Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
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
1
2
3
4
5
6
7
8
9
10
Country
India
China
USA
Indonesia
Japan
Pakistan
Russian Fed.
Brazil
Italy
Bangladesh
2030
People with
diabetes
(millions)
31.7
20.8
17.7
8.4
6.8
5.2
4.6
4.6
4.3
3.2
Country
India
China
USA
Indonesia
Pakistan
Brazil
Bangladesh
Japan
Philippines
Egypt
People with
diabetes
(millions)
79.4
42.3
30.3
21.3
13.9
11.3
11.1
8.9
7.8
6.7
5
Wild S et al. Diabetes Care 2004;27(5):1047-53.
Type of DM
1. Type 1 (IDDM: insulin dependent DM)
2. Type 2 (NIDDM: non insulin dependent DM)
- obese
- non obese
3. Others (genetic cell function & insulin action,
disease of exocrine pancreas, drugs,
endocrinopathies, infections, immune, others.
4. Gestasional
6
Fasting &
2h post-prandial
< 100
< 140
Diabetes mellitus
Fasting &
2h post-prandial
> 126
> 200
Impaired Glucose
Tolerance (IGT)
Fasting &
2h post-prandial
< 100
140-199
Impaired Fasting
Glucose (IFG)
Fasting &
2h post-prandial
100 - 125
< 140
NB:
In the absence of symptom, the diagnosis of DM must be confirmed by a
second
diagnosis test (i.e. fasting, random, or Oral Glucose Tolerance Test (OGTT) on7
a separate day
Examination:
BMI (body mass index weight (kg)/height2(m)
Clues for secondary causes
Cardiovascular system (BP + pulse)
Sign of autonomic and peripheral neuropathy
Eyes for retinopathy
Investigation:
Blood test for: urea & electrolytes, liver & thyroid
function, full lipid profil
Urine tests for ketones, macro and (if negative)
micro albuminuria
An ECG in all type 2 DM
10
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.
11
3
4
Kannel WB, et al. Am Heart J 1990; 120:672676. Gray RP & Yudkin JS. In Textbook of Diabetes 1997.
5
Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78S79.
Progressive
-cell
dysfunction
Type 2 Diabetes
Hepatic
glucose production
Impaired
incretin
signaling
1. Bode BW. Postgrad Med. 2009;121:82-93.
2. DeFronzo RA. Ann Intern Med. 1999;131:281-303.
3. DeFronzo RA. Diabetes. 2009;58:773-795.
Increased
lipolysis
Increased
renal
glucose transport
Lack of
cells
glucagon
suppression
PENGATURAN
MAKAN
4
LATIHAN
JASMANI
PENYULUHA
N
OBAT
CANGKOK
135
170
205
240
10
275
11
310
12
345
15
HbA1c HbA1c
HbA1c
135 mg/dl
7.8%
HbA1c
135 mg/dl
7.8%
Time
A1C1
Measures mean glycemia (past 3-4 months)
Reflects risk for T2DM complications
Menurunkan resiko*
Kematian karena
diabetes
-21%
Infark miokard
-14%
Komplikasi
mikrovaskuler
-37%
Gangguan pembuluh
darah perifer
-43%
1%
10%
25%
10%
25%
6.30
9.30
12.00
15.00
19.00
10%
21.00
Intensitas
Durasi
Tipe
Program Latihan
Teratur (3-4 kali seminggu)
20- 40 menit didahului
pemanasan 5-10 mnt dan
cool-down 10 mnt
CRIPE:
Continous
Rythmis
Interval
Progresif
Endurance
-glucosidase inhibitors
e.g. acarbose
Glinides/meglitinides
Non-sulfonylureic e.g. repaglinide
Amino acid derivatives e.g. nateglinide
Biguanides
e.g. metformin
Thiazolidinediones
e.g. rosiglitazone, pioglitazone
Insulin
regular
intermediate/long acting
pre-mixed
analogs
rapid acting
long acting
Metformin
How it works
Weight effects
CV effects
Sulfonylureas
How they work
Expected HbA1c
reduction
~ 1.5%
Adverse events
Weight effects
CV effects
Length of
action
Begins of
action
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%
26
Glinides
How they work
Expected HbA1c
reduction
~ 1.5% (repaglinide)
Adverse events
Weight effects
CV effects
Expected HbA1c
reduction
~0.8%
Adverse events
Minimal
Weight effects
Neutral
CV effects
Unknown
-Glucosidase Inhibitors
How they work
Expected HbA1c
reduction
0.50.8%
Adverse events
Weight effects
CV effects
Weight neutral
Unconfirmed report of reduction of
severe outcomes in one clinical trial
Thiazolidinediones
How they work
Expected HbA1c
reduction
0.51.4%
Adverse events
Weight effects
CV effects
How it works
Weight effects
CV effects
Expected HbA1c
reduction
~0.8%
Adverse events
Minimal
Weight effects
Neutral
CV effects
Unknown
Insulin
How it works
Expected HbA1c
reduction
1.52.5%
Adverse events
Hypoglycemia
Weight effects
CV effects
Weight gain of ~ 24 kg
100
75
Beta Cell
Function
(%)
IGT
Postpandrial
Hiperglycemi
T-2 DM phase I
Beta Cell function
50 %
50
Stages of Type
2 Diabetes
T2 DM
phase I
25
T2 DM
phase II
T2 DM
phase III
0
-12 -10
14
Lebovitz, 2000
-6
-2
10
35
Diet &
Exercise
1.5-2%
Metformin
Insulin
Secretagogues
1%
TZD
Alpha-glucosidase
Inhibitors
Combination
Oral
Agents
Insulin
3-4%
5% or more
<7%
<8%
1-1.5%
<8-10%
>10%
Diagnosis
Glucose
Fasting glucose
Insulin
Insulin resistance
Inadequate
-cell function
Microvascular changes
Macrovascular changes
NGT
Prediabetes
(IFG/IGT)
Diabetes
Insulin secretion
ADA1
IDF2
PERKENI3
FPG
<130 mg/dL
FPG
<110 mg/dl
FPG
<100 mg/dl
HbA1c
< 7.0%
PPG
<180 mg/dL
HbA1c
< 6.5%
PPG
<145 mg/dL
HbA1c
< 7%
PPG
<140 mg/dl
Good control is
7.0% HbA1c
HbA1c measures the
average
blood glucose level
HbA1c
over the
last three months
-1%
Myocardial
infarction
-14%
Microvascular
complications
-37%
Deaths related
to diabetes
-21%
Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al.
BMJ. 2000;321(7258):405-412.
Slide 40
Inzucci SE, et al. Diabetologia. 2012
Diabetes
Healthy life style
STEP 1
STEP 2
STEP 3
Note:
1.
2.
2 OAD Combination
+
Combination 2 OAD
Alternative option, if :
No insulin is available
Basal insulin
Insulin Intensification*
Contribution (%)
Target HbA1c will not be reached without bringing down postprandial hyperglycaemia
Woerle HJ, et al. Diabetes Res Clin Pract 2007;77:2805
Glucose
Insulin
Glucose
120
300
80
60
200
40
100
20
120
100
Insulin U/mL
Insulin U/mL
100
Insulin
400
Glucose mg/dL
400
Glucose mg/dL
300
80
60
200
40
100
20
06:00 10:00 14:00 18:00 22:00 02:00 06:00
Dinner
Lunch
Slide 44
Breakfast
Dinner
Lunch
Breakfast
Time of Day
Time of Day
0 4 8 12 16 20 24
Time (h)
FAST-ACTING
GIR (mg/kg/min)
GIR (mg/kg/min)
GIR (mg/kg/min)
BASAL
0 4 8 12 16 20 24
Time (h)
0 4 8 12 16 20 24
Time (h)
1. Hompesch M. Diabetes Obes Metab 2006; 8:568; 2. Weyer et al. Diabetes Care 1997;10:16121614.; 3. 1. Heinemann et al. Diabetes Care.
1998;21:19104
Inadequate
Lifestyle
+ 1 OAD
INITIATE INSULIN
+ 2 OAD
+ 3 OAD
LysB29(N-tetradecanoyl)des(B30)human insulin
C14
(My fatty a
risti
c
c a id cha
cid)
in
Thr
Lys
Pro
Pro
Thr
Tyr
A21
B29
A1
Phe
Phe
Asn
Gly
Cys
Lys
Gly
Arg
Glu
Gly
Cys
Val
Leu
Tyr
Asn
Tyr
Ile
Glu
Leu
Val
Leu
Ala
Gln
Glu
Glu
Gln
Cys
Tyr
Cys
Thr
Ser
Ile
Cys
Ser
Val
Leu
Leu
His
Gly
B1
Phe
Val
Asn
Gln
His
Leu
Cys
Ser
3 units
0 maintain
dose
decrease dose
3 units
70-130 mg/dl
Maintain dosage
130-180 mg/dl
>180 mg/dl
BASAL
INSULIN
Subsequent pre-meal
Glucose (mg/dl)
FAST-ACTING
INSULIN
Slide 50
Source: KONSENSUS: Insulin Treatment 2011
Premixed
Insulin
(Twice daily
Treat to target)
Lifestyle +
Metformin
+-other OAD
or GLP-1
agonists
Basal Insulin
(Basal + 3
prandial)
Basal Insulin
(Once-daily
treat-to-target)
HbA1c
7.0%
1c
Basal Insulin
(Basal + 1 or 2
prandial)
HbA1c
7.0%, FPG on target, PPG 160 mg/dl
1c
AAFP:
AACE:
High HbA1c
Support intensification from basal to premix or basal-bolus
Support intensification from premix to basal-bolus
IDF:
High HbA1c
Support intensification from basal to premix or basal-bolus
Support intensification from premix to basal-bolus
EASD:
add rapid-acting
switch to premix
Basal
Basal Insulin
Insulin Only
Only
Usually
with
OAD
Usually with OAD
Basal
Basal with
with Prandial
Prandial
Usually
keep
Usually keep OAD
OAD
Basal
Basal Bolus
Bolus
Usually
Usually keep
keep OAD
OAD
HbA1c >8%
FPG: 73-110 mg/dl
Dose change
-2U
0
+2 U
+4 U
+6 U
When the daily insulin dose in a OD regimen nears 40-50 U, intensifying the regimen to BID
BIAsp 30 distribution = 2:1:3 (breakfast:lunch:dinner)
BIAsp 30 TID: alternative to basal-bolus (fewer daily injection and only one device need)
LOKASI PENYUNTIKKAN
57
T2DM
300
15
200
10
100
Normal
0
6
Meal
Meal
10
14
Meal
18
0
22
Waktu (jam)
Comparison of 24-hour glucose levels in control subjects vs patients with diabetes (p<0.001).
Adapted from Polonsky K, et al. N Engl J Med 1988;318:12319.
20
INSULIN ANALOG:
1. NovoRapid
2. NovoMix
3. Levemir
Injectables
Current treatments for type 2 diabetes have limitations when renal function declines
Dose Reduction
Insulin
Liraglutide
Dose Reduction
Exenatide
Linagliptin
Oral drugs
Sitagliptin
Vildagliptin
Saxaglipti
n
Dose Reduction
Metformin
Acarbose
Repaglinid
e
Glimepirid
e
Dose Reduction
Gliclazide
Pioglitazo
ne
>60
30 60
Declining GFR
<30
Hemodialysis
Adapted from: Schernthaner G, et al. Nephrol Dial Transplant. 2011;26(2):4547 (in press) and respective EMEA SmPCs
61
well-validated therapies
At diagnosis:
Lifestyle +
Metformin
STEP 1
Lifestyle + Metformin
+ Basal insulin
Lifestyle + Metformin
+ Intensive insulin
Lifestyle + Metformin
+ Sulfonylurea
STEP 2
STEP 3
Tier 2:
Lifestyle + Metformin
+ Pioglitazone
No hypoglycaemia
Oedema/CHF
Bone loss
Lifestyle + metformin
+ GLP-1 agonist
No hypoglycaemia
Weight loss
Nausea/vomiting
Nathan DM, et al. Diabetes Care 2009;32 193-203.
Lifestyle + Metformin
+ Pioglitazone
+ Sulfonylurea
Lifestyle + metformin
+ Basal insulin
62
KASUS 1
Seorang wanita penderita Ca Mammae
usia 65 tahun dengan DM sejak 5 tahun
yll. dengan HbA1c 9,2%, GD puasa
225mg%, 2jpp 270 mg%, terapi metformin
3x500mg, Glibenclamid 1 0 0 tidak teratur.
Creatinin 1,9mg%, BUN 59mg%.
1, berapa target HbA1c?
2. TX sebaiknya apa?
Slide 64
Kasus 2.
Seorang Dosen Pria usia 45 tahun
dengan GDN 250mg%, 2jpp 350mg%,
telah mendapat terapi glimepirid 2mg 1-00 selama 2 tahun.
1. berapa target HbA1c?
2. Terapi apa agar HbA1c tercapai?
Slide 65
Kasus 3
Seorang ibu rumah tangga usia 42th, DM
dan HT, dengan kadar gula darah puasa
112 mg%, 2jpp 211mg%, HbA1c 7,0%, T
130/85mmhg terapi insulin basal 22 unit,
irbesartan 1x300mg
Apakah sudah tercapai target?
obat apa yang perlu dirubah atau
ditambah?
Slide 66
Less Hypoglycemia
Less Weight Gain
DM tipe 1
67
1980
1980
2009