DIABETES MELLITUS

Dr. dr. Shahrul Rahman, Sp.PD, FINA

Departemen Ilmu Penyakit Dalam
Fakultas Kedokteran
Universitas Muhammadiyah Sumatera Utara

KLASSIFIKASI DIABETES MELLITUS

1. DM tipe-1 (Autoimun dan Idiofatik)
2. DM tipe-2 - Gemuk :

Resistensi Insulin > Disfungsi sel

Tak gemuk : Disfungsi sel > Resistensi Insulin

3. DM tipe lain : MODY; Peny.Eksokrin pancreas,Cushing S dll
4. DM Gestasi. (Kalau hamil DM, tak hamil DM nya sembuh).

DM = Sekumpulan penyakit metabolisme yang ditandai dari adanya

hiperglikemia akibat gangguan sekresi insulin ataupun gangguan
kerja insulin atau kedua dua nya,dan hiperglikemia kronis akan
menyebabkan kerusakan dan disfungsi serta kegagalan fungsi dari
berbagai organ dalam jangka panjang, terutama pada mata, ginjal,syaraf,jantung dan pembuluh pembuluh darah

Diabetes is an Increasing Healthcare

Epidemic Throughout the World
Global Projections for the Number of People with Diabetes
(2079 age group), 20072025 (millions)

53.2
64.1
+21%
28.3
40.5
+43%

67.0
99.4
+48%

24.5
44.5
+81%

Africa
Eastern Mediterranean
and Middle East
Europe
North America
South and Central America
South-East Asia
Western Pacific
IDF. Diabetes Atlas 3rd Edition 2006

16.2
32.7
+102%

10.4
18.7
+80%

Worldwide:
246 million people in 2007
380 million projected for 2025
55% increase

46.5
80.3
+73%

The Indonesian Perspective

Adults with diabetes will increase from 6.9 million in

2010 to 11 million in 20301

1.
2.
3.
4.

Prevalence in urban regions was 5.7% in 20072

Rates are consistently higher in urban areas,
however many rural areas present with high rates2,3

Incidence of late diabetes complications will rise and have

huge impact on society (costs, healthcare services,
psychosocial burden)

Immediate country-wise measures to prevent and manage

diabetes are required

IDF Diabetes Atlas 5th Edition

Riskesdas (National Basic Health Research) 2007
Noncommunicable diseases in South-East Asia Region. WHO 2011
Soewondo et al. DiabCare Asia 2008 Study. Med J Indones 2010.

Number of People with Diabetes (20-79

years), 2010 and 2030

Indonesia: Cause of Death

Ministry of Health, Republic of Indonesia. 2007.

DM Prevalence by Provinces
in Indonesia (Riskesdas 2007)

Why is Diabetes on the Increase?

Ethnicity and family history are implicated
Closely associated with overweight or obese
people
Increased switch to Western diet and lifestyle

Obesity

Genetic component

Western lifestyle

TYPE 2 DIABETES
International Diabetes Federation. Diabetes Atlas, 2nd Edition, 2003

The Problem

Causes of Mortality in Diabetic

Patients
Myocardial
34.7
infarction
Stroke
Tumors

22
10

Infections
Diabetic coma

6.7
3.1

Renal insufficiency

2.9
2.7

Gangrene
Accident / suicide

2.1
0.9

Tuberculosis
Others
Not specified

11.4
3.4
0

% deaths in diabetics
10

Panzram G. Diabetologia 1987; 30: 120-31

20

30

40

H AT I

OTOT

Non Sugar

Glycogen

G
L

Glycogen

(+)

C
O
S

(+)

(-)
Glucose

cell pancreas
Adipose Tissue

Blood Glucose
Absorbed

Intestine

Insulin

Glucose
Insulin

Antilipolysis
Trigliserida

+
L.P.L

Asam Lemak
NORMAL /PHYSIOLOGIC CARBOHYDRATE METABOLISM

KERJA FISIOLOGIK INSULIN

MEMASUKKAN GLUKOSA DARI DALAM DARAH KE:
1. Hati: Glukosa di robah jadi glikogen (Glikogenesis)
Glikogen hati menjadi cadangan gula dalam tubuh
2. Otot: Glukosa di robah jadi Glikogen (Glikogenesis)
Glikogen otot dibakar menjadi sumber kalori.
3. Adiposa: Glucosa dirobah (?) jadi trigliserida .
Mencegah pemecahan lemak (Antilipolisis)
4. Mengaktifkan Lipoprotein Lipase di sel sel endotel P.darah
5. Jaringan lain :Meningkatkan sintesa protein dari A.Amino
INSULIN MENURUNKAN KADAR GLUKOSA DARAH

Many Organs Involved

in Glucose Balance
Absorb food
Produce incretin hormone to induce insulin release

Produce insulin to increase glucose absorption

Produce glucagon, which is involved in glucose production during
fasting
Store glucose in form of glycogen need insulin
Produce glucose from glycogen need glucagon
Major site for glucose metabolism (70 80%) need insulin

Site for deposition of excessive calories need insulin

Many Organs Involved

in Glucose Balance
Absorption
Incretin hormone

Blood
Glucose

Gluconeogenesis
Glycogenesis
Insulin hormone
Glucagon hormone
Glucose usage
Store energy (lypogenesis)
Release energy (lypolysis)

Many Organs Involved

in Glucose Balance

Incretin
Alfa-glucosidase
Glycogenesis
Gluconeogenesis

Blood
Glucose

Lipolysis

Adipocytes

Lipogenesis

Glucose
uptake

Muscle

-cell:
insulin

-cell:
glucagon
Pancreas

Insulin
NORMAL
Pintu
terbuka

Insulin

Insulin

Insulin
Insulin

Insulin

Tenaga
Glukosa dibakar
Glukosa darah

Pintu masuk sel

pembawa glukosa

Insulin
DIABETES

Glukosa darah

Pintu
tertutup

Tenaga
Tak ada yang dibakar
Glukosa darah

Pintu masuk sel

Pembawa glukosa

Loss of the early peak of insulin

secretion
Insulin
secretion

Type 2
diabetic
Non-diabetic

IV Glucose stimulus

time

RESISTENSI INSULIN
INSULIN DALAM JUMLAH YANG NOR
MAL TIDAK DAPAT BEKERJA SECARA
OPTIMAL DI JARINGAN SASARAN NYA
SEPERTI DI OTOT, HATI DAN ADIPOSA.
Sel sel pancreas mengkompensasi keadaan ini
dengan meningkatkan produksi insulin dan me
nyebabkan HIPERINSULINEMIA

Natural History of Type 2

Diabetes
Insulin sensitivity

Insulin secretion

30%

Type 2
diabetes

50%

50%

IGT

70-100%

70%

Impaired glucose
metabolism

150%

100%

Normal glucose metabolism

100%

Diabetes Obes Metab 1999; 1(1): S1

Risk Factors
Risk
Factors

Family history
History of gestational diabetes
High BMI/abdominal obesity
High blood pressure
Sedentary lifestyle

It is important to try to identify patients at

the prediabetes stage to help prevent the development
of T2DM and associated complications.

http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/?loc=DropDownDB-RiskTest

Autoimun

Destruksi sel

DM tipe -1

Idiofatik
Insulinopenia
DM tipe- 2

Delayed Insulin secretion

Komplikasi akut

+ Insulin Resistance

(DKA & HONK)

Kompl.Kronis

HIPERGLIKEMIA
Diuresis
Osmotik
KENCING
HAUS

GLUKOSURIA

(GLIKASI)
Mikroangiopati
Makroangiopati

Lemas / Mudah lelah

Neuropati dst

Semakin kurus

Pe HbA1c
dan lain lain

BANYAK MAKAN

PERKENI Guidelines 2011

FBG = Fasting Blood Glucose
RBG = Random Blood Glucose
IGT = Impaired Glucose Tolerance
IFG = Impaired Fasting Glucose

Diabetes Symptoms

Diabetes Classic Symptoms (+)

126

FBG

<126

Diabetes Classic Symptoms (-)

atau

126

100-125

<100

atau

RBG

>200

<200

RBG

>200

140-199

<140

FBG and RBG

>126

FPG

<126

atau

OGTT 2 hour BG

RBG

200

<200
>200

Diabetes Mellitus

Evaluation of Nutritional Status

Evaluation Diabetic Complications
Evaluation Dietary Need and Dietary Planning

140-199
IGT

<140
IFG

Education
Dietary Planning
Physical Exercise
Achieving Ideal Body Weight

Normal

Diagnostic Criteria for Prediabetes

Pre-Diabetes

Diabetes

100 < FBG < 126

140 < PPG < 200
5.7 < A1C < 6.5%*

* A1C not yet recommended in Indonesia

PERKENI Consensus Guidelines, 2011.

> 126
> 200
> 6.5%*

PERKENI: Diagnostic
Criteria for Diabetes Mellitus
Classic symptoms of diabetes + random glucose plasma level
200 mg/dL. Random glucose plasma level is a test which access glucose
plasma level at a single time without concerning about last meal schedule.
or

Classical symptoms of diabetes + fasting plasma glucose

126 mg/dL. Fasting means patients not getting intake calories
for minimum 8 hours.
or

2-h plasma glucose at glucose tolerance test 200 mg/dL . Glucose

tolerance test done by the WHO standard using 75g anhydrous glucose
which solvent in the 100 cc water

PERKENI Guideline 2011

PERKENI: Standard Values of Random Blood Glucose

and Fasting Blood Glucose for Screening and Diagnosis
of DM (mg/dL)
Non DM

Uncertain DM

DM

Random blood
glucose level
(mg/dL)

Venous plasma

<100

100-199

200

Capillary blood

<90

90-199

200

Fasting blood
glucose level
(mg/dL)

Venous plasma

<100

100-125

126

Capillary blood

<90

90-99

100

Note:
For high-risk groups which show no abnormal results, the
test should be done every year. For those aged > 45 years
without other risk factors, screening can be done every 3
years.
PERKENI GUIDELINES 2011

GEJALA KLINIS DIABETES MELLITUS TIPE-2

GEJALA KHAS

GEJALA TAK KHAS

1. Poliuria

1. Kesemutan

2. Polidipsia

2. Gatal di daerah genital

3. Polifagia

3. Keputihan

4. BB turun cepat

4. Infeksi sukar sembuh

5. Bisul hilang timbul
6. Penglihatan kabur
7. Cepat lelah
8. Mudah mengantuk

GAMBARAN KLINIS DM TIPE-1 DAN DM TIPE-2

GEJALA /GAMBARAN KLINIS :
DM tipe-1
DM tipe-2
Poliuria dan Polidipsia

++

Lemas dan mudah lelah

++

Kuat makan tapi tambah kurus

++

Penglihatan sering berulang kabur

++

Gatal /radang kemaluan

++

Neuropati periferal (kebas/kesemutan)

++

Selalu ngompol malam (Enuresis Noct)

++

Sama sekali tanpa gejala

++

KARAKTERISTIK D.M TIPE-1 DAN D.M TIPE-2

D.M.TIPE-1

DM TIPE-2

Mudah terjadi ketoasidosis

Jarang ketoasidosis (HONK bisa)

Pengobatan harus dgn insulin

Tidak mesti diberi insulin

Onset nya akut

Onsetlambat (pelan pelan)

Biasanya kurus /Umur muda

Gemuk atau tak gemuk / > 45 thn

Terkait dgn HLA-DR3 & DR4

Tak ada kaitan dengan HLA

ICA; GADA; & IAA selalu (+)

Tak ada autoantibodi

Riwayat keluarga (+) pd 10%

Riwayat keluarga (+) pada 30%

30-50% kembar identik terkena

100% kembar identik terkena

BG and A1C Goals for T1DM by

Age

ADA. Standards of Medical Care in Diabetes-2012. Diabetes Care 35(suppl 1).

Kriteria Pengendalian DM
Baik

Sedang

Buruk

Glukosa Darah puasa (mg/dL)

80-100

100-125

126

Glukosa Darah 2 jam PP (mg/dL)

80-144

145-179

180

A1c (%)

<6,5

6,5-8

>8

Kolesterol Total (mg/dL)

<200

200-239

240

Kolesterol LDL (mg/dL)

<100

100-129

130

Kolesterol HDL (mg/dL)

>45

Trigliserida (mg/dL)

<150

150-199

200

IMT (kg/M2)

18,5-23

23-25

>25

Tekanan Darah (mmHg)

130/80

130-140/80-90

>140/90

Konsensus Pengelolaan DMT2 di Indonesia PERKENI 2006, hal. 25

Target of Treatment
BMI (kg/m2)

Risk CVD (-)

Risk CVD (+)

18.5 <23

18.5 <23

Blood Glucose

FPG (mg/dL)

<100

<100

Post Prandial BG (mg/dL)

<140

<140

<7.0

<7.0

<130/80

<130/80

Total Cholesterol (mg/dL)

<200

<200

Triglyceride (mg/dL)

<150

<150

HDL Cholesterol (mg/dL)

>40 / >50

>40 / >50

LDL Cholesterol (mg/dL)

<100

<70

A1C (%)
Blood Pressure
Lipid

PERKENI GUIDELINES 2011

PEMERIKSAAN TAMBAHAN TIAP KUNJUNGAN BARU ;

Darah lengkap /Urinalisa (Anemia?,Proteinuria ? ,ISK ?)
FotoThorax : TBC paru ?, Pembesaran jantung ? dsb
E.K.G : Adakah Iskemi Miokard (PJK) ?
Funduskopi : Cataract ? , Retinopathy ?
Pemeriksaan faal syaraf sensorik,motorik, autonomik
Pemeriksaan pembuluh darah periferal : Hand Held Doppler

SUDAH ADAKAH KOMPLIKASI ?

SUDAH SEBERAPA PARAH ?

Need for an Early and Intensive Approach to

Type 2 Diabetes Management

At diagnosis of type 2 diabetes:

- 50% of patients already have complications1
up to 50% of -cell function has already
been lost2

Current management:
- two-thirds of patients do not achieve target
HbA1c3,4
- majority require polypharmacy to meet
glycemic goals over time5

UKPDS Group. Diabetologia 1991; 34:877890. 2Holman RR. Diabetes Res Clin Prac 1998; 40 (Suppl.):S21S25. 3Saydah SH, et al. JAMA 2004; 291:335342.
4

Liebl A, et al. Diabetologia 2002; 45:S23S28. 5Turner RC, et al. JAMA 1999; 281:20052012.

Defined glycaemic targets in T2DM

Glucose control

Healthy

ADA1

AACE2

JDS3

IDF4

<6

<7

6.5

5.86.4

6.5

Mean FPG
mmol/l (mg/dl)

<5.6
(<100)

57.2
(9013
0)

<6
(<110)

5.66.6
(1001
19)

<6
(<110)

Mean postprandial
PG mmol/l (mg/dl)

<7.8
(<140)

<10*
(<180)

<7.8**
(<140)

<7.8**
(<140)

HbA1c (%)

*12 hours postprandial; **2 hours postprandial.

FPG=fasting plasma glucose.
1. American Diabetes Association. Diabetes Care 2004;27(suppl 1):S1535.
2. American Association of Clinical Endocrinologists. Endocr Pract 2002;8(suppl 1):4384.
3. Japan Diabetes Society. Available at: http://www.jds.or.jp.
4. International Diabetes Federation Guidelines. Diabetes Voice September 2007

Intervention : Better Control Means Fewer Complications

(UKPDS 35 BMJ 2000;321:405-412)

EVERY 1% Reduction in AIC

AIC

1%

Reduced Risk*

Deaths from DM

-21%

Heart Attacks

-14%

Microvascular Complications

-37%

POAD

-43%
*p<0.0001

Principal Management in
Type 2 Diabetes Mellitus*
4
3
PHARMACOLOGIC
TREATMENT

1
MEDICAL NUTRITION
THERAPY

PHYSICAL
ACTIVITY

* Konsensus Pengelolaan Diabetes Melitus di Indonesia, Perkeni 2011.

EDUCATION

Why Diabetes Education Matters

Successful diabetes management depends upon the
patient to
implement healthy lifestyle strategies,
monitor blood glucose, and adhere
to the medication regimen
Persons with diabetes must provide 95% or more of
their own daily care
Glycemic control unsatisfactory despite oral medication

Educating Individuals with Diabetes:

What diabetes topics should be delivered?
Pathophysiology of diabetes mellitus
Exercise
Medical nutrition therapy
Pharmacologic treatment
Foot care
Acute & chronic complications
Self-monitoring blood glucose
Coping with special situations

Perencanaan Makan / Diit :

Ukur TB& Timbang BB

BB Idaman = (TB-100) 10%

BB dalam kg, TB dlm cm
Pria TB < 160, Wanita TB < 150
BB Idaman = TB - 100

BBR = (TB 100) 10%

BB dlm kg; TB dlm cm
Kurus /Underweight = <90%
Sedang /Normoweight: 90-110%
Gemuk : 110-120%
Overweight : > 120 %

KKB Pria = BBI x 30 Kkalori /hari

KKB wanita BBI x 25 Kkalori / hari

Kurus
Gemuk

+ 20%
- 20%

KALORI BASAL : Pria =BBI x 30 Kkalori / hari = ---- Kkal /H

Wanita = BBI x 25 Kkal / hari
Diit DM :
Umur > 40 thn : - 5% KKB
Karbohidrat 60-70% Aktifitas ringan : + 10% KKB
Protein 10-15%
Aktifitas sedang: + 20% KKB
Lemak : 20-25%
Aktifitas berat : + 30% KKB
Gemuk :
- 20% KKB
Overweight
- 10% KKB
Underweight :
+ 20% KKB
Sarapan : 20% Kal Stress metabolik + 10 sd 30% KKB
Snack 9.00 = 10% Hamil Trimester I /II : + 300 Kkal /hari
Mkn siang = 25% Hamil Trimester III /Laktasi + 500 Kkal /hari
Snack 16.00 = 10% KEBUTUHAN TOTAL = ------- Kkal / hari
Mkn malam = 25%
Snack 21.00 = 10%
MAKANAN HARUS DI HABISKAN

Exercise Program

Others:
C
R
I
P
E

=
=
=
=
=

continues
rhytmic
interval
progressive
endurans/aerobik

Safe for any complications

Continues
Start with low intensity, go slowly

OLAH RAGA TERATUR : PRINSIP NYA IALAH : CRIPE

Continuous, Rhythmic, Interval, Progressive , dan Endurance
FREKWENSI LATIHAN : 3x / minggu hingga 5 x sehari
SASARAN HR = 75% hingga 85% DENYUT NADI MAKSIMUM
DENYUT NADI MAKSIMUM = 220 - UMUR
Lakukan evaluasi penderita sebelum memulai program latihan
PJK ? , Hipertensi?, Retinopati ?, Nefropati?, Kel.Hati ?, PPD Per ?
Sesuaikan jenis latihan dengan kondisi kesehatan penderita
Latihan jasmani > 1 jam :beri asupan KH extra sdm tiap 30menit.
Usia >40 tahun :Lakukan Stress Test
Pakai sepatu / alas kaki yang enak sesuai, dan aman .
Mulai dengan warming (5 ),Latihan inti (15-20 ), Cooling down.
Ukur nadi sebelum pemanasan dan ulang sesudah 5 latihan inti !

Lifestyle Modification
Dietary intervention
Reduce intake by 5001000 kcal/day from total
daily intake

Increased physical activity

Moderate activity 30-45 mins/day, 3-5
times/week
Overweight and obese individuals: Moderate
activity 45-60 mins/day 5 times/week .
Purnamasari D et al. Identification, Evaluation and treatment of overweight and obesity in adults: Clinical
Practice Guidelines of the Obesity Clinic, Wellness Cluster Cipto Mangunkusumo Hospital, Jakarta, Indonesia

ADA EASD Position Statement 2012

ADA Position Statement 2015

Pathophysiology-based Therapy
for Type 2 Diabetes

Defect in insulin sensitivity

exercise
weight reduction
troglitazone
metformin

Defect in insulin secretion

sulfonylureas (mild defect)

insulin (severe defect)

Pathophysiology-based Therapy
of Type 2 Diabetes

Increased hepatic glucose output

metformin > pioglitazone

insulin (sulfonylurea)

Carbohydrate absorption (post-prandial

hyperglycemia)

acarbose

Insulin Resistance

troglitazone > metformin

Oral Diabetes Drugs in Indonesia

Golongan

Generik
Glibenclamid
Glipizid

Gliklazid
Sulfonilurea

Glikuidon

Glimepirid

Glinid

Tiazolidindion

Penghambat
Gluckosidase alfa

Nama Dagang

Metformin XR

Waktu

12 24

12

Minidiab

5 10

5 20

10 16

12

Glucotrol-XL

5 10

5 20

12 16**

80

80 320

10 20

12

30 60

30 120

24

30

30 120

68

23

Amaryl

1-2-3-4

0.5 6

24

Gluvas

1-2-3-4

16

24

Amadiab

1-2-3-4

16

24

Metrix

1-2-3-4

16

24

1.5 6

120

360

Actos

15 30

15 45

24

Deculin

15 30

15 45

24

Pionix

15 30

15 45

18 24

Glucobay

50 100

100 300

Eclid

50 100

100 300

500 850

250 3000

68

13

500

500 3000

68

23

24

24

Diamicron
Diamicron-MR
Glurenorm

Starlix

Biguanid

Frek/hari

2.5 15

Nateglinid

Metformin

Lama Kerja (jam)

2.5 5

Dexanorm

Acarbose

Dosis Harian (mg)

Daonil

Repaglinid

Pioglitazone

Mg/tab

Glucophage
Glumin
Glucophage XR
Glumin XR

500 750
500

500 2000

Sebelum
makan

Tidak
bergantung
jadwal
makan
Bersama
suapan
pertama

Bersama /
sesudah
makan

Oral Diabetes Drugs in Indonesia

Golongan
Penghambat
DPP-IV

Generik

Nama Dagang

Mg/tab

Dosis Harian (mg)

Lama Kerja (jam)

Frek/hari

Waktu

50

50 100

12 24

12

Januvia

25, 50, 100

25 100

24

Onglyza

24

12 24

12

Vildagliptin

Galvus

Sitagliptin
Saxagliptin

Tidak
bergantung
jadwal
makan

250/1.25
Metformin +
Glibenclamid

Glucovance

500/2.5

Total glibenclamid
maksimal 20 mg/hari

500/5

Obat Kombinasi
Tetap

Glimepirid +
Metformin

Amaryl-Met FDC

Pioglitazone +
Metformin

Pionix M

Sitagliptin +
Metformin

Janumet

1/250

2/500

2/500

4/1000

15/500
30/850
50/500
50/1000

Total pioglitazone
maksimal 45 mg/hari

18 24

Total sitagliptin maksimal

100 mg/hari

50/500
Vildagliptin +
Metformin

Galvusmet

50/850
50/1000

Total vildagliptin maksimal

100 mg/hari

12 24

Bersama /
sesudah
makan

Oral Therapy for Type 2 Diabetes

Target Sites of Action
Adipose
tissue

Sulfonylureas
Repaglinide

Pancreas

Gut

Insulin secretion

Glucose
uptake

Acarbose
Miglitol

FFA output

Hyperglycemia

Rosiglitazone
Pioglitazone

Metformin
Rosiglitazone
Pioglitazone

Liver
Hepatic
glucose
output

Rosiglitazone
Pioglitazone
Metformin

Glucose
absorption

Muscle
Glucos
e uptake

Tempat bekerja OAD

ABSORBSI GULA
A.

E.

Inkretin

INTESTIN

-glucosidase inhibitors

PRODUKSI GULA
LIVER

B.

Glukosa

C.

Biguanides
Thiazolidinediones

MUSCLE

ADIPOSE TISSUE

D.
SEKRESI INSULIN
Sulphonylureas
Meglitinides

PEMAKAIAN GLUKOSA DI
OTOT DAN
JARINGAN PERIFER

PANKREAS

Thiazolidinediones

Biguanides
Modified: Ann Intern Med 1999;131:281

TEMPAT DAN CARA KERJA BERBAGAI

OBAT ANTIDIABETIK ORAL
Tempat Kerja

Cara Kerja
Me

Me

Sekresi Insulin

Produksi Glukosa di hati

Memperlambat pen
cernaan karbohidrat
Meningkatkan kepekaan thd
Insulin di periferal

OBAT
Sulphonylureas
Other insulin
secretagogues
Biguanides
Thiazolidinediones
-glucosidase
inhibitors
Thiazolidinediones
Biguanides

DeFronzo. Ann Intern Med 1999;131:281-303

IFG / IGT
Implications for care

population

IFG or IGT

Individual with IGT

and IFG and any of
the following :

treatment
Lifestyle modification
(i.e., 5-10% weight
loss and moderate
intensity physical
activity~30min/day
Lifestyle modification
(as above ) and/or
Metformin 850 mg
Diabetes Care 30:753-759, March 2007

< 60 year of age

BMI > 35 kg/m2
Family history of DM in first-degree
relatives
Elevated triglyceride
Reduced HDL-cholesterol
Hypertension
A1c > 6%

David M. Nathan, MD1, Mayer B. Davidson, MD2, Ralph A. DeFronzo, MD3,

Robert J. Heine, MD, PHD, FRCP4, Robert R. Henry, MD5, Richard Pratley,
MD6 and Bernard Zinman, MD7

Diabetes Care 30:753-759, March 2007

Properties of anti-hyperglycemic agents

Class

Mechanism

Advantages DisadvantageCost
s

Biguanide
s

Activates AMPkinase
Hepatic glucose
production

Extensive
experience
No hypoglycemia
Weight neutral
? CVD

Gastrointestinal
Lactic acidosis
B-12 deficiency
CKD

Low

SUs /
Meglitinid
es

Closes K-ATPchannels
Insulin secretion

Extensive
experience
Microvasc. risk

Hypoglycemia
Weight gain
Low durability
? Ischemic
preconditioning

Low

TZDs

PPAR- activator
insulin
sensitivity

High

DPP-4
inhibitors

Inhibits DPP-4
Increases GLP-1,
GIP

No hypoglycemia
Well tolerated

Weight gain
Edema / heart
failure
Bone fractures
? MI (rosi)
Modest
A1c
? Bladder
ca (pio)
? Pancreatitis
Urticaria

No hypoglycemia
Durability
TGs, HDL-C
? CVD (pio)

High

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of

print]

Properties of anti-hyperglycemic agents

Class

Mechanism

Advantages DisadvantageCost
s

-GIs

Inhibits
glucosidase
Slows
carbohydrate
absorption

No hypoglycemia
Nonsystemic
Post-prandial
glucose
? CVD events

Gastrointestinal
Dosing frequency
Modest A1c

Mod.

GLP-1
receptor
agonists

Activates GLP-1 R
Insulin,
glucagon
gastric insulin
Activates
emptying
receptor
satiety
peripheral
glucose
uptake

Weight loss
No hypoglycemia
? Beta cell mass
CV protection
?Universally

GI
? Pancreatitis
? Medullary
cancer
Hypoglycemia
Injectable
Weight gain

High

Insulin

effective
Unlimited efficacy
Microvascular
risk

Varia
ble

? Mitogenicity
Injectable
Training
requirements
Stigma

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of

Adverse Effects of Sulfonylureas

Severe hypoglycemia
Overdose
Early in treatment
Most common with glybenclamide

Weight gain
Erythema, skin reactions
Blood dyscrasias (abnormal cellular elements)
Hepatic dysfunction and other GI
disturbances

Contraindications for Sulfonylureas

Pregnancy

Surgery

Severe infections

Severe stress or trauma

Severe hepatic or renal failure

Insulin therapy should be used in all of these

Meglitinides

Mechanism of action:

decrease ATP-sensitive K+ conductance

Action is glucose dependent

High potency
Elicited insulin release is rapid and brief

Taken with meals for postprandial hyperglycemia

Reduced risk of long-lasting hypoglycaemia

Side effects :

Hypoglycemia

Weight gain

Safe at higher levels of creatinin than

sulphonylureas

Biguanides

Mechanism of action: antihyperglycemic

Correct elevated hepatic glucose output
Inhibit gluconeogenesis
Inhibit glucose-6-phosphatase activity glycogen sparing
insulin resistance
Mediated by activation of 5AMP-activated protein kinase
(AMPK) in hepatocytes and muscle
Do not increase insulin secretion
Not hypoglycemic, even at high doses
Side Effects :

diarrhea and abdominal discomfort

lactic acidosis if inappropriately prescribed

Therapeutic Actions of Metformin:

Pancreas
Impaired
Insulin secretion

Increased
glucose
production

Liver

Hyperglycaemia

Metformin

Decreased
glucose
uptake

Muscle

Thiazolidinediones
CH3

Antihyperglycemic

Do not increase

ROSIGLITAZONE

O
NH

insulin secretion

Increase insulin

sensitivity in liver
and muscle

Reduce hepatic glucose output

Improve lipid profiles

Side effects :

PIOGLITAZONE

- weight gain, edema

- contraindicated with abnormal liver function

O
NH

a glucosidase inhibitors (Acarbose)

Mechanism of action: competitive and reversible inhibitors of
glucosidase in the small intestine
Delay carbohydrate digestion and absorption
Smaller rise in postprandial glucose

Clinical use
For mild to moderate fasting hyperglycemia
with significant postprandial hyperglycemia
Taken with the first bite of a meal

Adverse effects:
Gastrointestinal disturbances; Flatulence,
nausea, diarrhea Use gradual dose titration
Contraindicated with inflammatory bowel
disease and cirrhosis

PERKENI Guidelines 2011

< 7%

7 8%

Lifestyle
Modification

Lifestyle
Modification

8 - 9%

Lifestyle
Modification

Monotherapy

Met, SU, AGI,

Glinid, TZD,
DPP-IV

2 OADs
Combination
Met, SU, AGI,
Glinid, TZD,
DPP-IV

Notes:
Fail: not achieving A1c target < 7%
after 2-3 months of treatment
(A1c = average blood glucose conversion, ADA 2010)

> 9%

Lifestyle
Modification
+
3 OADs
Combination
Met, SU, AGI,
Glinid, TZD,
DPP-IV

9 - 10%

> 10%

Lifestyle
Modification
+
2 OADs
Combination
Met, SU, AGI,
Glinid, TZD,
DPP-IV

Lifestyle
Modification

Basal Insulin

+
Intensive
Insulin

Goal-Oriented Algorithm for T2DM

Goals: FBG <100 mg/dL; 2-hour PPG <160 mg/dL;
HbA1c as low as possible without severe hypoglycemia
HbA1c 6.0-<7.5

HbA1c 7.5-<9.0

HbA1c 9.0

Diet + exercise + 1 OAD (metformin)

Combine to control TZD/exenatide/sitagliptin

Add/switch to insulin*

Adjust insulin
Goal-oriented algorithm for the potential inclusion of glucagon-like peptide-1 analogues or dipeptidyl-peptidase inhibitor in
an existing treatment regimen of type 2 diabetes mellitus. This approach presents the placement of some of the newer
agents in the progression of therapy to insulin. Goals: fasting blood glucose (FBG) <100 mg/dL; 2-hour postprandial
plasma glucose (PPG) <160 mg/dL; glycosylated hemoglobin (HbA 1c) as low as possible without severe hypoglycemia.
*Exenatide and sitagliptin are not currently approved for concomitant use with insulin.

Aaron Vinik. Clin Ther;29 : 1249; 2007

INDIKASI PENGGUNAAN INSULIN

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.

DM tipe 1
Penurunan berat badan yg cepat
Hiperglikemia yg berat disertai dg ketosis
Ketoasidosis diabetik
Hiperglikemia hiperosmolar non ketotik
Hiperglikemia dg asidosis laktat
Gagal dg kombinasi OHO dosis hampir max
Stress berat
Kehamilan dg DM atau DM Gestasional
Gangguan fs. ginjal atau hati yg berat
Kontraindikasi dan atau alergi thp OHO

NEW THEORY
(Insulin can be added anytime)

Inadequate
Lifestyle
gains

1 x Oral
agent

2 x Oral
agents

3 x Oral
agents

ADD INSULIN EARLIER IN THE ALGORITHM

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

Insulin in Indonesia
Awal Kerja
(Onset)

Puncak Kerja
(Peak)

Lama Kerja
(Duration)

Kemasan

30-60 menit

30-90 menit

3-5 jam

Vial, pen/cartridge

Insulin Lispro (Humalog)

5-15 menit

30-90 menit

3-5 jam

Pen/cartridge

Insulin Glulisine (Apidra)

5-15 menit

30-90 menit

3-5 jam

Pen

Insulin Aspart (Novorapid)

5-15 menit

30-90 menit

3-5 jam

Pen, Vial

2-4 jam

4-10 jam

10-16 jam

Vial, Pen/cartridge

Insulin Glargine (Lantus)

2-4 jam

No Peak

20-24 jam

Pen

Insulin Detemir (Levemir)

2-4 jam

No Peak

16-24 jam

Pen

70% NPH 30% Reguler

(Mixtard, Humulin 30/70)

30-60 menit

Dual

10-16 jam

Pen/cartridge

70% Insulin Aspart Protamin

30% Insulin Aspart (Novomix 30)

10-20 menit

Dual

15-18 jam

Pen

75% Insulin Lispro Protamin

30% Insulin Lispro (HumalogMix 25)

5-15 menit

Dual

16-18 jam

Pen/cartridge

Sediaan Insulin
Insulin Prandial (Meal Related)
Insulin Short Acting
Reguler (Actrapid, Humulin R)
Insulin Analog Rapid Acting

Insulin Intermediate Acting

NPH (Insulatard, Humulin N)
Insulin Long Acting

Insulin Campuran

Insulin Preparations
Ultra
fast/ultra
short-acting

regular

Plasma [Insulin]

Short-acting

Lispro/aspart

NPH

Intermediateacting

lente
ultralente

Long-acting
glargine

Ultra long-

12

16

20

24

Figure. Pharmacokinetincs on various insulin drugs, and insulin from

pancreas
http://www.medscape.com/viewarticle/501976_6

Action Profiles of Insulin

Analogues
Aspart, lispro 4-5 hours
Regular 68 hours
NPH 8-16 hours
Ultralente 1824 hours

Plasma
insulin
levels

Glargine 24 hours

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Hours

Adverse Effects of Insulin Therapy

Hypoglycemia
Especially dangerous in Type 1 diabetics
Glucose or glucagon treatment
Allergy and resistance to insulin
Local cutaneous reactions or systemic
Switch to less antigenic form or desensitization
Lipohypertrophy
Due to lipogenic effect of insulin when small area used for frequent
injections
Absorption from such sites is unpredictable
Lipoatrophy
Due to impurities: switch to highly purified insulin
Lipogenic effect of insulin can repair lesion
Insulin edema- transient, rare

0tak
: stroke
Mata
: kebutaan
Jantung : jantung koroner
Ginjal : gagal ginjal
Kaki
: luka sukar
Sembuh
Disfungsi seks

Complications of Diabetes Mellitus

Chronic Complications of
Diabetes Mellitus

Microvascular

Retinopathy
(nonproliferative/proliferative
)
Nephropathy
Neuropathy
Sensory and motor (monoand polyneuropathy)
Autonomic

Macrovascular

Coronary artery disease

Peripheral vascular disease
Cerebrovascular disease

Acute Complications
of Diabetes Mellitus

Hyperglycemia crisis

Diabetic ketoacidosis
Hyperglycemia
hyperosmolar State
Lactic acidosis

Hypoglycemia