WORKSHOP TERAPI INSULIN K Heri Nugroho HS Sub Divisi Endokrin – Metabolisme Bagian Ilmu Penyakit Dalam FK Undip / RS Dr Kariadi Semarang UNISSULA 23 Juni 2012
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WORKSHOP
TERAPI INSULIN
K Heri Nugroho HS
Sub Divisi Endokrin – Metabolisme
Bagian Ilmu Penyakit Dalam
FK Undip / RS Dr Kariadi
Semarang
UNISSULA 23 Juni 2012
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Outline
The burden of diabetes mellitus
Who will need insulin treatment ?
Overview of type of insulin agents
Regimen insulin
Emergency in critically ill patients Summary
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The most important issues
Diabetes mellitus is more dangerous comparingthan HIV-AIDS or terrorisms
Every 30 seconds, one foot was amputated
One year, more than one million footamputation
85% cases of amputation can be prevented
Every 10 seconds, one people is death that may
be caused by DM complication The prevalence of diabetes mellitus increased
every year, 90% DMT-2
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Diabetic etiology: impaired secretion and insulinresistanceNatural History of Type 2 Diabetes
Glucose
Relative to normal
100
200150
300250
350
-10 -5 0 5 10 15 20 25 300
100
200
50
150
Post-prandial glucose
Fasting glucose
Insulin resistance
Insulin level
Years
At risk for diabetes Beta-cell dysfunction
250
R.M. Bergenstal, International Diabetes Center
mg/dL
(%)
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UKPDSIntensive glycemic control compare conventional
―> microvasc compl risk ↓
- A1C ↓ 1%, microvasc risk ↓ 35%
- Monotherapy (SU, Met, Insulin): maintainglycemic control :
47%-50% at 3 yrs
34%-37% at 6 yrs
24%-28% at 9 yrs- After 3 yrs 50% required combination therapy
After 9 yrs 75% required combination therapy
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Glycaemic goals for clinical management ofdiabetes
HbA1c : < 6,5%
Premeal (fasting) : 5,5 mmol/l (< 100 mg/dl)
2- hour postmeal : 7,8 mmol/l (<140 mg/dl)
Treatment of fasting and postmeal hyperglycaemia should beinitiated simultaneously at any HbA1c level
The frequency of SMBG in non insulin treated diabetes beindividualized to each person’s treatment regimen and level ofglycaemic control
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0.00
0.50
1.00
1.50
2.00
2.50
<6.1 6.1 –6.9 7.0 –7.7 7.8
11.1
7.8 –
11.0
<7.8
Fasting glucose (mmol/l) 2 - h o
u r g l u c o
s e
( m m
o l / l )
Decode Study Group. Lancet 1999;354:617 –21
Hazard Ratios for Death According to the Fasting Glucose
and 2-hour Glucose in Individuals Not Known As Diabetic
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0.00
0.50
1.00
1.50
2.00
2.50
<6.1 6.1 –6.9 7.0 –7.7 7.8
11.1
7.8 –
11.0
<7.8
Fasting glucose (mmol/l) 2 - h o
u r g l u c o
s e
( m m
o l / l )
Decode Study Group. Lancet 1999;354:617 –21
Hazard Ratios for Death According to the Fasting Glucose
and 2-hour Glucose in Individuals Not Known As Diabetic
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Efek insulin dan manfaat terapiinsulin
Efek metabolik karbohidrat, lipid, protein
Anabolik : ambilan glukosa perifer
hambat HGP dan lipolisis, sintesis protein Hambat faktor transkripsi proinflamasi
Anti apoptosis,anti oksidan, anti trombotik,
anti aterosklerotik, profibrinolitik Kendali status metabolik (glukosa darah)
dan luaran klinik yg lebih baik pasien kritis
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Exogenous insulin is not similar toendogenous insulin.
a. Day-long circulating endogenous insulin profile is
specific
b. Exogenous insulin administration can not mimick the
endogenous insulinc. Exogenous insulin is injected peripherally while
endogenous insulin goes directly to the portal system
d. Hexamerisation will occur when supraphysiological
insulin is given.
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Kebutuhan insulin bagi penderita diabetes
Pasien T1DM telah kehilangan fungsi sel β pankreas
secara total, menyebabkan defisiensi insulin absolut
T2DM adalah penyakit progresif yang menyebabkan
penurunan fungsi sel β secara bertahap,
mengakibatkan peningkatan kadar glukosa darah Pada T1DM, penyuntikan insulin basal dan prandial
eksogen dalam konsep basal–bolus sangat penting
untuk mempertahankan kontrol glukosa darah
Pada T2DM, suatu ketika akan membutuhkanpenyuntikan insulin baik berupa insulin basal + OAD
atau dengan insulin basal-bolus
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Indikasi tx insulin pada rawat jalan
Indikasi mutlak : DMT1
Indikasi Relatif :
- gagal OHO kombinasi (3-6 bln)
- DMT2 rawat jalan dng : kehamilan, TBCparu, kaki diabetik dng infeksi, brittlediabetes, ketoasidosis berulang, post
pankreotomiBeberapa indikasi khusus :penyakit hati
kronis, ggn fungsi ginjal, steroid dosis tinggi
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Terapi insulin yang ideal harus menyerupai sekresi insulin
fisiologis oleh pankreas
The basal–
bolus insulin regimen
I n s u l i n ( m U / L )
06:00 12:00 24:0018:000
15
30
45
06:00
Breakfast Lunch Dinner Physiological insulin
Ideal basal insulin
Ideal prandial insulin
Time
Di adaptasi dari Kruszynska YT, et al. Diabetologia 1987;30:16–21
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Human Insulins and Insulin Analogues
•The time course of action of any insulin can vary in different people or atdifferent times in the same person. For this reason, time periods indicated hereshould only be considered general guidelines.
Insulin Preparations Onset of Action Peak of Action (h) Duration of Action (h)
Rapid-acting
Regular human insulin1 30 to 60 minutes 2 to 4 6 to 8
Insulin glulisine 5 to 15 minutes2 1 to 23 3 to 44
Insulin lispro/aspart1 5 to 15 minutes 1 to 2 3 to 4
Intermediate-acting
NPH1 1 to 3 h 5 to 7 13 to 16
Lente1 1 to 3 h 4 to 8 13 to 20
Detemir 5,6,7
— 4 to 6 20 h
Long-acting
Insulin glargine1
1 to 2 h No Peak 24 h
Ultralente1 2 to 4 h 8 to 14 <20 h
Premix
Insulin NPL/lispro 75/258 10 minutes 1 to 4 10 to 20
Insulin aspart 70/309 10 minutes 1 to 4 16 to 20
1. Leahy JL. In Insulin Therap y. Leahy JL and Cefalu WT (Eds.) New York, NY: 2002:87-112; 2. Becker R, Frick A. HMR1964A-1009. CSR No.F2001CLN0373, Phase I Clinical Development. Frankfurt, Germany: Sanofi Aventis Pharma Deutschland GmbH; 2003; 3. Rave K, et a l. Diabetes .
2004;53 (suppl 2):A143; 4. Burger F, et al. Diabetes . 2004;53 (suppl 2):A557; 5. Heinemann L, et al. Diabet Med. 1999;16:332-338; 6. Goldman-Levineand Lee. Ann Pharmacother . 2005 March, Volume 39. Published online. 18 Jan 2005, www.theannals.com, DOI 10.1345/aph.1E334; 7. Pieber TR, et al.Diabetes . 2002;51(suppl 2):A53; 8. Humalog® Mix75/25 USPI; 9. Feher MD, Bailey CJ. Br J Diabetes Vasc Dis . 2004;4:39-42.Introduction
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DMT-1
Dosis insulin awal 0,5 unit/bb/hari
60% total dosis harian insulin prandial
40% total dosis harian insulin basal Insulin prandial : diberikan masing-
masing 1/3 dosis total harian sebelummakan pagi, siang dan malam
Upayakan waktu yang tetap untukinsulin basal
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Sebelum makanpagi
Sebelum makansiang
Sebelum makanmalam
Sebelum tidur
IP IP IP IB
IP + IB IP IP IP
IP + IB TANPA INSULIN IP IB
IP + IB IP + IB IP + IB TANPA INSULIN
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Saat
diagnosis:
Gaya hidup
+
Metformin
Gaya hidup +
Metformin +
Insulin basal
Gaya hidup +
Metformin +
Sulfonilurea
Gaya hidup +
Metformin +
Insulin intensif
Gaya hidup +
Metformin +
Pioglitazon
Gaya hidup +
Metformin +
GLP-1 agonis
Gaya hidup +
Metformin +
Pioglitazon +
sulfonilurea
Gaya hidup +
Metformin +
Basal insulin
Well validatedcore therapies
Less wellvalidated core
therapies
Tahap 1 Tahap 2 Tahap 3
Nathan DM et al, Diabetes Care 32:193 –203, 2009
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Kadar GDP (mg/dl) Dosis Insulin awal
< 70 Turunkan dosis 2 unit
70 - 130 Pertahankan dosis
> 130 Naikkan dosis 2 U tiap 3 hari
> 180 Naikkan dosis 4 U tiap 3 hari
Dosis insulin basal yang diberikan biasanya 10 unit
Penyesuain dosis insulin basal
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Konsep basal plus dan basal bolus
Insulin tambahan yang diberikanuntuk perbaiki kendali glikemik yakni
dengan insulin prandial Basal plus : penambahan insulin
prandial tuk turunkan glukosa darah
stlh makan ( saat OHO dan insulinbasal gagal)
IP bisa 1 – 3 kali pemberian
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Basal bolus dan basal plus
Basal bolus biasanya IB + 3 kali IP
IP dimulai dengan dosis 0,1 unit /
kgBB atau secara praktis 4 unit
Titrasi dosis naik 2 unit / 3 hari
Perencanaan makan yang tepat,
pemantauan glukosa darah ketat(SMBG)
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Insulin premixed
Campuran kerja cepat atau pendekdan kerja menengah.
Human insulin dan analog
Tak dianjurkan pada DMT-1
Biasanya setelah gagal OHO atau
insulin basal
Masih dimungkinkan 2-3 kali
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Cara praktis konversi dari IB :
total dosis dibagi 2
Cara praktis mengganti insulin premixed 1kali mjd 2 kali :
bagi dosis menjadi 2 untuk pagoi danmalam
Cara praktis mengganti insulin premixed 2
kali menjadi 3 kali :tambah 2-6 U atau 10% total dosis
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Bila dosis siang ditambahkan, dosispagi mungkin diperlukan dikurangi 2-4
unit Titrasi 3 hari, atau praktisnya 1 mgg
Stop sulfonilurea, teruskan metformin
Golongan glitazon sebaiknyadihentikan.
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DM Gestasional, wanita hamil denganDMT-1 atau DMT-2
FifthInternational Workshop-Conference on GD (2007)
Waktu pemeriksaan Target (mg/dl)
DM Gestasional puasa < 95
1 jam makan < 140
2 jam makan < 120
DMT-1 atau DMT-2 Sblm makan,waktu tidur,sepanjang malam
60 - 99
Puncak ssdh makan 100 - 129
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Pasien rawat nginap
Tidak semua pasien harus insulin
Biasanya datang dengan stres akut akibatpenyakit tambahan, komplikasi akut DM,perioperatif
Bila perlu regulasi cepat insulin terpilih Kombinasi oral, insulin SC atau syringe
pump.
Dosis insulin : 0,2 U/kgBB/hari, 50% IB dan50% IP
Target GDP , 140 mg/dl, GDS < 180 mg/dl
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Pasien kritis di ruang intensif
Sasaran glukosa 140 – 180 mg/dl
Pemantauan ketat GDS harus
dilakukan, evaluasi tergantung situasibisa 1 jam sampai diturunkan hingga 4- 6 jam
Tidak ada protokol baku, terpenting jgn sampai hipoglikemia !!
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Cara pemberian insulin
Semprit insulin 1 cc
Pen insulin
Pompa insulin (CSII)
Efek samping Insulin :
Hipoglikemia
Peningkatan BB Edema
Lipoatrofi
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KETOASIDOSIS DIABETIKA (KAD)
DEKOMPENSASI METABOLIK AKUT
DEFESIENSI RELATIF – ABSOLUT INSULIN
AKIBAT ------ FATAL BISA KEMATIAN
DIAGNOSIS DAN PENANGANAN CEPAT TEPAT
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EPIDEMIOLOGI
Insidens :Indonesia : data pasti ??
AS : 8/1000 pts/ th
Semua kelompok umur
Angka kematian 1922 : 100%
1932 : 29%
1950 : 15%
skrg : 2-9%
Prognosis dipengaruhi umur,asidosis,kesadaran,hiperosmolaritas, azotemia,pengelolaan
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PATOFISIOLOGI KAD
Insulin Defisiensi
Lipolisis >> Hiperglikemia
Ketogenesis >>
Ketoasidosis
Diuretik Osmotik
hiperosmolaritas
Pure KAD Pure HONK
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Faktor Pencetus
Infeksi >> 20 – 40 %tr. Urinarius, tr respiratorius
Stroke
Alkoholoisme
Pankreatitis
AMI
Trauma
Obat (KS, thiazide, dobutamin, terbutalin)Stop insulin mendadak (DM tipe 1)
Psikologis berat
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Diagnosis KAD
ANAMNESIS
LABORATORIUMPEMERIKSAAN FISIK
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Laboratorium
Glukosa darah ≥ 250 mg/dl
pH < 7,35
HCO3 rendah
Anion gap tinggi
Keton serum positif
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Prinsip- prinsip tatalaksana KAD
R ehidrasi dan ci elektrolit
I nsulin
T rigger
M onitoring - E valuasi
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Treatment protocol
Umpierrez GE, Diabetes Care 2004 ; 27 : 1873-18
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Apa yang perlu diawasi dan dievaluasi
Keadaan umum Tanda vital
Kadar gula darah
Keton darah – urin Elektrolit : Na, K, Ca, Mg
AGD
Dosis Insulin dan cara pemberian
Intake cairan dan kalori, produksi urin
Balance cairan
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Komplikasi KAD
Hipokalemi
Hipoglikemia
Hipofosfatemia Hipokalsemia
Edema paru
Respirasi distres sindrom Jrg (anak) : edema otak, trombosis vena,
emboli paru
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Ringkasan
Insulin sebagai salah satu pilar terapipengelolaan diabetes melitus.
Untuk bisa memberikan terapi insulindengan baik, harus memahamipatofisiologi dengan baik, pemahaman
tentang insulin yang benar, denganmemperhatikan indikasi dan situasipasien.