INSULIN THERAPY IN TYPE 2 DIABETES

Presentation Point of View

Background Pathogenesis of Type 2 DM Insulin choices Rationality of Insulin Therapy for Type 2 DM INSULIN TREATMENT ON OUTPATIENT

Normal islet cell

Deposition of amyloid in T2DM

Natural History of Type 2 Diabetes

Timing of Intervention
(Window of Opportunity)
TLC OAD ACEI AIIA Post-prandial glucose Fasting glucose

Plasma glucose

-cell function

OADs Insulin Rx

Insulin resistance Insulin secretion

10

20

30

Years of Diabetes
Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota

Successful Insulin Therapy

Simple insulin initiation

Comfortable injections
Peralatan suntik sederhana & mudah

Emotional support
Education in diabetes management

Pasien taat / patuh menjalani

Persentation Point of View

Background Pathogenesis of Type 2 DM Insulin choices & KINETICS Rationality of Insulin Therapy for Type 2 DM INSULIN REGIMEN

Loss of the early peak of insulin secretion

Insulin secretion

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

Persentation Point of View

Background Pathogenesis of Type 2 DM Insulin choices & Kinetics Rationality of Insulin Therapy for Type 2 DM INSULIN REGIMEN

INDICATION OF INSULIN THERAPY

Type 2 DM in certain condition
DM + secondary failure DM + Celulitis/Gangren/Infeksi lainnya DM + underweight DM + Fracture DM + Chronic Hepatitis / Cirrhosis DM + Pulmonary TBC DM + Graves Disease DM + Cancer DM + Severe liver dysfunction DM + Late stage Nephropaty Type 2 DM with Early Insulin Therapy

Insulin Therapy for Type 2 Diabetes:

Augmentation Supplemental or corrective Replacement of Beta-Cell Function Short Term Rescue Therapy

Selecting a Regimen
Provide Simple Flexible Suit

adequate control

patient needs

KISS = Keep It Safe and Simple (Keep It Simple and Stupid)

Normal Insulin Secretion The Basal-Bolus Insulin Concept

Endogenous Insulin

Bolus Insulin

Insulin Effect

Basal Insulin

D
Time of Administration

HS

B, breakfast; L, lunch; D, dinner; HS, bedtime.

Adapted from: 1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002. 2. Bolli GB et al. Diabetologia. 1999;42:1151-1167.

Basal Insulin
Menurunkan produksi glukosa
antar makan dan malam (overnight) Bervariasi per individu 50 60 % dari kebutuhan harian

Bolus Insulin (Mealtime or Prandial)

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.

Insulin Left At 1, 2, 3, and 4 Hours After A Dose Of Humalog Or Novorapid, Apidra

Dose Given 1 unit 2 units 3 units 4 units 5 units

Units Left To Work After:

1 Hr 0.80 u 1.60 u 2.40 u 3.20 u 4.00 u 2 Hr 0.60 u 1.20 u 1.80 u 2.40 u 3.00 u 3 Hr 0.40 u 0.80 u 1.20 u 1.60 u 2.00 u 4 Hr 0.20 u 0.40 u 0.60 u 0.80 u 1.00 u 5 Hr 0 0 0 0 0

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

20% of a dose will be used each hour after it is given

HUMAN INSULIN
A chain
Gly

S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn

IIe

Val Glu Gln Cys Cys Thr Ser

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

Regular : Poor prandial, poor basal

NPHL: Poor prandial, fair basal (better
small at daytime, large at night) with small dose QID,

Ultralente: Fair basal

HUMAN INSULIN
A chain
Gly IIe

S
Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn

Val Glu Gln Cys Cys Thr Ser

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

Val Glu Gln Cys Cys Thr Ser

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

Lispro Excellent prandial, excellent basal if used in a CSII program

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

Val Glu Gln Cys Cys Thr Ser

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

Val Glu Gln Cys Cys Thr Ser

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

Aspart Excellent prandial, excellent basal if used in a CSII program

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

Val Glu Gln Cys Cys Thr Ser

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

Val Glu Gln Cys Cys Thr Ser

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

Glargine, Detemir Promise to be excellent basal insulin

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

Insulin Glargine versus NPH-Insulin clear solution vs. suspension

NPH

Glargine

NPH

NPH

Factors that speed insulin absorption

Injecting into an exercised area such as the thigh High temperatures, for example, shower, bath, hot water bottle, spa or sauna Massaging the area around the injection site Injecting into muscle the deeper the injection into muscle, the faster the insulin will be absorbed

Factors that delay insulin absorption

Cigarette smoking. Over-use of the same injection site, which causes the flesh to become hard, lumpy or scarred, and leads to erratic absorption of insulin. Cold insulin, for example, injecting immediately after taking the insulin from the fridge.

Persentation Point of View

Background Pathogenesis of Type 2 DM Insulin choices & KINETICS Rationality of Insulin Therapy for T2DM INSULIN REGIMEN

KAPAN INSULIN DIPERLUKAN?

UKPDS Study data 50% DMT2 perlu insulin setelah 6 tahun Lowest B-cell function at diagnosis greatest risk of OAD failure

Marre M. Int J Obesity (2002) ; 26 (Suppl 3) : S25-S30

Rationale for Early insulin therapy

UKPDS demonstrated that early intervention to achieve tight glycemic control (A1C 7.0%) resulted in 25% reduction (P=.0099) in the risk for microvascular complications and a 16% risk reduction (P=.052) for mycocardial infarction. During the first 6 years of UKPDS, slightly more than half (53%) of the patients treated with maximal sulfonylurea therapy could not maintain glucose control

Rationale for Early insulin therapy

The addition of insulin to sulfonylurea therapy resulted in significantly improved glycemic control. Without an increased incidence of hypoglycemia or weight gain

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

Insulin Is Unnecessarily Delayed

Before insulin initiation Mean HbA1c (%HB) After insulin initiation (1-4y)
N=272 N=52

11 10 9 8 7 6
N=735 N=883 N=31

Hayward et al.30 USA

de Sonnaville et al.31 Netherlands

de Grauw et al.32 Netherlands

Rosendal et al.33 Netherlands

Vahatalo et al.34 Finland

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

Insulin Intensification -Effects on BG

Before intensification After intensification

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

Intensification of insulin therapy. Data from Schifferdecker et al.

Davies M. Int J Obesity (2004) ; 28 (Suppl. 2) : S14-S22

Insulin Improved Glycaemic Control

12 11
HbA1c (%)

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

Long-Term Control With Insulin

10

HbA1c (%)

9 Sulphonylurea group Insulin group 8

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.

Marre M. Int J Obesity (2002) ; 26 (Suppl. 3) : S25-S30

Figure 1. ADA consensus on therapy for type 2 diabetes. Adapted with permission from the American Diabetes Association. Diabetes Care. 1995;18:1516.2

Persentation Point of View

Background Pathogenesis of Type 2 DM Insulin choices & KINETICS Rationality of Insulin Therapy for Type 2 DM INSULIN REGIMEN

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

KISS = Keep It Safe and Simple (Keep It Simple and Stupid)

Insulin Treatment in Type 2 Diabetes

Options: Terapi oral + Suntik NPH atau Glargine sebelum tidur NPH + short acting insulin BID Multiple daily injections (MDI)

Meltzer et al. CMAJ 1998;159(Suppl 8):S1-S29.

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

Recommended Strategies for Initiating Insulin in Type 2 Diabetes*

A1C Threshold Therapeutic Strategy Suggested Initial Dose Follow-up

7.0% to 10.0% despite 2 oral medications

Initiate basal insulin

Continue oral medications

10 U every day for insulin glargine

Advance insulin dose weekly until FPG is within target

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

Terapi Kombinasi Oral Insulin Glargine

Pagi

Siang

Malam

Sebelum tidur

Oral Suntik Insulin Glargine

Sample Plan for Bedtime Basal Insulin Dosing in T2DM

FBG target is 70 100 mg/dl, plans should be individualized Start 10 units bedtime basal insulin, adjust the dose weekly If mean FBG during the previous 4 days is > 180 mg/dl Increase the dose with 8 unit If mean FBG during the previous 4 days is 140 - 180 mg/dl Increase the dose with 6 unit If mean FBG during the previous 4 days is 120 - 140 mg/dl Increase the dose with 4 unit If mean FBG during the previous 4 days is 100 - 120 mg/dl Increase the dose with 2 unit If mean FBG during the previous 4 days is 70 - 100 mg/dl Maintain current dose If mean FBG during the previous 4 days is 140 - 180 mg/dl Return to the previous dose If mean FBG during the previous 4 days is 140 - 180 mg/dl Reduce the dose by 2 4 units

Skyler, 2004

Recommended Strategies for Initiating Insulin in Type 2 Diabetes*

A1C Threshold > 10.0% despite 2 oral medications Therapeutic Suggested Initial Strategy Dose Initiate basalprandial insulin Discontinue oral secretagogu es Basal, as above Follow-up Optimize prandial doses for each meal

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

SAMPLE MIXED-SPLIT INSULIN REGIMEN (1)

Regular Insulin

NPH/Lente

NPH/Lente

S Meals

HS

SAMPLE MIXED-SPLIT INSULIN REGIMEN (2)

Regular Insulin

NPH/Lente

NPH/Lente

S Meals

HS

SAMPLE MULTIPLE COMPONENT INSULIN REGIMEN (1)

Regular Insulin

NPH/Lente

S Meals

HS

SAMPLE MULTIPLE COMPONENT INSULIN REGIMEN (2)

Regular Insulin

NPH/Lente

S Meals

HS

SAMPLE MULTIPLE COMPONENT INSULIN REGIMEN (3)

Regular Insulin

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

More insulin pen introductions in the

1990s

From syringes to safe and convenient portable 1985 pens with insulin cartridges 1960

FUTURE INSULIN TREATMENT

NON INJECTABLE INSULIN DELIVERIES

Transdermal insulin delivery

Oral insulin delivery

Pulmonary insulin delivery

Buccal insulin delivery

Treatment Options
Bedtime Insulin and Daytime OHA
Replacement Insulin Therapy twice daily insulin Intensive therapy QID (rarely indicated)

ALGORITMA KOMBINASI INSULIN DAN OHO

OHO* (TT & TK)

STT**

OHO + 10 U Insulin (kerja menengah/panjang)

OHO stop jk nyaman

Sesuiakan dosis 2-4 U dlm 3-4 hari

Jika jml Ins > 30 U/hari, hentikan OHO

*: 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

Dose titration schedule

Start with 10 IU/day bedtime basal insulin dose and adjust weekly in addition to current oral therapy

Mean of self-monitored FPG values from preceding 2 days >10 mmol/L (180 mg/dl) >7.810.0 mmol/L (140180 mg/dl)

Increase in insulin dosage (IU/day) 8 6

>6.77.8 mmol/L (120140 mg/dl) >5.66.7 mmol/L (100120 mg/dl)

Riddle M et al. Diabetes Care 2003;26(11):30806.

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

Initiating Insulin in Type 2 DM Target

Improve BG control target : HbA1C < 6.5% Fasting sugar of < 108 mg/dL PP sugars of < 144 mg/dL

 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

Sepuluh Langkah Untuk Mencapai Sasaran Glikemik Penderita Diabetes

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

5. Pengobatan ditujukan kepada dasar patofisiologinya termasuk resistensi insulin 6. Obati penderita secara intensif hingga mencapai sasaran A1C < 6,5% dalam waktu 6 bulan setelah didiagnosis
7. Setelah 3 bulan, jika sasaran A1C < 6,5% tidak tercapai pertimbangkan terapi kombinasi 8. Mulai dengan terapi kombinasi atau insulin segera untuk semua penderita dengan A1C 9% pada saat diagnosis

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

3.5 5.5 7.5 9.5 11.5 13.5 15.5 17.5 19.5

65 100 135 170 205 240 275 310 345

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

CARA PEMBERIAN INSULIN

Pasien rawat jalan :
dapat dimulai dgn insulin kerja menengah dosis rendah pagi hari Penyesuaian : 2 4 unit setiap 3 4 hari Bila dosis dibutuhkan tinggi : dapat dibagi pagi malam, perbandingan 2:1

CARA PEMBERIAN INSULIN

Pasien rawat inap :
Makanan tidak selalu dalam bentuk padat dosis insulin basal dan insulin nutrisional Insulin nutrisional : Jumlah insulin yang dibutuhkan untuk mengatasi glukosa yg diberikan lewat intravena, TPN, sonde lambung, nutrisi tambahan dan makanan bebas Bila hanya makan makanan padat : kebutuhan insulin nutrisional setara (equivalen) dengan insulin prandial

CARA PEMBERIAN INSULIN

Pasien rawat inap :
Kebutuhan insulin meningkat akibat pengaruh hormon kontrainsulin (respons thd stres) o.k: tindakan operasi, kortikosteroid, pressor agent, obat diabetogenik, dll. Tambahan kebutuhan = insulin koreksi (supplement) Komponen insulin utk rawat inap tdd.:
Insulin basal Insulin prandial (nutrisional) Insulin koreksi (supplemental)

CARA PEMBERIAN INSULIN

Dosis insulin basal dan insulin prandial dicatat sebagai insulin program (scheduled insulin) Dosis insulin koreksi dicatat sebagai algoritme untuk ditambah pada insulin program Tujuan algoritme koreksi : mengatasi hiperglikemia yang melampaui target dan sering tak terduga pada pasien dgn stres Jenis insulin koreksi : insulin kerja cepat dan insulin kerja pendek Dosis insulin koreksi : berdasarkan glukosa preprandial dan kebutuhan insulin total perhari

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

CARA PEMBERIAN INSULIN

Dosis insulin perhari : 0,3 1,5 U/kgBB Dua per tiga dari total dosis
dalam bentuk insulin kerja pendek diberikan setengah jam sebelum makan

Sepertiga dari total dosis

Dalam bentuk insulin kerja menengah atau insulin kerja panjang Diberikan malam 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

TEKNIK MENYUNTIK SUBKUTAN

Jepit kulit dengan dua jari tusukkan jarum dengan posisi 90 derajat lepaskan jepitan sambil disuntik tunggu + 5 detik baru jarum dicabut Untuk pasien kurus : arahkan jarum 45 derajat agar insulin tidak masuk ke otot Ketika jarum sudah berada di subkutan, sebelum disuntikkan tidak perlu dilakukan penyedotan

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)