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Insulin Treatment
Agus Yuwono
Sejarah Perkembangan
insulin
s/d 1983
1921
: penemuan insulin
: era insulin hewan
Menggunakan ekstrak pankreas hewan (sapi / babi)
1983
1999
Sejarah Perkembangan
Rationale for
Aggressive Treatment
r:ndei:6855:slides:bernsteintitle
2 to 4 fold increase in
cardiovascular
mortality and stroke3
Cardiovascular
Disease
8/10 diabetic patients
die from CV events4
Diabetic
Nephropathy
Leading cause of
end-stage renal disease2
Diabetic
Neuropathy
Leading cause of
non-traumatic lower
extremity amputations5
Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99S102. 2Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94S98.
3
Kannel WB, et al. Am Heart J 1990; 120:672676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.
5
Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78S79.
Prevalence
(%)*
Any complication
50
Retinopathy
21
Abnormal ECG
18
14
Myocardial infarction/angina/claudication
* Some patients had more than one complication at time of diagnosis
Stroke/transient
ischaemic attack
ECG = electrocardiogram
7
~23
~1
76%
(P0.002)
Nephropathy
54%
(P<0.04)
Neuropathy
60%
(P0.002)
Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:9
Komplikasi Diabetes
per 1000 pasien / tahun
140
120
103.2
100
74.5
65.5
80
48.7
60
35.9
40
20
0
10
11
The UKPDS
Type 2 diabetes
1%
HbA1c
Time of diagnosis
80
60
Pancreatic function
= 50% of normal
40
20
0
10
Time (years)
HOMA=homeostasis model assessment.
UKPDS Group. Diabetes 1995;44:124958.
Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(suppl 1):S215.
PRINCIPLES OF INSULIN
TREATMENT
Insulin regiment mimicking
(endogenous) physiologic
insulin secretion
Insulin long-acting
(Insulin basal)
Long-acting SU
Metformin
Glitazone
Insulin prandial
Short-acting Insulin
Short-acting SU
Glinide
Glitazones
Acarbose
Basal
Pancreatic output :
basal prandial
Prandial insulin
Basal insulin
Prandial glucose
Basal glucose
Insulin Effect
Bolus Insulin
Basal Insulin
HS
Time of Administration
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.
Insulin Analogs:
Fatty Acid Acylated insulins
Insulin Lispro (Humalog) (1996)
Insulin Aspart (NovoRapid) (2000)
Insulin Glargine (Lantus) (2002)
Insulin Detemir (Levemir) (Jun.,2005)
Insulin Glulisine (Apidra) (Jan., 2006)
Insulin Bolus
Disuntikkan sesaat sebelum
makan atau sesudah makan
Menurunkan GD postprandial
Dapat digunakan untuk drip iv
Larutan jernih
- Insulin Basal
-Disuntikkan sesaat sebelum tidur
malam, sekali sehari
- Menurunkan GD puasa
- Tidak dapat digunakan untuk drip iv
- Larutan jernih
PRINSIP TERAPI
Insulin Basal: mengatasi hiperglikemia puasa akibat
glukoneogenesis (intermediate-acting insulin long-acting
insulin)
Insulin Prandial/ Nutrisional: mengatai glukosa yang
diberikan lewat intravena, TPN, lewat sonde lambung,
nutrisi tambahan dan makanan bebas (rapid-acting
insulin short-acting insulin)
Insulin suplemen/koreksi: memenuhi kebutuhan insulin
yang meningkat akibat penyakit akut / stres (rapid-acting
insulin atau short-acting insulin)
Time (h)
SC injection
Insulin basal
Prandial Hyperglycemi
Insulin prandial
-------
Insulin endogen
Levemir
NovoRapid
NovoMix
Makan
Pagi
Makan
Siang
Makan
Malam
Sebelum tidur
Insulin Regiments
Insulin Treatment
for Type 2 Diabetes Patients
Basal First
Basal Plus
Basal Bolus
Tahap 1
Tahap 2
Tahap 3
Gaya hidup +
Saat diagnosis:
Metformin +
Gaya hidup
Insulin basal
+
Metformin
Well validated
core therapies
Gaya hidup +
Metformin +
Metformin +
Insulin intensif
+
Basal insulin
Sulfonilurea
Gaya hidup +
Metformin +
Less well
validated core
therapies
Gaya hidup +
Gaya hidup +
Metformin +
Pioglitazon
Pioglitazon +
sulfonilurea
Gaya hidup +
Gaya hidup +
Metformin +
Metformin +
GLP-1 agonis
Basal insulin
Nathan DM et al, Diabetes Care 32:193203, 2009
Inadequate
Lifestyle
1 OAD
2 OAD
Initiate
3 OAD
Insulin
Indication: Permanent
Not permanent
T1DM
Infection
OAD failure
Pregnancy
Hospitalized
Diabetic Ketoacidosis
Perioperative
Strategy of
Insulin Treatment ?
Hyperglycemia
Basal
Prandial Insulin
(NovoRapid)
Recommendation
Insulin Treatment
for Type 2 Diabetes Patients
Basal First !!!
A
Morning
Evening
Afternoon
Night
Oral
DETIMIR/glargin
S
MEALS
HS
Oral
Lunch
Dinner
Plasma
insulin
Glargine
Or Detemir
4:00
Date
8:00
12:00
16:00
Time
Presentation title
20:00
24:00
4:00
8:00
54
Basal bolus
Additional prandial
doses as needed
Basal Plus
Add prandial insulin at main meal
Basal
Add basal insulin and titrate
Oral agents
Lifestyle changes
Date
Adapted from Raccah D, et al. Diabetes Metab Res Rev 2007 (in press).
55
10
Date
56
Date
Presentation title
57
Summary
Starting insulin therapy with basal insulin
analogue to achieve optimum FPG
Insulin treatment must be evaluated
because diabetes as progressive disease
Novomix as simple and effective
intensification after basal failed
Basal bolus is an ideal treatment option,
since provide optimal A1C control but has
a limitation as 4 times injection daily
58
Smart insulin pumps. Smart insulin pumps have several software enhancements
that estimate the appropriate correction bolus based on the current blood glucose
(BG) minus any active insulin on board from a prior insulin bolus plus the amount of
insulin to cover the carbohydrates consumed.