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 : 14-05-2008 Pekerjaan: • 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 1
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CV: dr. R Bowo Pramono SpPD KEMD · PDF fileCV: dr. R Bowo Pramono SpPD KEMD • Lahir TEGAL 27-jan 1959 • Istri: dr. Astuti SpS, 2 putri • Dokter Umum: FK UGM • 17-01-1985...
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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
1
DIAGNOSIS & MANAJEMEN DM TIPE 2
DIAGNOSIS:
DIAGNOSED FASTINGBG/mg%
POSTPRANDIALBG/mg%
RANDOMBG/mg%
NODIABETES
80 - <110 80 - <140 80 - <140
PREDIABETES
110 - 125 140 - 199
DIABETES ≥ 126 ≥ 200 ≥ 200
Prinsip Dasar Terapi Diabetes Mellitus
1
PENGATURAN MAKAN
2
LATIHANJASMANI
OBAT HIPOGLIKEMIK
4
3
PENYULUHAN
CANGKOK PANKREAS
5
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
6
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
PRINSIP PENGOBATAN DIETKebutuhan kalori sesuai : kelamin, umur , berat badan, aktifitas fisik, pekerjaan, kehamilan, menyusui, komplikasi
• Fixed-dose oral antidiabetic drug combinations– e.g. glyburide/metformin,
glipizide/metformin, rosiglitazone/metformin
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.
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.
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%
15
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.
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.
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.
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.
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.
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.
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.
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.
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
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 %
25
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.
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.
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
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 %
29
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
Klasifikasi InsulinKelas Mulai efek Puncak Lama Aksi pendekActrapid, Humulin R
60 mnt 1-8jam 14-15 jamAksi sedangHumulin N, Insulatard
2-4jam 1-8jam 14-15 jam
Aksi panjangLantus , Levemir
Tanpa Puncak 24 jam
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……..
32
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
LOKASI PENYUNTIKKAN
35
Insulin Regimen Evolution
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
Dahulu:Agar tidak salah dosis,kemasan insulin40U/ml atau 100U/mldisesuaikan denganskala pada spuit,bisa 40 atau 100
Sekarang: ?Tidak tersedia lagi
38
NovoPen®
39
40
Sistem NovoLet®
INSULIN ANALOG: 1.NovoRapid2.NovoMix3.Levemir
45
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.
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.
48
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