01. diabetes mellitus part 2 - prof.askandar

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201217-928-M

SURABAYA, 5 MARCH 2012

GARIS BESAR KULIAH UNTUK MAHASISWA SEMESTER-6

DIABETES MELLITUS-IIFAKULTAS KEDOKTERAN UNIVERSITAS AIRLANGGA, SURABAYA

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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 HOSPITALFACULTY OF MEDICINE AIRLANGGA UNIVERSITY, SURABAYA

Division of Endocrinology and Metabolism – Dept. of Internal Medicine

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(Summarized : Tjokroprawiro 1996-2012)MAP OF ORAL ANTI DIABETES (OAD) IN DAILY PRACTICE

III INTESTINAL ENZYME INHIBITORS -Glucosidase Inhibitor: Acarbose

-Amylase Inhibitor: Tendamistase

1

2

V FIXED DOSE COMBINATION (FDC) TYPESGlucovance® , Amaryl-M®, Galvusmet®, Janumet® , ACTOplusmet®, Duet act®

4

II

- Metformin , Metformin XR (Glucophage® XR) , 3-Guanidinopropionic-Acid

1

3 BIGUANIDE :

ab

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*) Withdrawn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®)

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I INSULIN SECRETAGOGUES

- NON-SUs (Metaglinides : Nateglinide, Repaglinide)

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

IV INCRETIN-ENHANCERS DPP-4 INHIBITORSSita-, Vilda-, Saxa-, Lina-, Alo-, Dena-,Duto-, Melo-, Teneli-gliptin, SYR-322, TA-666

VI OTHER SPECIFIC (OS) TYPESASP1941, BI 10773 , Canagliflozin, Dapagliflozin, Seragliflozin, Remogliflozin, AVE-2268, KGT-1681, LX-4211, TS-033, YM-543

3 Oxphos-Blocker FBPase – Inhibitor4 INCB13739 (11HSD1–inhibitor)5

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

2 Glucokinase Activator (GKA): MTBL1, MK-0941.

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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 pernahsuntik insulin : kebutuhan insulin kurang dari 20 unit per hari

4 BELUM PERNAH MENGIDAP KETO ASIDOSIS DIABETIK

J1 = Jumlah J2 = Jadwal J3 = Jenis

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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, misalnyaActrapid (Short-Action = Kerja Pendek, identik dengan Insulin Reguler), semua dari Novo Industries, ~ Humalog (Eli Lily)Ada juga Insulatard (identik dengan NPH) dan Mixtard (campuran shortdan long acting insulin dengan perbandingan 30:70), keduanya dari Novo.

3 INSULIN MANUSIA = Human Insulin (HM = Human Monocomponent).

(Summarized : Tjokroprawiro, 2003-2012)(Summarized : Tjokroprawiro, 2003-2012)

Macam Insulin dalam Praktek Sehari-hariMacam 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

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PHARMACOKINETICS OF HUMAN INSULIN AND INSULIN ANALOGUES(Summarized : Tjokroprawiro 2008-2012)

INTERMEDIATE-ACTING NPH Lente

1-3 hrs1-3 hrs

5-74-8

13-1613-20

INSULIN PREPARATION ONSET OF ACTION

PEAK OF ACTION (HRS)

DURATION OF ACTION (HRS)

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RAPID ACTING **) SHORT ACTING *) Regular Human Insulin = RHI*)

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

30-60 mins5-15 mins5-15 mins5-15 mins

2-41-21-21-2

6-83-43-43-4

LONG-ACTING Insulin Glargine (lantus) Detemir (Levemir) Ultralente Ultra-long-acting insulin DEGLUDEC

1-3 hrs1-3 hrs2-4 hrs

2424

22-24 hrs

No PeakNo Peak

8-14

10 mins10 mins

1-41-4

10-2016-20

PREMIXED Insulin Lispro 75/25 (Humalog Mix25) Insulin Aspart 70/30 (NovoMix)

: New Gen. Basal Ins. that forms Soloble Hexamers upon SC inj.

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INDIKASI INJEKSI INSULININDIKASI INJEKSI INSULIN(KONSENSUS PERKENI 2011)(KONSENSUS PERKENI 2011)

1 PENURUNAN BERAT BADAN YANG CEPAT2 HIPERGLIKEMIA BERAT YANG DISERTAI KETOSIS3 KETOASIDOSIS DIABETIK (KAD)4 HIPERGLIKEMIA HIPEROSMOLAR NON KETOTIK (K-HONK)

5 HIPERGLIKEMIA DENGAN ASIDOSIS LAKTAT (KAAL)6 Gagal dengan kombinasi OHO dosis optimal7 Stres berat (infeksi sistemik, operasi besar, IMA, stroke)8 Kehamilan dengan DM/Diabetes Mellitus Gestasional (GDM)

yang tidak terkendali dengan Perencanaan Makan9 Gangguan Fungsi Ginjal dan atau Hati yang berat

10 Kontraindikasi dan atau alergi terhadap OHO

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Lihat Slide no 50 dan 51

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(Clinical Experiences : Tjokroprawiro 1993-2012)

INSULIN INJECTION SITES : CLOCK WISE ROTATION

Sites of SC Insulin Injection should be at the Healthy AreasDistance between the Two SITES of Injection : Minimally 2.5 cm

46-60 31-45

61-75 16-30

76-90 1-15

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PRACTICAL TOOL FOR INSULIN RESISTANCE AND -CELL FUNCTIONPRACTICAL TOOL FOR INSULIN RESISTANCE AND -CELL FUNCTION

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

HOMA-R and HOMA-BUseful in Daily Practice

:1

2 FOLLOW-UP OF TREATMENT

RATIONALE TREATMENT

HOMA-B-Cell Function : (N: 70–150%)20 x Fasting Insulin (U/ml)

FPG (mmol/l) – 3.5

HOMA-RInsulin Resistance

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

22.5

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PREVALENCE OF IR IN SELECTED METABOLIC DISORDERSPREVALENCE OF IR IN SELECTED METABOLIC DISORDERS(Bonora 1998, Summarized and Illustrated : Tjokroprawiro 2006-2012)(Bonora 1998, Summarized and Illustrated : Tjokroprawiro 2006-2012)

4 HYPERTENSION

IFG & IGT2

URIC ACID 7

LOW HDL-C 6

3 The MetS

HYPER-CHOL 8

1st Phase and IR in LiverIFG = Impaired Fasting Glucose

1st Phase and IR in PeripheryIGT = Impaired Glucose Tolerance

IR = INSULIN RESISTANCEIR = INSULIN RESISTANCE

DISORDERSDISORDERSMETABOLICMETABOLIC

SEQUENTIALSEQUENTIALPREVALENCES OF IRPREVALENCES OF IR

in

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HYPERTRIGLYCERIDAEMIA

5

T2DM1

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COMBINED THERAPY OF ORAL AGENT AND INSULIN (CTOI)Terapi Kombinasi Tablet Oral dan Insulin (TKOI)


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 %

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FORMULA FORMULAFORMULA

50

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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)


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ARGININE ↑BUN( N < 20)

ARGINASE

KTT & OTHERPROTEIN CKD

Lantus® or Levemir®

Apidra® or Novorapid®

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(Summarized – Illustrated : Tjokroprawiro 2009-2012)

The 21 ENDOCARDIOMETABOLIC PROPERTIES OF INSULIN

GLYCEMIC CONTROLGLYCEMIC CONTROL

A1CA1C1

LIPOLYSIS via HSL(Hormone Sensitive Lipase)18

ADMA IN PLASMAADMA IN PLASMAAND IN ENDOTHELIUMAND IN ENDOTHELIUM

14

BONE ANABOLICBONE ANABOLIC(( OSTEOGENESIS) OSTEOGENESIS)

13

PLASMA ARGINASE( UREA ~ BUN)

12

RESTORELH, FSH, TESTOSTERON

19

VASPIN mRNA IS INCREASED WITH INSULIN INJECTION IN SEVERE INSULIN RESISTANCE20

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GLYCOGEN SYNTHESISGLYCOGEN SYNTHESIS15

PROTEIN SYNTHESISPROTEIN SYNTHESIS16

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

3

PROFIBRINOLYSIS (PROFIBRINOLYSIS ( PAI-I) PAI-I)4

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

8

ANTI-PLATELET (ANTI-PLATELET ( c-AMP) c-AMP)6

VASODILATATIONVASODILATATION(( NO, NO, eNOS) eNOS)

5

ANTI-THROMBOSISANTI-THROMBOSIS (( T TISSUE ISSUE FFACTORACTOR)

7

CARDIO-PROTECTIONCARDIO-PROTECTION (ANIMALS, HUMAN(ANIMALS, HUMAN)

2

ANTI-INFLAMMATION

IB, NFB, TNF,ICAM-1, MCP-1,CRP

9

ANTI-OXIDANT (ANTI-OXIDANT ( ROS) ROS)10

GROWTH DEVELOPMENTGROWTH DEVELOPMENT

HYPOTHETICAL WAY TOHYPOTHETICAL WAY TO TUMORTUMORVIA IGFVIA IGF11 –– RECEPTOR ?RECEPTOR ?

11

LIPOGENESIS via LIPOGENESIS via LPL LPL(Lipoprotein Lipase)(Lipoprotein Lipase)

17

21 INSULINPROPERTIES

HSP 70 / HSP 72HSP 70 / HSP 72(For Wound Healing, (For Wound Healing, EEtc)tc)

21

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NUTRITION IN DIABETES MELLITUSClinical Experiences : Tjokroprawiro 1978-2012

DIABETIC DIETS

MEDICAL NUTRITION THERAPY

(MNT) P.E.N. P-P.E.N.

PAR ENTERAL NUTRITION ( "SONDE" )

E1 , E2 , E3 , E4 , E5 , E6

:08.00

:14.00

:20.00

INSULIN

E1

E3

E5

:11.00

:17.00

:23.00

NO INSULIN

E2

E4

E6

ORAL NUTRITIONSince 1978

ENTERAL NUTRITIONSince 1995

PAR ENTERAL NUTRITION = P.E.N.

Since 1993

PERIPHERAL PPAR PENTERAL ENUTRITION N

Ten Principlesof

P-P.E.N. in DM

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21 Types of Diabetic Diets

at Dr. Soetomo Hospital

From the B-Diet 1978to

21 Types of Diabetic Diets(2004)

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NUTRITION IN DIABETES MELLITUSClinical Experiences : Tjokroprawiro 1978-2012

PAR ENTERAL NUTRITION = P.E.N.Since 1993

P.E.N. P-P.E.N.

PAR ENTERAL NUTRITION

PERIPHERAL PPAR PENTERAL ENUTRITION N

TEN PRINCIPLESof

P-P.E.N. in DM

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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 = B2, dg tetesan 14 tt/mnt.Contoh : Cairan B , Infus 500ml Martos 10% = B1 14 tt/mnt

Jadi : Cairan A : 500 ml NaCl 3% 7 tt/mnt (500 ml/24 jam) dan CairanB : 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.

Bila Osmol >1000

di Cabang dengan Cairan B Isotonis (275-300 mOsm/l) atauHipertonis-Ringan (300-600 mOsm/l)

A (Misalnya Cairan A : 500ml NaCl 3% (1200 mOsm/l) 7 tt/mnt

Infus Cabang : Cairan A dan Cairan BContoh : Cairan Cairan A > 1000 mOsm/l, Cairan B 275-600 mOsm/l

1 LARUTAN NPE : OSMOLARITAS IDEAL< 600 Maksimal-1000 mOsm/L

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2 PEDOMAN JUMLAH CAIRAN : + 30 ml/kg BB; ENERGI : + 30 kcal/kg BBKarbohidrat (Glukosa) minimal 100-150 g/hariTambahan : - 300 ml untuk kenaikan 1oC

- 300 ml untuk tambahan cairan Intra Seluler (Anabolik)

LaksanakanRegulasi CepatLebih 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 NPETUJUAN : GLUKOSA < 200 mg/dl (Agar Fungsi Lekosit Normal)

SEPULUH PETUNJUK NPE PERIFER-DIABETIK(Pengalaman Klinik : Tjokroprawiro 1993-2012)

(Continued)

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5 KALORI HARI 1-3 : BASAL (400-800 Kcal)Naik Pelan, Turun Pelan, Stop Pelan (Start Slow, Go Slow, SStop 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


6 GLUKOSA 5% atau MALTOSA 10%; usahakan minimal 100-150 g/hari

Glukosa 5% atau Maltosa 10% " aman", Beri Insulin + 10 u dalam Botol Infus1 unit Insulin Dalam Botol per 5g Maltosa; 1 unit untuk setiap 2.5g GlukosaDosis 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)

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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 ENERGIMELAINKAN UNTUK REGENERASI DAN SINTESIS PROTEIN VISCERAL


10 Bila no. 1 s/d no. 9 sudah dipenuhi, laksanakan NPE + FLUID THERAPY :

GLUCOSE , EAA – BCAANa+, K+, Cl– Ca++, P, Mg++ Zn+ RATIONALE

MAINTENANCE FLUID THERAPYSHOULD CONTAIN

ALE : Asam Lemak Essensial

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TEN GUIDELINES OF PERIPHERAL P.E.N.(Clinical Experiences : Tjokroprawiro 1993-2012)

START SLOW GO SLOW STOP SLOW

MAINTENANCE FLUID THERAPYInsulin Dose : Formula 5-1 or 2.5-1

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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 CONTROLWITH 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

9SHOULD BE CONTINUOUS INFUSION 500 ml/ 24 h

FAT EMULSION : 10 ADVANTAGES

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TARGET PENGENDALIAN DIABETES MELLITUSTARGET PENGENDALIAN DIABETES MELLITUS(KONSENSUS PERKENI-2011)(KONSENSUS PERKENI-2011)

Keterangan : KV = KARDIOVASKULAR, PP = POST PRANDIAL,

IMT = INDEX MASSA TUBUH

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IMT (kg/m2) 18.5 - <23 18.5 - <23

Tekanan Darah Sistolik (mmHg) < 130 <130

HbA1c (%) < 7 < 7

Kolesterol LDL (mg/dl) < 100 < 70

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

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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)(Clinical Experiences : Tjokroprawiro 2003-2012)

PRANDIAL APIDRA or NOVORAPID®

AMARYL-M® or GLUCOVANCE®


LANTUS or LEVEMIR®

6-30 u sc

AMARYL-M® or GLUCOVANCE®

OPTIONAL THERAPYMETFORMIN

GLIPTIN CLASS: DPP4-Is

Fritsche et al 2003

Morning (Method – A) LANTUS® or LEVEMIR®

is Better than Bedtime

(Method – B)

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

(Clinical Experiences : Tjokroprawiro 2003-2012)(Clinical Experiences : Tjokroprawiro 2003-2012)

OAD : AMARYL-M® or GLUCOVANCE®, ADMINISTERED AFTER MEALS

LANTUSor LEVEMIR®

6-30 u sc AMARYL-M® or GLUCOVANCE®



OADS

AMARYL-M® AMARYL-M® or GLUCOVANCE®

OPTIONAL TxMETFORMIN

GLIPTIN CLASS : DPP4-Is

Fritsche et al 2003

Morning (Method – A) LANTUS® or LEVEMIR®

is Better than Bedtime

(Method – B)

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ASK-SDNCASK-SDNC

KOMPLIKASI AKUT DIABETES MELLITUSKOMPLIKASI AKUT DIABETES MELLITUS(Pengalaman Klinik : Tjokroprawiro 1993-2012)(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 StateNKHC : Non-Ketotic Hyperosmolar ComaHONK : Hiperosmoler Non Ketotik

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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 HIPOGLIKEMIADENGAN FORMULA 3-2-1-1

KADAR GLUKOSA TERAPI HIPOGLIKEMIA DENGAN

FORMULA 3-2-1-1

GLUKOSA 40%

(mg/dl)1 FLAKON : 25 mlIsi 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 - 250-70 mg/dl *) : I.V GLUKOSA 40%, BOLUS 1 FLAKON FORMULA - 170-90 mg/dl **) : FORMULA - 1I.V GLUKOSA 40%, BOLUS 1 FLAKON

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

Hindarkan : HONEY MOON PHENOMENA

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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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2 00 - 300 1x 3 x 43 00 - 400 2x 3 x 64 00 - 500 3x 3 x 85 00 - 600 4x 3 x 106 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 RUMATANSebelum R-C (mg/dl) Intravena ã 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/dl66

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2 00 - 300 4 3 x 43 00 - 400 6 3 x 64 00 - 500 8 3 x 85 00 - 600 10 3 x 106 00 - 700 12 3 x 12

GLUKOSA AWAL DOSIS INSULIN DOSIS RUMATANSebelum 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/dl67

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1 REHIDRASI : NaCl 0.9% atau RL, 2 L / 2 jam pertama, lalu 80 tt/mselama 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 TIME2 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 INFUSBIKARBONAT

: 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 : 2,4,18,24–Time ; FORMULA : 2,80,30,20–Fluid *) F4 : 25 meq K+, dlm 100 ml RL, drip 5 jam

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CLINICAL DIAGNOSIS : 1 YES & 3 NO

PROTOCOL FOR DIAGNOSIS AND THERAPY OF HONK or HHS(Clinical Experiences and Illustrated : Tjokroprawiro 1991-2012)

THERAPYPATHOGENESIS

PRECIPITATING FACTORS

12

43

56

87

ThiazideGlucose DrinksInfectionCorticosteroidBeta BlockerPhenytoinCimetidineChlorpromazine

PATHOPHYSIOLOGY

Grossly Elevated GlucagonRelative Insulin DeficiencySufficient Insulin to inhibit lipolysis

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

12

43

YES: Glycemia >600 mg/dl NO: History of DMNO: Kussmaul’s Breathing NO: Ketonuria or

--

- +

TETRALOGY HONK : 1 YES & 3 NO

SIMILAR WITH DKA THERAPY

PLASMA Na <150 mEq/la

NORMAL SALINE

SOLUTION NaCL 0.45%

PLASMA Na >150 mEq/lb

SUPPORTING FINDINGS

pH > 7.30Neurological Sign Prerenal UremiaMental Impairment Severe DehydrationAge : More than 60 Years Old

12

43

56

Glucose (mg/dl) 18

Osm/l = 2x (Na) + > 3255

HHS : HYPERGLYCEMIC HYPEROSMOLAR STATE HONK : HYPEROSMOLAR NON KETOTIK

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

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Tx : Kausal (Tipe A atau B, dan Regulasi DM)

Dx : Hiperglikemia plus Anion Gap > 20 mEq

(K + Na) - (Cl + CO2) > 20 mEq atau

(Na) - (Cl + CO2) > 15 mEq

ISKHEMIA

Infeksi, Shock, Peny. Kardiovaskuler/Angiopati, GangguanLFT-RFT , DM + Biguanide, Gg. Oksigenasi : PPOK, dll

ASAM LAKTAT + H2O + O2 BIKARBONAT

KOMA ASIDOSIS ASAM LAKTAT (KAAL)

(Pengalaman Klinik : Tjokroprawiro 1991-2012)(Tipe A dan Tipe B )

70

(PRIMER : HIPOKSIA)1. Semua jenis shock2. Decomp. Cordis3. Asfiksia4. Intoksikasi CO

KELAINAN SISTEMIK1. DM2. Neoplasia3. RFT/LFT terganggu4. Konvulsi

1. Biguanide2. Salisilat3. 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

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KLASFIKASI IMPOTENSI DIABETIKSekarang 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

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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)1SUPPORTING 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

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SEPULUH PETUNJUK POLA HIDUP SEHATGULOH-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-CS2

(OBESITAS): Target LPLP = Lingkar Pinggang(HIPERTENSI): Untuk Pasien Hipertensi,

Pria < 90 cmWanita < 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 danKonsultasi 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-BKTKW – 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)

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Short and Long Sleep Durations as Risk Factor for T2DMShort and Long Sleep Durations as Risk Factor for T2DM(Yaggi et al 2006; Summarized : Tjokroprawiro 2006-2012)(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 VIAENDOGENOUS TESTOSTERON LEVELS

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LIFESTYLE RELATED DISEASES AND THE STAGING OF OBESITY(Clinical Experiences and Illustrated : Tjokroprawiro 2005-2012)

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

ATP-III 2001 - Criteria

IndonesianIndonesianHealthy LifestyleHealthy Lifestyle

STAGESTAGE –– 0 0““Westernized”Westernized”

Unhealthy LifestyleUnhealthy Lifestyle

STAGESTAGE –– 11Abdominal ObesitAbdominal Obesityy(Adult & Adolescent)(Adult & Adolescent)

STAGESTAGE –– 22PrePreccliniliniccalal : : the the MetSMetS, CMR, CMR

Pre-DM : Adult & Adol.Pre-DM : Adult & Adol.**))

STAGESTAGE –– 33

4 BLOOD PRESSURE

> 130/85 mmHg

5 FASTING PLASMA GLUCOSE

> 100 mg/dl

2 TRIGLYCERIDE

> 150 mg/dl

IDF 2005 - CriteriaGULOH*** CISAR***

3 from 5

STAGESTAGE –– 44Clinical CMDClinical CMDSS : CAD, : CAD,

STROKE, T2DMSTROKE, T2DM******** (Adult & Adol.) (Adult & Adol.)

3 HDL-CHOL

< 40 mg/dl < 50 mg/dlo+o

***TLCS : Therapeutic Lifestyle Changes

WAIST CIRCUMFERENCE = WC1INDONESIA : ♂ > 90; ♀ > 80 JAPAN : ♂ > 85; ♀ > 90

METFORMIN

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

WC >90 or >80plus

2 from no. 2–5

CMR: Cardio Metabolic Risk

CMD: Cardio Metabolic Disease

*ELDERLY MetS/T2DM

**LRDS : Lifestyle Related Diseases

****Adult & Adolescent T2DM

*ADOLESCENT MetS/T2DM

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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%Naïve DM : 59.0%

DM After Treatment : 43.3%DM – Obesity : 81.7%

MALE PREVALENCE : 4–5 x Fold than FEMALE

( Preliminary Survey ) WAIST CIRCUMFERENCE : WCINDONESIA : ♂ >90; ♀ >80 JAPAN : ♂ > 85; ♀ > 90

4 FASTING GLUCOSE

> 100 mg/dl

IndonesianIndonesianHealthy LifestyleHealthy Lifestyle

STAGESTAGE –– 0 0““Westernized”Westernized”

Unhealthy LifestyleUnhealthy Lifestyle

STAGESTAGE –– 11Abdominal ObesitAbdominal Obesityy(Adult & Adolescent)(Adult & Adolescent)

STAGESTAGE –– 22

Pre-DM -Pre-DM - the the MetSMetS*, CMR*, CMR

PrePreccliniliniccalal : : Adult & Adol.Adult & Adol.**))

STAGESTAGE –– 33 STAGESTAGE –– 44Clinical CMDClinical CMDSS: CAD, : CAD,

SSTROKETROKE, T2DM, T2DM******** (Adult & Adol.) (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/dlo+o

3 BLOOD PRESSURE

> 130/85 mmHg

2 INSULIN RESISTANCE, PRE-DM, T2DM

3 ATHEROGENIC DYSLIPIDEMIA

4 RAISED BLOOD PRESSURE

5 PROINFLAMMATORY STATE

6 HYPERURICEMIA7 PROTHROMBOTIC STATE8 VASCULAR ABNORMALITIES9 ADRENAL INCIDENTALOMA

1 VISCERAL FAT

FATTY ACID DEPOSITION (FATTY LIVER)10

HYPOGONADISM (TESTOSTERONE)11

THE METABOLIC SYNDROME11 FEATURES OF

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MYSTERY OF FAT CELL : 67 BIOLOGIC SUBSTANCES(Illustrated : Tjokroprawiro 1997-2012)

Adiponectin 12

TF10IGT - T2DM

LPL & FFA

VCAM-1

TG HDL LDL3

Fribrinogen PAI-1 F VII

INSULINRESISTANCE

GLUT-4EXPRESSION

Body Weight

INSULINSECRETION

Cell STAT-3

IRS-1 IRTK

4

Renal Renin (AII)1

NPY, AGRP

Inhibits Bone Formation(Central Relay)

2

3

Estrogen1

Ob Protein (LEPTIN)2

Agouti RelatedProtein (AgRP)

3

TNF4

5IL-1, IL-6

Ob Protein (LEPTIN)

6

AII7

ASP, Adipsin, Factors : B, C3

Adhesive Proteins8

PAI-1(Esp. Omental Fat)

9Resistin 11

VISFATIN 13

HSL, DGAT 14

Perilipsins 16

Lipotransin 15

FFAs 17

MIF 18

TGF, VEGF,IGF-1, IGF BP 19

Eicosanoids,PGE2, PGI2

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

NecrosisApoptosisProliferative Effect

Hypertension

ESM-134

Monobutyrin32Galectin-1233

Apelin35FATPI36

aP237UCP, P450, ZAG38 Complement System Products39Macrophage CSF40 Macrophage Inflammatory Protein 141

Lactate, Lysophospholipid, Adenosine, Glutamine31

42VISFATINADMA

OMENTINA-FABP

Predictor of the MetS

FAT CELLFAT CELL

VASPIN43Chemerin44

LCN245 STAMP2

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IL-6IL-1

RESISTINTNF-

MCP-1

JNK1NFB

IR

IR, the METS & CMR – the CMDs CHRONIC LOW GRADE INFLAMMATION

INFLAMMED ADIPOSE TISSUE

ADMA

VISFATIN

OMENTINOMENTIN

CCHEMERINHEMERIN

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

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

METABOLIC

SYNDROME

INSULIN

RESISTANCE

LEPTIN

RESISTANCE

NONALCOHOLICFATTY LIVERNORMAL ADIPOCYTE

ADIPOCYTE

PREADIPOCYTE

FETUIN-AFETUIN-A*)*)

LCN-2

ADIPOCYTE DYSFUNCTION

MCP-1

Angiogenesis

LeptinVEGF

EndothelialCell

TNF-

FFA

FROM NORMAL (STAGE-0) TO OBESITY STAGE-3

MACROPHAGE – INFLAMMATORY PATHWAY

MCP-1, PAI-1, FFA

Physical Stress/OxidativeDamage to Endothelium?

WEIGHT GAIN

LRDS = Lifestyle Related Diseases HSP70HSP70 // HSPHSP7272

LEPTIN

A-FABPA-FABP

VASPINVASPIN

– ApnApnSTAMP2STAMP2WEIGHT GAIN

*) FETUIN-A = Hepatic Secretory Protein

NAFLD → NASH / CIRRHOSIS

BAFF = B-cell Activating Factor

MACROPHAGE RECRUITMENTPREADIPOCYTE MACROPHAGE

DIO

Apn = Adiponectin

VASPIN = Visceral Adipose tissue–derived 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

TNF, IL-6, IL-1, CRP

CERAMIDE

MACROPHAGERECRUITMENT

BAFFBAFF

ASK-SDNC

The 8 CORE STAFFS of SDNC 1986 - 2012PLUS 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

SDWPEPICDIAPIC

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

Ari Sutjahjo Agung Pranoto Sri Murtiwi Soebagijo Adi Sony Wibisono

SUMETSU-8 MECARSU-8 SOBU-418-19 FEBRUARY 2012

Alm. Hendromartono

Alm. Soeharjono

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01. diabetes mellitus part 2 - prof.askandar

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