Diabetes Melitus

Hemi Sinorita
 Why do we see a massive increase in people
with Type 2 DM across the World?
Unhealthy lifestyle choices Aging population Family History

Sedentary life style Hypertension Obesity

Cockram CS 2000. HKMJ; 6 (1): 43-52 Mohan et al 2007. Indian J Med Res; 125: 217-230 Adapted from IDF Diabetes Atlas 4th ed., 2009
 Step 1: Risk Factors – PERKENI screening risk factor
guideline

Unmodifiable Risk Modifiable Risk Diabetes Associated Risk

1. Race and Ethnic 1. Overweight (BMI >23) • PCOS or another

2. Family History 2. Hypertension > 140/90 clinical condition
3. History of mmHg related to insulin
Gestational DM 3. Dyslipidemia (HDL < 35 resistance
4. History of delivery mg/dl and/or • Metabolic
a baby >4.000g triglycerides >250 Syndrome (IGT,
5. History of low birth mg/dl IFG, History of
weight <2.500g 4. Unhealthy Diet CAD, stroke
5. Limited Physical Activity and/or PAD)
Slide 4

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Carbohydrate
Glucose
Hyperglycemia
Defective insulin
secretion Insulin Excessive
fatty acid
release
Excessive Reduced
glucose
production
glucose
uptake

Resistance to the action of insulin

 Klasifikasi Diabetes Melitus

1. Diabetes Tipe 1
2. Diabetes Tipe 2 , jumlahnya > 95%
3. Diabetes Tipe Lain
4. Diabetes Mellitus Gestational
Penyebab DM tipe 2
Hiperinsulin
Resisten Kelelahan
Insulin sel 

Gangguan
toleransi
glukosa
Decreased insulin
Obesitas secretion
Diabetes
awal
Kegagalan sel 

Diabetes
Normal akhir
7
Adapted from Saltiel AR. J Clin Invest 2000;106:163–164.
 Criteria for the Diagnosis
Normal Prediabetes DM
IFG IGT
FPG
< 100 100-125 <100 > 126
(mg/dL)

2-h PG < 140 < 140 140-199* > 200

(mg/dL)

FPG : Fasting Plasma Glucose

2-h PG : 2- hour Plasma Glucose
IFG : Impaired Fasting Glucose
IGT : Impaired Glucose Tolerance
OGTT : Oral Glucose Tolerance Test * OGTT : post load 75 g
 PPAR α L162V HNF4A, GCK,
Genetik OBESITAS Genetik

F HNF1A, IPF1,
TCF2,NEUROD1

Adipositokin Antibodi anti insulin

a STRES Kortisol

Sitokin inflamasi
X X Antibodi anti reseptor
-Sindrom tipe A/B

k Adrenal X X
-Leprachaunisme
-Rabson-Mendenhal

t ROKOK
GH Reseptor insulin Aktivitas
o Glukokortikoid X
X
IRS- 1 X X fisik rendah
X
AMPK
r hPL
hPGH
MAPK PI3K

Kehamilan
X AKT/PKB

r PTEN

e
Genetik X
GLUT 4
GLUT 4
N
s Kelebihan nutrisi mTOR Bradikinin

i
k RESISTEN INSULIN
o DM tipe 2 9
The natural progression of type 2 diabetes
Post-meal BG
Glucose (mg/dL) 350 DIAGNOSIS
300 Fasting BG
250
200
150
100
50

250
200 Insulin resistance
Relative -cell
function (%)

150
100
50 -cell failure Insulin level
0

Obesity IGT Diabetes Uncontrolled hyperglycaemia

MACROVASCULAR CHANGES
MICROVASCULAR CHANGES
-10-5 0 5 10 15 20 25 30

Adapted from Type

2 Diabetes BASICS.
International
Diabetes Center;
2000.
 Prinsip Dasar Terapi Diabetes Mellitus
1 2 3

PENYULUHAN DIET AKTIFITAS FISIK

4 5

OBAT SMBG
ANTIDIABETES/INSULIN
 Physical activity
30 minutes of moderate-intensity exercise (brisk walking)
5 days of the week.
Training zone 50-70% (220 – age).
Asian Food Information Centre. 2010. Calorie Expenditures Through Exercise and Other Activities. Available from
http://www.afic.org/Burner.htm. Accessed 21 June 2010.
Enhanced insulin sensitivity in successful, long-term weight
loss maintainers compared with matched controls with no
weight loss history

Successful
weight
reduction:
weight loss of
⩾10%,
maintained for
>12 months

Nutr Diabetes. 2017 Jun; 7(6): e282 Clamp etal, 2017.

A Single Session of Low-Intensity Exercise Is
Sufficient to Enhance Insulin Sensitivity Into the Next
Day in Obese Adults

CONCLUSIONS
A relatively modest
single session of
exercise in obese adults
improved insulin
sensitivity the next day,
and a reduction in
systemic fatty acid
uptake in the several
hours after exercise
may be important for
this effect.

Newsom et al, Diabetes Care 2013 Sep; 36(9): 2516-2522

 Loss of Early- phase Insulin Secretion
in Type 2 Diabetes
Pattern of insulin secretion is altered early in type 2 diabetes

Type 2 diabetes
Normal 20g glucose
Plasma insulin
(µU/ml)

120 120

Plasma insulin
(µU/ml)
20g
glucose
100 100
80 80
60 60
40 40
20 –30 0 30 60 90 120 20 –30 0 30 60 90 120
Time (minutes) Time (minutes)
0 0
Ward WK, et al. Diabetes Care 1984;7:491–502.
Enhanced Fat Oxidation Through Physical Activity Is
Associated With Improvements in Insulin Sensitivity in
Obesity

The improvement in
insulin sensitivity
resulting from
a program combining
exercise and diet
is associated with an
increased reliance on
fat oxidation during
fasted conditions

Brett et al, Diabetes 2003 Sep; 52(9): 2191-2197

 Algoritme Pengelolaan DM Tipe 2 di Indonesia
KONSENSUS PERKENI 2015
Modifikasi pola hidup sehat
HbA1c ≥ 9.0%
HbA1c < 7.5% HbA1c ≥ 7.5%
Gejala (-) Gejala (+)
Monoterapi* salah Kombinasi 2 obat*
satu obat di bawah ini Kombinasi 3 obat Kombinasi
mekanisme berbeda
2 obat
Metformin Agonis GLP-1
Metformin atau obat lini pertama yang lain +

Agonis GLP-1
Insulin

Metformin atau obat lini pertama yang lain +

Agonis GLP-1 DPP-IV inh DPP-IVinh
± obat jenis
DPP-IV inhibitor Tiazolidindion
Tiazolidindion lain

Obat lini kedua +

Alfa Glukosidase SGLT-2 inh SGLT-2 inh
Kombinasi
inhibitor Insulin Basal Insulin Basal 3 obat
SGLT-2 inhibitor SU/Glinid Alfa glukosidase Mulai atau
Tiazolidindion Alfa glukosida inh intensifikasi
Keterangan Insulin
*Obat yang terdaftar, pemilihan dan
Sulfonilurea se inhibitor
Kolsevelam**
penggunaannya disarankan mempertimbangkan
Bromokriptin-QR
Glinid Kolsevelam** faktor keuntungan, kerugian biaya, dan
Jika belum memenuhi sasaran dalam 3 ketersediaan sesuai tabel 11
Bromokriptin-QR
Jika HbAc1 > 6.4% bulan, mulai terapi insulin atau intensif ** Kolsevelam belum tersedia di Indonesia
dalam 3 bulan tambahan obat Jika belum memenuhi sasara ikasi terapi insulin Bromokriptin QR umumnya digunakan pada
ke 2 (kombinasi 2 obat) n dalam 3 bulan, masuk ke k
ombinasi 3 obat
terapi tumor hipofisis
 Mekanisme kerja OAD
a-glucosidase
Sulfonilurea,
Karbohidrat inhibitor
meglitinide

Glukosa
Insulin
DPP4
Biguanid inhibitor

Thiazolidinediones

SGLT 2
inhibitor
Adapted from Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl. 1):S32–S40. Nattrass M & Bailey CJ. Baillieres Best
Pract Res Clin Endocrinol Metab 1999; 13:309–329.
 Jenis Insulin

2hPG
GIR (mg/kg/min)

BASAL INSULIN
PRE-MIX INSULIN
FAST-ACTING
INSULIN

FPG
0 4 8 12 16 20 24
Time (h)

Slide 21
 Hyperglycaemia
A1C

1%

12% 14% 21% 37% 43%

Sltratlon IM et at. UKPDS35. BMJ 2000..321 (7258) 405-12.

ALHAMDULILLAH
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