DIABETES MELITUS

ADVISOR : dr. Prima Nugroho

Member :
Dr. Danil Eko
Dr. Danti Nelfa Riza
Dr. Ariani Putri Devanti
Dr. Marina Ayrin Puspita
Dr. Citra Kusuma Putri
Dr. Musdah Mulia Mukmin
1

What is diabetes (DM)?

Sugar (glucose) in your blood is from 2 mayor
sources: food and the liver
DM is a disease characterized by elevated blood
glucose level, it is result of defective insulin
secretion or action (resistance) or both.
Resulting chronic hyperglycemia is damage or
dysfunction of various organ (the eyes, kidneys,
nerves, heart, and blood vessels).
Clinical symptoms: 3P Excessive thirst (polydipsia)
increased urination (polyuria), increased appetite
(polyphagia) and weight loss.

IMPORTANT
Healthy pancreas have: 100 000
Langerhans island and every
Langerhans: 100 cells (insulin
production) 10.000.000
Insulin and insulin receptors like
key and the door

Historical milestones in DM
Date

Source

Observation

1550 BC
1-2nd cntry AD
5th century

Egypttian papyrus
Galen (Roman), Aretaeus (Greek)
Susruta, Charuka (Indian)

10th century

Avicenna (Arabia)

17th century
18th century

Willis (England)
Dobson, Cawley (England)

Exessive ammount of urine

Sugary urine, Exessive
thirst
Described sugary urine
distinguished obese and
thinpatients
Sugary urine, gangrene &
impotence as
complications
Diabetic urine contains
sugar
Sugar in serum in
diabetes, diabetes may
follow pancreatic damage
Glucose stored as glycogen
on liver, exocrine
degeneration of pancreas
occurs after ligature of the
pancreatic duct
Pancreatic islets,
pancreatomy
causes
4
diabetes

19th century

19th century
20th century
20th century

Bernard (French)

Langerhans, Minkowski,von
Mering (Germany)
Banting (Nov 14th ), Best,
Macleod, Collip (Canadian)
Hodgekin, Sanger (England)

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
5

DeFronzo ADF 2006

Septicidal Septet
Decreased
Incretin effect

Impaired Insulin
secretion

Increased
lipolysis

??

Islet -cell

Hyperglycemia

Increase
Glucagon
secretion

Neurotransmitter
Decreased Glucose
dysfunction

Increased
HGP

uptake

Septem = seven

Diagnosis (WHO
classification)
Venous plasma glucose
(mg/dL)
Normal

Fasting &
2h post-prandial

< 110
< 140

Diabetes mellitus Fasting &

2h post-prandial

> 126
> 200

Impaired
Glucose
Tolerance (IGT)

< 110
140-199

Fasting &
2h post-prandial

Impaired Fasting Fasting &

110 - 125
Glucose (IFG)
2h post-prandial < 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) on a separate day
7

Diagnose Criteria DM (ADA

2010)
WHO Criteria (+)
HbA1c >6,5%

MANAGEMENT of DM
1. EDUCATION
2. EXERCISE
3. NUTRITION & DIET
4. PHARMACOLOGY

Education
Very important, included:
Pathophysiology of DM
Targets of DM management
Management of nutrition and diet
Phamacologik intervention
Exercise and physical activity
Self monitoring blood glucose (SMBG)
Prevent and manage of acute and chronic
complication
Psychosocial aspect
Management of Stress
Health care system
10

Criteria of DM management
Good

Moderate

Poor

Fasting blood glucose (mg/dL)

80 - 109

110 125

> 120

2Hour post prandial (mg/dL)

110 144

145 179

> 180

HbA1c (%)

< 6,5

6,5 8

>8

Total Cholesterol (mg/dL)

< 200

200 239

> 240

LDL Cholesterol (mg/dL)

< 100

100 129

> 130

HDL Cholesterol (mg/dL)

45

Triglyseride (mg/dL)

< 150

150 199

> 200

BMI (kg/m2)

18,5 - 22,9

23 25

> 25

Blood Pressure (mmHg)

< 130/80

130-140/80- > 140/90

90
11

Correlation between HbA1c level and mean plasma

glucosa levels on multiple testing over 2-3 months
HbA1c

Mean plasma glucose (mg/dL)

135

170

205

240

10

275

11

310

12

345

12

MANAGEMENT of DM
1. EDUCATION

2. EXERCISE
3. NUTRITION & DIET
4. PHARMACOLOGY

13

Excersice
Minimal 30 minutes (fat burning), 150
minutes/weeks
CRIPE:
Continous
Rhythmic
Interval (Sai)
Progresive
Endurance maximum PULSE=80%
(220-age in year)

14

MANAGEMENT of DM
1. EDUCATION

2. EXERCISE

3. NUTRITION & DIET

4. PHARMACOLOGY

15

NUTRITION and DIET

Important of Food
1. Various/contents
2. Schedule
3. Total weight or calories
Standard diet:
.< 30% form all fats (< 10% form saturated
fats)
.50-60% form carbohydrate (complex high
fibre)
.15-20% form protein
.Sugar limited 25 g/day
.Sodium <6 g/day, if hypertensive <3 g/day
16

MANAGEMENT of DM
EDUCATION
2. EXERCISE
3. NUTRITION & DIET
4.PHARMACOLOGY
1.

17

DeFronzo ADF 2006

Septicidal Septet
Decreased

Incretin effect

Impaired Insulin
secretion

Incretin
DPP4
inhbt

Sulf Urea
Insulin

Islet -cell
Incretin
DPP4
inhbtr

Increase
Glucagon
secretion

Increased
lipolysis

insulin

Hyperglycemia
Insulin
Metformin

Increased
HGP

Rimona
bant

Metformin
Glitazon

Neurotransmitte
Decreased Glucose
dysfunction
uptake

??

Septem = seven

PHARMACOLOGY
1.INCREASED INSULIN
SECRETION
2.
3.
4.
5.

INCREASED INSULIN SENSITIVITY

ALPHA GLUCOSILASE INHIBITORS
DPP IV Inhibitor
INSULIN

19

INCREASED INSULIN SECRETION

Sulfonilureas:
First line treatment in non obese
patients with type 2 DM
Stimulating a receptor on the
surface cells closing K+ channel and
opening Ca++ channel insulin release
Reduction HbA1c 1-2% in long term
Side effects hypoglycemia and weight gain, skin
reaction, alteration liver function, minor
gastrointestinal symptom and cholestatic
jaundice and marrow supression
20

INCREASED INSULIN SECRETION

Sulfonylure
a

Length
of
action

Begins
of
action

Daily
dose
(mg)

Route of
excretion

Glibenclamid
e

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

R21= 5%, B =

PHARMACOLOGY
1. INCREASED INSULIN SECRETION

2.INCREASED INSULIN
SENSITIVITY
3. ALPHA GLUCOSILASE INHIBITORS
4. DPP IV Inhibitor
5. INSULIN

22

INCREASED INSULIN SENSITIVITY

Biguanides
First line treatment for obese patient with
type 2 DM
Used combination with insulin treatment
The UKPDS showed significantly better
metformin compared with the other therapies
in reduced complication and mortality in the
overweight DM
Although 1-2 Kg weight loss is seen, but not
signifucant in over a 10 years period, and not
make hypoglycemia
Decreasing hepatin gluconeogenesis,
increasing muscle glucose uptake and insulin
sensitivity
Long period 0,8 2,0% HbA1c reduction
23

INCREASED IN SULIN SENSITIVITY

Side effects:
The major side effects of metformin is
gastrointestinal with nausea, vomiting and
diarrhoea prominent (taken with meals or
started at low dose minimized side effects
Not given to high risk patients with:
Severe cardiac failure
Renal failure
Hepatic cirrhosis
Respiratory failure
Alcoholism
24

INCREASE INSULIN
SENSITIVITY
Thiazolidinedione
PPAR agonist (reducing HbA1c 1%)
Act on adipose tissue, liver and muscle as insulin
sensitizers, potentiating the action of insulin
Improved glycaemic control and beneficial effects on lipid
profile, Blood Pressure and microalbuminuria
Be careful with hepatic failure fatalities (troglitazone)
Rosiglitazone (4-8mg/day) & Pioglitazone (15-30mg/day)
Combination with sulfonylureas or metformin, or both.
Side effects: fluid retention & hepatotoxicity

25

PHARMACOLOGY
1. INCREASED INSULIN SECRETION

2. INCREASED INSULIN SENSITIVITY

3. ALPHA GLUCOSILASE
INHIBITORS
4. DPP IV inhibitor
5. INSULIN

26

ALPHA GUCOSIDASE INHIBITORS

Acarbose
Act by inhibiting disaccharidases in the small
bowel
Delay enzymatic digestion of complex
carbohydrate delay absortion gradual flux
in of glucose concetration in portal vessels
Reducing postprandial hyperglycemia (HbA1c:
0,5%)
Side effects:
Significant carbohydrate malabsorption
flatulence, abdominal bloating and diarrhoea
Reduced the starting dose of 50 mg/day and
maintenance 50-100 mg each meal
27

PHARMACOLOGY
1. INCREASED INSULIN SECRETION

2. INCREASED INSULIN SENSITIVITY

3. ALPHA GLUCOSILASE INHIBITORS

4.DPP IV inhibitor
5. INSULIN

28

PHARMACOLOGY
1. INCREASED INSULIN SECRETION

2. INCREASED INSULIN SENSITIVITY

3. ALPHA GLUCOSILASE INHIBITORS
4. DPP IV inhibitor

5.INSULIN

29

Onset of
action
(hours)

Peak
action
(hours)

Effective
duration of
action
(hours)

Insulatard

2-4

4-10

10-16

Humulin N

2-4

4-10

10-16

Lente

3-4

4-12

12-18

Insulin glargine
(lantus)

2-4

No peak

insulin detemir
(Levemir)

2-4
6-10

No peak
8-10

Insulin preparat
Insulin
intermediate
acting

Insulin longacting

Insulin preparat

Onset of
action
(Menits)

Peak
action
(menits)

Effective
duration
of action
(menits)

30-60

30-90

3-5

5-15

30-90

3-5

30-90

3-5

30-90

3-5

Insulin prandial (meal

related)
Human Insulin short
acting
Actrapid,Humulin R
Insulin analog rapid
acting
Insulin lispro (Humalog R)
Insulin glulisine (Apidra)
Insulin aspart (Novo
Rapid)

5-15
5-15

Onset
of
action
(Menits)

Peak
action
(hours)

Effective
duration
of action
(hours)

Mixtard (30/70)

30-60

Dual

10-16

Humulin 30/70

30-60

Dual

10-16

Novomixv30 ( 30%
insulin aspart, 70%
insulin aspart protamine

10-20

Dual

15-18

Humalog Mix 25 (25%

insulin lispro, 75%
insulin lispro protamine

5-15

1-2

16-18

Insulin preparat
Mixed insulin (short
& intermediate
acting

INSULIN ANALOG:
1. NovoRapid
2. NovoMix
3. Levemir

Lokasi Penyuntikan Insulin

Lokasi penyuntikkan adalah di abdomen

deltoid
paha atas depan
bokong.

Therapy for DM
Metformin
Sulfonil
urea

Glitazone

-glucosidase
inhibitors

Insulin
37

Weekly adjusments dose

Fasting blood
glucose

Insulin
dose

<80
mg/dL

-2units
80-109

mg/dL

no
change

110-139
mg/dL

+2
units

140-179
mg/dL

+4units
>180

mg/dL

+6units

38

Should combination therapy be the

first-line choice?
Stepwise treatment

Diet /
exercise

Oral
Oral
Oral
Oral
Oral
monotherapyuptitration combination +/- insulin + insulin

Early combination therapy

ADA &
EASD
guideline
+ basal insulin

Type 2DM
Lifestyle changes+
metformin
A1c >7%

A1c >7%
Insulin
intensification

+ Glitazon without
hipoglikemia

+ Sulfonil urea
A1c >7%
+ glitazon

+ sulfonilurea

+ basal
insulin
A1c >7%

A1c >7%
Insulin intensification
+Metformin +/- glitazon

A1c >7%

+ basal insulin or insulin

intensification

Refferences
Consensus PERKENI : Type 2
Diabetes Mellitus Management , PB
PERKENI, 2006, Jakarta
Consensus PERKENI: Insulin for
Diabetes Mellitus, PB PERKENI, 2007,
Jakarta
ADA, Standard of Medical Care in
Diabetes 2010, Diabcare Januari
2010 vol 33, Supplement 1, S1-61,

THANK YOU