CV: dr. R Bowo Pramono SpPD KEMD · PDF fileCV: dr. R Bowo Pramono SpPD KEMD • Lahir...
Transcript of CV: dr. R Bowo Pramono SpPD KEMD · PDF fileCV: dr. R Bowo Pramono SpPD KEMD • Lahir...
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CV: dr. R Bowo Pramono SpPD KEMD • Lahir TEGAL 27-jan 1959• Istri: dr. Astuti SpS, 2 putri• Dokter Umum: FK UGM • 17-01-1985• SPPD : FK UGM 24-11-1997• KEMD : 14-05-2008Pekerjaan:• 1987-2002 PKM Kedung Waringin Bekasi• 1999-2004 RSU Selong Lombok Timur• 2004-2010 RS DR Sardjito/FK UGM• 2006-2013 Sekretaris Bagian Penyakit Dalam FK UGM• 2007-2011 Sekretaris PAPDI Cabang Yogyakarta
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DIAGNOSIS & MANAJEMEN DM TIPE 2
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DIAGNOSIS:
DIAGNOSED FASTINGBG/mg%
POSTPRANDIALBG/mg%
RANDOMBG/mg%
NODIABETES
80 - <110 80 - <140 80 - <140
PREDIABETES
110 - 125 140 - 199
DIABETES ≥ 126 ≥ 200 ≥ 200
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Prinsip Dasar Terapi Diabetes Mellitus
1
PENGATURAN MAKAN
2
LATIHANJASMANI
OBAT HIPOGLIKEMIK
4
3
PENYULUHAN
CANGKOK PANKREAS
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Correlation between HbA1c level and mean plasma glucosa levels on multiple testing
over 2-3 months
HbA1c Mean plasma glucose (mg/dL)
6 135
7 170
8 205
9 240
10 275
11 310
12 345
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1%
Hasil dari UKPDS: Kontrol yang baik pada DM T2 mampu menurunkan resiko
komplikasi
Kematian karena diabetes
Infark miokard
Komplikasi mikrovaskuler
Gangguan pembuluh darah perifer
‐21%
‐14%
‐37%
‐43%
Menurunkan resiko*Penurunan 1% HbA1c
*p<0.0001 n=3,642 type 2 diabetes patients
Stratton IM et al. BMJ 2000;321:405–412
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PRINSIP PENGOBATAN DIETKebutuhan kalori sesuai : kelamin, umur , berat badan, aktifitas fisik, pekerjaan, kehamilan, menyusui, komplikasi
3 kali makan utama dan 3 kali makan kecil
Jumlah dan waktu makan harus tepat
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JADWAL MAKAN DIABETES
Komposisi diet: 60-70 % hidrat arang 20-25 % lemak 10-15 % protein
6.30 9.30 12.00 15.00 19.00 21.00
20% 10% 25% 10% 25% 10%
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PRINSIP OLAHRAGA PADA DIABETES
Pilih olahraga yang disenangi
Melibatkan otot-otot besarFrekuensi : Teratur 3-5 kali perminggu
Intensitas : Ringan sampai sedang
Durasi : 30 –60 menit / 5 X30 menit /minggu
Tipe : Aerobik (jalan, joging, ber sepeda)
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Program Latihan• Teratur (3-4 kali seminggu)• 20- 40 menit didahului
pemanasan 5-10 mnt dan cool-down 10 mnt
• CRIPE:Continous
RythmisInterval
ProgresifEndurance
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Treatment options for type 2 diabetes
• Sulfonylureas– 1st generation e.g. chlorpropamide,
tolbutamide– 2nd generation e.g. glyburide,
gliclazide, glipizide, gliquidone– 3rd generation e.g. glimepiride– Modified release
• Glinides/meglitinides– Non-sulfonylureic e.g. repaglinide– Amino acid derivatives e.g. nateglinide
• Biguanides– e.g. metformin
• Thiazolidinediones– e.g. rosiglitazone, pioglitazone
• α-glucosidase inhibitors– e.g. acarbose
• Insulin– regular– intermediate/long acting– pre-mixed– analogs
• rapid acting• long acting
• Fixed-dose oral antidiabetic drug combinations– e.g. glyburide/metformin,
glipizide/metformin, rosiglitazone/metformin
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MetforminHow it works • Decreases hepatic glucose output
• Lowers fasting glycemiaExpected HbA1creduction
~ 1.5%
Adverse events • GI side effects• Lactic acidosis (quite rare)
Weight effects Weight stability or modest weight loss
CV effects Unconfirmed beneficial effect demonstrated in UKPDS
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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SulfonylureasHow they work Enhance insulin secretion
Expected HbA1creduction
~ 1.5%
Adverse events Hypoglycemia (but severe episodes are infrequent)
Weight effects ~ 2 kg weight gain common when therapy initiated
CV effects UGDP suggested potential cause of increased CVD mortality; not substantiated by UKPDS
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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INCREASED INSULIN SECRETIONSulfonylurea Length of
actionBegins ofaction
Daily dose(mg)
Route of excretion
Glibenclamide 16 – 24h 2 – 4h 1,25 – 15 R = 50%, B = 50%
Gliclazide 10 – 24h 2 – 4h 40 – 320 R = 70%, B = 30%
Glipizide 6 – 24h 2 – 4h 2,5 – 40 R = 80%, B =20%
Chlorpramide 24 – 72h 2 – 4h 100 – 500 Renal
Tolbutamide 6 – 10h 2 – 4h 100 – 1000 Renal
Glimepiride 24h 2 – 4h 1 - 6 R = 40%, B =60%
gliquidon 18 - 24h 2 - 4h 30 - 120 R = 5%, B = 95%
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GlinidesHow they work Stimulate insulin secretion (but
differently from sulfonylureas)Expected HbA1creduction
~ 1.5% (repaglinide)
Adverse events Hypoglycemia (may be less frequent than some sulfonylureas)
Weight effects ~ 2 kg weight gain common when therapy initiated
CV effects None mentioned in ADA recommendations
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Dipeptidyl Peptidase IV InhibitorsHow they work Inhibit degradation of endogenous
GLP-1
Expected HbA1creduction
~0.8%
Adverse events Minimal
Weight effects Neutral
CV effects Unknown
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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α-Glucosidase InhibitorsHow they work ↓ rate of digestion of polysaccharides in
proximal small intestine (primarily lowering PPG levels without causing hypoglycemia)
Expected HbA1creduction
0.5–0.8%
Adverse events • Increased gas production • GI symptoms
Weight effects Weight neutralCV effects Unconfirmed report of reduction of
severe outcomes in one clinical trial
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Thiazolidinediones
How they work Increase sensitivity of muscle, fat, and liver to endogenous and exogenous insulin
Expected HbA1creduction
0.5–1.4%
Adverse events Weight gain and fluid retention
Weight effects • Increase in subcutaneous adiposity• Redistribution from visceral deposits
CV effects • New / worsened CHF or peripheral edema (due to fluid retention)
• Reduction in some secondary CV endpoints demonstrated in PROactive study
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Glucagon-like Peptide 1 Agonist(exenatide)
How it works Stimulates insulin secretion
Expected HbA1creduction
0.5–1%
Adverse events GI side effects (nausea, vomiting, diarrhea)
Weight effects Weight loss of ~ 2–3 kg over 6 months (may be result of GI effects)
CV effects None mentioned in ADA recommendations
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Dipeptidyl Peptidase IV InhibitorsHow they work Inhibit degradation of endogenous
GLP-1
Expected HbA1creduction
~0.8%
Adverse events Minimal
Weight effects Neutral
CV effects Unknown
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Amylin Agonists (pramlintide)How it works Synthetic amylin analogue that inhibits
glucagon production in a glucose-dependant fashion
Expected HbA1creduction
0.5–0.7%
Adverse events GI effects (nausea)
Weight effects Weight loss ~ 1–1.5 kg over 6 months (may be due to GI effects)
CV effects None mentioned in ADA recommendations
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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InsulinHow it works Direct compensation for lack of
insulin sensitivityExpected HbA1creduction
1.5–2.5%
Adverse events Hypoglycemia
Weight effects Weight gain of ~ 2–4 kgCV effects • Beneficial effect on TG and HDL
• Weight gain may have an adverse effect on CV risks
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Indikasi terapi Insulin:• DM tipe 1• DM tipe 2 yang tidak terkontrol diet, olah raga,
OHO.• DM gestasional• Gangguan faal hati & ginjal yang berat.• Dengan infeksi akut (selulitis, gangren), TBC
berat, penyakit kritis (stroke/AMI)• Dengan KAD/HHS• Dengan fraktur atau pembedahan mayor• Kurus (BB rendah), terkait malnutrisi (DMTM)• Dengan penyakit Grave’s• Dengan tumor ganas• Dengan pemberian kortikosteroid
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Years From Diagnosis
T2 DMphase I
T2 DMphase II
Stages of Type 2 Diabetes
Lebovitz, 2000
T2 DM phase III
-12 -10 -6 -2 0 2 6 10 14
100
75
50
25
0
Beta CellFunction
(%)IGT Postpandrial
Hiperglycemi T-2 DM phase IBeta Cell function
± 50 %
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Summary: Expected HbA1c ReductionIntervention Expected ↓ in HbA1c
Insulin 1.5 to 2.5%Metformin 1.5%Sulfonylureas 1.5%Glinides 1 to 1.5%a
TZDs 0.5 to 1.4%α-Glucosidase inhibitors 0.5 to 0.8%GLP-1 agonist 0.5 to 1.0%Pramlintide 0.5 to 1.0%DPP-IV inhibitors ~0.8%
a Repaglinide is more effective than nateglinide Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Factors that May Affect ComplianceWeight Gain
GI Side Effects
2-3x Daily Dosing
Insulin – intermediate/long XInsulin – short/rapid X XMetformin X XSulfonylurea XGlinides X XTZDs Xα-Glucosidase inhibitors X XGLP-1 agonist X XPramlintide X XDPP-IV inhibitors
Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Which second-line therapy?HbA1C
Pros Cons
SU 1.5 Large clinical database, inexpensive Weight gain and hypoglycaemia
TZD 0.5–1.4 No hypoglycaemia, some benefits on
lipids
Oedema, heart failure, weight gain,
expensive
Insulin 1.5–3+ Large clinical database, most effective Hypoglycaemia, weight gain, need for
SMBG
AGI 0.5–0.8 No hypoglycaemia, weight neutral GI side-effects, expensive
GLP-1 analogue 0.5–1.0 No hypoglycaemia, weight loss GI side-effects, expensive, injected
Meglitinide 1.0–1.5 Fewer hypos than sulfonylurea TID dosing, expensive
SU: sulfonylurea; TZD: thiazolidinedione; AGI: α-glucosidase inhibitor SMBG: self monitoring of blood glucose
ADA/EASD. Diabetes Care 2006; 29: 1963-1972, Diabetologia 2006; 49: 1711-21
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Years From Diagnosis
T2 DMphase I
T2 DMphase II
Stages of Type 2 Diabetes
Lebovitz, 2000
T2 DM phase III
-12 -10 -6 -2 0 2 6 10 14
100
75
50
25
0
Beta CellFunction
(%)IGT Postpandrial
Hiperglycemi T-2 DM phase IBeta Cell function
± 50 %
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Effectiveness of Type 2 Diabetes Therapy
Diet & Exercise 1% <7%
TZDAlpha-glucosidase
Inhibitors
Metformin Insulin
Secretagogues
1.5-2%
1-1.5%<8%
CombinationOral
Agents3-4% <8-10%
Insulin 5% ormore >10%
Starting HbA1c
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Klasifikasi InsulinKelas Mulai efek Puncak Lama Aksi pendekActrapid, Humulin R
15-30 mnt 2-4jam 6-8jamCampuran (premixed)Humulin 30/70,Mixtard 30/70
60 mnt 1-8jam 14-15 jamAksi sedangHumulin N, Insulatard
2-4jam 1-8jam 14-15 jam
Aksi panjangLantus , Levemir
Tanpa Puncak 24 jam
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What are the reasons for the shortcomings of insulin?
Subcutaneoustissue
Mol/l
Diffusion
Capillarymembrane
10‐3 10‐4 10‐5 10‐8
Adapted from Brange J et al. Diabetes Care 1990;13:923
Dissociation in subcutaneous tissue
That has to dissolve in SC fluids and dissociate into monomers……..
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Klasifikasi Insulin yang baruKelas Mulai efek Puncak Lama Aksi cepat (analog)Lyspro (Humalog)Aspart (Novo Rapid)Apiora
5-15 mnt 2 jam 4-6jam
Campuran (premixed)Humalog Mix 25/75Novomix 30/70
5-15mnt 2-4jam 12-14 jam
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LOKASI PENYUNTIKKAN
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Insulin Regimen Evolution
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Pemakaian semprit dan jarum memungkinkan Anda untuk mengatur dosis dan membuat formulasi campuran insulin. Keterbatasannya adalah membutuhkan ketrampilan yang cukup untuk menarik dosis insulin dengan tepat.
Cara menyuntik insulin
Insulin > Cara pemberian insulin > Semprit dan jarum
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Dahulu:Agar tidak salah dosis,kemasan insulin40U/ml atau 100U/mldisesuaikan denganskala pada spuit,bisa 40 atau 100
Sekarang: ?Tidak tersedia lagi
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NovoPen®
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Sistem NovoLet®
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INSULIN ANALOG: 1.NovoRapid2.NovoMix3.Levemir
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Summary: Expected HbA1c ReductionIntervention Expected ↓ in HbA1c
Insulin 1.5 to 2.5%Metformin 1.5%Sulfonylureas 1.5%Glinides 1 to 1.5%a
TZDs 0.5 to 1.4%α-Glucosidase inhibitors 0.5 to 0.8%GLP-1 agonist 0.5 to 1.0%Pramlintide 0.5 to 1.0%DPP-IV inhibitors ~0.8%
a Repaglinide is more effective than nateglinide Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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Factors that May Affect ComplianceWeight Gain
GI Side Effects
2-3x Daily Dosing
Insulin – intermediate/long XInsulin – short/rapid X XMetformin X XSulfonylurea XGlinides X XTZDs Xα-Glucosidase inhibitors X XGLP-1 agonist X XPramlintide X XDPP-IV inhibitors
Adapted from Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
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ADA/EASD consensus algorithm
At diagnosis:Lifestyle + Metformin
Lifestyle + Metformin+ Basal insulin
Lifestyle + Metformin+ Sulfonylurea
Lifestyle + Metformin+ Intensive insulin
Tier 1:well-validated therapies
STEP 1 STEP 2 STEP 3
Call to action if HbA1c is ≥7%
Tier 2:Less well validated therapies
Lifestyle + Metformin+ PioglitazoneNo hypoglycaemiaOedema/CHFBone loss
Lifestyle + Metformin+ Pioglitazone+ Sulfonylurea
Lifestyle + metformin+ Basal insulin
Lifestyle + metformin+ GLP-1 agonistNo hypoglycaemiaWeight lossNausea/vomiting
Nathan DM, et al. Diabetes Care 2009;32 193-203.
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DM tipe 1
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1980
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1980 2009