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

ASK-SDNC

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

ASK-SDNC

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.

Continued

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 (PIQRE DIABETES).

Th. 1909

JEAN d MEYER (Belgia) memberi nama hormon INSULIN

(Latin : Insulina = Island)

Continued
ASK-SDNC

SEJARAH

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
Continued
ASK-SDNC

DIABETES MELLITUS
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.
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).
ASK-SDNC

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
1970 : 1061 1987 : 11475 1993 : 19039 1999 : 31457 2005 : 43264
1975 : 2914
1980 : 5654
1984 : 8222
1985 : 9150

1988 : 12608 1994 : 20366 2000 : 33636

1989 : 13818 1995 : 22029 2001 : 35606

2006 : 45536
2007

MANUAL
ELECTRONIC

2008 : 33157
1990 : 15381 1996 : 26406 2002 : 37704 2009 : 32862
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
ASK-SDNC

CHRONIC DIABETIC COMPLICATIONS AND PROVIDED INFORMATION

Tjokroprawiro 1993 (Revised : 2002)
Dyslipidemia
Symptomatic Neuropathy
Erectile Dysfunction
Retinopathy
Joint Manifestation
Cataract
Pulmonary Tbc
Hypertension (WHO,1983)
CHD
CLINICAL NEPHROPATHY
Stroke
Cellulitis - Gangrene
Symptomatic Gall Stone

ADA 2005-2010
67.0
51.4
50.9

27.2
25.5

30 million in USA

16.3
(FELDMAN, et al 1994)
12.8
12.1
Based on JNC7, 2003 : + 32%
10.0
5.7
Commulative Prevalence of CVD : +82%
4.2
(in line with Dyslipidemia)
3.8
3.0
0.0

10.0

20.0

RETINOPATHY : "THE WINDOW OF MICROANGIOPATHY"

30.0

40.0

50.0

60.0

70.0

80.0 %

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 : 1075%

GINGIVITIS AND PERIODONTIS ARE MOST PREVALENT
ASK-SDNC

DIFFERENCES IN RATES (%) OF T2DM IN MAJOR ETHNIC GROUPS

(McCarty & Zimmet 1994, Provided : Tjokroprawiro 1989-2012)

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
- Urban-Surabaya (Pranoto et al 2006) 6.0%
African Rural Tanzania
1.2
(Arab) Rural Tunisia
1.2

HIGHEST REPORTED RATES

(Asian Indian) Fijian Island
(Micronesian) Urban Kiribati
(Arab) Oman
(Hispanic) US Mexican
(Oriental) Mauritian Chinese
(Polynesian) Urban Western Samoa
(African) US African American
(European) Southern Italy
(Melanesian) Urban Fiji

22.0
14.6
14.2
14.1
13.1
10.6
10.3
10.2
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.
ASK-SDNC

Global Diabetes Statistics

(Diabetes Atlas IDF 2003, Provided : Tjokroprawiro 2004-2012)
4%
20%
30%

Prevalence of DM, Netherlands, 2003

Prevalence of DM, UAE, 2003
Prevalence of DM, Nauru, 2003

28%
80%

Proportion of DM attributable to weight gain, Southeast Asia Males, 2003

104,800
430,000
194,000,000
333,000,000

Number of Children with TIDM, Southeast Asia, 2003

Number of Children with TIDM, Worldwide, 2003
Number of People with DM, 2003
Predicted number of People with DM, 2025

314,000,000
472,000,000

Number of People with IGT, 2003; No Data for IFG

ASK-SDNC

Proportion of DM attributable to weight gain, Western Europe Males, 2003

Predicted Number of People with IGT, 2025

THE ROLES OF
METFORMIN

10
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
MILLIONS

2030
MILLIONS

INCREASE
%

Africa
Middle East and Noth Africa
South-East Asia
South and Central America
Western Pacific
North America and Caribbean
Europe

14.7
32.8
71.4
25.1
131.9
37.7
52.6

28.0
59.7
120.9
39.9
187.9
51.2
64.0

90%
83%
69%
59%
42%
36%
22%

World

366.2

551.8

51%

REGION

ASK-SDNC

11

NO. OF CASES (MILLIONS)

60

*) Number of People with Diabetes (20-79 Years): in Million

*
50.8

50

43.2

40

DM-by IDF 2009

26.8

30
20

10
0

ASK-SDNC

INDIA

CHINA

9.6

7.6

*
7.5

*
7.1

*
7.1

7.0

6.8

10

INA

MEXICO

USA RUSSIAN BRAZIL GERM PKTAN JAPAN

FEDERATION

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

NO. OF CASES (MILLIONS)

90

90.0

*) Number of People with Diabetes (20-79 Years) : in Million

80

**) Diabetes National Prevalence (%)

70

Germany and Pakistan : Out of the TOP TEN

61.3

60
50
40

Bangladesh and Egypt : Newcomers of the TOP TEN

**

9.29

DM-by IDF 2011

**

30

8.31

20

**

10.94

10
0

ASK-SDNC

23.7

CHINA

INDIA

12.6

12.4

10.7

10.3

**
11.54

**
9.72

11.20

14.85

**

**

7.3

*
7.3

9.58

15.16

**

4.73

10

8.4

**

**

USA RUSSIAN BRAZIL JAPAN MEXICO BANGLA EGYPT INA

FEDERATION
DESH

12

13

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

(Summarized : Tjokroprawiro 2011-2012)

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
ASK-SDNC

NORMAL : A1C < 5.7 %

STANDARDS OF MEDICAL CARE IN DIABETES ADA-2012

CLASSIFICATION OF DIABETES MELLITUS

14

(ADA-2012, Added by KONSENSUS PERKENI-2011 and SURABAYA-1986)

I TYPE 1 DIABETES*

(Results from -cell destruction, usually leading to absolute insulin deficiency)

A. Immune Mediated
B. Idiopathic

II TYPE 2 DIABETES*

(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 G Uncommon form of Immune-mediated Diabetes
= CFRD)
H Other Genetic Syndromes associated with
D Drug-or CHEMICAL-INDUCED (such
as in-the TREATMENT of AIDS or
after ORGAN TRANSPLANTATION)

Diabetes

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
ASK-SDNC

15

PERKENI 2011,
2011, ADA 2012
CRITERIA for the DIAGNOSIS of DIABETES: PERKENI
(Summarized : Tjokroprawiro 2011-2012)

HbA1c1c>>6.5
6.5%% by NGSP Certified and Standardized to DCCT Assay
1 HbA

(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
ASK-SDNC

Criteria for Testing for Diabetes in Asymptomatic Adult Individuals

16

(Standards of Medical Care in Diabetes - ADA 2012)

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
C

In the absence of the above criteria, TESTING for DIABETES SHOULD BEGIN at AGE 45 YEARS
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.

ASK-SDNC

17

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
ASK-SDNC

Langkah-langkah Diagnostik DM dan Gangguan Toleransi Glukosa

(KONSENSUS PERKENI 2011)
KELUHAN KLINIK DIABETES

KELUHAN KLASIK DIABETES (+)

GDP
atau
GDS

> 126

< 126

> 200

< 200

KELUHAN KLASIK (-)

GDP
atau
GDS

> 126

100-125

< 100

> 200

140-199

< 140

Ulang GDS atau GDP

GDP
atau
GDS

> 126

< 126

> 200

< 200

TTGO
GD 2 Jam

> 200

D I AB E T E S M E LL I T U S
GDP = Glukosa Darah Puasa
GDS = Glukosa Darah Sewaktu
GDPT = IFG = Glukosa Darah Puasa Terganggu
TGT = Toleransi Glukosa Terganggu

ASK-SDNC

- Evaluasi Status Gizi

- Evaluasi Penyulit DM
- Evaluasi Perencanaan Makan
Sesuai Kebutuhan

140-199

TGT

< 140

GDPT

NORMAL

- Nasihat Umum
- Perencanaan Makan
- Latihan Jasmani
- Berat Idaman
- Belum Perlu Obat Penurun Glukosa

18

19

PRACTICAL TOOL FOR INSULIN RESISTANCE AND -CELL FUNCTION

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

Fasting Insulin (U/ml) x FPG (mmol/l)

(N: < 4.0)
:
Insulin Resistance
22.5

HOMA-R

HOMA-B

:
-Cell Function

20 x Fasting Insulin (U/ml)

FPG (mmol/l) 3.5

HOMA-R and HOMA-B :

Useful in Daily Practice

ASK-SDNC

(N: 70150%)

1 RATIONALE TREATMENT
2 FOLLOW-UP OF TREATMENT

PREVALENCE OF IR IN SELECTED METABOLIC DISORDERS

(Bonora 1998, Summarized and Illustrated : Tjokroprawiro 2006-2012)
IFG = Impaired Fasting Glucose

1st Phase and IR in Liver

HYPER-CHOL

URIC ACID

T2DM
1

IGT = Impaired Glucose Tolerance

1st Phase and IR in Periphery

2 IFG & IGT

SEQUENTIAL
PREVALENCES OF IR
in

3 The MetS

METABOLIC
DISORDERS
LOW HDL-C

4 HYPERTENSION

5
IR = INSULIN RESISTANCE
ASK-SDNC

HYPERTRIGLYCERIDAEMIA

IR = INSULIN RESISTANCE

20

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
ASK-SDNC

MACAM DM DI PRAKTEK SEHARI-HARI

22

(Rangkuman : Tjokroprawiro 1993-2012)

DM-Tipe 1
(DMT1)

DM-Tipe 2
(DMT2)

Dx Dugaan :
1 DM
1 Gejala mendadak 2 Diet - Dependent
atau OHO
2 Insulin Dependent
Dependent
3 Anak, atau Dewasa
muda (<20th)
3 Tanpa Insulin
> 10 hr. tidak
4 Kurus mendadak
timbul KAD
Dx-Definitif :
Dx-Dugaan ditambah 4 C-peptide
Puasa > 1.1
1 C-peptide O: < 0.5
2 jam : < 0.5
2 Ax : tanpa
insulin lebih
dari 10 hari,
timbul KAD
3 GAD 65 +

"DM-Tipe X"
Surabaya-Kobe 1989 (Askandar, 1991)
DMTM = MRDM

Dx-Dugaan :
OHO dan Insulin
1 DM
dependent
2 Umur sekitar 14-40 th
3 BBR <80%, IMT <19
DM-Type X1
4 Resisten insulin
DM-Type X2
5 Resisten ketosis
Dx-Definitif :
Dx-Dugaan ditambah
1 PABA test <60%
2 C-peptide >0.6
Tes glukosa sesudah
60 menit
C-peptide
naik >200%

Calon DM-Type X-3

DM-Tipe X-3
(Tjokroprawiro 1991)
atau LADA
(Tuomi et al 1993)

MODY
DMT2 pada
usia sekitar
20 th

MODY-1
MODY-2
MODY-3
MODY-4
MODY-5
MODY-6
MODY-7

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

KADAR INSULIN DARAH PUASA : 2.6 24.9 U/ml *) Tergantung KITSnya

ASK-SDNC

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.
ASK-SDNC

23

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)

Type Stage
B2*)
B2*)
B2*)
B3*)
Be*)

1
2
3
4a
4b
5
Be*)
ESDN

Micro/Macro
Albuminuria

eGFR (mL/min)**

SC (mg/dl)
Micro/Macro Alb eGFR > 90 (N)
Macro Alb.
eGFR 60-89 (< 2.5)
Macro Alb.
eGFR 30-59 (2.5-4)
eGFR 15-29 (4-8)
Macro Alb.
eGFR 15-29 (8-10)
Macro Alb.

eGFR < 15

(> 10)

KTT : Kacang, Tahu, Tempe

Life Expectancy
MNT = DIET
(1986)
OAD - INS
B2, OAD, INS
-?B2, OAD, INS
> 5 years
B2, OAD, INS
> 2 years
B3, INS, Pre HD
4-18 Months
Be, INS, HD
Be, INS, HD
2-5 Months
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
*) 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
o)
(140-Age) x Body Weight (Kg)
(140-Age) x Body Weight (Kg)
eGFR ( o )
eGFR ( +
=
=
(mL/min.)
(mL/min.)
Plasma Creatinine (mg/dl) x 72
Plasma Creatinine (mg/dl) x 72
ASK-SDNC

x 0.85

** THE FORMULA OF GFR MEASUREMENT RELY ON A STABLE SERUM CREATININE CONCENTRATION

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

STAGE

DESCRIPTION

GFR (MDRD)
(mL/min/1.73 m2)

KIDNEY DAMAGE*) with

NORMAL or GFR

>90

KIDNEY DAMAGE*) with

MILDLY GFR

60-89

MODERATELY GFR

30-59

SEVERELY GFR

15-29

KIDNEY FAILURE

<15 or DIALYSIS

MDRD : Modification of Diet in Renal Disease

CG : Cockcroft Gault

ASK-SDNC
*) Kidney Damage Defined as Abnormalities in Pathologic, Urine, Blood, or Imaging Tests)

25

THE FORMULA OF COCKROFT GAULT : eGFR (estimated GFR)

S

SC = SERUM CREATININE
eGFR CREATININE CLEARANCE
Other FORMULA : MDRD (Modification of Diet in Renal Disease)
(Summarized : Tjokroprawiro 2010-2012)

eGFR (o )
=
(mL/min.)

(140-AGE) X BODY WEIGHT (Kg)

PLASMA CREATININE (mg/dl) x 72

(140-AGE) X BODY WEIGHT (Kg)

eGFR ( o+ )
x 0.85
=
(mL/min.)
PLASMA CREATININE (mg/dl) x 72
ASK-SDNC

26

27

SC = SERUM CREATININE

eGFR

THE MDRD FORMULA (MODIFICATION OF DIET IN RENAL DISEASE)

CREATININE CLEARANCE

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)
ASK-SDNC

DEFINITION OF ABNORMALITIES IN ALBUMIN EXCRETION

28

(ADA 2006, Provided : Tjokroprawiro 2006 2012)

CATEGORY
NORMAL

MICRO ALBUMINURIA
MACRO ALBUMINURIA
CLINICAL ALBUMINURIA

(mg/24 h)

(g/min)

Spot Collection : ACR

g/mg Creatinine
Easiest to Carry Out

< 30

< 20

< 30

30 - 299

20 - 199

30 - 299

> 300

> 200

> 300

24-h COLLECTION TIMED COLLECTION

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

ASK-SDNC

PENTALOGI-TERAPI DIABETES MELLITUS

29

(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)

4
5

OHO = OAD

OBAT HIPOGLIKEMIK ORAL (OHO)

INSULIN

OBAT ANTI DIABETES (OAD)

CANGKOK PANKREAS

Sel Beta : pada Tikus*)

Total

: pada Anjing*)

Pusat Diabetes dan

Nutrisi
(1989, 1991)

*) SUDAH DIKERJAKAN OLEH PUSAT DIABETES DAN NUTRISI

RSUD DR. SOETOMO FK UNAIR PADA TH 1989 DAN 1991
ASK-SDNC

NUTRITION IN DIABETES MELLITUS

30

Clinical Experiences : Tjokroprawiro 1978-2012

ORAL NUTRITION
Since 1978

PAR ENTERAL NUTRITION = P.E.N.

Since 1993

ENTERAL NUTRITION
Since 1995

DIABETIC DIETS

PAR ENTERAL NUTRITION

( "SONDE" )

MEDICAL NUTRITION THERAPY

(MNT)

21 Types of Diabetic Diets

at Dr. Soetomo Hospital
From the B-Diet 1978
to
The B1-L 2004
ASK-SDNC

P.E.N.

P-P.E.N.

Ten Principles
of
P-P.E.N. in DM
PERIPHERAL
PAR
ENTERAL
NUTRITION

P
P
E
N

E1 , E 2 , E 3 , E 4 , E 5 , E 6

E1 :08.00 E2 :11.00
E3 :14.00 E4 :17.00
E5 :20.00 E6 :23.00
INSULIN NO INSULIN

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

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

ASK-SDNC

The Diet-B 1978 (Revised TNM-2002) : The Mother - Diet

32

Prospective Study (1978) and Clinical Experiences (1978-2011)

(Tjokroprawiro 1978-2012; TNM = Terapi Nutrisi Medik)

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)
9 Diet-M Fasting
10 Diet-G*** ) : for Gangrene

(1989)
(1989)
(1999)

11 Diet-KV : for CVD (1999)

12 Diet-GL
(2000)
13 Diet-H (Hepar)
(2001)
14
15
16
17
18
19
20
21

Diet KV-T1
(2004)
For (2004)
Diet KV-T2
Diet KV-T3 Pre GDM (2004)
Diet KV-L
(2004)
Diet B1-T1
(2004)
For (2004)
Diet B1-T2
Diet B1-T3 GDM (2004)
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
ASK-SDNC

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-KV : Stroke, CAD, POAD

Diet-G = Diet-H : Gangrene or Hepar

Diet-B1 plus 5 Specifications
Diet-B1 (% Cal): 60% CHO, 20% F, 20% P
(Chol. < 300 mg/day)

1
2
3
4
5

Arginin Content
Fiber 25-35 g/day
Folate
Vit B6 These are able to lower
Homocysteine Level
Vit B12

Diet-B plus 5 Specifications

Diet-B (% Cal) : 68% Cbh, 20% F, 12% P
(Chol. < 300 mg/day)

1
2
3
4
5

ARGININ : Atheroprotective via Nitric Oxide (NO)

HOMOCYSTEINE : Oxidative Stress , ADMA
ASK-SDNC

Arginin Content
Fiber 25-35 g/day
Folate
Vit B6 These are able to lower
Homocysteine Level
Vit B12

Asymmetric Di Methyl Arginine

(ADMA)

DIET-B (1978)* : The Mother Diet

34

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)
ASK-SDNC

THERAPEUTIC DIETS FOR DIABETICS AND OR DYSLIPIDEMICS

MACRONUTRIENT
THE B-DIET*)
(Tjokroprawiro 1978, Revised : 2002)
FIBER

RECOMMENDATION

CHO

60-70%
(CHO plus MUFA**)
***)
<30%
<300 mg/day
?
7-10%
10%
Mentioned Above
15-20%
20-35 g/day

LIPID
CHOL
P/S Ratio
SAFA & TUFA
PUFA
MUFA
PROTEIN
FIBER

68%
Starch
"Sugar Free"
20%
<300 mg/day
1.0
5%
5%
10%
12%
25 - 35 g/day

(ADA, 2002, 2003)

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
ASK-SDNC

***) Acceptable Daily Intake

(Established by FDA)

35

PEDOMAN DIET-B2, DIET-B3, dan DIET-Be

36

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
Proteinuria > 3 g/hari, atau
Albuminuria Berat (Positif 4 )
Kandungan Protein : 0.8 g/kgBB/hari

ASK-SDNC

Intensivitas Menghambat
Progresivitas Gagal Ginjal

Vitamin C Maks. 100 mg,

Pantang NSAID, dll

37

PERBANDINGAN GOLONGAN OHO

(KONSENSUS PERKENI 2011)
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

Golongan

Generik
Glibenclamid

Nama Dagang

Mg/tab

Dosis harian

Keterangan :
* Produk orisinal
38
** Belum beredar di Indonesia
*** Kadar plasma efektif terpelihara selama 24 jam

Lama kerja
(jam)

Glimepirid

Daonil*
Minidiab
Glucotrol-XL
Diamicron
Diamicron-MR
Glurenom
Amaryl*
Gluvas
Amadiab

2,5-5
5-10
5-10
80
30-60
30
1-2-3-4
1-2-3-4
1-2-3-4

2,5-15
5-20
5-20
80-320
30-120
30-120
0,5-6
1-6
1-6

Glinid

Repaglinid
Nateglinid

Metrix
Dexanorm
Starlix

1-2-3-4
1
120

1-6
1,5-6
360

24
-

1
3
3

Tiazolidindion

Pioglitazon

Actos*
Deculin

15-30
15-30

15-45
15-45

24
24

1
1

15-30
50-100
50-100
500-850

15-45
100-300
100-300
250-3000

18-24

Acarbose

Pionix
Glucobay
Eclid
Glucophage

6-8

1
3
3
1-3

Glumin
Glucophage-XR*
Glumin-XR
Galvus
Januvia
Onglyza

500
500-750
500
50
25, 50, 100
120
250/1,25
500/2,5
500/5
1/250
2/500
15/500
30/850

500-3000

6-8

2-3

500-2000
50-100
25-100
5

24
12-24
24
24
12-24

1
1-2
1
1
1-2

Glipizid
Gliklazid
Glikuidon

Penghambat
Glukosidase
Biguanid

Metformin
Metformin XR

Penghambat DPP-IV

Obat Kombinasi
Tetap

Vildagliptin
Sitagliptin
Saxagliptin
Metformin +
Glibenklamid
Glimepirid +
Metformin
Pioglitazone +
Metformin
Sitagliptin +
Metformin
Vildagliptin +
Metformin

ASK-SDNC

Glucovance
Amaryl-Met
FDC
Pionix M
Janumet
Galvusmet

50/500
50/1000
50/500
50/850
50/1000

Total Glibenclamid
maksimal 20 mg/hr

12-24
10-16
12-16**
10-20
24
6-8
24
24
24

Frek/hari
1-2
1-2
1
1-2
1
2-3
1
1
1

2/500
4/1000
Total Pioglitazone
maksimal 45 mg/hr
Total Sitagliptin
maksimal 100mg/hr

18-24

Total Vildagliptin
maksimal 100mg/hr

12-24

1
2

Waktu

Sebelum
makan

Tidak bergantung
jadwal makan
Bersama suapan
pertama
Bersama/sesudah
makan
Tidak bergantung
jadwal makan

Bersama/sesudah
makan

MEKANISME KERJA, EFEK SAMPING UTAMA, DAN A1C

39

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

OAD

INSULIN

CARA KERJA UTAMA

Sulfonilurea

Meningkatkan sekresi insulin

Glinid

Meningkatkan sekresi insulin

Metformin

Menekan produksi glukosa hati

Menambah sensitivitas insulin

EFEK SAMPING UTAMA PENURUNAN A1C

BB naik,
hipoglikemia
BB naik,
hipoglikemia

1.0 2.0 %

Diare, dispepsia,
asidosis laktat

1.0 2.0 %

Penghambat
Menghambat absorpsi glukosa
Glukosidase Alfa

Flatulens,
tinja lembek

0.5 0.8 %

Tiazolidindion
(Glitazon)

Menambah sensitivitas terhadap

insulin

Edema

0.5 1.4 %

INLACIN

Novel Insulin Sensitizer (2011)

"Non"

1.13 % (6 minggu)

Insulin

Menekan produksi glukosa hati,

stimulasi pemanfaatan glukosa

Hipoglikemia,
BB naik

ASK-SDNC

0,5-1,5%

1`.5 3.5 %

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

RSUD Dr. SOETOMO

ASK-SDNC

PDNS Lt-7
(1200 m2)

RSUD Dr. SOETOMO, 1938 2012 : Bed Capacity 1550

PDNS : Core Stafs 8, Expert Members : 52

40