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DIABETES MELLITUS

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SEJARAH
1550 th SM : Penyakit atau "Sindroma Diabetes", mulai dikenal di
Mesir 1550 SM (The Egyptian Papyrus Ebers)

200 th SM : ARETAEUS (Greek Physician) : Diabetes berarti

SIPHON = Flow-Through = Run-through, mengalir
terus. Sehabis minum banyak, diikuti kencing banyak.
Mellitus : madu, manis.
Diabetes Mellitus = Kencing manis.
Th. 1674 : Thomas Willis (Inggris), rasa manis pada urine
(Abad 5-6 rasa manis ini sudah pernah dilaporkan oleh
Dokter Indian).

Th. 1869 : Paul Langerhans (Jerman) : timbunan Glukosa dalam

Hepar sbg Glikogen, dan Hiperglikemia Akut akibat
perusakan Medulla Oblongata (Piqre Diabetes).
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SEJARAH
Th. 1909 : Jean d Meyer (Belgia) memberi nama hormon INSULIN
(Latin : Insulina = Island)

Th. 1921 : Frederik G. Banting (Ahli Bedah) dan Charles H. Best

(Asisten Student) dari Univertisy of Toronto-Canada
bekerja sama dengan James B. Collip (Ahli Biokimia)
dan J.J.R Macleod (Ahli Ilmu Faal) menemukan Insulin.
Mulai digunakan di bulan Januari 1922, kepada pria 14
tahun (nama : Leonard Thompson)

Th. 1954 : Franke dan Fuchs mulai menggunakan OHO

("Obat Hipoglikemik Oral) pada manusia

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Data DM Di RS Pendidikan Dr. Soetomo (Hospital Data)

(1964 - 2003)

Jumlah DM yang terdaftar di Poli Endokrinologi RSU Dr. Soetomo

Surabaya sejak 1964

1964 : 133 px 1985 : 9150 1990 : 15381 1995 : 22029 2000 : 33636
1970 : 1061 1986 : 10278 1991 : 16567 1996 : 26406 2001 : 35606
1975 : 2914 1987 : 11475 1992 : 17667 1997 : 27824 2002 : 37704
1980 : 5654 1988 : 12608 1993 : 19039 1998 : 29394 2003 : 39875

1984 : 8222 1989 : 13818 1994 : 20366 1999 : 31457 Menyusul

Dari 133 pada tahun 1964 menjadi 39875 di th 2003 (300 x lipat),
dengan pertambahan pasien baru rerata +1.022 DM pertahun
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Chronic Diabetic Complications and Providing Information
(Tjokroprawiro, 1993, Revised : 1998, 2002)

Dyslipidemia 67.0
Symptomatic Neuropathy 51.4
Erectile Dysfunction 50.9
Retinopathy 27.2
30 million in USA
Joint Manifestation 25.5
(FELDMAN, et al 1994)
Cataract 16.3
Pulmonary Tbc 12.8
Hypertension in Europe : 30 %
12.1% Hypertension (WHO,1983) 12.1
CHD 10.0 (Williams, 1991)
5.7% Clinical Nephropathy 5.7
Stroke 4.2 Commulative Prevalence of CVD : 63.0%
Cellulitis - Gangrene 3.8 (in line with Dyslipidemia)
Symptomatic Gall Stone 3.0
0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 %

Retinopathy : "The Window of Microangiopathy" CHD : "The Window of Macroangiopathy"

Microalbuminuria (30-299 mg/day or 20-199 g/min) : is referred to as having Incipient Nephropathy
Microangiopathy : Retinopathy, Nephropathy, Neuropathy Macroangiopathy : CHD, Stroke, POAD
Inability to achieve or maintain an erection sufficient
Erectile Dysfunction = ED (NIH-Consensus 1993) :
for satisfactory sexual performance
PAD (ABI < 0.9; N : 0.9-1.3) : An Important Marker of Systemic Atherosclerosis
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Differences in Rates (%) of T2DM in Major Ethnic Groups

(McCarty & Zimmet 1994, Provided : Tjokroprawiro 1989, 1994, 2000)

LOWEST REPORTED RATES HIGHEST REPORTED RATES

(Hispanic) Central Mexico 5.6 (Asian Indian) Fijian Island 22.0
(Micronesian) Rural Kiribati 4.3 (Micronesian) Urban Kiribati 14.6
(Polynesian) Rural Western Samoa 4.0 (Arab) Oman 14.2
(European) Poland 3.5 (Hispanic) US Mexican 14.1
(Asian Indian) Rural India 2.7 (Oriental) Mauritian Chinese 13.1
(Melanesian) Rural Fiji 1.9 (Polynesian) Urban Western Samoa 10.6
(Oriental) Rural Chinese 1.6 (African) US African American 10.3
Indonesia (East Java) : (European) Southern Italy 10.2
- Urban (Adimasta et al 1980) 1.43 (Melanesian) Urban Fiji 8.5
- Rural (Tjokroprawiro et al 1989) 1.47
Susp. MRDM : +21% of DM in Rurals Prevalence Rates of Small Populations :
Pima Indians 50.3%, Nauru 41.3%,
African Rural Tanzania 1.2
(Arab) Rural Tunisia 1.2 Manado (Indonesia) : 6-8%.

Rates are age-standardized to Segi's world population for ages 30 to 64.

Prevalence rates of smaller populations such as the Pima Indians in North America (50.3),
Pacific Islanders of Nauru (41.3) & Australian Aborigin (22.5) , have not been included.
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Regional Estimates of Diabetes Mellitus : 1994-2020

(McCarty & Zimmet 1994, Tattersall 1996, Tjokroprawiro 1994, 1996, 1997, 1998, 2002)

6.6
18.5
EUROPE 15.1 USA
T2DM : 8.7 Million 51.4 T2DM : 12 Million

5.3
4.5
12.6
0.9

DM in Indonesia (Minimally) DM in the World (Estimated)

Year 1994 : 2.5 Million Year 1994 : 110.4 Million
Year 1998 : 3.5 Million Year 1998 : + 150 Million
Year 2000 : 4.0 Million Year 2000 : 1.5x = 175.4 Million
Year 2002 = 4.5 Mill. Year 2002 = 4.5 Mill.
Year 2010 : 5.0 Million Year 2010 : 2x = 239.3 Million
Year 2020 : 6.5 Million Year 2020 : + 300 Million

Indonesia (2002) : 205 Mill. Inhabitants More than 4.5 Mill DM

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Global Projections for the Diabetes Epidemic : 2003-2025
IDF, Diabetes Atlas, Second Edition 2003, Provided : Tjokroprawiro 2006

48.4
58.62
21% 43.0
23.0 75.8
36.2 76%
57%
19.2
39.4
105%
7.1
14.2 39.3
15.0
26.2 81.6
110%
84% 107%

All T2DM WORLD 70% - 90% of Cases

High Risk of CVD
> 2003 = 194 Million
> 2025 = 333 Million
72% in Developing World

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Type 2 Diabetes in the Top 10 Countries
IDF, Diabetes Atlas, Second Edition 2003

1 * Affects 5% to 7% of the World's Population

35
* Global Prevalence of DM will be Double between
30 1995 and 2025 will reach 333 Millions
No. of Cases (Millions)

25 2

20
3
15

10 4
5 6 7 8
5 9 10

0
INDIA CHINA USA PKTAN JAPAN INA MEXI EGYPT BRAZIL ITALY

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Global Diabetes Statistics
(Diabetes Atlas IDF 2003, Provided : Tjokroprawiro 2004, 2005)

Expert Committee of ADA (Fall 2003) : Lower Cut Point for IFG !!
IFG therefore as Pre-Diabetes has been redefined as 100-125 mg/dl

4% Prevalence of DM, Netherlands, 2003

20% Prevalence of DM, UAE, 2003
30% Prevalence of DM, Nauru, 2003
28% Proportion of DM attributable to weight gain, Southeast Asia Males, 2003
80% Proportion of DM attributable to weight gain, Western Europe Males, 2003
104,800 Number of Children with TIDM, Southeast Asia, 2003
430,000 Number of Children with TIDM, Worldwide, 2003
194,000,000 Number of People with DM, 2003
333,000,000 Predicted number of People with DM, 2025
314,000,000 Number of People with IGT, 2003; No Data for IFG The Roles of
472,000,000 Predicted number of People with IGT, 2025 METFORMIN
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Report of the Expert Committee on the Diagnosis of DM
ADA : Committe Report 2003, 2004 (Summarized : Tjokroprawiro 2003, 2004, 2006)

Classical Symptoms : Polyuria, Polydipsia, Unexplained Weight Loss

1 CPG > 200 mg/dl

Plus Classical Symptoms Pre - DM : IGT, IFG
or
2 FPG > 126 mg/dl
(No Caloric Intake > 8 hours)
or DM : Two Positive Findings
3 2-h PG > 200 mg/dl
(75 g Glucose Load) 1 FPG 2 CPG 3 2h-PG

Each must be Confirmed, on Subsequent Day by one of

FPG > 126 2h-PG > 200 CPG > 200
Sampling Darah untuk Diagnosis adalah Darah Vena.
FPG : Fasting Plasma Glucose
CPG : Casual Plasma Glucose (Glukosa Darah Sewaktu = GDS atau Acak = GDA)
2hPG : Two Hour Plasma Glucose
IFG : Impaired Fasting Glucose (> 100 mg/dl)
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Expert Committee Report : ADA 2003, 2004
Etiologic Classification of Diabetes Mellitus
(Consensus PERKENI 2006; ADA 2003, 2004; Summarized: Tjokroprawiro 2003, 2004)

I Type 1 Diabetes* (-cell destruction, usually leading to absolute insulin deficiency)

A. Immune Mediated
B. Idiopathic
II Type 2 Diabetes* (may range from predominantly insulin resistance with relative
insulin defiency to a predominantly secretory defect with insulin resistance)
III Other Specific Types
A Genetic Defects of -cell function E Drug-or Chemical-Induced
B Genetic Defects in insulin F Infections
C Diseases of the Exocrine G Uncommon form of Immune-mediated
Pancreas Diabetes
D Endocrinophathies H Other Genetic Syndromes sometimes
associated with Diabetes
IV Gestational Diabetes Mellitus ( GDM )
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Kriteria Diagnostik Diabetes Mellitus *)
(Konsensus PERKENI-2006)

Gejala Klasik DM adalah Poliuria, Polidipsia, dan Penurunan BB yang tidak

jelas sebabnya.
1 Kadar Glukosa Darah Sewaktu (plasma vena) > 200 mg/dl
plus Gejala Klasik DM
atau
2 Kadar Glukosa Darah Puasa (plasma vena) > 126 mg/dl
atau
3 Kadar Glukosa Plasma >200 mg/dl pada 2 jam sesudah beban glukosa
75 gram pada TTGO**)
*) Kriteria diagnosis tersebut harus dikonfirmasi ulang pada hari yang lain,
kecuali untuk keadaan khas hiperglikemia dengan dekompensasi
metabolik akut, seperti ketoasidosis, berat badan yang menurun cepat.
**) Cara diagnosis dengan kriteria ini tidak dipakai rutin di klinik
Untuk penelitian epidemiologis pada penduduk dianjurkan memakai
kriteria diagnosis kadar glukosa darah puasa.
Untuk DM Gestasional juga dianjurkan kriteria diagnostik yang sama
(Lihat Buku Konsensus Pengelolaan Diabetes dan Kehamilan).

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Tes Penyaring untuk DM yg dalam keadaan Asimptomatik
(PERKENI-2006, ADA-2006, Rangkuman : Tjokroprawiro 2006)

A Umur > 45 th, terutama dengan IMT > 23; bila Normal : ulangi tiap 3 th
B Usia lebih muda, terutama IMT > 23; yang disertai :
1 Hipertensi (> 140/90 mmHg)
2 Riwayat DM dalam Garis Keturunan Derajat-Pertama (Orang Tua)
3 Riwayat kehamilan : BB lahir bayi > 4000 gram; Abortus berulang
4 Riwayat DM pada kehamilan (GDM)
5 Dislipidemia (HDL < 35 mg/dl dan atau Trigliserida > 250 mg/dl)
6 Pernah TGT = IGT atau Glukosa Darah Puasa Terganggu = GDPT
(GDPT = IFG : Kadar Glukosa Plasma Vena 100-125 mg/dl)
7 PCOS, Acanthosis, Nigricans, atau keadaan klinis yang lain yang
terkait dengan Resistensi Insulin
8 Kebiasaan aktifitas kurang (Inaktifitas)
9 Mempunyai sejarah penyakit pembuluh darah
PRE DIABETES : TGT dan GDPT
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Pelaksanaan TTGO
(ADA-2006, Perkeni-2006, Rangkuman : Tjokroprawiro 2006)

1 3 hari sebelumnya makan karbohidrat cukup

2 Kegiatan Jasmani seperti yang biasa dilakukan
3 Puasa semalam 10-12 jam (minimal 8 jam)
4 Diperiksa Glukosa Darah Puasa
5 Diberikan glukosa 75 gram, dilarutkan dalam air 250 ml,
diminum dalam waktu 5 menit.
6 Berpuasa kembali sampai pengambilan darah untuk 2 jam
sesudah minum larutan glukosa selesai
7 Diperiksa Glukosa Darah 2 (dua) jam sesudah beban Glukosa
8 Selama permeriksaan, pasien yang diperiksa tetap
istirahat dan tidak merokok; boleh minum air putih
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 Langkah-langkah Diagnostik DM dan Gangguan Toleransi Glukosa 16
(Konsensus Perkeni 2006)

KELUHAN KLINIK DIABETES

Keluhan Klasik Diabetes (+) Keluhan Klasik (-)

GDP > 126 < 126 GDP > 126 110-125 < 100
atau atau
GDS > 200 < 200 GDS > 200 140-199 < 140

Ulang GDS atau GDP

GDP > 126 < 126 TTGO

atau
GDS > 200 < 200 GD 2 Jam

> 200 140-199 < 140

D I AB E T E S M E LL I T U S TGT GDPT Normal

GDP = Glukosa Darah Puasa - Evaluasi Status Gizi - Nasihat Umum

GDS = Glukosa Darah Sewaktu - Evaluasi Penyulit DM - Perencanaan Makan
GDPT = IFG = Glukosa Darah Puasa Terganggu - Evaluasi Perencanaan Makan - Latihan Jasmani
TGT = Toleransi Glukosa Terganggu Sesuai Kebutuhan - Berat Idaman
ASK-DNC - Belum Perlu Obat Penurun Glukosa
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Insulin Resistance (HOMA-R) and -Cell Function (HOMA-B)

(Mathews et al 1985, Falutz et al 2002, Clinical Experiences : Tjokroprawiro 2005, 2006)

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

Insulin Resistance 22.5

HOMA-B 20 x Fasting Insulin (U/ml)

: (N: 70150%)
-Cell Function FPG (mmol/l) 3.5

HOMA-R and HOMA-B : 1 Rationale Treatment

Useful in Daily Practice 2 Follow-up of Treatment

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Prevalence of IR in Selected Metabolic Disorders
(Bonora 1998, Designed : Tjokroprawiro 2006)

Hyper-Chol
1

The MetS 8 2 Hypertension

Sequential
Prevalences of IR
Low HDL-C 7 in 3 Uric Acid
Metabolic
Disorders

Hyper TG 6 4 IFG-IGT

5
IFG IGT
T2DM
1st Phase and IR in Liver 2nd Phase and IR in Peripheral
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1. DM TIPE-1 (DMT1) : Idiopatik dan Imunologik

2. PATOFISIOLOGI DM TIPE-2 (DMT2)

(Rangkuman : Tjokroprawiro 2003)

IR + Impaired AIR T2DM

* Sekresi Insulin : 1 First Phase ( Acute ) = AIR : 0-5 menit

2 Second phase
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Macam DM di Praktek Sehari-hari
(Rangkuman : Tjokroprawiro 1993-2006)
DM-Tipe 1 DM-Tipe 2 DMTM = MRDM "DM-Tipe X"*)
(DMT2) Surabaya-Kobe 1989 (Askandar, 1991) MODY
(DMT1)
Dx Dugaan : 1 DM Dx-Dugaan : OHO dan Insulin DMT2 pada
1 Gejala mendadak 2 Diet - Dependent 1 DM dependent usia sekitar
2 Insulin Dependent atau OHO 2 Umur sekitar 14-40 th 20 th
3 Anak, atau Dewasa Dependent 3 BBR <80%, BMI <19
4 Resisten insulin DM-Type X1
muda (<20th) 3 Tanpa Insulin
4 Kurus mendadak > 10 hr. tidak 5 Resisten ketosis DM-Type X2
timbul KAD Dx-Definitif : MODY-1
Dx-Definitif :
4 C-peptide Dx-Dugaan ditambah MODY-2
Dx-Dugaan ditambah Calon DM-Type X-3
1 C-peptide O: < 0.5 Puasa > 0.8 1 PABA test <60% MODY-3
2 jam : < 0.5 2 C-peptide >0.6 MODY-4
2 Ax : tanpa MODY-5
DM-Tipe X-3
insulin lebih MODY-6
(Tjokroprawiro 1991)
dari 10 hari, Tes glukosa sesudah
atau LADA MODY-7
timbul KAD 60 menit C-peptide
naik >200% (Tuomi et al 1993)

C-Peptide Darah Puasa Pagi, Normal : 0.8-4.0 ng/ml

Kadar Insulin Darah Puasa : 6 - 27 U/ml
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Diagnosis dan Klasifikasi Nefropati Diabetik

(Kriteria Surabaya 1985)

3 Persyaratan Diagnosis Nefropati-Diabetik (ND) :

1 DM
2 Retinopati Diabetik
3 Proteinuria yang positif tanpa penyebab lain, atau
selama 2 kali pemeriksaan dengan interval 2 minggu
apabila penyebab lain (misalnya infeksi) sudah teratasi.
Atau
(Kriteria ND 1989) : DM, Retinopati Diabetik, kreatinin
Darah >2.5 mg/dl, Proteinuria 1 (satu) kali pemerik-
saan tanpa adanya penyebab proteinuria lain.

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Surabaya Classification of Diabetic Nephropathy-2005
Div. Endocrinology-Metab. and Div. Nephrology-Hypertension 1986 (Revised: 2005, 2006)
(Tjokroprawiro, Yogiantoro et al 2004)

Micro/Macro eGFR (mL/min)** MNT = DIET Life Expectancy

Type Stage
Albuminuria SC (mg/dl) OAD - INS (1986)
B2*) 1 Micro/Macro Alb eGFR > 90 (N) B2, OAD, INS -?-
B2*) 2 Macro Alb. eGFR 60-89 (< 2.5) B2, OAD, INS > 5 years
B2*) 3 Macro Alb. eGFR 30-59 (2.5-4) B2, OAD, INS > 2 years
B3*) 4a eGFR 15-29 (4-8) B3, INS, Pre HD
Macro Alb. 4-18 Months
Be*) 4b eGFR 15-29 (8-10) Be, INS, HD
5 Be, INS, HD
Be*) Macro Alb. eGFR < 15 (> 10) 2-5 Months
ESDN Transplantation

MNT : Medical Nutrition Therapy or Diet. Treatment : B2, B3, Be (Types of MNT), OAD (Oral Agents for Diabetic), INS (Insulin)
B2 & B3-Diets (Pre-HD Phase) : With Specific Composition plus Low K + & Na+, Protein 0.6-0.8 g/kg BW
( 10% of Daily Cal.). Be-Diet (HD-Phase) : Low K + & Na+, Protein 1-1.2 g/kg BW/day, etc
S

*) Diabetic Diets for DN are supplemented with Low Vit C, Folic Acid, Vit B6, Vit B12, Arginine, Glutamine
The Formula of Cockroft Gault : eGFR (estimated GFR); SC = Serum Creatinine
eGFR ( o ) (140-Age) x Body Weight (Kg) eGFR ( +o) (140-Age) x Body Weight (Kg)
= = x 0.85
(mL/min.) Plasma Creatinine (mg/dl) x 72 (mL/min.) Plasma Creatinine (mg/dl) x 72

ASK-DNC ** The Formula of GFR measurement rely on a stable serum creatinine concentration
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Pentalogi-Terapi Diabetes Mellitus

(Askandar Tjokroprawiro 1983-2006)

1 Penyuluhan (tentang Diabetes Mellitus)

2 Pola Makan = PM (Diet atau Nutrisi)

3 Latihan Fisik : Primer dan Sekunder

Obat Hipoglikemik Oral : OHO
4 Obat Hipoglikemik
Insulin
Sel Beta : pada Tikus*) Pusat
5 Cangkok Pankreas Diabetes dan Nutrisi
Total : pada Anjing*) Surabaya (1989)
*) Sudah dikerjakan oleh Pusat Diabetes dan Nutrisi
RSUD Dr. Soetomo dan FK Unair pada th 1989
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Nutrition in Diabetes Mellitus
Disertation (1978) : Followed by Clinical Experiences (1978-2006)

Oral Nutrition Enteral Nutrition Par Enteral Nutrition = PEN

Since 1978 Since 1995 Since 1993

Diabetic Diets
( "SONDE" )
Medical Nutrition Therapy PEN P-PEN
(MNT) E1 , E2 , E3 , E4 , E5 , E6

21 Types of Diabetic Diets E1 :08.00 E2 :11.00 Ten Principles

at Dr. Soetomo Hospital of
The Modified KV-Diets E3 :14.00 E4 :17.00 P-PEN in DM
with higher MUFA (2003)
Revised B2, B3, Be Diets E5 :20.00 E6 :23.00 Peripheral P
Symposium 6 April 2002 Par P
Diets for DM and Pregnancy Enteral E
Diet KV : T1, T2, T3, L INSULIN No Insulin Nutrition N
Diet B1 : T1, T2, T3, L
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DIET - ENTERAL dalam Praktek Sehari-hari
("SONDE")
(Tjokroprawiro, 1995, 1996, 1997, 1998, 1999, 2000, 2002)

1 6 kali sehari; 2 Mulai jam 08.00; 3 Interval 3 jam

Enteral-1 Enteral-2 Enteral-3 Enteral-4 Enteral-5 Enteral-6

(E-1) (E-2) (E-3) (E-4) (E-5) (E-6)
08.00 11.00 14.00 17.00 20.00 23.00

1 2 3 4 5 6
*) Phar. Form **) Mixer *) Phar. Form **) Mixer *) Phar. Form Neomune
Nephrisol
Aminoleban EN
Insulin Insulin Insulin Falkamin, Nephrisol

Hospital Formula (Mixer) : E 2, E4, Pharm. Formula : E 1, E3, E5 AAE : E5 atau E6

*) Nutrition atau Mixer **) Mixer : Tanpa atau Rendah Gula, Rendah Lemak

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The Diet-B (Revised-2002) : The Mother - Diet
Prospective Study (1978) and Clinical Experiences (1978-2006)
(Askandar Tjokroprawiro 1978-2006)

1 Diet-B*) : The Mother-Diet (1978) 11 Diet-KV (1999)

2 Diet-B Fasting (1978) 12 Diet-GL (2000)
3 Diet-B1 (1980) 13 Diet-H (2001)
4 Diet-B1 Fasting (1980) 14 Diet KV-T1 (2004)
5 Diet-B2** ) (1982) 15 Diet KV-T2 (2004)
16 Diet KV-T3 (2004)
6 Diet-B3** ) (1983)
17 Diet KV-L (2004)
7 Diet-Be** ) (1983) 18 Diet B1-T1 (2004)
8 Diet-M (1989) 19 Diet B1-T2 (2004)
9 Diet-M Fasting (1989) 20 Diet B1-T3 (2004)
10 Diet-G*** ) (1999) 21 Diet B1-L (2004)

*) Diet-B : 68% CHO, 12% Protein, 20% FATs : Prospective-Cross Over Design (1978)
SAFA 5%, PUFA 5%, PS = 1.0, MUFA 10%, Chol. <300 mg/day, Fiber 25-35 g/day
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SPECIFICATIONS : 3 of 21 Diabetic Diets at Dr. Soetomo Hospital
DIET-G = Diet-H and DIET-KV
(Tjokroprawiro et al, 1999, 2001, 2004; Hari Witarti et al, 1999)

Diet-G = Diet-H : Gangrene or Hepar Diet-KV : Stroke, CAD, POAD

Diet-B1 plus 5 Specifications Diet-B plus 5 Specifications

Diet-B1 (% Cal): 60% CHO, 20% F, 20% P Diet-B (% Cal) : 68% Cbh, 20% F, 12% P
(Chol. < 300 mg/day) (Chol. < 300 mg/day)
1 Arginin Content 1 Arginin Content
2 Fiber 25-35 g/day 2 Fiber 25-35 g/day
3 Folate 3 Folate
4 Vit B6 These are able to lower 4 Vit B6 These are able to lower
5 Vit B12 Homocysteine Level 5 Vit B12 Homocysteine Level

Arginin : Atheroprotective
Homocysteine : Atherogenic
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 28

DIET-B (1978)*
Kbh 68% kal, L 20% kal, Protein 12% kal, Kolesterol < 300 mg/hari,
SAFA 5%, PUFA 5%, MUFA 10%, Rasio PS + 1.0, Serat 25-35 g/hari

Indikasi :
1 Diabetisi yang tidak tahan lapar
2 Dislipidemia (TG , HDL , Kol. Tot. , LDL )
3 DM lebih dari 10 tahun
* Hasil Disertasi S3 (Askandar Tjokroprawiro 1978)

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SPECIFICATIONS : 3 of 21 Diabetic Diets in Dr. Soetomo Hospital
DIET-G = Diet-H AND DIET-KV
(Tjokroprawiro et al, 1999, 2001, 2004; Hari Witarti, Indrawati, Frieda et al, 1999, 2004)

Diet-G = Diet-H : Gangrene or Hepar Diet-KV : Stroke, CAD, POAD

Diet-B1 plus 6 Specifications Diet-B plus 5 Specifications

Diet-B1 (% Cal) : 60% Cbh, 20% F, 20% P Diet-B (% Cal) : 68% Cbh, 20% F, 12% P
(Chol. < 300 mg/day)
1 Arginin Content
2 Fiber 25-35 g/day 1 Arginin Content
3 Cholesterol < 300 mg/day 2 Fiber 25-35 g/day
4 Folate 3 Folate
May Reduce 4 Vit B6 May Reduce
5 Vit B6
Homocysteinemia 5 Vit B12 Homocysteinemia
6 Vit B12

Arginin : Atheroprotective
Homocysteine : Atherogenic
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 30

Pedoman Diet-B2, Diet-B3, dan Diet-Be

Konsensus : Diabetologi, Nefrologi, Gizi
RSUD Dr. Soetomo - FK Unair Surabaya
(Surabaya : 6 April 2002)

Fase Pra-Hemodialisa : Diet-B2, B3) Fase Hemodialisa : Diet-Be

(Fase Pra-HD) (Fase HD)

1 Pra-HD Umum : Diet-B2 Diabetisi Fase HD : Diet-Be

Kandungan Protein : 0.6 g/kgBB/hari Kandungan Protein : 1.0-1.2 g/kgBB/hari

2 Pra-HD Khusus : Diet-B3 Intensivitas Menghambat

Proteinuria > 3 g/hari, atau Progresivitas Gagal Ginjal
Albuminuria Berat (Positif 4 ) Vitamin C Maks 100 mg,
Kandungan Protein : 0.8 g/kgBB/hari
Pantang NSAID, dll

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 Obat Hipoglikemik Oral Keterangan : 31
* Produk orisinal
(Konsensus PERKENI 2002) ** Belum beredar di Indonesia
*** Kadar plasma efektif terpelihara selama 24 jam

Golongan Generik Nama Dagang Mg/tab Dosis harian Lama kerja Frek/hari Waktu
Sulfonilurea Klorpropamid Diabenese 100-250 100-500 24-36 1
Glibenklamid Daonil* 2,5-5 2,5-15 12-24 1-2
Glipizid Minidiab 5-10 5-20 10-16 1-2
Glucotrol-XL 5-10 5-20 12-16*** 1
Gliklazid Diamicron 80 80-320 10-20 1-2
Diamicron-MR 30 30-120 24 1 Sebelum
Glikuidon Glurenom 30 30-120 6-8 2-3 makan
Glimepirid Amaryl* 1,2,3,4 0,5-6 24 1
Gluvas 1,2,3,4 1-6 24 1
Amadiab 1,2,3,4 1-6 24 1
Metrix 1,2,3,4 1-6 24 1
Glinid Repaglinid NovoNorm 0,5, 1, 2 1,5-6 - 3
Nateglinid Starlix 120 360 - 3
Tiazolidindion Rosiglitazon Avandia 4 4-8 24 1 Tidak bergantung
Pioglitazon Actos* 15,30 15-45 24 1 jadwal makan
Deculin 15, 30 15-45 24 1
Penghambat Acarbose Glucobay 50-100 100-300 3 Bersama suapan
Glukosidase pertama
Biguanid Metformin Glucophage 500-850 250-3000 6-8 1-3 Bersama/sesudah
Glumin 500 500-3000 6-8 2-3 makan
Metformin XR Glucophage-XR* 500-750
Glumin-XR 500 500-2000 24 1
Obat Metformin + Glucovance* 250/1,25 Total 12-24 1-2 Bersama/sesudah
Kombinasi tetap Glibenklamid 500/2,5 Glibenclamid makan
500/5 mid 20 mg/hr
Rosiglitazon + Avandamet 2mg/500mg 8mg/2000mg 12 2
Metformin 4mg/500 mg dosis max.
Glimepirid + Amaryl-M** 1mg/250mg 2mg/500mg - 2
Metformin 2mg/500mg 4mg/1000mg
Rosiglitason + Avandaryl** 4mg/1mg 8mg/4mg 24 1 Bersama/sesudah
Glimepirid 4mg/2mg (dosis max.) makan pagi
4mg/4mg

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 32
Map of Oral Antidiabetic Drugs in Clinical Practice
(Summarized : Tjokroprawiro 1996, 1998,1999, 2001, 2002, 2003, 2004, 2005)

1 INSULIN SECRETAGOGUES : SULPHONYLUREAS = SUS NON-SUS : METAGLINIDES

(Nateglinide, Repaglinide)
Gen I : Tolbutamide, Chlorpropamide, etc.
Gen II : Glibenclamide , Glipizide-GITS, Gliquidone, Gliclazide - MR Novel PGR
2
Gen III : No Effects at CV KATP Channels, 3B-3A-9D Properties,
Glimepiride 1 ATHEROPROTECTIVE 5
Insulin Sparing, Glycogenic, Antiplatelet, Adiponectin-Raiser
4 3 6 7

2 INSULIN SENSITIZERS AND ANTIHYPERGLYCEMIC AGENTS :

A THIAZOLIDINEDIONES = TZDs : Glitazone Class
1 Ciglitazone 4 Rosiglitazone
2 Englitazone 5 Pioglitazone
3 Troglitazone 6 Darglitazone
B NON-TZDs : 1 Glitazar Class (Muraglitazar, Ragaglitazar, Tesaglitazar)
2 Metaglidazen (Non Edema and Non Weight Gain)
C BIGUANIDES : 1 METFORMIN
2 3-GUANIDINOPROPIONIC-ACID

3 INTESTINAL ENZYME INHIBITORS :

A -GLUCOSIDASE INHIBITORS : Acarbose , Voglibose (AD-128), Miglitol, MDL-73945, Castanospermine
B -AMYLASE INHIBITOR : Tendamistase

4 FIXED DOSE COMBINATION TYPES : Glucovance, Avandamet, Amamet

5 OTHER SPECIFIC TYPES :

A Insulin Mimetic Drugs (Glimepiride, Chromium, -Lipoic Acid, Vanadium)
B Inhibitors of Dipeptidyl Peptidase-IV (DPP-IV) : Metformin, Liraglutide, Vidagliptin
C Suppresors of Glucagon Secretion : Amylin Analogues e.g Pramlintide
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 33

Mekanisme Kerja, Efek Samping Utama, dan A1c

(Konsensus PERKENI 2006)

Cara Kerja Utama Efek Samping Utama Penurunan A1c

Sulfonilurea Meningkatkan sekresi insulin BB naik, 1,5 - 2,5 %
hipoglikemia
Glinid Meningkatkan sekresi insulin BB naik, Data Belum Ada
hipoglikemia
Metformin Menekan produksi glukosa hati Diare, dispepsia, 1,5 - 2,0 %
Menambah sensitivitas insulin asidosis laktat
Penghambat Menghambat absorpsi glukosa Flatulens 0,5 - 1,0 %
Glukosidase Alfa tinja lembek
Tiazolidindion Menambah sensitivitas terhadap Edema 1,3 %
(Glitazon) insulin
Insulin Menekan produksi glukosa hati, Hipoglikemia, Potensial
stimulasi pemanfaatan glukosa BB naik normal

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 34

Kemungkinan OHO = OAD berhasil baik adalah :

Pola Hidup (Diet dan Latihan Fisik) harus
dilaksanakan dengan benar (3J) penderita DM yang
(Tjokroprawiro, 1980-2006) :
1 Umur > 40 th
2 Lama DM-nya 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 mengalami Keto Asidosis Diabetik
J1 = Jumlah ; J2 = Jadwal; J3 = Jenis

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 35
Macam Insulin
1. Insulin Konvensional , mengandung komponen a,b,dan c,
misalnya : IR = Insulin Reguler ( Novo dan Organon), NPH (Novo),
PZI (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, identik dengan Insulin Reguler),
Ada juga Insulatard (identik dengan NPH) dan Mixtard (campuran
short dan long acting insulin dengan perbandingan 30:70), semua dari
Novo Industries. Beredar ketiganya dalam bentuk Novolet (@ 300u)
yang disposible.
3. Insulin Manusia = Human Insulin (HM = Human Monocomponent).
4. Insulin Analogues ( 2 macam )
A. Rapid-Acting Insulin Analogue : Lis Pro (R/ Humalog), Glulisin (R/ Apidra),
Aspar (R/ Aspart)
B. Long-Acting Peakless Insulin Analogue : Insulin Glargine (R/Lantus)
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 Insulin yang beredar di Indonesia 36

(Tjokroprawiro 2006)

Macam Insulin Buatan Efek Puncak (jam) Lama Kerja (jam)

Cepat : 2-4 6-8
Humalog* Eli Lily (U-100)
Apidra* Aventis (U-100)
Aspart* Novo (U-100)
Pendek :
Actrapid Novo (U-40 dan U-100)
Humulin-R Eli Lily (U-40 dan U-100)
Menengah : 4 - 12 18 - 24
Insulatard Human Nov (U-40 dan U-100)
Monotard Human Novo (U-40 dan U-100)
Humulin-N Eli Lily (U-100)
Campuran : 1-8 14 - 15
Mixtard 30/70 Novo (U-40 dan U-100)
Humulin 30/70 Eli Lily (U-100)
Humalog Mix 25 Eli Lily (U-100)
Panjang : Tanpa Puncak 24
Lantus* Aventis (U-100) (Peakless Insulin)
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 Indikasi Injeksi Insulin 37

(Konsensus PERKENI 2006)

1 Penurunan Berat Badan yang cepat

2 Hiperglikemia berat yang disertai ketosis
3 Ketoasidosis Diabetik
4 Hiperglikemia Hyperosmolar Non Ketotik
5 Hiperglikemia dengan Asidosis Laktat
6 Gagal dengan kombinasi OHO dosis hampir maksimal
7 Stres berat (injeksi sistemik, operasi besar, IMA, stroke)
8 Kehamilan dengan DM/Diabetes Mellitus Gestasional
yang tidak terkendali dengan Pola Makan
9 Gangguan fungsi Ginjal dan atau Hati yang berat
10 Kontraindikasi dan atau alergi terhadap OHO
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 38
Insulin Injection Sites : Clock Wise Rotation
(Clinical Experiences : Tjokroprawiro 1993)

76-90 1-15

61-75 16-30
46-60 31-45

Jarak antara Suntikan 1, 2

dan seterusnya 2,5 cm
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 39
Kriteria Pengendalian
(ADA-2006, PERKENI-2006, Tjokroprawiro 2006)

Baik Sedang Buruk

Glukosa Darah Puasa (mg/dl) 80 - 100 100 - 125 > 126
Glukosa Darah 2 jam (mg/dl) 126 - 144 145 - 179 > 180

A1C (%) <6,5 6,5 - 8 >8

Kolesterol Total (mg/dl) < 200 200 - 239 > 240
Kolesterol LDL (mg/dl) < 100 100 - 129 > 130
Kolesterol HDL (mg/dl) > 45
Trigeliserida < 150 150 - 199 > 200
IMT (kg/m2 ) 18,5 - 22,9 23 - 25 > 25

Tekanan Darah <130/80 130-140/80-90 >140/90

Keterangan :
Angka di atas adalah hasil pemeriksaan plasma vena
Perlu konservasi nilai kadar glukosa darah dari kapiler darah utuh ke plasma vena
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 40
Indikasi TKOI
(Pengalaman Klinik : Tjokroprawiro 1997-2006)

1 Meskipun Pola Hidup (Diet + Latihan Fisik) sudah adekuat,

Dosis OHO Maksimal, Tanpa adanya Faktor Pengganggu
(Infeksi, dll), tapi Glukosa Darah Tetap Tinggi

2 DMT2 + Fraktur
3 DMT2 + Nefropati Diabetik Sedang Berat, HD
4 DMT2 + KP Aktif dengan Gizi Kurang
5 DMT2 + Sirosis dengan Gizi Kurang
6 DMT2 + Penurunan Berat Badan yang cepat
7 DMT2 dengan Indikasi Khusus : Gangren, dll

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 41
Method-A : Cardioprotective Combined Therapy GLIMGLAR
(Clinical Experiences : Tjokroprawiro 1997-2006)

Glargine (R/ Lantus)**

(10 - 30 u sc)
30 Min. Pre-Breakfast Breakfast Lunch Dinner

30 Minutes 9.30 am 3.30 pm 9.30 pm

Snack Snack Snack

6.30 am 0.30 pm 6.30 pm

Glimepiride (R/ Amaryl)*

(3 - 6 mg)
30 Min. Pre-Breakfast
* Or Other Oral Agents
** Or Other Intermediate / Long Acting Insulins
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 42

Method-B : Cardioprotective Combined Therapy GLARGLIM

(Clinical Experiences : Tjokroprawiro 1997-2006)

Breakfast Lunch Dinner

30 Minutes 9.30 am 3.30 pm 9.30 pm

Snack Snack 30 Min. Snack

6.30 am 0.30 pm 6.30 pm

Glargine (R/ Lantus)** Glimepiride (R/ Amaryl)*

(10 - 30 u sc) (3 - 6 mg)
30 Min. Pre-Breakfast 30 Min. Pre-Breakfast

* Or Other Oral Agents

** Or Other Intermediate / Long Acting Insulins
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 43

Method-C : Cardioprotective Combined Therapy GLIMGLAR

(Clinical Experiences : Tjokroprawiro 1997-2006)

Breakfast Lunch Dinner

30 Minutes 9.30 am 3.30 pm 9.30 pm

Snack Snack 30 Min. Snack

6.30 am 0.30 pm 6.30 pm

Glimepiride (R/ Amaryl)* Glargine (R/ Lantus)**

(3 - 6 mg) (10 - 30 u sc)
30 Min. Pre-Breakfast 30 Min. Pre-Breakfast

* Or Other Oral Agents

** Or Other Intermediate / Long Acting Insulins
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 44
Komplikasi Akut Diabetes Mellitus
(Pengalaman Klinik : Tjokroprawiro 1993-2006)

1 Hipoglikemia

2 Ketoasidosis Diabetik (KAD)

3 Hiperosmoler Non Ketotik (HONK)

4 Koma Asidosis Asam Laktat (KAAL)

No. 2 dan No. 3 disebut Krisis Hiperglikemia

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 45

PETUNJUK PRAKTIS TERAPI HIPOGLIKEMIA

DENGAN RUMUS 3-2-1
(Pengalaman Klinik : Askandar Tjokroprawiro 1996-2006)

Kadar Glukosa Glukosa

(mg/dl) Terapi Hipoglikemia Dengan Rumus 3-2-1 1 Flakon = 25 ml
40% (10 gram)

< 30 mg/dl : Injeksi I.V Dekstrosa 40%, bolus 3 Flakon Rumus - 3

30-60 mg/dl : Injeksi I.V Dekstrosa 40%, bolus 2 Flakon Rumus - 2

60-100*) mg/dl : Injeksi I.V Dekstrosa 40%, bolus 1 Flakon Rumus - 1

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 46

REGULASI CEPAT DENGAN INSULIN

(Pengalaman Klinik : Askandar Tjokroprawiro, 1993-2006)

Dapat dibagi menjadi : 1 R.C. Intravena

2 R.C. Subkutan
Perlu diketahui, bahwa pada pelaksanaan RC (Regulasi Cepat),
perlu diingat beberapa rumus antara lain :
1 Rumus Minus-Satu : -1
2 Rumus Kali-Dua : x2

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 47
Hiperglikemia >200 mg/dl
(Contoh : Kasus Glukosa Darah 650 mg/dl)

Regulasi Cepat Intravena (RCI)

(Tjokroprawiro 1987-2006)

Glukosa Awal Dosis Insulin Dosis Rumatan

Sebelum R-C (mg/dl) Intravena a 4 U/jam Insulin Subkutan (unit)

2 00 - 300 1x 3x 4
3 00 - 400 2x 3x 6
4 00 - 500 3x 3x 8
5 00 - 600 4x 3 x 10
6 00 - 700 5x 3 x 12

Rumus Minus Satu Rumus Kali Dua

6 Minus 1 = 5 6 Kali 2 = 12

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 48
Hiperglikemia >200 mg/dl
(Contoh : Kasus Glukosa Darah 650 mg/dl)

Regulasi Cepat Subkutan (RCS)

(Tjokroprawiro 1987-2006)

Glukosa Awal Dosis Insulin Dosis Rumatan

Sebelum R-C (mg/dl) Subkutan (unit) Insulin Subkutan (unit)

2 00 - 300 4 3x 4
3 00 - 400 6 3x 6
4 00 - 500 8 3x 8
5 00 - 600 10 3 x 10
6 00 - 700 12 3 x 12

Rumus Kali Dua

6 Kali 2 = 12

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 49
Terapi
Terapi KAD
KAD -- Revisi
Revisi 1998
1998
(Askandar Tjokroprawiro, 1991-2006)

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) : Rumus 2,4,18-24
2 IDRIV : 4-8 unit/jam i.v (Rumus Minus Satu)
FASE-I 3 Infus K+ : 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 BIK : bila pH < 7.2 - 7.3 atau BIK <12 mEq/l : 50-100 mEq drip
dalam 2 jam (bolus BIK 50-100 mEq diberikan bila pH < 7.0)
5 Antibiotika : up to date dan dosis adekuat
Glukosa Darah + 250 mg/dl atau reduksi +
1 Maintenance : NaCl 0.9% atau Pot. R (IR 4-8u) , Maltosa 10% (IR 6-12u)
bergantian : 20 tt/m (Start Slow, Go Slow, Stop Slow)
FASE-II 2 Kalium : p.e (bila K+ < 4 mEq/l) atau per os (air tomat/kaldu)
3 IR : 3 x 8-12 U sc (ingat : Rumus Kali Dua)
4 Makanan lunak Kbh kompleks per oral

Rumus : 2,80,30,20 ; Rumus 2,4,18,24 ; Minus Satu; Kali Dua; Rumus 5-1 ; Rumus 2,5-1 ;

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 50
DIABETIC NON-KETOTIC HYPEROSMOLAR SYNDROME
(HONK-DIABETIK)
(Summarized : Tjokroprawiro 1991-2006)

Pathogenesis Diagnosis : 1 YES, 3 NO Therapy

Precipitating Factors : Clinical Dx (Suspect): Supporting Findings : 1 Tx DKA

1 Thiazide (Tetralogy HONK : 1 (pH > 7.30) 2 a Plasma Na <150 mEq/l
2 Glucose Drinks 1 YES, 3 NO) 2 Neurological Sign +
3 Infection 1 YES: Glycemia >600 mg/dl 3 Prerenal uremia Normal Saline
4 Corticosteroid 2 NO: DM History or + 4 Mental Impairment +
5 Beta Blocker 3 NO: Kussmaul , 5 Severe Dehydration b Plasma Na >150 mEq/l
6 Phenytoin 4 NO: Ketonuria or + 6 More than 60 years old
7 Cimetidine Hypotonic Saline
8 Chlorpromazine TETRALOGY HONK (1 YES, 3 NO) : 1H + 3 NO
Pathophysiology
Glucose (mg/dl) Ureum (mg/dl)
Grossly Elevated Glucagon 5 Osm/l = 2x (Na + K) + + > 325
Relative Insulin Deficiency 18 6
Sufficient Insulin to inhibit lipolysis
Tetralogy + 5 = PENTALOGY HONK (Definite Dx)
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 51

KAAL - Tipe A KOMA ASIDOSIS ASAM LAKTAT (KAAL)

(Primer : Hipoksia)
1. Semua jenis shock (Tipe A dan Tipe B )
2. Decomp. Cordis (Summarized : Tjokroprawiro 1991-2006)
3. Asfiksia
4. Intoksikasi CO
ASAM LAKTAT + H2 O + O2 Bikarbonat
KAAL - Tipe B
Kelainan Sistemik
1. DM Terganggu
2. Neoplasia
3. RFT/LFT terganggu Infeksi, Shock, Peny. Kardiovaskuler/Angiopati
4. Konvulsi LFT-RFT , DM + Biguanide, Gg. Oksigenasi : PPOM, dll
Obat
Dx : Hiperglikemia plus Amino Gap > 20 mEq
1. Biguanide
(K + Na) - (Cl + CO2 ) > 20 mEq atau
2. Salisilat
3. Alkohol (Metanol, Etanol) (Na) - (Cl + CO2 ) > 15 mEq
4. Glukosa-Alkohol (Sorbitol, dll)
Tx : Kausal

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 52

KOMPLIKASI KRONIK DM

1 Infeksi 5 Tractus Urogenetalis :

Nefropati Diabetik = Sindroma Kiemmelstiel Wilson
2 Mata
6 Disfungsi Ereksi (DE)
3 Mulut 7 Saraf
4 Jantung 8 Kulit

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 53

Klasfikasi Impotensi Diabetik

(Sekarang disebut : Disfungsi Ereksi Diabetik = DE-D)

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. Psikogenik dan Organik (prognosis lebih parah).
- Terapi Disfungsi Ereksi

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 54
Five Guidelines of Sexual Intercourse (SI)
for
PADAM and Pts with DM
(Clinical Experiences : Tjokroprawiro 1995-2006)

Blood Sugar Level : Should be <200 mg/dl

OBLIGATORY Fit : Physically + Mentally Use Apidra or Humalog if >200 mg/dl

1 Do not SI just after Meal; Minimally 2-3 Hours after Meal

2 Take Levitra (or Viagra or Cialis) minimally One Hour before SI
3 Avoid Drugs Decreasing Sexual Ability, and Avoid Fatty Foods
4 Stimulations : Mentally and Manually, and then SI can be Started
5 Use Lubricants on Mr. P and Mrs. V just before Penetration
Results : 95% Failure : Increase Levitra Dose or Adhere to Guidelines
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 55
TEN GUIDELINES FOR HEALTHY LIFE
GULOH-CISAR = SYNDROME-10
(Tjokroprawiro 1995,1996,1997,1998,1999,2000,2001,2003,2006)

1 G Limits Sugar Consumption 6 C Quits Smoking

+300 kcal/day or 3 km walk
2 U Restricts Purine Intake : JAS-BUKET 7 I Daily Regular Exercise : +Sit up 50-100 x/day
3 L Consumes Low Fat Diet : TEK-KUK-CS2 8 S TAKES MINIMALLY 6-HOUR SLEEP/DAY
4 O Prevents Obesity (Target : BMI < 25) 9 A Stops Alcohol

5 H Avoids Excess of Sodium Intake 10 R Regular Check-Up

(Less than 3 g Sodium/day) Esp. > 40 years Old : 3, 6 or 12 Months

JAS-BUKET : Jerohan, Alkohol, Sarden - Burung Dara, Unggas, Kaldu, Emping, Tape
(Bowels, Alcohol, Sardines - Pigeon, Fowls, Meat-Broth, Beaten Nut, Fermented Cassava)

TEK-KUK-CS2 : Telor, Keju - Kepiting, Udang, Kerang - Cumi, Susu, Santen

(Egg, Cheese - Crab, Shrimp, Mussel - Squid, Milk, Coconut - Juice)

"MABUK" (Rich in Chromium) : Mrica, Apel, Brokoli, Udang, Kacang-kacangan; good for DM

Recommended Food Supplements G

: reen Bean, Onions, Green Tea, Pepper, ARGININE, TKW-PJKA-BK
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 56

Short and Long Sleep Durations as Risk Factor for T2DM

(Yaggi et al 2006; Summarized : Tjokroprawiro 2006)

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
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 57
Staging of Lifestyle Related Disease
(Clinical Experiences : Tjokroprawiro 2005, 2006)

STAGE 0 STAGE 1 STAGE 2 STAGE 3 STAGE 4

"Westernized" Obesity Preclinical : the MetS Clinical : CAD
Healthy Lifestyle
Unhealthy Lifestyle (Abdominal Obesity) IFG, IGT, Adol.-Obese T2DM, Adol.-T2DM, Stroke

1 Waist Circumference
o > 90 cm o
+ > 80 cm

5 Fasting Glucose 2 Triglyceride

> 100 mg/dl > 150 mg/dl

3 HDL-Chol
4 Blood Pressure o < 40 mg/dl
> 130/85 mmHg o
+ < 50 mg/dl
The Metabolic Syndrome (ATP III-2001) : At Least 3 of the 5
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 58
Staging of Lifestyle Related Disease
(Clinical Experiences : Tjokroprawiro 2005, 2006)

STAGE 0 STAGE 1 STAGE 2 STAGE 3 STAGE 4

"Westernized" Obesity Preclinical : the MetS Clinical : CAD
Healthy Lifestyle
Unhealthy Lifestyle (Abdominal Obesity) Pre-DM, Adol.-Obese T2DM, Adol.-T2DM, Stroke

Waist Circumference = WC
o > 90 cm o
+ > 80 cm

4 Fasting Glucose 1 Triglyceride

> 100 mg/dl > 150 mg/dl

2 HDL-Chol
3 Blood Pressure o < 40 mg/dl
> 130/85 mmHg o
+ < 50 mg/dl

The MetS (IDF 2005) : Plus Any 2 of the Following 4 Factors

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 Syndrome-37 The Quality of Endothelial Cell The Quality of Life 59
7 Cigarette
Year 2003
17Alcohol Abuse
3Glucose Intolerance DM No. ? Killer
9 19
Inactivity 13 Age Inhibitors & Promoters
Year 1993 & 1995
1 11
Genetic 5 Lipids Stress The 1st Killer

21 22 23 24,25 26 27 28 29 30 31 32 33 34 35 36 37
ASCVD
Year 1972
12 Sex The 11th Killer
4 20
Uric Acid 10 LVH 21,22,23,24,25,26,27,28,
Platelet
6 Aggregation 18 Race 21
Obesity 29,30,31,32,33,34,35,36,37 PAF
22
2 8 Androgen
Insulin Resistance Hypertension 14Fibrinogen, 15F.VIIIc, F.VII, FVa, FXa, FXIIIa, 16Free Radicals 23
Interleukines
24
Catecholamine
= Uncorrectable 25
Cortisol
26
Growth Hormon
27
Estrogen

SYNDROME - 37 28
29
30
Leptin
TNF
Homocysteine (HCY)
(Tjokroprawiro 1992,1993,1994,1995,1996,1997,1998,1999,2000,2001,2002,2003) 31
32
Cu
Fe
33
Inflammation
34
TGF
Chronology of ASCVD as a Killer in Indonesia 35
Endothelin
36
1972 (No.11), 1986 (No.3), 1992 (No.2), 1993 (No.1), 2003 (No...?) Gamma-GT
37
Infection
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 60
MAP of FAT Cell : 53 Hormones and Biologic Substances
(Summarized : Tjokroprawiro 1997-2006)
NO 27 28 PC-1
29 Aquaporins
ApoE, LPL, ICAL, CETP, PLTP 26 30 FIAF
31 Lactate
RBP 25 32 Monobutyrin
33 Galectin-12
Metallothionein 24 34 ESM-1
35 Apelin
36 FATPI
Aromatase 23
37 aP2
Necrosis
11 HSD-1 22 38 UCP, P450, ZAG Apoptosis
1 Estrogen Proliferative Effect
ACTH, Cortisol 21 2 ob Protein (LEPTIN) 1 Renal Renin (AII)
Hypertension
Eicosanoids Agouti Related
PGE2 , PGI2
20 3
Protein (AgRP) Hyperuricemia
2 NPY, AGRP Body Weight
TGF , VEGF, IGF-1 19 FAT CELL VCAM-1
MIF 18 3
Inhibits Bone Formation
4 TNF (Central Relay)
FFAs 17 5 4
Perilipins 16 IL-1, IL-6
IRS-1
Lipotransin 15 6
IRTK Insulin Cell
HSL, DGAT 14 Angiotensinogen Resistance STAT-3
VISFATIN 13 TG
7 AII LPL & FFA
Adiponectin 12 HDL GLUT-4 Insulin
ASP, Adipsin, Factors : B, C3 LDL3 Expression Secretion
Resistin 11
8 Adhesive Proteins Fribrinogen
TF 10 PAI-1
PAI-1
9 (Esp. Omental Fat) F VII IGT - T2DM
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