1

DIABETES MELLITUS-I
GARIS BESAR KULIAH UNTUK MAHASISWA SEMESTER-6
FAKULTAS KEDOKTERAN UNIVERSITAS AIRLANGGA, SURABAYA

2012
16-927-B
Kuliah DM-I : SLIDE 1 – 40

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

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

SURABAYA, 05 MARCH 2012

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 2
SEJARAH
HISTORY (Tattersall 2003) : Polyuric states resembling DIABETES
MELLITUS have been described for over 3500 years. The name
‘DIABETES’ comes from the Greek word for a SYPHON; the sweet
taste of DIABETIC URINE was recognized at the beginning of the
millenium, but the adjective ‘MELLITUS’ (honeyed) was only added by
John Rollo in the late 18th century.

1550 th SM Penyakit atau "SINDROMA DIABETES", mulai dikenal

di Mesir 1550 SM (The Egyptian Papyrus Ebers)

200 th SM ARETAEUS (Greek Physician) : DIABETES atau

SIPHON = FLOW-THROUGH = RUN-THROUGH, berarti
mengalir terus. Sehabis minum banyak, diikuti kencing
banyak. MELLITUS : MADU atau MANIS.
DIABETES MELLITUS = KENCING MANIS.

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Continued
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SEJARAH

Th. 1674 THOMAS WILLIS (Inggris), merasakan 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 sebagai Glikogen, dan Hiperglikemia Akut
akibat kerusakan Medulla Oblongata (PIQÛRE DIABETES).

Th. 1909 JEAN d MEYER (Belgia) memberi nama hormon INSULIN

(Latin : Insulina = Island)

Continued
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 SEJARAH 4

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 11 JANUARI 1922, kepada pria umur
14 tahun (nama : LEONARD THOMPSON). The name
‘INSULIN’ was coined by MACLEOD

Th. 1954 - 1955

FRANKE dan FUCHS (1954) mulai menggunakan OHO
(Obat Hipoglikemik Oral) atau OAD (Obat Anti Diabetes)
pada manusia. The first oral hypoglycaemic agents
suitable for clinical use were the SULPHONYLUREAS,
developed by Auguste Loubatieres in the early 1940s.
CARBUTAMIDE was introduced in 1955 and
TOLBUTAMIDE in 1957. The biguanide PHENFORMIN
became available in 1959, and METFORMIN in 1960
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Continued
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DIABETES MELLITUS
DM TYPE 2 (Tattersall 2003)
INSULIN RESISTANCE and Β-CELL FAILURE, the fundamental
defects of type 2 diabetes (T2D), have been investigated by many
researchers. The ‘insulin clamp’ method devised by Ralph
DeFronzo was the first accurate technique for measuring insulin
action. Maturity-Onset Diabetes of the Young (MODY) was described
as a distinct variant of type 2 diabetes by Robert Tattersall in 1974.

DM TYPE 1 (Tattersall 2003)

THE Β-CELL DESTRUCTION causing type 1 diabetes (T1D) was
suggested to be autoimmune by Deborah Doniach and GianFranco
Bottazzo in 1979. The significance of chronic lymphocytic infiltration
of the islets (‘insulitis’), first observed by Eugene Opie in 1901, was
highlighted by Willy Gepts in 1965. Andrew Cudworth and John
Woodrow first described the association of type 1 diabetes with
specific HUMAN LEUCOCYTE ANTIGENS (HLA).
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Data DM Di RS Pendidikan Dr. Soetomo (Hospital Data)
(1964 – 2011)

JUMLAH DM TERDAFTAR DI POLI ENDOKRINOLOGI RSU Dr. SOETOMO

Surabaya 1964 – 2010 (Selama 46 Tahun)

1964 : 133 px 1986 : 10278 1992 : 17667 1998 : 29394 2004 : 42149
: 43264
1970 : 1061 1987 : 11475 1993 : 19039 1999 : 31457 2005
2006 : 45536
1975 : 2914 1988 : 12608 1994 : 20366 2000 : 33636 MANUAL
2007 ELECTRONIC
1980 : 5654 1989 : 13818 1995 : 22029 2001 : 35606
2008 : 33157
1984 : 8222 1990 : 15381 1996 : 26406 2002 : 37704 2009 : 32862
1985 : 9150 1991 : 16567 1997 : 27824 2003 : 39875 2010 : 35717

Dari 133 Pasien terdaftar pada tahun 1964 menjadi 35717 pd th 2010 (46 tahun)
meningkat 268 x lipat, dengan pertambahan pasien baru rerata +110 DM pertahun
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 CHRONIC DIABETIC COMPLICATIONS AND PROVIDED INFORMATION 7
Tjokroprawiro 1993 (Revised : 2002) ADA 2005-2010

Dyslipidemia 67.0
Symptomatic Neuropathy 51.4
Erectile Dysfunction 50.9
Retinopathy 27.2
Joint Manifestation 25.5
30 million in USA
Cataract 16.3 (FELDMAN, et al 1994)
Pulmonary Tbc 12.8
Hypertension (WHO,1983) 12.1 Based on JNC7, 2003 : + 32%
CHD 10.0
CLINICAL NEPHROPATHY 5.7
Stroke 4.2 Commulative Prevalence of CVD : +82%
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 = ACR) : IS REFERRED TO AS HAVING INCIPIENT NEPHROPATHY
MICROANGIOPATHY : RETINOPATHY, NEPHROPATHY, NEUROPATHY, MACROANGIOPATHY : CHD, STROKE, PVD

DIABETIC ORAL MANIFESTATIONS : 10–75%

GINGIVITIS AND PERIODONTIS ARE MOST PREVALENT
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DIFFERENCES IN RATES (%) OF T2DM IN MAJOR ETHNIC GROUPS
(McCarty & Zimmet 1994, Provided : Tjokroprawiro 1989-2012)

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
(Melanesian) Rural Fiji 1.9 (Oriental) Mauritian Chinese 13.1
(Oriental) Rural Chinese 1.6 (Polynesian) Urban Western Samoa 10.6
Indonesia (East Java) : (African) US African American 10.3
- Urban-Surabaya (Adimasta et al 1980) 1.43 (European) Southern Italy 10.2
- Rural (Tjokroprawiro et al 1989) 1.47 (Melanesian) Urban Fiji 8.5
Suspect MRDM : + 21% of DM in Rurals Prevalence Rates of Small Populations :
- Urban-Surabaya (Pranoto et al 2006) 6.0%
Pima Indians 50.3% Nauru 41.3%
African Rural Tanzania 1.2
(Arab) Rural Tunisia 1.2 Manado : 8-10% Surabaya : 6.0%

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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 9
Global Diabetes Statistics
(Diabetes Atlas IDF 2003, Provided : Tjokroprawiro 2004-2012)

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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IDF Regions and Global Projections of the Number of People with Diabetes (20-79 years) : 2011 and 2030

IDF, Diabetes Atlas 5th Edition-2011, Provided : 2012

The 21th World Diabetes Congress : Dubai, 5-8 December 2011

2011 2030 INCREASE

REGION MILLIONS MILLIONS %
Africa 14.7 28.0 90%
Middle East and Noth Africa 32.8 59.7 83%
South-East Asia 71.4 120.9 69%
South and Central America 25.1 39.9 59%
Western Pacific 131.9 187.9 42%
North America and Caribbean 37.7 51.2 36%
Europe 52.6 64.0 22%
World 366.2 551.8 51%
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The TOP 10 COUNTRIES of People with Diabetes (20-79 Yrs) – IDF 2009
(IDF Diabetes Atlas 4th Edition-2009, Illustrated : Tjokroprawiro 2012)

60
* *) Number of People with Diabetes (20-79 Years): in Million
50.8
NO. OF CASES (MILLIONS)

50 *
43.2
40 DM-by IDF – 2009
*
30 26.8

20
* * *
9.6 7.6 * * * 7.0 *
10 7.5 7.1 7.1 6.8

0
1 2 3 4 5 6 7 8 9 10
INDIA CHINA USA RUSSIAN BRAZIL GERM PKTAN JAPAN INA MEXICO
FEDERATION

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 12
The TOP 10 COUNTRIES of People with Diabetes (20-79 Yrs) – IDF 2011
(IDF Diabetes Atlas 5th Edition-2011, Illustrated : Tjokroprawiro 2012)

*
90.0
90 *) Number of People with Diabetes (20-79 Years) : in Million
NO. OF CASES (MILLIONS)

80 **) Diabetes National Prevalence (%)

70 * Germany and Pakistan : Out of the TOP TEN
61.3
60 Bangladesh and Egypt : Newcomers of the TOP TEN
50 **
9.29
40 DM-by IDF – 2011
30
**
8.31
*
23.7
20 * * * * * * *
12.6 12.4 10.7 10.3 8.4 7.3
** 7.3
10 10.94 **
11.54 ** ** ** ** ** **
9.72 11.20 14.85 9.58 15.16 4.73
0
1 2 3 4 5 6 7 8 9 10
CHINA INDIA USA RUSSIAN BRAZIL JAPAN MEXICO BANGLA EGYPT INA
FEDERATION DESH
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 13

CATEGORIES OF INCREASED RISK FOR DIABETES (IRD = PREDIABETES*) : ADA 2012

(Summarized : Tjokroprawiro 2011-2012)

1 FPG 100 mg/dl to 125 mg/dl : IFG – PREDIABETES

2 2-h PG 140 mg/dl to 199 mg/dl in the 75 g OGTT : IGT – PRE DIABETES

3 HbA1c 5.7 – 6.4% : IRD or PREDIABETES

THE TERM PRE-DIABETES MAY BE APPLIED IF DESIRED
* For all Three tests, risk is continuous extending below the lower limit of the
range and becoming disproportionately greater at higher ends of the range
ADA = American Diabetes Association NORMAL : A1C < 5.7 %
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STANDARDS OF MEDICAL CARE IN DIABETES ADA-2012
CLASSIFICATION OF DIABETES MELLITUS
(ADA-2012, Added by KONSENSUS PERKENI-2011 and SURABAYA-1986)

I TYPE 1 DIABETES*
A. Immune Mediated
B. Idiopathic
II TYPE 2 DIABETES*
(Results from -cell destruction, usually leading to absolute insulin deficiency)
(Results from a progression Insulin Secretory Defect on the background of
Insulin Resistance)

III OTHER SPECIFIC TYPES OF DIABETES due to other causes, e.g. :

A Genetic Defects of -CELL FUNCTION Based on PERKENI 2011 & Surabaya (E-I) :
B Genetic Defects in INSULIN ACTION E Endocrinophathies
C Diseases of the Exocrine Pancreas F Infections
(such as Cystic Fibrosis-Related Diabetes
= CFRD)
G Uncommon form of Immune-mediated Diabetes
D Drug-or CHEMICAL-INDUCED (such H Other Genetic Syndromes associated with
as in-the TREATMENT of AIDS or Diabetes
after ORGAN TRANSPLANTATION) I MRDM (Surabaya 1986)
IV GESTATIONAL DIABETES MELLITUS (GDM) : DM diagnosed during Pregnancy
DM Variation : DM Type X (Tjokroprawiro et al, 1991) – LADA (Tuomi et al 1993) – DM 1.5 (Zimmet 1993
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CRITERIA for the DIAGNOSIS of DIABETES: PERKENI 2011, ADA 2012

(Summarized : Tjokroprawiro 2011-2012)

1 HbA
HbA1c1c>>6.5
6.5%% by NGSP Certified and Standardized to DCCT Assay
(NGSP : The National Glycohemoglobin Standardization Program)
or
2 FPG > 126 mg/dl FASTING means NO CALORIC INTAKE > 8 Hours
or
3 2-h PG > 200 mg/dl during OGTT (WHO, GLUCOSE LOADING 75g)
or
4 RANDOM PLASMA GLUCOSE > 200 mg/dl in Patients with :
CLASSIC SYMPTOMS of HYPERGLYCEMIA or HYPERGLYCEMIC CRISIS

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 Criteria for Testing for Diabetes in Asymptomatic Adult Individuals 16

(Standards of Medical Care in Diabetes - ADA 2012)

A Testing should be considered in all adults who are OVERWEIGHT (BMI >25 kg/m2*, Indonesia: >23 kg/m2)
and WHO HAVE ONE OR MORE ADDITIONAL RISK FACTORS :
1 PHYSICAL INACTIVITY
2 First-degree Relative with Diabetes
3 High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian
American, Pacific Islander)
4 WOMEN who delivered a baby weighing >9 lb or who were diagnosed with GDM
5 HYPERTENSION (blood pressure >140/90 mmHg or on therapy for hypertension)
6 HDL CHOLESTEROL level <35 mg/dL (0.90 mmol/L) and/or a TRIGLYCERIDE level >250 mg/dL
(2.82 mmol/L)
7 WOMEN with PCOS
8 A1C >5.7%, IGT, or IFG on PREVIOUS TESTING
9 OTHER CLINICAL CONDITIONS associated with INSULIN RESISTANCE (e.g.,
severe obesity, acanthosis nigricans)
10 HISTORY of CVD
B In the absence of the above criteria, TESTING for DIABETES SHOULD BEGIN at AGE 45 YEARS
C IF RESULTS are NORMAL, testing should be REPEATED at LEAST at 3-YEAR INTERVALS, with
consideration of more-frequent testing depending on initial results (e.g., those with prediabetes should be
tested yearly) and risk status.
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PELAKSANAAN TES TOLERANSI GLUKOSA ORAL (TTGO)
(Perkeni-2006, ADA-2007, Tjokroprawiro 2006-2012)

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 tersebut 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 18
(KONSENSUS PERKENI 2011)
KELUHAN KLINIK DIABETES

KELUHAN KLASIK DIABETES (+) KELUHAN KLASIK (-)

GDP > 126 < 126 GDP > 126 100-125 < 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

DIABETES MELLITUS 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-SDNC - Belum Perlu Obat Penurun Glukosa
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PRACTICAL TOOL FOR INSULIN RESISTANCE AND -CELL FUNCTION

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

HOMA-R Fasting Insulin (U/ml) x FPG (mmol/l)

: (N: < 4.0)
Insulin Resistance 22.5

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

-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 20

(Bonora 1998, Summarized and Illustrated : Tjokroprawiro 2006-2012)

IFG = Impaired Fasting Glucose IGT = Impaired Glucose Tolerance

T2DM
 1st Phase and  IR in Liver  1st Phase and  IR in Periphery
1

HYPER-CHOL 8 2 IFG & IGT

SEQUENTIAL
PREVALENCES OF IR
 URIC ACID 7 in 3 The MetS
METABOLIC
DISORDERS

LOW HDL-C 6 4 HYPERTENSION

5
IR = INSULIN RESISTANCE HYPERTRIGLYCERIDAEMIA IR = INSULIN RESISTANCE
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 1. DM TIPE-1 (DMT1) : FROM -CELL DESTRUCTION TO
21
ABSOLUTE INSULIN DEFICIENCY

2. PATOFISIOLOGI DM TIPE-2 (DMT2) :

PROGREESSIVE INSULIN SECRETORY DEFECT ("AIR") ON THE BACKGROUND OF I.R.

GABUNGAN IR + IMPAIRED "AIR" T2DM

IR : INSULIN RESISTANCE
"AIR" : ACUTE INSULIN RESPONSE (FIRST PHASE)

*SEKRESI INSULIN : 1 FIRST PHASE (ACUTE) = "AIR" : 0-5 menit

2 SECOND PHASE
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 MACAM DM DI PRAKTEK SEHARI-HARI
22

(Rangkuman : Tjokroprawiro 1993-2012)

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%, IMT <19
muda (<20th) 3 Tanpa Insulin 4 Resisten insulin DM-Type X1
4 Kurus mendadak > 10 hr. tidak 5 Resisten ketosis DM-Type X2
Dx-Definitif : timbul KAD Dx-Definitif : MODY-1
Dx-Dugaan ditambah 4 C-peptide Dx-Dugaan ditambah Calon DM-Type X-3 MODY-2
1 C-peptide O: < 0.5 Puasa > 1.1 1 PABA test <60% MODY-3
2 jam : < 0.5 2 C-peptide >0.6 MODY-4
2 Ax : tanpa MODY-5
insulin lebih DM-Tipe X-3
(Tjokroprawiro 1991) MODY-6
dari 10 hari, Tes glukosa sesudah
timbul KAD atau LADA MODY-7
60 menit C-peptide
3 GAD 65 + naik >200% (Tuomi et al 1993)

C-PEPTIDE DARAH PUASA PAGI, NORMAL : 1.1 – 4.4 ng/ml*)

KADAR INSULIN DARAH PUASA : 2.6 – 24.9 U/ml *) Tergantung KITSnya
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DIAGNOSIS DAN KLASIFIKASI NEFROPATI DIABETIK
(Kriteria Surabaya 1985 dan 1989)

TIGA PERSYARATAN DIAGNOSIS NEFROPATI-DIABETIK (ND) :

1 DIABETES MELLITUS

2 RETINOPATI DIABETIK HARUS : POSITIF

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 pemeriksaan tanpa adanya
penyebab proteinuria lain.

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 SURABAYA CLASSIFICATION OF DIABETIC NEPHROPATHY (DN)-2005 24
Nefropati Diabetik St. 2 (Serum Kreatinin 1.5 – 2.5 mg/dl : Rendah Protein dan Batasi KTT)
Nefropati Diabetik St. 3 & 4 (Serum Kreatinin > 2.5 mg/dl : Rendah Protein dan Pantang KTT)
(Tjokroprawiro 2004, Yogiantoro et al 2004) KTT : Kacang, Tahu, Tempe

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, 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-SDNC ** THE FORMULA OF GFR MEASUREMENT RELY ON A STABLE SERUM CREATININE CONCENTRATION
 25
STAGES OF CHRONIC KIDNEY DISEASE : CKD
(National Kidney Foundation-Levey et al 2003; Position Statement ADA 2012)

CHRONIC KIDNEY DISEASE IS DEFINED AS EITHER KIDNEY DAMAGE OR

GFR (MDRD) <60 mL/min/1.73 m2 FOR > 3 MONTHS by FORMULA : MDRD or CG

GFR (MDRD)
STAGE DESCRIPTION
(mL/min/1.73 m2)
KIDNEY DAMAGE*) with
1 >90
NORMAL or  GFR

KIDNEY DAMAGE*) with

2 60-89
MILDLY  GFR

3 MODERATELY  GFR 30-59

4 SEVERELY  GFR 15-29

5 KIDNEY FAILURE <15 or DIALYSIS
MDRD : Modification of Diet in Renal Disease CG : Cockcroft Gault
*) Kidney
ASK-SDNC Damage Defined as Abnormalities in Pathologic, Urine, Blood, or Imaging Tests)
 26
THE FORMULA OF COCKROFT – GAULT : eGFR (estimated GFR)
SC = SERUM CREATININE eGFR CREATININE CLEARANCE

S
Other FORMULA : MDRD (Modification of Diet in Renal Disease)
(Summarized : Tjokroprawiro 2010-2012)

eGFR (o ) (140-AGE) X BODY WEIGHT (Kg)

=
(mL/min.) PLASMA CREATININE (mg/dl) x 72

eGFR ( o+ ) (140-AGE) X BODY WEIGHT (Kg)

= x 0.85
(mL/min.) PLASMA CREATININE (mg/dl) x 72

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 27

THE MDRD FORMULA (MODIFICATION OF DIET IN RENAL DISEASE)

SC = SERUM CREATININE eGFR CREATININE CLEARANCE

S
eGFR (MDRD) for MALE

186 x (SC)–1.154 x (AGE)–0.203 x (1.212 IF BLACK/ASIA)

eGFR (MDRD) for FEMALE

186 x (SC)–1.154 x (AGE)–0.203 x (0.742) x (1.212 IF BLACK/ASIA)

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DEFINITION OF ABNORMALITIES IN ALBUMIN EXCRETION
(ADA 2006, Provided : Tjokroprawiro 2006 – 2012)

24-h COLLECTION TIMED COLLECTION Spot Collection : ACR

CATEGORY g/mg Creatinine
(mg/24 h) (g/min) Easiest to Carry Out
NORMAL < 30 < 20 < 30
MICRO ALBUMINURIA 30 - 299 20 - 199 30 - 299
MACRO ALBUMINURIA
CLINICAL ALBUMINURIA
> 300 > 200 > 300

Eight Causes 1 Excercise within 24 h, 2 Marked Hyperglycemia, 3 Marked Hypertension,

of
Elevated AER 4 Infection, 5 Fever, 6 CHF
ANY TWO OF THREE SPECIMENS COLLECTED WITHIN A 3-6 MONTH PERIOD
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 29
PENTALOGI-TERAPI DIABETES MELLITUS
(Askandar Tjokroprawiro 1983-2012)

1 PENYULUHAN (tentang DIABETES MELLITUS)

2 POLA MAKAN = PM (DIET ATAU TERAPI NUTRISI MEDIS = TNM)

3 LATIHAN FISIK : * PRIMER (1.0 – 2 jam sesudah makan)
* SEKUNDER (Pagi dan Sore sebelum mandi)

OBAT HIPOGLIKEMIK ORAL (OHO) OHO = OAD

4
OBAT ANTI DIABETES (OAD) INSULIN
Sel Beta : pada Tikus*) Pusat Diabetes dan
5 CANGKOK PANKREAS Nutrisi
Total : pada Anjing*) (1989, 1991)
*) SUDAH DIKERJAKAN OLEH PUSAT DIABETES DAN NUTRISI
RSUD DR. SOETOMO – FK UNAIR PADA TH 1989 DAN 1991
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 30
NUTRITION IN DIABETES MELLITUS
Clinical Experiences : Tjokroprawiro 1978-2012

ORAL NUTRITION PAR ENTERAL NUTRITION = P.E.N. ENTERAL NUTRITION

Since 1978 Since 1993 Since 1995

DIABETIC DIETS PAR ENTERAL NUTRITION ( "SONDE" )

MEDICAL NUTRITION THERAPY
P.E.N. P-P.E.N. E1 , E 2 , E3 , E4 , E5 , E6
(MNT)

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

of
at Dr. Soetomo Hospital P-P.E.N. in DM E3 :14.00 E4 :17.00

From the B-Diet 1978 PERIPHERAL P E5 :20.00 E6 :23.00

PAR P
to
ENTERAL E
The B1-L 2004 NUTRITION N INSULIN NO INSULIN
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 THE 6-E (E-1 UP TO E-6) REGIMEN OF ENTERAL NUTRITION FOR DIABETICS 31
("TUBE FEEDING" "SONDE")
(Clinical Experiences : Tjokroprawiro 1995-2012)

1 6 Times/day 2 Started at 08.00 am 3 3-Hour Interval

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 am 11.00 am 02.00 pm 05.00 pm 08.00 pm 11.00 pm

1 2 3 4 5 6
DIANERAL® MUFA or D DIANERAL® MUFA or D DIANERAL® MUFA or D

INSULIN INSULIN INSULIN

EXAMPLE : DIANERAL® (D) OR HOSPITAL FORMULA

TIMING OF INSULIN INJECTION : 30 MIN. BEFORE OR PRECISELY on E1 , E3 , E5

Hospital Formula : E1, E3, E5 Pharm. Formula : E2, E4, E6 : Sites of MUFA
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 32
The Diet-B 1978 (Revised TNM-2002) : The Mother - Diet
Prospective Study (1978) and Clinical Experiences (1978-2011)
(Tjokroprawiro 1978-2012; TNM = Terapi Nutrisi Medik)

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

2 Diet-B Fasting (1978) 12 Diet-GL (2000)
3 Diet-B1 (60% Cbh, 20% P, 20% L) (1980) 13 Diet-H (Hepar) (2001)
4 Diet-B1 Fasting (1980) 14 Diet KV-T1 (2004)
5 Diet-B2** ) : ND(DKD)-Stage 2 (1982) 15 Diet KV-T2 For (2004)
16 Diet KV-T3 Pre GDM (2004)
6 Diet-B3** ) : ND(DKD)-St 3 & 4 (1983)
17 Diet KV-L (2004)
7 Diet-Be** ) : REGULAR HD (1983) 18 Diet B1-T1 (2004)
8 Diet-M (Malnutrisi) (1989) 19 Diet B1-T2 For (2004)
9 Diet-M Fasting (1989) 20 Diet B1-T3 GDM (2004)
10 Diet-G*** ) : for Gangrene (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 (TNMs) at Dr. SOETOMO HOSPITAL 33

DIET-G = Diet-H and DIET-KV

(Tjokroprawiro, Hari Witarti, Indrawati, Frieda et al, 1999-2007)

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 via  Nitric Oxide (NO) Asymmetric Di Methyl Arginine

HOMOCYSTEINE : Oxidative Stress , ADMA  (ADMA)
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 34
DIET-B (1978)* : The Mother Diet
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
(Salah satu atau lebih : TG , HDL , Kol. Tot. , LDL )

3 DM LEBIH DARI 10 TAHUN

* Hasil Disertasi S3 (Askandar Tjokroprawiro 1978)
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 THERAPEUTIC DIETS FOR DIABETICS AND OR DYSLIPIDEMICS 35

MACRONUTRIENT THE B-DIET*) RECOMMENDATION

FIBER (Tjokroprawiro 1978, Revised : 2002) (ADA, 2002, 2003)

CHO 68% 60-70%

Starch (CHO plus MUFA**)
"Sugar Free" ***)
LIPID 20% <30%
CHOL <300 mg/day <300 mg/day
P/S Ratio 1.0 ?
SAFA & TUFA 5% 7-10%
PUFA 5% 10%
MUFA 10% Mentioned Above
PROTEIN 12% 15-20%
FIBER 25 - 35 g/day 20-35 g/day
Connor (1982) : Single Diet (CBH 65%, L 20%, P 15%, Chol. 100 mg/day)
*) Disertation-1978 (The B as The Mother-Diet) ***) Acceptable Daily Intake
**) The Percentage must be Individualized (Established by FDA)
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 36
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
Albuminuria Berat (Positif 4 )
Kandungan Protein : 0.8 g/kgBB/hari
Progresivitas Gagal Ginjal
Vitamin C Maks. 100 mg,
Pantang NSAID, dll

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 PERBANDINGAN GOLONGAN OHO 37
(KONSENSUS PERKENI 2011)

Cara kerja utama Efek samping Reduksi Keuntungan Kerugian

utama A1C
Sulfonilurea Meningkatkan sekresi BB naik, 1,0-2,0% Sangat efektif Meningkatkan berat badan,
insulin hipoglikemia hipoglikemia (glibenklamid dan
klorpropamid)
Glinid Meningkatkan sekresi BB naik, 0,5-1,5% Sangat efektif Meningkatkan berat badan, pemberian
insulin hipoglikemia 3x/hari, harganya mahal dan
Hipoglikemia
Metformin Menekan produksi Dispepsia, diare, 1,0-2,0% Tidak ada kaitan Efek samping gastrointestinal,
glukosa hati & asidosis laktat dengan berat badan kontraindikasi pada insufisiensi renal
menambah sensitifitas
terhadap insulin
Penghambat Menghambat absorpsi Flatulens, tinja 0.,5-0,8% Tidak ada kaitan Sering menimbulkan efek
glukosidasealfa glukosa lembek dengan berat badan gastrointestinal, 3x/hari dan mahal
Tiazolidindion Menambah sensitifitas Edema 0,5-1,4% Memperbaiki profil Retensi cairan, CHF, fraktur,
terhadap insulin Lipid (pioglitazon), berpotensi berpotensi menimbulkan infark
menurunkan infark miokard miokard, dan mahal
(pioglitazon)
DPP-4 inhibitor Meningkatkan sekresi Sebah, muntah 0,5-0,8% Tidak ada kaitan dengan berat Penggunaan jangka panjang tidak
insulin, menghambat badan disarankan, mahal
sekresi glukagon
Inkretin Meningkatkan sekresi Sebah, muntah 0,5-1,0% Penurunan berat badan Injeksi 2x/hari, penggunaan jangka
analog/mimetik insulin, menghambat panjang tidak disarankan, dan mahal
sekresi glukagon
Insulin Menekan produksi Hipoglikemi, BB 1,5-3,5% Dosis tidak terbatas, Injeksi 1-4 kali/hari, harus dimonitor,
glukosa hati, stimulasi naik memperbaiki profil lipid da meningkatkan berat badan,
pemanfaatan glukosa sangat efektif hipoglikemia dan analognya mahal

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 Keterangan :
OBAT HIPOGLIKEMIK ORAL : KONSENSUS PERKENI 2011 * Produk orisinal
** Belum beredar di Indonesia
38
*** Kadar plasma efektif terpelihara selama 24 jam
Golongan Generik Nama Dagang Mg/tab Dosis harian Lama kerja Frek/hari Waktu
(jam)
Glibenclamid Daonil* 2,5-5 2,5-15 12-24 1-2
Minidiab 5-10 5-20 10-16 1-2
Glipizid Glucotrol-XL 5-10 5-20 12-16** 1
Diamicron 80 80-320 10-20 1-2 Sebelum
Gliklazid Diamicron-MR 30-60 30-120 24 1 makan
Glikuidon Glurenom 30 30-120 6-8 2-3
Amaryl* 1-2-3-4 0,5-6 24 1
Gluvas 1-2-3-4 1-6 24 1
Glimepirid Amadiab 1-2-3-4 1-6 24 1
Metrix 1-2-3-4 1-6 24 1
Repaglinid Dexanorm 1 1,5-6 - 3
Glinid
Nateglinid Starlix 120 360 - 3
Actos* 15-30 15-45 24 1
Tiazolidindion Pioglitazon Deculin 15-30 15-45 24 1 Tidak bergantung

Pionix 15-30 15-45 18-24 1 jadwal makan

Penghambat Glucobay 50-100 100-300 3 Bersama suapan
Acarbose
Glukosidase  Eclid 50-100 100-300 3 pertama
Biguanid Glucophage 500-850 250-3000 6-8 1-3
Metformin
Glumin 500 500-3000 6-8 2-3
Bersama/sesudah
Glucophage-XR* 500-750
Metformin XR makan
Glumin-XR 500 500-2000 24 1
Vildagliptin Galvus 50 50-100 12-24 1-2 Tidak bergantung
Penghambat DPP-IV Sitagliptin Januvia 25, 50, 100 25-100 24 1 jadwal makan
Saxagliptin Onglyza 120 5 24 1
Metformin + 250/1,25 Total Glibenclamid 12-24 1-2
Glibenklamid Glucovance 500/2,5 maksimal 20 mg/hr
Obat Kombinasi 500/5
Tetap Glimepirid + Amaryl-Met 1/250 2/500 - 2
Metformin FDC 2/500 4/1000
Pioglitazone + Pionix M 15/500 Total Pioglitazone
Metformin 30/850 18-24 1 Bersama/sesudah
maksimal 45 mg/hr
Sitagliptin + 50/500 Total Sitagliptin makan
Janumet 1
Metformin 50/1000 maksimal 100mg/hr
Vildagliptin + 50/500 Total Vildagliptin
Galvusmet
Metformin 50/850 12-24 2
50/1000 maksimal 100mg/hr
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 MEKANISME KERJA, EFEK SAMPING UTAMA, DAN A1C 39

(KONSENSUS PERKENI 2011, Provided : Tjokroprawiro 2011-2012)

OAD CARA KERJA UTAMA EFEK SAMPING UTAMA PENURUNAN A1C

INSULIN
Sulfonilurea Meningkatkan sekresi insulin BB naik, 1.0 – 2.0 %
hipoglikemia
Glinid Meningkatkan sekresi insulin BB naik, 0,5-1,5%
hipoglikemia
Metformin • Menekan produksi glukosa hati Diare, dispepsia, 1.0 – 2.0 %
• Menambah sensitivitas insulin asidosis laktat
Penghambat Menghambat absorpsi glukosa Flatulens, 0.5 – 0.8 %
Glukosidase Alfa tinja lembek
Tiazolidindion Menambah sensitivitas terhadap Edema 0.5 – 1.4 %
(Glitazon) insulin

INLACIN® Novel Insulin Sensitizer (2011) "Non" 1.13 % (6 minggu)

Insulin Menekan produksi glukosa hati, Hipoglikemia, 1`.5 – 3.5 %
stimulasi pemanfaatan glukosa BB naik

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 PUSAT DIABETES & NUTRISI SURABAYA (PDNS) :1986-2012 40

RSUD Dr. SOETOMO PDNS Lt-7

(1200 m2)

RSUD Dr. SOETOMO, 1938 – 2012 : Bed Capacity 1550

PDNS : Core Stafs 8, Expert Members : 52
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