 mOsm/l, Cairan B 275-600 mOsm/l
1 LARUTAN NPE : OSMOLARITAS IDEAL< 600 Maksimal-1000 mOsm/L
55
ASK-SDNC
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 1
o
C
- 300 ml untuk tambahan cairan Intra Seluler (Anabolik)
Laksanakan
Regulasi Cepat
Lebih Dahulu !!
3A PERBAIKI HEMODINAMIK (RESUSCITATION) LALU : NPE

3B
BILA GLUKOSA >250 mg/dl JANGAN LAKSANAKAN NPE
4
BILA GLUKOSA <250 mg/dl (Syarat dimulainya NPE)
LAKSANAKAN NPE
TUJUAN : GLUKOSA < 200 mg/dl (Agar Fungsi Lekosit Normal)
SEPULUH PETUNJUK NPE PERIFER-DIABETIK
(Pengalaman Klinik : Tjokroprawiro 1993-2012)
(Continued)
56
START SLOW - GO SLOW - STOP SLOW : S-G-S
ASK-SDNC
5 KALORI HARI 1-3 : BASAL (400-800 Kcal)
Naik Pelan, Turun Pelan, Stop Pelan (Start Slow, Go Slow, Stop Slow : SGS)
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
SEPULUH PETUNJUK NPE PERIFER-DIABETIK
(Pengalaman Klinik : Tjokroprawiro 1993-2012)
6
GLUKOSA 5% atau MALTOSA 10%; usahakan minimal 100-150 g/hari
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
(atau 3-4 g/kg BB) : untuk OTAK , LEUKOSIT, ERITROSIT, MEDULLA RENALIS
(Continued)
57
START SLOW - GO SLOW - STOP SLOW : S-G-S
ASK-SDNC
8 Infus Lipid : 20 - 40% KNP (Kalori Non Protein)
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
INFUS AA JANGAN DIPERHITUNGKAN SEBAGAI SUMBER ENERGI
MELAINKAN UNTUK REGENERASI DAN SINTESIS PROTEIN VISCERAL
SEPULUH PETUNJUK NPE PERIFER-DIABETIK
(Pengalaman Klinik : Tjokroprawiro 1993-2012)
10 Bila no. 1 s/d no. 9 sudah dipenuhi, laksanakan NPE + FLUID THERAPY :
GLUCOSE , EAA BCAA
Na
+
, K
+
, Cl

Ca
++
, P, Mg
++
Zn
+

RATIONALE
MAINTENANCE FLUID THERAPY
SHOULD CONTAIN
ALE : Asam Lemak Essensial
58
START SLOW - GO SLOW - STOP SLOW : S-G-S
ASK-SDNC

TEN GUIDELINES OF PERIPHERAL P.E.N.
(Clinical Experiences : Tjokroprawiro 1993-2012)
START SLOW GO SLOW STOP SLOW
MAINTENANCE FLUID THERAPY Insulin Dose : Formula 5-1 or 2.5-1
59
2
4
5 DAY 1-3 : SGS (400-800 Kcal/day)
FLUID & CALORIE (per kg BW) :
FLUID : 30 ml & CALORIE : 30 kcal/kg BW
P-P.E.N. IF GLUCOSE < 250 mg/dl
1 CHECK OSMOL.: < 600-1000 mOsm/l
3
a. RESUSCITATION & HEMODYNAMIC!!
b. RAPID GLYCEMIC CONTROL
WITH TARGET : BS < 250 mg/dl
6
Maltose/Glucose: 100-150 g/day
8 Fat Emulsion : 20-40 % NPC,
20% Sol. is Recommended 500 ml/24 jam
10
P-P.E.N. & MAINTENANCE FLUID THER.
7 AA-INFUSION: CONTINUOUS INFUSION
Day 2-3; Backed up: 25 kcal/1g AA
9
SHOULD BE CONTINUOUS INFUSION 500 ml/ 24 h
FAT EMULSION : 10 ADVANTAGES
ASK-SDNC
TARGET PENGENDALIAN DIABETES MELLITUS
(KONSENSUS PERKENI-2011)
Keterangan :
KV = KARDIOVASKULAR, PP = POST PRANDIAL,
IMT = INDEX MASSA TUBUH
60
IMT (kg/m
2
) 18.5 - <23 18.5 - <23

Tekanan Darah Sistolik (mmHg) < 130 <130

HbA
1c
(%) < 7 < 7


Kolesterol LDL (mg/dl) < 100 < 70

Kolesterol HDL (mg/dl)
Pria > 40
Wanita > 50

Trigeliserida < 150 < 150
Risiko KV (-) Risiko KV (+) PARAMETER
Tekanan Darah Diastolik (mmHg) < 80 < 80
Glukosa Darah Puasa (mg/dL) < 100 <100
Glukosa Darah 2 jam PP (mg/dL) < 140 <140
Pria > 40
Wanita > 50
ASK-SDNC
Breakfast : 6.30 am Lunch : 0.30 pm Dinner : 6.30 pm
Snack
9.30 am
Snack
3.30 pm
Snack
9.30 pm
OAD : AMARYL-M

or GLUCOVANCE

, ADMINISTERED AFTER MEALS

METFORMIN DOSE : 1500 2000 mg/day
METHOD-A: LANTUS

or LEVEMIR

+ AMARYL-M

or GLUCOVANCE

: SAFE FOR CANCER RISK

METHOD-A : CTOI (TKOI) with MORNING LANTUS

or LEVEMIR

and AMARYL-M

or GLUCOVANCE

(Clinical Experiences : Tjokroprawiro 2003-2012)
PRANDIAL APIDRA

or
NOVORAPID

AMARYL-M

or GLUCOVANCE

PRANDIAL APIDRA

or
NOVORAPID

LANTUS

or LEVEMIR

6-30 u sc
AMARYL-M

or GLUCOVANCE

OPTIONAL THERAPY
METFORMIN
GLIPTIN CLASS: DPP4-Is
Fritsche et al 2003
Morning (Method A)
LANTUS

or LEVEMIR

is
Better than Bedtime
(Method B)
61
ASK-SDNC
Snack
3.30 pm
Snack
9.30 pm
Snack
9.30 am
Breakfast : 6.30 am Lunch : 0.30 pm Dinner : 6.30 pm
METFORMIN DOSE : 1500 2000 mg/day
METHOD-B : LANTUS

or LEVEMIR

in the EVENING or BEDTIME

METHOD-B : CTOI (TKOI) with EVENING LANTUS

or LEVEMIR

+ AMARYL-M

or GLUCOVANCE

(Clinical Experiences : Tjokroprawiro 2003-2012)
OAD : AMARYL-M

or GLUCOVANCE

, ADMINISTERED AFTER MEALS

LANTUS

or LEVEMIR

6-30 u sc
AMARYL-M

or
GLUCOVANCE

PRANDIAL APIDRA

or
NOVORAPID

PRANDIAL APIDRA

or
NOVORAPID

OAD
S
AMARYL-M

AMARYL-M

or
GLUCOVANCE

OPTIONAL Tx

METFORMIN
GLIPTIN CLASS : DPP4-Is
Fritsche et al 2003
Morning (Method A)
LANTUS

or LEVEMIR

is
Better than Bedtime
(Method B)
62
ASK-SDNC
ASK-
SDNC
KOMPLIKASI AKUT DIABETES MELLITUS
(Pengalaman Klinik : Tjokroprawiro 1993-2012)
4
KOMA ASIDOSIS ASAM LAKTAT (KAAL)
1 HIPOGLIKEMIA : TRUE, REACTIVE
2 KETOASIDOSIS DIABETIK (KAD)
3
HHS / NKHC / HONK
No. 2 dan No. 3 DISEBUT KRISIS HIPERGLIKEMIA
HHS : Hyperosmolar Hyperglycemic State
NKHC : Non-Ketotic Hyperosmolar Coma
HONK : Hiperosmoler Non Ketotik
63
ASK-SDNC
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).
**) 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)
(Pengalaman Klinik : Tjokroprawiro 1996-2012)
PETUNJUK PRAKTIS TERAPI HIPOGLIKEMIA
DENGAN FORMULA 3-2-1-1
KADAR
GLUKOSA
TERAPI HIPOGLIKEMIA DENGAN
FORMULA 3-2-1-1
GLUKOSA 40%
(mg/dl)
1 FLAKON : 25 ml
Isi 10 g Glukosa
< 30 mg/dl *) : I.V GLUKOSA 40%, BOLUS 3 FLAKON FORMULA - 3
30-50 mg/dl *) : I.V GLUKOSA 40%, BOLUS 2 FLAKON
FORMULA - 2
50-70 mg/dl *) : I.V GLUKOSA 40%, BOLUS 1 FLAKON
FORMULA - 1
70-90 mg/dl **) : FORMULA - 1
I.V GLUKOSA 40%, BOLUS 1 FLAKON
GLUKOSA DARAH DIPERIKSA LAGI 30 MENIT SESUDAH I.V. GLUKOSA 40%
Hindarkan : HONEY MOON PHENOMENA
64
ASK-SDNC
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
65
ASK-SDNC
2 00 - 300 1x 3 x 4
3 00 - 400 2x 3 x 6
4 00 - 500 3x 3 x 8
5 00 - 600 4x 3 x 10
6 00 - 700 5x 3 x 12
RUMUS MINUS SATU
6 Minus 1 = 5
RUMUS KALI DUA
6 Kali 2 = 12
GLUKOSA AWAL DOSIS INSULIN DOSIS RUMATAN
Sebelum R-C (mg/dl) Intravena 4 U/jam Insulin Subkutan (unit)
REGULASI CEPAT INTRAVENA (RCI)
(Pengalaman Klinik : Tjokroprawiro 1987-2012)
(Contoh : Kasus Glukosa Darah 650 mg/dl)
HIPERGLIKEMIA >200 mg/dl
66
ASK-SDNC
2 00 - 300 4 3 x 4
3 00 - 400 6 3 x 6
4 00 - 500 8 3 x 8
5 00 - 600 10 3 x 10
6 00 - 700 12 3 x 12
GLUKOSA AWAL DOSIS INSULIN DOSIS RUMATAN
Sebelum R-C (mg/dl) Subkutan (unit) Insulin Subkutan (unit)
Rumus Kali Dua

6 Kali 2 = 12
REGULASI CEPAT SUBKUTAN (RCS)
(Pengalaman Klinik : Tjokroprawiro 1987-2012)
(Contoh : Kasus Glukosa Darah 650 mg/dl)
HIPERGLIKEMIA >200 mg/dl
67
ASK-SDNC
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)

5
ANTIBIOTIK : HARUS RASIONAL dengan DOSIS ADEKUAT
1 MAINTENANCE : 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 NovoRapid

: 3 x 8-12 U sc (ingat : FORMULA KALI DUA)
4 MAKANAN LUNAK : KARBOHIDRAT KOMPLEKS PER ORAL
Glukosa Darah + 250 mg/dl atau Reduksi Urine +
IDRIV : INSULIN DOSIS RENDAH INTRA VENA
FASE-II
FASE-I
FORMULA KAD :
2 4 18 24 TIME
2 80 30 20 FLUID
(Clinical Experiences and Illustrated : Tjokroprawiro 1991-2012)
TERAPI KETOASIDOSIS DIABETIK (KAD) - REVISI 2010
Koreksi HIPOKALEMIA gunakan FORMULA sbb :

Hati hati pada pasien CKD dan GAGAL JANTUNG
HIPO K: F1, F2, F3, F4 (251005)
*)
IDRIV AMAN pada kasus HIPOKALEMIA
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
BIKARBONAT
: 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
dan sisanya (50 mEq) diberikan dengan drip selama 2 jam

FORMULA : 2,4,18,24Time ; FORMULA : 2,80,30,20Fluid
*)
F4 : 25 meq K
+
, dlm 100 ml RL, drip 5 jam
68
ASK-SDNC
CLINICAL DIAGNOSIS : 1 YES & 3 NO
PROTOCOL FOR DIAGNOSIS AND THERAPY OF HONK or HHS
(Clinical Experiences and Illustrated : Tjokroprawiro 1991-2012)
THERAPY PATHOGENESIS
PRECIPITATING FACTORS
1
2
4
3
5
6
8
7
Thiazide
Glucose Drinks
Infection
Corticosteroid
Beta Blocker
Phenytoin
Cimetidine
Chlorpromazine
PATHOPHYSIOLOGY
l
l
l
Grossly Elevated Glucagon
Relative Insulin Deficiency
Sufficient Insulin to inhibit lipolysis
TETRALOGY HHS (1 YES & 3 NO) : 1 H + 3 NO
1
2
4
3
YES: Glycemia >600 mg/dl
NO: History of DM
NO: Kussmauls Breathing
NO: Ketonuria or
-
-
- +
TETRALOGY HONK :
1 YES & 3 NO
SIMILAR WITH DKA THERAPY
PLASMA Na <150 mEq/l
a
NORMAL SALINE
SOLUTION NaCL 0.45%
PLASMA Na >150 mEq/l b
SUPPORTING FINDINGS
pH > 7.30
Neurological Sign
Prerenal Uremia
Mental Impairment
Severe Dehydration
Age : More than 60 Years Old
1
2
4
3
5
6
Glucose (mg/dl)

18
Osm/l = 2x (Na) +
> 325
5
HHS : HYPERGLYCEMIC HYPEROSMOLAR STATE HONK : HYPEROSMOLAR NON KETOTIK
PENTALOGY HONK : 1 YES, 3 NO, Osmol/l > 325
69
ASK-SDNC
Tx : Kausal (Tipe A atau B, dan Regulasi DM)
Dx : Hiperglikemia plus Anion Gap > 20 mEq
(K + Na) - (Cl + CO
2
) > 20 mEq atau
(Na) - (Cl + CO
2
) > 15 mEq
ISKHEMIA

Infeksi, Shock, Peny. Kardiovaskuler/Angiopati, Gangguan
LFT-RFT , DM + Biguanide, Gg. Oksigenasi : PPOK, dll
ASAM LAKTAT + H
2
O + O
2
BIKARBONAT
KOMA ASIDOSIS ASAM LAKTAT (KAAL)
(Pengalaman Klinik : Tjokroprawiro 1991-2012)
(Tipe A dan Tipe B )
70
(PRIMER : HIPOKSIA)
1. Semua jenis shock
2. Decomp. Cordis
3. Asfiksia
4. Intoksikasi CO
KELAINAN SISTEMIK
1. DM
2. Neoplasia
3. RFT/LFT terganggu
4. Konvulsi
1. Biguanide
2. Salisilat
3. Alkohol (Metanol, Etanol)
4. Glukosa-Alkohol (Sorbitol, dll)
KAAL - Tipe A
KAAL - Tipe B
OBAT
ASK-SDNC
KOMPLIKASI KRONIK DM
(Summarized : Tjokroprawiro 1991-2012)
KULIT : NECROBIOSIS LIPOIDICA DIABETICORUM,
DIABETIC DERMOPATHY, SELULITIS/ GANGRENE
8
INFEKSI : SELULITIS/GANGRENE, ISK, CHOLECYSTITIS, PARU
(TBC), ORAL INFECTION, SEPSIS (GANGREN: 3.8%)
1
MATA : RETINA, LENSA, CILIARY BODY (RETINOPATI: 27.2%)
2
MULUT : XEROSTOMIA, PERIODONTITIS (10-75%)
3
JANTUNG : PIK, IMA (Makrovaskuler), KARDIOMIOPATI (Mikrovaskuler)
4
TRACTUS UROGENETALIS :
NEFROPATI DIABETIK (5.7%)
5
DISFUNGSI EREKSI (DE) : 50.9% 6
SARAF (Lihat slide no. 5) : 51.4%
7
71
ASK-SDNC
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
72
ASK-SDNC
FIVE (5) TIPS for DIABETIC PATIENTS : Tjokroprawiro 1998 2012
FORMULA-5: FIVE GUIDELINES (FOR ED) PRIOR TO SEXUAL INTERCOURSE
PATIENT SHOULD be PHYSICALLY and MENTALLY FIT 2
DURING the D-day of S.I, : DAILY-MEAL SHOULD be LOW-FAT CONSUMPTION 3
AVOID DRUG INDUCED ERECTILE DYSFUNCTION (ED) : SMOKING, Etc 4
BLOOD SUGAR < 200mg/dl and TESTOSTERONE > 400ng/dl (Median 426)
1
SUPPORTING FINDINGS (mmHg/mg/dl) : BP < 130/80, LDL < 100, TG <150
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.
5
USE LUBRICANT (if needed) FOR PENETRATION
S.I. = SEXUAL INTERCOURSE
73
ASK-SDNC
SEPULUH PETUNJUK POLA HIDUP SEHAT
GULOH-SISAR = SINDROMA-10
(Askandar Tjokroprawiro 1995-2012)
Pusat Diabetes dan Nutrisi Surabaya, RSUD Dr. Soetomo FK Universitas Airlangga
G
U
L
O
H
1
2
3
4
5
(GULA) : Pantang Gula bagi DM. Bagi
Non-DM Kurangilah Konsumsi Gula
(asam URAT) : Batasi JAS-BUKKET
(LEMAK) : Batasi TEK-KUK-CS
2

(OBESITAS): Target LP
LP = Lingkar Pinggang
(HIPERTENSI): Untuk Pasien Hipertensi,
Pria < 90 cm
Wanita < 80 cm
Batasi Garam, Ikan Asin, Kacang Asin, dll
S
I
S
A
R
6

7
8
9
10
(SIGARET) : Stop Merokok
Fisik 300 kcal/hr atau Jalan 3 km/hari, atau SIT-UP 50-100 X/hr
(STRESS) : Usahakan Tidur 6-7 Jam Sehari untuk meredakan Stress
(ALKOHOL) : Stop Alkohol
(REGULAR CHECK UP) : Usahakan check up Teratur dan
Konsultasi Ahli, bagi umur > 40 th, setiap 3, 6,12 Bulan
(INAKTIVITAS): Hindarkan Inaktivitas, dan Rutinkanlah Latihan
JAS-BUKKET :
Jerohan, Alkohol, Sarden - Burung Dara, Unggas, Kaldu, Kacang, Emping, Tape
B N I
TeK-KUK-CS2 : Telor, Keju - Kepiting, Udang, Kerang - Cumi, Susu, Santen
B N I
"MABUK" (Mengandung banyak Chromium) : Mrica, Apel, Brokoli, Udang, Kacang-kacangan
Chromium (Cr) Dapat Memperbaiki Kerja Insulin. Ini berarti Cr bermanfaat bagi Penderita Diabetes
B N I
HABIBIE-AWARD CEREMONY Jakarta, 30 November 2006. TVRI Surabaya : TALK SHOW Acara SEMANGGI. 21 September 2011
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
BAGI PASIEN DIABETES (DM) : HINDARKAN SEMUA YANG MANIS, atau SANGAT BATASILAH YANG MANIS TERSEBUT
(LAKSANAKAN HIDUP SEHAT GULOH-SISAR dengan PEDOMAN BNI : BATASI, NIKMATI, IMBANGI)
74
ASK-SDNC
Short and Long Sleep Durations as Risk Factor for T2DM
(Yaggi et al 2006; Summarized : Tjokroprawiro 2006-2012)
TWICE AS LIKELY TO DEVELOP DIABETES
MORE THAN THREE TIMES AS LIKELY TO DEVELOP DIABETES
Men with Short Sleep Duration (5 h Sleep per Night) -
Men with Long Sleep Duration (> 8 h Sleep per Night)
-
THE EFFECTS OF SLEEP ON DM COULD BE MEDIATED VIA
ENDOGENOUS TESTOSTERON LEVELS
-
75
ASK-SDNC
LIFESTYLE RELATED DISEASES AND THE STAGING OF OBESITY
(Clinical Experiences and Illustrated : Tjokroprawiro 2005-2012)
LRD
S
**RISKS: OBESITY, INSULIN RESISTANCE, the METS, CMR as TIME BOMB PRECLINICAL DISEASES
ATP-III 2001 - Criteria
Indonesian
Healthy Lifestyle
STAGE 0
Westernized
Unhealthy Lifestyle
STAGE 1
Abdominal Obesity
(Adult & Adolescent)
STAGE 2
Preclinical : the MetS, CMR
Pre-DM : Adult & Adol.*
)

STAGE 3
4 BLOOD PRESSURE
> 130/85 mmHg
5 FASTING PLASMA GLUCOSE
> 100 mg/dl
2 TRIGLYCERIDE
> 150 mg/dl
IDF 2005 - Criteria
GULOH*** CISAR***
3 from 5
STAGE 4
Clinical CMD
S
: CAD,
STROKE, T2DM**** (Adult & Adol.)
3 HDL-CHOL
< 40 mg/dl
< 50 mg/dl
o
+
o
***TLC
S
: Therapeutic Lifestyle Changes
WAIST CIRCUMFERENCE = WC 1
INDONESIA : > 90; > 80 JAPAN : > 85; > 90
METFORMIN
STAGE - 3 (the MetS & CMR ) will be the "TIME-BOMB PRECLINICAL DISEASES by 2020?
WC >90 or >80
plus
2 from no. 25
CMR: Cardio Metabolic Risk
CMD: Cardio Metabolic Disease
*ELDERLY MetS/T2DM
**LRD
S
: Lifestyle Related Diseases
****Adult & Adolescent T2DM
*ADOLESCENT MetS/T2DM
76
ASK-SDNC
METABOLIC SYNDROME
(IDF 2005)
WC (INA) : > 90 cm () and > 80 cm ()
Plus 2 from the 4 above mentioned Factors
:
IDF = International Diabetes Federation, INA = Indonesia, AMI = Acute Miocardial Infarction, CHD = Coronary Heart Disease
The Prevalence of the MetS in Surabaya 2005
Non DM : 32.0%
Nave DM : 59.0%
DM After Treatment : 43.3%
DM Obesity : 81.7%
MALE PREVALENCE : 45 x Fold than FEMALE
( Preliminary Survey )
WAIST CIRCUMFERENCE : WC
INDONESIA : >90; >80 JAPAN : > 85; > 90
4 FASTING GLUCOSE
> 100 mg/dl
Indonesian
Healthy Lifestyle
STAGE 0
Westernized
Unhealthy Lifestyle
STAGE 1
Abdominal Obesity
(Adult & Adolescent)
STAGE 2
Pre-DM - the MetS*, CMR
Preclinical : Adult & Adol.*
)
STAGE 3 STAGE 4
Clinical CMD
S
: CAD,
STROKE, T2DM**** (Adult & Adol.)
THE STAGING of OBESITY and the PREVALENCE of METS in SURABAYA
(Tjokroprawiro 2005-2012)
SURABAYA DIABETES AND NUTRITION CENTER, Dr. SOETOMO TEACHING HOSPITAL - FACULTY OF MEDICINE AIRLANGGA UNIVERSITY
1 TRIGLYCERIDE
> 150 mg/dl
2 HDL-CHOL
< 40 mg/dl
< 50 mg/dl
o
+
o
3 BLOOD PRESSURE
> 130/85 mmHg
2 INSULIN RESISTANCE, PRE-DM, T2DM
3 ATHEROGENIC DYSLIPIDEMIA
4
RAISED BLOOD PRESSURE
5 PROINFLAMMATORY STATE
6 HYPERURICEMIA
7 PROTHROMBOTIC STATE
8 VASCULAR ABNORMALITIES
9 ADRENAL INCIDENTALOMA
1 VISCERAL FAT
FATTY ACID DEPOSITION (FATTY LIVER) 10
HYPOGONADISM (+TESTOSTERONE) 11
THE METABOLIC SYNDROME
11 FEATURES OF
77
ASK-SDNC
MYSTERY OF FAT CELL : 67 BIOLOGIC SUBSTANCES
(Illustrated : Tjokroprawiro 1997-2012)
Adiponectin 12
TF 10
IGT - T2DM
+ LPL & | FFA
VCAM-1 |
| TG
+ HDL
| LDL3
| Fribrinogen
| PAI-1
| F VII
INSULIN
RESISTANCE
GLUT-4
EXPRESSION
+ Body Weight
INSULIN
SECRETION
| Cell
| STAT-3
+ IRS-1
+ IRTK
4
Renal Renin (AII)
1
+ NPY, + AGRP
Inhibits Bone Formation
(Central Relay)
2
3
Estrogen 1
Ob Protein (LEPTIN) 2
Agouti Related
Protein (AgRP)
3
TNFo 4
5
IL-1|, IL-6
Ob Protein (LEPTIN)
6
AII
7
ASP, Adipsin, Factors : B, C3
Adhesive Proteins 8
PAI-1
(Esp. Omental Fat)
9
Resistin 11
VISFATIN 13
HSL, DGAT 14
Perilipsins 16
Lipotransin 15
FFAs 17
MIF 18
TGF|, VEGF,
IGF-1, IGF BP
19
Eicosanoids,
PGE
2
, PGI
2

20
ACTH, Cortisol 21
11 |HSD-1 22
Aromatase 23
Metallothionein 24
RBP4 25
ApoE,LPL,ICAL,CETP,PLTP 26
NO 27
PC-1 28
Aquaporins 29
FIAF 30
Hyperuricemia
Necrosis
Apoptosis
Proliferative Effect
Hypertension
ESM-1 34
Monobutyrin
32
Galectin-12
33
Apelin
35
FATPI 36
aP
2
37
UCP, P450, ZAG 38
Complement System Products

39
Macrophage CSF 40
Macrophage Inflammatory Protein 1o

41
Lactate, Lysophospholipid, Adenosine, Glutamine
31
42
VISFATIN
ADMA
OMENTIN
A-FABP
Predictor of the MetS
FAT CELL
VASPIN 43
Chemerin 44
LCN2 45 STAMP2
78
ASK-SDNC
IL-6
IL-1|
RESISTIN
TNF-o
MCP-1
JNK1
NFkB
IR
IR, the METS & CMR the CMDs
CHRONIC LOW GRADE INFLAMMATION
INFLAMMED ADIPOSE TISSUE
|ADMA
| VISFATIN
+ OMENTIN
|CHEMERIN
(Wellen et al 2003, Takahashi et al 2008, Provided : Tjokroprawiro 2006-2012)
OBESITY and Its CONSEQUENCES : IR, the METS, CMR to CMDs
M
E
T
A
B
O
L
I
C

S
Y
N
D
R
O
M
E
I
N
S
U
L
I
N

R
E
S
I
S
T
A
N
C
E
L
E
P
T
I
N

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

L
I
V
E
R
NORMAL ADIPOCYTE
ADIPOCYTE
PREADIPOCYTE
|FETUIN-A
*)
|LCN-2
ADIPOCYTE DYSFUNCTION
MCP-1
Angiogenesis
Leptin
VEGF
Endothelial
Cell
TNF-o
FFA
FROM NORMAL (STAGE-0) TO OBESITY STAGE-3
MACROPHAGE INFLAMMATORY PATHWAY
| MCP-1,
| PAI-1, |FFA
Physical Stress/Oxidative
Damage to Endothelium?
WEIGHT GAIN
LRD
S
= Lifestyle Related Diseases
HSP70

/

HSP72

| LEPTIN
|A-FABP
| VASPIN

+ Apn
+STAMP2
WEIGHT GAIN
*)
FETUIN-A = Hepatic Secretory Protein
NAFLD NASH / CIRRHOSIS
BAFF = B-cell Activating Factor
MACROPHAGE RECRUITMENT
PREADIPOCYTE MACROPHAGE
DIO
Apn = Adiponectin
VASPIN = Visceral Adipose tissuederived Serine Protease INhibitor
CMR : Cardio Metabolic Risk
CMDs : Cardio Metabolic Diseases
LCN-2 : Lipocalin-2
STAMP2 : Six TrAns Membrane Protein of prostate 2
ATM : Adipose Tissue Macrophage
DIO : Diet Induced Obesity
ATM
79
| TNFo, | IL-6,
| IL-1|, | CRP
| CERAMIDE
MACROPHAGE
RECRUITMENT
|BAFF

ASK-SDNC
The 8 CORE STAFFS of SDNC 1986 - 2012
PLUS 52 EXPERT MEMBERS FROM MULTIPLE DISCIPLINES
SURABAYA DIABETES AND NUTRITION CENTER (SDNC)
Dr. SOETOMO TEACHING HOSPITAL
FACULTY OF MEDICINE AIRLANGGA UNIVERSITY SURABAYA
Askandar Tj.
Jongky Hendro
Hermina Novida
SDU 22
NOS 2
SUMETSU 8
MECARSU 8
SOBU 4
OBELAR
SDW
PEPIC
DIAPIC

* EDUCATION
* HEALTH SERVICE
* INVESTIGATION:
WDF, GIANT, Etc
Ari Sutjahjo Agung Pranoto Sri Murtiwi Soebagijo Adi Sony Wibisono
SUMETSU-8 MECARSU-8 SOBU-4
18-19 FEBRUARY 2012
Alm.
Hendromartono
Alm.
Soeharjono
80