ASK-SDNC

GARIS BESAR KULIAH UNTUK MAHASISWA SEMESTER-6

DIABETES MELLITUS-I

FAKULTAS KEDOKTERAN UNIVERSITAS AIRLANGGA, SURABAYA
1
2012
16-927-B
Prof. Dr. dr. Askandar Tjokroprawiro Sp.PD, K-EMD, FINASIM
SURABAYA DIABETES AND NUTRITION CENTRE - Dr. SOETOMO TEACHING HOSPITAL
FACULTY OF MEDICINE AIRLANGGA UNIVERSITY, SURABAYA
Division of Endocrinology and Metabolism Dept. of Internal Medicine
SURABAYA, 05 MARCH 2012
Kuliah DM-I : SLIDE 1 40
dr. Sri Murtiwi Sp.PD, K-EMD, FINASIM
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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 atau

SIPHON = FLOW-THROUGH = RUN-THROUGH, berarti
mengalir terus. Sehabis minum banyak, diikuti kencing
banyak. MELLITUS : MADU atau MANIS.
DIABETES MELLITUS = KENCING MANIS.
2
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.
Continued
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Th. 1909 JEAN d MEYER (Belgia) memberi nama hormon INSULIN
(Latin : Insulina = Island)
SEJARAH
3
Th. 1869 PAUL LANGERHANS (Jerman) : timbunan Glukosa
dalam Hepar sebagai Glikogen, dan Hiperglikemia Akut
akibat kerusakan Medulla Oblongata (PIQRE DIABETES).
Th. 1674 THOMAS WILLIS (Inggris), merasakan rasa manis pada
Urine (Abad 5-6 rasa manis ini sudah pernah dilaporkan
oleh Dokter Indian).
Continued
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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
SEJARAH
4
Continued
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DM TYPE 2 (Tattersall 2003)
INSULIN RESISTANCE and -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.
5
DIABETES MELLITUS
DM TYPE 1 (Tattersall 2003)
THE -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)
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
6
: 133 px
: 1061
: 15381
: 16567
: 2914
: 22029
: 26406
: 27824
: 5654
: 8222
: 10278
: 11475
: 12608
: 13818
: 19039
: 20366
: 17667 : 29394
: 31457
: 33636
: 35606
: 37704
: 39875 : 9150
: 42149
: 43264
: 45536
1990
1991
1986
1987
1988
1989
1964
1970
1975
1980
1984
1985
1995
1996
1997
1992
1993
1994
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
MANUAL
ELECTRONIC
: 33157
: 32862
2010 : 35717
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% 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0
Commulative Prevalence of CVD : +82%
(in line with Dyslipidemia)
30 million in USA
(FELDMAN, et al 1994)
Tjokroprawiro 1993 (Revised : 2002) ADA 2005-2010
CHRONIC DIABETIC COMPLICATIONS AND PROVIDED INFORMATION
DIABETIC ORAL MANIFESTATIONS : 1075%
GINGIVITIS AND PERIODONTIS ARE MOST PREVALENT
CHD : "THE WINDOW OF MACROANGIOPATHY" RETINOPATHY : "THE WINDOW OF MICROANGIOPATHY"
MICROALBUMINURIA (30-299 mg/day = ACR) : IS REFERRED TO AS HAVING INCIPIENT NEPHROPATHY
MICROANGIOPATHY : RETINOPATHY, NEPHROPATHY, NEUROPATHY, MACROANGIOPATHY : CHD, STROKE, PVD
67.0
Dyslipidemia
51.4 Symptomatic Neuropathy
50.9 Erectile Dysfunction
27.2 Retinopathy
25.5 Joint Manifestation
16.3 Cataract
12.8 Pulmonary Tbc
12.1 Hypertension (WHO,1983)
10.0 CHD
5.7 CLINICAL NEPHROPATHY
4.2 Stroke
3.8 Cellulitis - Gangrene
3.0 Symptomatic Gall Stone
Based on JNC7, 2003 : + 32%
7
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(McCarty & Zimmet 1994, Provided : Tjokroprawiro 1989-2012)
DIFFERENCES IN RATES (%) OF T2DM IN MAJOR ETHNIC GROUPS
LOWEST REPORTED RATES
(Hispanic) Central Mexico 5.6
(Micronesian) Rural Kiribati 4.3
(Polynesian) Rural Western Samoa 4.0
(European) Poland 3.5
(Asian Indian) Rural India 2.7
(Melanesian) Rural Fiji 1.9
(Oriental) Rural Chinese 1.6
Indonesia (East Java) :
- Urban-Surabaya (Adimasta et al 1980) 1.43
- Rural (Tjokroprawiro et al 1989) 1.47
Suspect MRDM : + 21% of DM in Rurals
African Rural Tanzania 1.2
(Arab) Rural Tunisia 1.2
- Urban-Surabaya (Pranoto et al 2006) 6.0%
8
HIGHEST REPORTED RATES
(Asian Indian) Fijian Island 22.0
(Micronesian) Urban Kiribati 14.6
(Arab) Oman 14.2
(Hispanic) US Mexican 14.1
(Oriental) Mauritian Chinese 13.1
(Polynesian) Urban Western Samoa 10.6
(African) US African American 10.3
(European) Southern Italy 10.2
(Melanesian) Urban Fiji 8.5
Prevalence Rates of Small Populations :
Pima Indians 50.3% Nauru 41.3%
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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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

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
472,000,000 Predicted Number of People with IGT, 2025
THE ROLES OF
METFORMIN
28%
Proportion of DM attributable to weight gain, Southeast Asia Males, 2003
80%
Proportion of DM attributable to weight gain, Western Europe Males, 2003

9
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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 5
th
Edition-2011, Provided : 2012
10
The 21
th
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 4
th
Edition-2009, Illustrated : Tjokroprawiro 2012)
N
O
.

O
F

C
A
S
E
S

(
M
I
L
L
I
O
N
S
)

0
10
20
30
40
50
60
INDIA
*
50.8
1
CHINA
*
43.2
2
USA
*
26.8
3
RUSSIAN
FEDERATION
*
9.6
4
BRAZIL
*
7.6
5
GERM
*
7.5
6
PKTAN
*
7.1
7
JAPAN
*
7.1
8
MEXICO
*
6.8
10
INA
9
*
7.0
11
*) Number of People with Diabetes (20-79 Years): in Million
DM-by IDF 2009
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The TOP 10 COUNTRIES of People with Diabetes (20-79 Yrs) IDF 2011
(IDF Diabetes Atlas 5
th
Edition-2011, Illustrated : Tjokroprawiro 2012)
12
N
O
.

O
F

C
A
S
E
S

(
M
I
L
L
I
O
N
S
)

0
10
20
30
40
50
60
70
80
90
BRAZIL
5
*
12.4
**
9.72
EGYPT
9
*
7.3
**
15.16
RUSSIAN
FEDERATION
4
*
12.6
**
11.54
USA
3
*
23.7
**
10.94
**) Diabetes National Prevalence (%)
*) Number of People with Diabetes (20-79 Years) : in Million
INA
10
**
4.73
*
7.3
CHINA
1
**
9.29
*
90.0
INDIA
2
*
61.3
**
8.31
BANGLA
DESH
8
*
8.4
**
9.58
MEXICO
7
*
10.3
**
14.85
JAPAN
6
*
10.7
**
11.20
Germany and Pakistan : Out of the TOP TEN
Bangladesh and Egypt : Newcomers of the TOP TEN
DM-by IDF 2011
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CATEGORIES OF INCREASED RISK FOR DIABETES (IRD = PREDIABETES*) : ADA 2012
(Summarized : Tjokroprawiro 2011-2012)
NORMAL : A1C < 5.7 %
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
THE TERM PRE-DIABETES MAY BE APPLIED IF DESIRED
HbA
1c
5.7 6.4% : IRD or PREDIABETES
* 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
13
(IRD = PREDIABETES*)
ADA = American Diabetes Association
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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)
Drug-or CHEMICAL-INDUCED (such
Genetic Defects of -CELL FUNCTION
Genetic Defects in INSULIN ACTION
Diseases of the Exocrine Pancreas
(such as Cystic Fibrosis-Related Diabetes
= CFRD)
as in-the TREATMENT of AIDS or
after ORGAN TRANSPLANTATION)
D
A
B
C
DM Variation : DM Type X (Tjokroprawiro et al, 1991) LADA (Tuomi et al 1993) DM 1.5 (Zimmet 1993
I TYPE 1 DIABETES* (Results from -cell destruction, usually leading to absolute insulin deficiency)
II TYPE 2 DIABETES*
III OTHER SPECIFIC TYPES OF DIABETES due to other causes, e.g. :
IV
GESTATIONAL DIABETES MELLITUS (GDM) : DM diagnosed during Pregnancy
14
Infections
Uncommon form of Immune-mediated Diabetes
Other Genetic Syndromes associated with
Diabetes
Endocrinophathies
E
F
G
H
Based on PERKENI 2011 & Surabaya (E-I) :
A. Immune Mediated
B. Idiopathic
(Results from a progression Insulin Secretory Defect on the background of
Insulin Resistance)
MRDM (Surabaya 1986) I
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CRITERIA for the DIAGNOSIS of DIABETES: PERKENI 2011, ADA 2012
(Summarized : Tjokroprawiro 2011-2012)
HbA
1c
> 6.5 % by NGSP Certified and Standardized to DCCT Assay
(NGSP : The National Glycohemoglobin Standardization Program)
1 HbA
1c
> 6.5 %
4
RANDOM PLASMA GLUCOSE > 200 mg/dl in Patients with :
CLASSIC SYMPTOMS of HYPERGLYCEMIA or HYPERGLYCEMIC CRISIS
2 FPG > 126 mg/dl FASTING means NO CALORIC INTAKE > 8 Hours
3
2-h PG > 200 mg/dl during OGTT (WHO, GLUCOSE LOADING 75g)
15
or
or
or
PERKENI 2011, ADA 2012
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Criteria for Testing for Diabetes in Asymptomatic Adult Individuals
(Standards of Medical Care in Diabetes - ADA 2012)
A
Testing should be considered in all adults who are OVERWEIGHT (BMI >25 kg/m
2
*, Indonesia: >23 kg/m
2
)
and WHO HAVE ONE OR MORE ADDITIONAL RISK FACTORS :
16
PHYSICAL INACTIVITY 1
First-degree Relative with Diabetes
2
High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian
American, Pacific Islander)
3
WOMEN who delivered a baby weighing >9 lb or who were diagnosed with GDM
4
HYPERTENSION (blood pressure >140/90 mmHg or on therapy for hypertension)
5
HDL CHOLESTEROL level <35 mg/dL (0.90 mmol/L) and/or a TRIGLYCERIDE level >250 mg/dL
(2.82 mmol/L)
6
WOMEN with PCOS
7
A1C >5.7%, IGT, or IFG on PREVIOUS TESTING
8
OTHER CLINICAL CONDITIONS associated with INSULIN RESISTANCE (e.g.,
severe obesity, acanthosis nigricans)
9
HISTORY of CVD 10
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
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
17
Kegiatan Jasmani seperti yang biasa dilakukan 2
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
(KONSENSUS PERKENI 2011)
GDP = Glukosa Darah Puasa
GDS = Glukosa Darah Sewaktu
GDPT = IFG = Glukosa Darah Puasa Terganggu
TGT = Toleransi Glukosa Terganggu
KELUHAN KLASIK (-) KELUHAN KLASIK DIABETES (+)
KELUHAN KLINIK DIABETES
D I A B E T E S M E L L I T U S TGT GDPT NORMAL
- Evaluasi Status Gizi
- Evaluasi Penyulit DM
- Evaluasi Perencanaan Makan
Sesuai Kebutuhan
- Nasihat Umum
- Perencanaan Makan
- Latihan Jasmani
- Berat Idaman
- Belum Perlu Obat Penurun Glukosa
GDP

GDS
atau
GDP

GDS
atau
> 126

> 200
< 126

< 200
GDP

GDS
atau
> 126

> 200
< 126

< 200
Ulang GDS atau GDP
> 126

> 200
100-125

140-199
TTGO
GD 2 Jam
> 200 140-199 < 140


< 100
< 140
18
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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 and HOMA-B
Useful in Daily Practice
:
1
2 FOLLOW-UP OF TREATMENT
RATIONALE TREATMENT
HOMA-B
-Cell Function
:
(N: 70150%)
20 x Fasting Insulin ( U/ml)
FPG (mmol/l) 3.5
HOMA-R
Insulin Resistance
:
(N: < 4.0)
Fasting Insulin (U/ml) x FPG (mmol/l)
22.5
19
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PREVALENCE OF IR IN SELECTED METABOLIC DISORDERS
(Bonora 1998, Summarized and Illustrated : Tjokroprawiro 2006-2012)
4 HYPERTENSION
IFG & IGT 2
URIC ACID
7
LOW HDL-C 6
3
The MetS
HYPER-CHOL
8
1
st
Phase and IR in Liver
IFG = Impaired Fasting Glucose
1
st
Phase and IR in Periphery
IGT = Impaired Glucose Tolerance
IR = INSULIN RESISTANCE IR = INSULIN RESISTANCE
DISORDERS
METABOLIC
SEQUENTIAL
PREVALENCES OF IR
in
20
HYPERTRIGLYCERIDAEMIA
5
T2DM
1
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1.
DM TIPE-1 (DMT1) : FROM -CELL DESTRUCTION TO
ABSOLUTE INSULIN DEFICIENCY
PROGREESSIVE INSULIN SECRETORY DEFECT ("AIR") ON THE BACKGROUND OF I.R.
2. PATOFISIOLOGI DM TIPE-2 (DMT2) :
*SEKRESI INSULIN :
1
FIRST PHASE (ACUTE) = "AIR" : 0-5 menit
2 SECOND PHASE
GABUNGAN IR + IMPAIRED "AIR" T2DM
IR : INSULIN RESISTANCE
"AIR" : ACUTE INSULIN RESPONSE (FIRST PHASE)
21
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MACAM DM DI PRAKTEK SEHARI-HARI
(Rangkuman : Tjokroprawiro 1993-2012)
BBR <80%, IMT <19
Dx-Dugaan :
DM
Umur sekitar 14-40 th
Resisten insulin
Resisten ketosis
Dx-Definitif :
Dx-Dugaan ditambah
PABA test <60%
C-peptide >0.6
Tes glukosa sesudah
60 menit C-peptide
naik >200%

Diet - Dependent
DM
atau OHO
Dependent
Tanpa Insulin
10 hr. tidak
timbul KAD
C-peptide
Puasa > 1.1

>
Dx Dugaan :
Gejala m endadak
Insulin Dependent
Anak, atau Dewasa
(<20th)
Kurus mendadak
Dx-Definitif :
Dx-Dugaan ditambah
C-peptide O: < 0.5
Ax : tanpa
insulin lebih
dari 10 hari,
timbul KAD
muda
2 jam : < 0.5
DMT2 pada
usia sekitar
20 th
MODY-6
MODY-7
OHO dan Insulin
dependent
Calon DM-Type X-3
DM-Tipe X-3
(Tjokroprawiro 1991)
atau LADA
(Tuomi et al 1993)
DM-Type X
1
DM-Type X
2
1
2
1
3
4
2
GAD 65 3 +
MODY-1
MODY-2
MODY-3
MODY-4
MODY-5
1
2
3
4
1
2
3
4
5
1
2
22
DMTM = MRDM
Surabaya-Kobe 1989
DM-Tipe 2
(DMT2)
DM-Tipe 1
(DMT1)
MODY
"DM-Tipe X"
(Askandar, 1991)
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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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.
(Kriteria ND 1989) : DM, Retinopati Diabetik, Kreatinin Darah
>2.5 mg/dl, Proteinuria 1 (satu) kali pemeriksaan tanpa adanya
penyebab proteinuria lain.


DIAGNOSIS DAN KLASIFIKASI NEFROPATI DIABETIK
(Kriteria Surabaya 1985 dan 1989)
Atau
TIGA PERSYARATAN DIAGNOSIS NEFROPATI-DIABETIK (ND) :

23
ASK-SDNC
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
*) Diabetic Diets for DN are supplemented with Low Vit C, Folic Acid, Vit B6, Vit B12, Glutamine
S

** THE FORMULA OF GFR MEASUREMENT RELY ON A STABLE SERUM CREATININE CONCENTRATION
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
B 2*) 3 Macro Alb. eGFR 30-59 (2.5-4) B2, OAD, INS > 2 years
5 Be, INS, HD
ESDN Transplantation
Be*) Macro Alb. eGFR < 15 (> 10) 2-5 Months
4a eGFR 15-29 (4-8) B3, INS, Pre HD
4b eGFR 15-29 (8-10) Be, INS, HD
B3*)
Macro Alb. 4-18 Months
Be*)
(1986)
Type Stage
Life Expectancy
eGFR (mL/min)**
Micro/Macro
Albuminuria
MNT = DIET
OAD - INS
SC (mg/dl)
eGFR ( )
(mL/min.)
o
(140-Age) x Body Weight (Kg)
Plasma Creatinine (mg/dl) x 72
=
eGFR ( )
(mL/min.)
(140-Age) x Body Weight (Kg)
Plasma Creatinine (mg/dl) x 72
=
+
o
x 0.85
The Formula of Cockroft Gault : eGFR (estimated GFR); SC = Serum Creatinine

SURABAYA CLASSIFICATION OF DIABETIC NEPHROPATHY (DN)-2005
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
24
ASK-SDNC
STAGES OF CHRONIC KIDNEY DISEASE : CKD
(National Kidney Foundation-Levey et al 2003; Position Statement ADA 2012)
STAGE DESCRIPTION
GFR (MDRD)
(mL/min/1.73 m
2
)
1
KIDNEY DAMAGE
*)
with
NORMAL or GFR
>90
2
KIDNEY DAMAGE
*)
with
MILDLY GFR
60-89
5 KIDNEY FAILURE <15 or DIALYSIS
CHRONIC KIDNEY DISEASE IS DEFINED AS EITHER KIDNEY DAMAGE OR
GFR (MDRD) <60 mL/min/1.73 m
2
FOR > 3 MONTHS by FORMULA : MDRD or CG
3 MODERATELY GFR 30-59
4 SEVERELY GFR
15-29
MDRD : Modification of Diet in Renal Disease CG : Cockcroft Gault
25
*) Kidney Damage Defined as Abnormalities in Pathologic, Urine, Blood, or Imaging Tests)
ASK-SDNC
THE FORMULA OF COCKROFT GAULT : eGFR (estimated GFR)
SC = SERUM CREATININE eGFR CREATININE CLEARANCE S

eGFR ( )
(mL/min.)
o
=
(140-AGE) X BODY WEIGHT (Kg)
PLASMA CREATININE (mg/dl) x 72
=
(140-AGE) X BODY WEIGHT (Kg)
PLASMA CREATININE (mg/dl) x 72
eGFR ( )
(mL/min.)
+
o
x 0.85
Other FORMULA : MDRD (Modification of Diet in Renal Disease)
(Summarized : Tjokroprawiro 2010-2012)
26
ASK-SDNC
THE MDRD FORMULA (MODIFICATION OF DIET IN RENAL DISEASE)
SC = SERUM CREATININE eGFR CREATININE CLEARANCE S

186 x (SC)
1.154
x (AGE)
0.203
x (0.742) x (1.212 IF BLACK/ASIA)
eGFR (MDRD) for FEMALE
186 x (SC)
1.154
x (AGE)
0.203
x (1.212 IF BLACK/ASIA)
eGFR (MDRD) for MALE
27
ASK-SDNC
DEFINITION OF ABNORMALITIES IN ALBUMIN EXCRETION
(ADA 2006, Provided : Tjokroprawiro 2006 2012)
NORMAL
< 30 < 20 < 30
MACRO ALBUMINURIA
CLINICAL ALBUMINURIA
> 300 > 200 > 300
ANY TWO OF THREE SPECIMENS COLLECTED WITHIN A 3-6 MONTH PERIOD
30 - 299 30 - 299 20 - 199
MICRO ALBUMINURIA
Eight Causes
of
Elevated AER
1 Excercise within 24 h, 2 Marked Hyperglycemia, 3 Marked Hypertension,
4 Infection, 5 Fever, 6 CHF
28
24-h COLLECTION TIMED COLLECTION
(mg/24 h) (g/min)
CATEGORY
Spot Collection : ACR
g/mg Creatinine
Easiest to Carry Out
ASK-SDNC
3
LATIHAN FISIK : * PRIMER (1.0 2 jam sesudah makan)
* SEKUNDER (Pagi dan Sore sebelum mandi)
*) SUDAH DIKERJAKAN OLEH PUSAT DIABETES DAN NUTRISI
RSUD DR. SOETOMO FK UNAIR PADA TH 1989 DAN 1991
PENTALOGI-TERAPI DIABETES MELLITUS
(Askandar Tjokroprawiro 1983-2012)
1 PENYULUHAN (tentang DIABETES MELLITUS)
2 POLA MAKAN = PM (DIET ATAU TERAPI NUTRISI MEDIS = TNM)
5
CANGKOK PANKREAS
Pusat Diabetes dan
Nutrisi
(1989, 1991)
Sel Beta : pada Tikus*)
Total : pada Anjing*)
OBAT HIPOGLIKEMIK ORAL (OHO)
OHO = OAD
INSULIN
4
OBAT ANTI DIABETES (OAD)
29
ASK-SDNC
NUTRITION IN DIABETES MELLITUS
Clinical Experiences : Tjokroprawiro 1978-2012
DIABETIC DIETS

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

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

:08.00
:14.00
:20.00
INSULIN
E
1

E
3

E
5

:11.00
:17.00
:23.00
NO INSULIN
E
2

E
4

E
6

ORAL NUTRITION
Since 1978
ENTERAL NUTRITION
Since 1995
PAR ENTERAL NUTRITION = P.E.N.
Since 1993
PERIPHERAL P
PAR P
ENTERAL E
NUTRITION N
Ten Principles
of
P-P.E.N. in DM
30
21 Types of Diabetic Diets
at Dr. Soetomo Hospital
From the B-Diet 1978
to
The B
1
-L 2004
ASK-SDNC
THE 6-E (E-1 UP TO E-6) REGIMEN OF ENTERAL NUTRITION FOR DIABETICS
("TUBE FEEDING" "SONDE")
(Clinical Experiences : Tjokroprawiro 1995-2012)
Hospital Formula : E
1
,

E
3
,

E
5
Pharm. Formula : E
2
, E
4
, E
6
: Sites of MUFA
ENTERAL- 1
(E-1)

08.00 am
ENTERAL- 4
(E-4)

05.00 pm
ENTERAL- 5
(E-5)

08.00 pm
ENTERAL- 3
(E-3)

02.00 pm
ENTERAL- 2
(E-2)

11.00 am
ENTERAL- 6
(E-6)

11.00 pm
1 6 Times/day 2 Started at 08.00 am 3 3-Hour Interval
TIMING OF INSULIN INJECTION : 30 MIN. BEFORE OR PRECISELY on E
1
, E
3
, E
5

EXAMPLE : DIANERAL

(D) OR HOSPITAL FORMULA

1
DIANERAL

INSULIN
6
MUFA or D
2
MUFA or D
4
MUFA or D
3
DIANERAL

INSULIN
5
DIANERAL

INSULIN
31
ASK-SDNC
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)

*) 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
)
)
)
)
1 Diet-B*) : The Mother-Diet (1978)

2 Diet-B Fasting (1978)

3 Diet-B1 (60% Cbh, 20% P, 20% L) (1980)

4 Diet-B1 Fasting (1980)

5 Diet-B2** : ND(DKD)-Stage 2 (1982)
6 Diet-B3** : ND(DKD)-St 3 & 4 (1983)
7 Diet-Be** : REGULAR HD (1983)

8 Diet-M (Malnutrisi) (1989)

9 Diet-M Fasting (1989)

10
Diet-G*** : for Gangrene
(1999)
12 Diet-GL (2000)
13 Diet-H (Hepar) (2001)
14 Diet KV-T1 (2004)
15 Diet KV-T2 (2004)
16 Diet KV-T3 (2004)
17 Diet KV-L (2004)
18 Diet B1-T1 (2004)
19 Diet B1-T2 (2004)
20 Diet B1-T3 (2004)
21 Diet B1-L (2004)
For
Pre GDM
For
GDM
11 Diet-KV : for CVD (1999)
32
ASK-SDNC
(Tjokroprawiro, Hari Witarti, Indrawati, Frieda et al, 1999-2007)
SPECIFICATIONS : 3 of 21 DIABETIC DIETS (TNMs) at Dr. SOETOMO HOSPITAL
DIET-G = Diet-H and DIET-KV
Diet-B
1
plus 5 Specifications
Diet-G = Diet-H : Gangrene or Hepar

Diet-B plus 5 Specifications
Diet-KV : Stroke, CAD, POAD
These are able to lower
Homocysteine Level
(Chol. < 300 mg/day)

1 Arginin Content
2 Fiber 25-35 g/day
3 Folate
4 Vit B
6


5 Vit B
12

Diet-B (% Cal) : 68% Cbh, 20% F, 12% P
These are able to lower
Homocysteine Level
(Chol. < 300 mg/day)

1 Arginin Content
2 Fiber 25-35 g/day
3 Folate
4 Vit B
6


5 Vit B
12

Diet-B
1
(% Cal): 60% CHO, 20% F, 20% P
ARGININ : Atheroprotective via Nitric Oxide (NO)
HOMOCYSTEINE : Oxidative Stress , ADMA
Asymmetric Di Methyl Arginine
(ADMA)
33
ASK-SDNC
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
3 DM LEBIH DARI 10 TAHUN
2 DISLIPIDEMIA
(Salah satu atau lebih : TG , HDL , Kol. Tot. , LDL )
* Hasil Disertasi S3 (Askandar Tjokroprawiro 1978)
34
ASK-SDNC
(CHO plus MUFA**)
***)
<300 mg/day
?
7-10%
10%
Mentioned Above
15-20%
"Sugar Free"
<300 mg/day
1.0
5%
5%
10%
12%
CHO

LIPID
CHOL
P/S Ratio
SAFA & TUFA
PUFA
MUFA
PROTEIN
FIBER
68%
Starch
20%
25 - 35 g/day 20-35 g/day
<30%
60-70%
THERAPEUTIC DIETS FOR DIABETICS AND OR DYSLIPIDEMICS
Connor (1982) : Single Diet (CBH 65%, L 20%, P 15%, Chol. 100 mg/day)
*) Disertation-1978 (The B as The Mother-Diet)
**) The Percentage must be Individualized
***) Acceptable Daily Intake
(Established by FDA)
35
(ADA, 2002, 2003)
RECOMMENDATION
(Tjokroprawiro 1978, Revised : 2002)
THE B-DIET*)
MACRONUTRIENT
FIBER
ASK-SDNC
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)
1 PRA-HD UMUM Diet-B2
Kandungan Protein : 0.6 g/kgBB/hari
2 PRA-HD KHUSUS Diet-B3
Proteinuria > 3 g/hari, atau
Kandungan Protein : 0.8 g/kgBB/hari
Albuminuria Berat (Positif 4 )
(FASE PRA-HD)
DIABETISI FASE HD : Diet-Be
Kandungan Protein : 1.0-1.2 g/kgBB/hari
Intensivitas Menghambat
Progresivitas Gagal Ginjal
Vitamin C Maks. 100 mg,
Pantang NSAID, dll
FASE HEMODIALISA : Diet-Be
(FASE HD)
36
ASK-SDNC
PERBANDINGAN GOLONGAN OHO
(KONSENSUS PERKENI 2011)
37
Cara kerja utama Efek samping
utama
Reduksi
A1C
Keuntungan Kerugian
Sulfonilurea Meningkatkan sekresi
insulin
BB naik,
hipoglikemia
1,0-2,0% Sangat efektif Meningkatkan berat badan,
hipoglikemia (glibenklamid dan
klorpropamid)
Glinid Meningkatkan sekresi
insulin
BB naik,
hipoglikemia
0,5-1,5% Sangat efektif Meningkatkan berat badan, pemberian
3x/hari, harganya mahal dan
Hipoglikemia
Metformin Menekan produksi
glukosa hati &
menambah sensitifitas
terhadap insulin
Dispepsia, diare,
asidosis laktat
1,0-2,0% Tidak ada kaitan
dengan berat badan
Efek samping gastrointestinal,
kontraindikasi pada insufisiensi renal
Penghambat
glukosidasealfa
Menghambat absorpsi
glukosa
Flatulens, tinja
lembek
0.,5-0,8% Tidak ada kaitan
dengan berat badan
Sering menimbulkan efek
gastrointestinal, 3x/hari dan mahal
Tiazolidindion Menambah sensitifitas
terhadap insulin
Edema 0,5-1,4% Memperbaiki profil
Lipid (pioglitazon), berpotensi
menurunkan infark miokard
(pioglitazon)
Retensi cairan, CHF, fraktur,
berpotensi menimbulkan infark
miokard, dan mahal
DPP-4 inhibitor Meningkatkan sekresi
insulin, menghambat
sekresi glukagon
Sebah, muntah 0,5-0,8% Tidak ada kaitan dengan berat
badan
Penggunaan jangka panjang tidak
disarankan, mahal
Inkretin
analog/mimetik
Meningkatkan sekresi
insulin, menghambat
sekresi glukagon
Sebah, muntah 0,5-1,0% Penurunan berat badan Injeksi 2x/hari, penggunaan jangka
panjang tidak disarankan, dan mahal
Insulin Menekan produksi
glukosa hati, stimulasi
pemanfaatan glukosa
Hipoglikemi, BB
naik
1,5-3,5% Dosis tidak terbatas,
memperbaiki profil lipid da
sangat efektif
Injeksi 1-4 kali/hari, harus dimonitor,
meningkatkan berat badan,
hipoglikemia dan analognya mahal
ASK-SDNC
OBAT HIPOGLIKEMIK ORAL : KONSENSUS PERKENI 2011
Keterangan :
* Produk orisinal
**
*** Kadar plasma efektif terpelihara selama 24 jam
Belum beredar di Indonesia
38
Golongan Generik Nama Dagang Mg/tab Dosis harian
Lama kerja
(jam)
Frek/hari Waktu
Glibenclamid 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 30-60 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 Dexanorm 1 1,5-6 - 3
Nateglinid Starlix 120 360 - 3
Tiazolidindion 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 Eclid 50-100 100-300 3
Glumin 500 500-3000 6-8 2-3
Biguanid
Metformin
Glucophage 500-850 250-3000 6-8 1-3
Bersama/sesudah
makan Metformin XR
Glucophage-XR* 500-750
Glumin-XR 500 500-2000 24 1
Obat Kombinasi
Tetap
Metformin +
Glucovance
250/1,25
Total Glibenclamid
maksimal 20 mg/hr
12-24 1-2
Bersama/sesudah
Glibenklamid
500/2,5
makan
500/5
Glimepirid + Amaryl-Met
FDC
1/250 2/500 - 2
Metformin
2/500 4/1000
Pionix 15-30 15-45 18-24 1
Penghambat DPP-IV
Sitagliptin Januvia 25, 50, 100 25-100 24 1
Saxagliptin Onglyza 120 5 24 1
Tidak bergantung
jadwal makan
Vildagliptin Galvus 50 50-100 12-24 1-2
Metformin
Pionix M
Total Pioglitazone
maksimal 45 mg/hr
18-24 1
Pioglitazone + 15/500
30/850
Metformin
Janumet
1
Sitagliptin +
50/1000
50/500 Total Sitagliptin
maksimal 100mg/hr
Metformin
Galvusmet
2
Vildagliptin +
50/850
50/500
Total Vildagliptin
maksimal 100mg/hr
12-24
50/1000
ASK-SDNC
ASK-
SDNC
MEKANISME KERJA, EFEK SAMPING UTAMA, DAN A1C
(KONSENSUS PERKENI 2011, Provided : Tjokroprawiro 2011-2012)
CARA KERJA UTAMA EFEK SAMPING UTAMA PENURUNAN A1C
Insulin Menekan produksi glukosa hati, Hipoglikemia, 1`.5 3.5 %
stimulasi pemanfaatan glukosa BB naik
Sulfonilurea Meningkatkan sekresi insulin BB naik, 1.0 2.0 %
hipoglikemia
Metformin Menekan produksi glukosa hati
Menambah sensitivitas insulin
Diare, dispepsia, 1.0 2.0 %
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
Glinid Meningkatkan sekresi insulin 0,5-1,5% BB naik,
hipoglikemia
OAD
INSULIN
"Non" 1.13 % (6 minggu) INLACIN

Novel Insulin Sensitizer (2011)
39
ASK-SDNC
RSUD Dr. SOETOMO
PUSAT DIABETES & NUTRISI SURABAYA (PDNS) :1986-2012
40
PDNS Lt-7
(1200 m
2
)
RSUD Dr. SOETOMO, 1938 2012 : Bed Capacity 1550
PDNS : Core Stafs 8, Expert Members : 52