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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
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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
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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
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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 ASK-SDNC
SEJARAH
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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 Continued ASK-SDNC
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). ASK-SDNC
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Data DM Di RS Pendidikan Dr. Soetomo (Hospital Data)
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(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 1975 : 2914
1988 : 12608 1994 : 20366 2000 : 33636
1980 : 5654
1989 : 13818 1995 : 22029 2001 : 35606
1984 : 8222 1985 : 9150
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
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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 : 10–75% GINGIVITIS AND PERIODONTIS ARE MOST PREVALENT ASK-SDNC
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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
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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
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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
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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)
NO. OF CASES (MILLIONS)
60
* 50.8
*) Number of People with Diabetes (20-79 Years): in Million
* 43.2
50
DM-by IDF – 2009
40
* 26.8
30 20
* 9.6
* 7.6
* 7.5
* 7.1
* 7.1
* 7.0
* 6.8
4
5
6
7
8
9
10
INA
MEXICO
10 0
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1
2
INDIA
CHINA
3
USA RUSSIAN BRAZIL GERM PKTAN JAPAN FEDERATION
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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
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*
23.7
1
2
CHINA
INDIA
3
*
12.6
*
12.4
*
10.7
*
10.3
*
8.4
*
7.3
* 7.3
** 11.54
9.72
11.20
14.85
9.58
15.16
**
4.73
4
5
6
7
8
9
10
**
**
**
**
**
USA RUSSIAN BRAZIL JAPAN MEXICO BANGLA EGYPT INA FEDERATION DESH
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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 ASK-SDNC
NORMAL : A1C < 5.7 %
STANDARDS OF MEDICAL CARE IN DIABETES ADA-2012 CLASSIFICATION OF DIABETES MELLITUS
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(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
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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 ASK-SDNC
Criteria for Testing for Diabetes in Asymptomatic Adult Individuals
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(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 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.
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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 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
DIABETES MELLITUS GDP = Glukosa Darah Puasa GDS = Glukosa Darah Sewaktu GDPT = IFG = Glukosa Darah Puasa Terganggu TGT = Toleransi Glukosa Terganggu
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- 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
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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
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(N: 70–150%)
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
8
2 IFG & IGT SEQUENTIAL PREVALENCES OF IR in
7
3 The MetS
METABOLIC DISORDERS LOW HDL-C
6
4 HYPERTENSION
5 IR = INSULIN RESISTANCE ASK-SDNC
HYPERTRIGLYCERIDAEMIA
IR = INSULIN RESISTANCE
20
1. DM TIPE-1 (DMT1) : FROM -CELL DESTRUCTION TO
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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
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(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 : 1 DM 2 Umur sekitar 14-40 th 3 BBR <80%, IMT <19 4 Resisten insulin 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%
OHO dan Insulin dependent
MODY DMT2 pada usia sekitar 20 th
DM-Type X1 DM-Type X2 Calon DM-Type X-3
DM-Tipe X-3 (Tjokroprawiro 1991) atau LADA (Tuomi et al 1993)
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
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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. ASK-SDNC
SURABAYA CLASSIFICATION OF DIABETIC NEPHROPATHY (DN)-2005
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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)
Be*)
eGFR (mL/min)**
Life Expectancy MNT = DIET (1986) OAD - INS SC (mg/dl) 1 Micro/Macro Alb eGFR > 90 (N) B2, OAD, INS -?2 Macro Alb. eGFR 60-89 (< 2.5) B2, OAD, INS > 5 years Macro Alb. eGFR 30-59 (2.5-4) B2, OAD, INS > 2 years 3 4a eGFR 15-29 (4-8) B3, INS, Pre HD Macro Alb. 4-18 Months 4b eGFR 15-29 (8-10) Be, INS, HD Be, INS, HD 5 Macro Alb. eGFR < 15 (> 10) 2-5 Months ESDN Transplantation
Type Stage B2*) B2*) B2*) B3*) Be*)
KTT : Kacang, Tahu, Tempe
Micro/Macro Albuminuria
MNT : Medical Nutrition Therapy or Diet. Treatment : B2, B3, Be (Types of MNT), OAD (Oral Agents for Diabetic), INS (Insulin)
S
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)
1
KIDNEY DAMAGE*) with NORMAL or GFR
>90
2
KIDNEY DAMAGE*) with MILDLY GFR
60-89
3
MODERATELY GFR
30-59
4
SEVERELY GFR
15-29
5
KIDNEY FAILURE
<15 or DIALYSIS
CG : Cockcroft Gault MDRD : Modification of Diet in Renal Disease ASK-SDNC *) Kidney Damage Defined as Abnormalities in Pathologic, Urine, Blood, or Imaging Tests)
25
S
THE FORMULA OF COCKROFT – GAULT : eGFR (estimated GFR) 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
S
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
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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 , E2 , E 3 , E4 , E5 , E6
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
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 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)
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) 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) Diet KV-T2 For (2004) 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 FIBER CHO
LIPID CHOL P/S Ratio SAFA & TUFA PUFA MUFA PROTEIN FIBER
RECOMMENDATION
THE B-DIET*) (Tjokroprawiro 1978, Revised : 2002)
(ADA, 2002, 2003)
68% Starch "Sugar Free" 20% <300 mg/day 1.0 5% 5% 10% 12% 25 - 35 g/day
60-70% (CHO plus MUFA**) ***) <30% <300 mg/day ? 7-10% 10% Mentioned Above 15-20% 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) **) The Percentage must be Individualized ASK-SDNC
***) Acceptable Daily Intake (Established by FDA)
35
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 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
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
18-24
1
Janumet
50/500 50/1000
2/500 4/1000 Total Pioglitazone maksimal 45 mg/hr Total Sitagliptin maksimal 100mg/hr
Galvusmet
50/500 50/850 50/1000
Total Vildagliptin maksimal 100mg/hr
12-24
Amaryl-Met FDC Pionix M
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 ASK-
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
