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Plasma glucose
-cell function
OADs Insulin Rx
10
20
30
Years of Diabetes
Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota
Comfortable injections
Peralatan suntik sederhana & mudah
Emotional support
Education in diabetes management
Type 2 diabetic
Non-diabetic time
IV Glucose stimulus
Four biochemical pathways that are sensitive to glucose and produce ROS. The islet is particularly at risk for chronic oxidative stress when exposed to long-term hyperglycemia because it expresses very low levels of antioxidant mRNA, protein, and activity Robertson et al, 2003
Selecting a Regimen
Provide Simple Flexible Suit
adequate control
patient needs
Bolus Insulin
Insulin Effect
Basal Insulin
D
Time of Administration
HS
Basal Insulin
Menurunkan produksi glukosa
antar makan dan malam (overnight) Bervariasi per individu 50 60 % dari kebutuhan harian
Mengatasi hiperglikemia setelah makan Meningkat segera dan mencapai puncak dalam 1 jam 10-20% dari total insulin tiap kali makan
Action Profiles
Preparations Onset(h) Peak(h) Duration(h)
Lispro/Aspart Regular NPH Ultralente < 0.25 0.5 - 1 1-3 2-4 1-2 2-4 5-7 8 - 14 3-4 6-8 13 - 16 < 20
Glargine
1-2
> 24
Modified after Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
6 units
7 units 8 units 9 units
4.80 u
5.60 u 6.40 u 7.20 u
3.60 u
4.20 u 4.80 u 5.40 u
2.40 u
2.80 u 3.20 u 3.60 u
1.20 u
1.40 u 1.60 u 1.80 u
0
0 0 0
10 units
8.00 u
6.00 u
4.00 u
2.00 u
HUMAN INSULIN
A chain
Gly
S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn
IIe
S S
10
15
S
21
S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly 1 5 10 20 15 Phe Phe
25
Pro Thr
Phe Tyr
30 The Lys
HUMAN INSULIN
A chain
Gly IIe
S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn
S S
10
15
S
21
S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly 1 5 10 20 15 Phe Phe
25
Pro Thr
Phe Tyr
30 The Lys
INSULIN LISPRO
A chain
Gly IIe
S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn
S S
10
15
S
21
S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly 1 5 10 20 15 Phe Phe
25
The Pro Lys Thr
Phe Tyr
30
HUMAN INSULIN
A chain
Gly IIe
S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn
S S
10
15
S
21
S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly 1 5 10 20 15 Phe Phe
25
Pro Thr
Phe Tyr
30 The Lys
INSULIN ASPART
A chain
Gly IIe
S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn
S S
10
15
S
21
S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly 1 5 10 20 15 Phe Phe
25
Asp Thr
Phe Tyr
30
The Lys
HUMAN INSULIN
A chain
Gly IIe
S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn
10
15
S
21
S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly 1 5 10 20 15 Phe Phe
25
Human insulin
A chain 21 amino acids B chain 30 amino acids
30 The Lys
Phe Tyr
Pro Thr
INSULIN GLARGINE
A chain
Gly IIe
S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Gly
S S
10
15
S
21
S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly 1 5 10 20 15 Phe Phe
25
Phe Tyr
32 31 30
Arg Arg The Lys
Pro Thr
Figure. Pharmacokinetincs on various insulin drugs, and insulin from pancreas http://www.medscape.com/viewarticle/501976_6
HumaPen Ergo II
HumaPen LUXURA
NPH
Glargine
NPH
NPH
These data underscore a critical concept in type 2 diabetes: Given the progressive decline in beta-cell function, combination therapy, such as oral agent(s) with insulin, is often necessary to achieve treatments goals
UKPDS Lancet 1998: 837-853
11 10 9 8 7 6
N=735 N=883 N=31
Initiation of insulin in Type 2 diabetes. Data from retrospective or prospective longitudinal surveys where the glycaemic level of initiation of insulin is not protocol driven.
Davies M. Int J Obesity (2004) ; 28 (Suppl. 2) : S14-S22
12 11 HbA1c (%) 10 9 8 7 6 5
Knight et al.37 Mohrie et al.38 Howorka et al.39 Reichard et al.40 Schifferdecker et al.35
10 9 8 7 0 1 2 3 4 5 6
Two injections daily (Mix Insulin) Morning insulin (Insulin NPH) + SU Evening insulin (Insulin NPH) + SU
Time (months)
Twice-daily insulin therapy, or combination therapy with a sulphonylurea (SU) markedly improved metabolic control in patients where OADs had failed. Marre M. Int J Obesity (2002) ; 26 (Suppl. 3) : S25-S30
HbA1c (%)
7 0 3 6 9 12
Time (months)
Insulin therapy can improve and maintain glycaemic control more effectively than sulphonylurea treatment. Patients had an HbA1c of 8-10% on entry and were stably controlled at that level.
Figure 1. ADA consensus on therapy for type 2 diabetes. Adapted with permission from the American Diabetes Association. Diabetes Care. 1995;18:1516.2
Insulin regimens
No insulin injection regimen satisfactorily mimics normal physiology
The choice will depend on many factors:
age, duration of diabetes, lifestyle (dietary patterns, exercise schedules, school, work commitments, etc), targets of metabolic control and, particularly, individual patient/family preferences
Selecting a Regimen
Provide Simple Flexible Suit
adequate control
patient needs
DERAJAT KEPARAHAN DM
DMT2 ringan: GDP < 126 mg/dl (Jarang perlu insulin) DMT2 sedang: GDP 126 200 mg/dl (Insulin basal) DMT2 berat: GDP > 200 mg/dl (Insulin premixed 2 x) DMT2 sangat berat: GDP > 250 300 mg/dl (Insulin dosis multipel)
Skyler, 2004
10 U every day If A1C remains > or twice daily for 7.0% and PPG is NPH elevated, add prandial insulin starting with largest daily meal
Monitor A1C every 3 months until < 7.0%; every 6 months thereafter
Hirsch, 2005
Pagi
Siang
Malam
Sebelum tidur
Skyler, 2004
Prandial: 5-10 U at Advance insulin dose each meal weekly until PPG and (Approximately 1 U for FPG are within target every 10-15 g of carbohydrate to start) Premixed insulin is not usually recommended, but can consider 10 U before breakfast and dinner Monitor A1C every 3 months until < 7.0%; every 6 months thereafter
Hirsch, 2005
Regular Insulin
NPH/Lente
NPH/Lente
S Meals
HS
Regular Insulin
NPH/Lente
NPH/Lente
S Meals
HS
NPH/Lente
S Meals
HS
NPH/Lente
S Meals
HS
Glargine
S Meals
HS
http://www.medscape.com/viewarticle/501976_6
INJECTION DEVICE DEVELOPMENT IN THE 80S AND 90S HAS ADDRESSED THESE ISSUES 1925 1920s
1989
1990s
From syringes to safe and convenient portable 1985 pens with insulin cartridges 1960
Treatment Options
Bedtime Insulin and Daytime OHA
Replacement Insulin Therapy twice daily insulin Intensive therapy QID (rarely indicated)
STT**
*: obat hipo- oral, terapi tunggal, kombinasi **: sasaran tak tercapai
- Insulin Kombinasi (basal + bolus) - Insulin Campuran (2/3 pagi dan 1/3 malam)
Konsensus Perkenii 2006
Mean of self-monitored FPG values from preceding 2 days >10 mmol/L (180 mg/dl) >7.810.0 mmol/L (140180 mg/dl)
4
2
Smaller dose reductions allowed in the event that FPG drops below 3.0 mmol/L (56 mg/dl) or of a severe hypoglycaemic episode
If more than 30-36 IU of insulin necessary to obtain good metabolic control, consider stopping insulin secretagogues and continue on same total dose of insulin + metformin or TZD Divide the dose into 2 daily injections:
2/3 before breakfast 1/3 at bedtime
1. Sasaran Kendali Glikemik yg baik adalah A1C < 6,5% 2. Pantau A1c setiap 3 bln disamping pemeriksaan glukosa darah
3. Pengelolaan agresif hiperglikemia, dislipidemia dan hipertensi dengan intensitas yang sama untuk mencapai luaran penderita yang terbaik 4. Rujuk semua penderita diabetes baru ke unit perawatan diabetes bila memungkinkan
Sepuluh Langkah Untuk Mencapai Sasaran Glikemik Penderita Diabetes 9. Gunakan kombinasi obat oral dengan mekanismekerja yang saling melengkapi 10. Lakukan pendekatan tim multidisiplin dalam pengelolaan diabetes untuk meningkatkan pemahaman penderita meliputi edukasi, perawatan mandiri,tanggung jawab bersama untuk mencapai sasaran glukosa yang baik
A1C
Table. MPG as estimated from the regression line and approximate MPG (based on MPG change of 35 mg/dl or 2 mmol/l per 1% change in A1C) at different A1C levels (assessed in the DCCT) Mean plasma glucose A1C (%)
4 5 6 7 8 9 10 11 12
mmol/l mg/dl
Patients average glycemia over the preceding 2-3 months First at initial assessment and then as a part of continuing care At least two times a year (stable glycemic control)
Rohlfing et al. Diabetes Care 25: 275-278, 2002
ALGORITME INSULIN KOREKSI PREPRANDIAL Glukosa preprandial (mg/dl) 150 199 200 249 250 299 300 349 > 349 Dosis insulin koreksi (unit) Algoritme Algoritme Algoritme dosis rendah dosis sedang dosis tinggi 1 2 3 4 5 1 3 5 7 8 2 4 7 10 12
Catatan : Gunakan algortime dosis rendah bila pasien membutuhkan < 40 unit insulin/hari Gunakan algortime dosis sedang bila pasien membutuhkan 40-80 unit insulin/hari Gunakan algortime dosis tinggi bila pasien membutuhkan > 80 unit insulin/hari
Insulin program dan insulin koreksi dinaikkan bertahap untuk mencapai kebutuhan tertinggi dari insulin basal dan insulin prandial
MENYUNTIK INSULIN
Kebanyakan diberikan subkutan Semua insulin suspensi : kocok secara lembut sebelum disuntikkan Untuk mencampur insulin kerja cepat / pendek dengan insulin kerja menengah / panjang : insulin kerja cepat / pendek harus disedot lebih dahulu baru insulin kerja menengah / panjang
MENYUNTIK INSULIN
Bila area suntikan cukup bersih tidak perlu dibersihkan lagi dengan alkohol Suntikan intramuskuler mempercepat absorbsi secara rutin tidak dianjurkan Melakukan pijatan / pemanasan pada tempat suntikan mempercepat absorbsi insulin
TEMPAT SUNTIKAN
Abdomen : 2 inchi di sekeliling pusat Sisi lateral lengan atas Sisi anterolateral paha Untuk menghindari variasi absorbsi rotasi suntikan pada 1 tempat saja, misalnya di abdomen
EFEK SAMPING DAN KOMPLIKASI SUNTIKAN INSULIN Hipoglikemia Reaksi alergi (lokal, sistemik) Lipohipertrofi (penebalan lemak subkutan pada tempat suntikan) Lipoatrofi (penipisan lemak subkutan pada tempat suntikan)