EPIDEMIOLOGY,PATOPHYSIOLOGY

DIABETES MELLITUS
Husaini Umar

DIABETES AN LIPID CENTRE

Dr. WAHIDIN SUDIROHUSODO HOSPITAL
SUB DIVISION ENDOKRINOLOGY – METABOLIC
INTERNAL MEDICINE, MEDICAL OF FACULTY
HASANUDDIN UNIVERSITY
Definition

Diabetes mellitus is a chronic illness that

characterized by hyperglycaemia, requires
continuing medical care and patient self
management education to prevent acute
complications and to reduce the risk of long
term complications

Diabetes care 2006;29(suppl)S4

KLASIFIKASI

Type 1 diabetes,
β-cell
destruction Type 2 diabetes,
Defect insulin
secretion, insulin
resistance
Other types of
diabetes

Gestational
diabetes
EPIDEMIOLOGI

Prevelansi Diabetes
246 juta (2007)
+ 380 juta pada 2025
Epidemic = 5.9% dewasa
 Global diabetes epidemic
350 333
diabetes world wide (millions)
Number of people with

300
250
72%
194 increase
200
150
100
50
0
2003 2025
Year
International Diabetes Federation
 Increased Prevalence of Diabetes
Highest in Developing Countries
1995
300 %170 
Projection
250 2025
Diabetic Patients (millions)

228
200

150
%42 
100

50 84
72
51
0

Develoved Develoving
Countries Countries

King et al. Diab Care 1998;21:1414–31

EPIDEMIOLOGI

Persentase Jumlah Pasien Diabetes etnis Asia

CHINA 2.7
PHILIPPINES 3.1
THAILAND 3.7
INDONESIA 4.6
KOREA 6.1
MALAYSIA 6.3
JAPAN 7.4

TAIWAN 9.1
SINGAPORE 11.3
HONG KONG 12.1

0 3 6 9 12 15

Source : Diabetes Atlas 2000

By 2030, 7 of the 10 Countries with the
Most Diabetic Patients Will Be in Asia
2000 2030

People with People with

Ranking Country diabetes Country diabetes
(millions) (millions)

1 India 31.7 India 79.4

2 China 20.8 China 42.3
3 USA 17.7 USA 30.3
4 Indonesia 8.4 Indonesia 21.3
5 Japan 6.8 Pakistan 13.9
6 Pakistan 5.2 Brazil 11.3
7 Russian Fed. 4.6 Bangladesh 11.1
8 Brazil 4.6 Japan 8.9
9 Italy 4.3 Philippines 7.8
10 Bangladesh 3.2 Egypt 6.7

Wild S et al. Diabetes Care 2004;27(5):1047-53.

Current and Projected Prevalence
of Diabetes in Southeast Asia and
the Western Pacific
Prevalence of
Region Diabetes* in % Increase
2000 2030
Southeast Asia 47 M 120 M 255%

Western Pacific 36 M 71 M 199%

*In millions
Adapted from: World Health Organization. Retrieved March 14, 2007:
http://www.who.int/diabetes/facts/world_figures/en/index5.html
http://www.who.int/diabetes/facts/world_figures/en/index6.html
Type-2 Diabetes Mellitus
WHO Diabetes Program:
• 150 million people with DM today  2 x in
2025
• The heaviest burden will fall on
developping countries  Urbanised
Western lifestyles.
• India & China have the highest numbers of
Diabetes patients
• By 2030, 7 of the 10 countries with the
most diabetic patients will be in Asia

Diabetes Care 2000;(suppl.2): B5-B10.

 Type-2 Diabetes Mellitus

• 5-8% of the population are diagnosed T2DM,

another 2-5% affected , but not yet diagnosed.
• A chronic asymptomatic disease (“mild -
hyperglycaemia”)
• Frequently detected AFTER Cardio Vascular Event

Erland.erdmann@ uni-koeln-de 13 aug.2004

DM tipe 2: A silent killer

 30% of people T2DM are not diagnosed

 50% of those diagnosed with T2DM already have

advanced disease with signs of complications

 65-80% of T2DM  cause of death CVD

 2-4X of T2DM risk of CVD and 2X stroke

National Institute of Diabetes and Digestive and Kidney Diseases. http://diabetes.niddk.nih.gov/

dm/pubs/statistics/index.htm#7 [Accessed 1 December 2005]
Wingard DL et al. Diabetes Care 1993;16:1022-5
• Early detection , and prompt treatment
may reduce the burden of T2DM & its
complications.
• Healthy individuals testing should be
considered in high risk population
• Screening of the general population is
not considered to be costly-effective.
The Pathophysiology of Type 2 DM
Pancreas

LIVER
GLYCOGENOLYSIS

Insulin supply or action

G LYCOGEN

-
HGP +
+ GLUCOSE G L UC O S E

GLUCONEO FFA
GENESIS
LIPOLYSIS Lactic Acid
ADIPOSE TISSUE
PATHOGENESIS OF TYPE 2 DIABETES

Diabetes mellitus is a group of metabolic diseases

characterized by hyperglycemia resulting from defect
of insulin action, insulin secretion or both

Insulin Type 2 βcell

resistance diabetes dysfunction

DeFronzo et al. Diabetes Care 1992;15:318-68

PATOGENESIS
BOTH ISLET DYSFUNCTION AND INSULIN
RESISTANCE CONTRIBUTE TO THE ONSET AND
PROGRESSION OF TYPE 2 DM
Unhealthy Insulin Normal pancreatic Healthy
lifestyle and resistance islet function
Pancreas
environmental =
factors Insulin Normal
X Glucose
Sufficient Appropriate Tolerance
Insulin Glucagon (NGT)

Pancreatic islet
Reduced dysfunction Unhealthy
Glucose uptake Pancreas
More Insulin =
needed to Impaired GT
compensate which likely
progresses to
Insufficient Excess
More work for Insulin Glucagon Type 2 DM
Central Obesity
-cells

GT = glucose tolerance; NGT = normal glucose tolerance; T2DM = type 2 diabetes mellitus
Type 2 Diabetes: a chronic progressive disease
Obesity IGT IPH Overt Diabetes

Postprandial
Plasma
Glucose
(mg/dl) 126
Fasting

Insulin Resistance
ß-cell
function
(%)
100
Insulin Level

-20 -10 0 10 20 30
Diabetes duration (years)
Adapted from IDC, Minneapolis
MANIFESTASI KLINIS

-Asimtomatis
-DM overt:
Polyuria
Polydipsia
Weight loss
Sometimes polyphagia
Blurred vision
infeksi (paru-paru, kaki),
stroke, PJK
DIAGNOSIS KENCING MANIS

pasien masuk dengan tidak sadar (koma)

pasien masuk dengan abses di punggung
SKRINING & DIAGNOSIS
SKRINING DAN DIAGNOSIS

Skrining
Mendeteksi penderita diabetes melitus diantara
mereka yang bukan diabetes melitus
(asimptomatis)
Diagnosis
Memastikan apakah menderita diabetes atau
tidak pada seseorang dengan keluhan / tanda
diabetes melitus
SKRINING & DIAGNOSIS

Jenis skrining
1. Skrining di populasi untuk mengetahui berapa
prevalensi DM di suatu daerah / negara
2. Skrining di klinik untuk mendeteksi penderita
DM sebanyak mungkin

Siapa yang perlu skrining?

 American Diabetes Association “ hanya yang

berisiko tinggi saja”
Criteria for testing for diabetes in asymptomatic
adult individuals
1. Testing should be considered in all adults who are
overweight (BMI >25 kg/m ) and have additional risk
factors:
First-degree relative with diabetes (father / mother)
Women who delivered a baby weighing > 4000 gr or
were diagnosed with GDM
Hypertension (>140/90 mmHg or on therapy for hypertension)
HDL cholesterol level <35 mg/dl (0.90 mmol/l) and /or
a triglyceride level >250 mg/dl (2.82 mmol/l)
A1C >5.7%, IGT, or IFG on previous testing
History of CVD

Standards of Medical Care in Diabetes - 2010, Diabetes Care 2010 33:S11-S61

Criteria for testing for diabetes in asymptomatic
adult individuals

2. In the absence of the above criteria, testing

diabetes should begin at age 45 years
3. If results are normal, testing should be
repeated at least at 3-year intervals, with
consideration of more frequent testing
depending on initial results and risk status.

Standards of Medical Care in Diabetes - 2010, Diabetes Care 2010 33:S11-S61

CRITERIA FOR THE DIAGNOSIS DIABETES (ADA,
DIAGNOSIS AND CLASSIFICATION OF DIABETES
MELLITUS. Diabetes Care 2011;34:S13-)

A1C > 6,5%. The test should be performed in a laboratory using a

method that is NGSP certified and standardized to the DCCT assay
OR
FPG > 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake
for at least 8 h
OR
Two-hour plasma glucose > 200 mg/dl (11.1 mmol/l) during an OGTT,
using a glucose load 75 gr s glucose dissolved in water
OR
In a patient with classic symptoms of hyperglycemia hyperglyce-mic
crisis, a random plasma glucose > 200 mg/dl (11.1 mmol/l)

In the absence of unequivocal hyperglycemia, criteria 1 - 3 should be confirmed by

repeat testing.
CATEGORIES OF INCREASED RISK
FOR DIABETES (PREDIABETES)

FPG (GPT) 100 - 125 mg/dl

or
2-h plasma glucose in the 75 gram OGTT
140 - 199 mg/dl
or
A1C 5,7 - 6,4%

(ADA, classification and diagnosis of diabetes mellitus. Diabetes

Care 2011;34:S36-S69)
 DIAGNOSIS DM
TES TOLERANSI GLUKOSA ORAL
Perlu diingat:

- kadar 2 jam setelah TTGO tidak sama dengan

2 jam setelah makan

- pemeriksaan glukosa 2 jam setelah makan (2

jam pp) hanya untuk mengetahui keberhasil-
an pengobatan yang telah dilakukan
 PENATALAKSANAAN
Tujuan

Jangka pendek Jangka panjang

Menghilangkan keluhan Mencegah / menghambat
Mempertahankan rasa sehat komplikasi kronik
Mencegah kematian

Cara
Normalisasi glukosa,
Lipid dan tekanan darah

JMF 20
PENATALAKSANAAN
PENATALAKSANAAN
 ORAL ANTI DIABETIK

Sulphonylurea - Glibenklamid, Daonil

Meglitinides - Novonorm
Metformin - Glucophage
 - glucosidase inhibitors - Acarbose
Thiazolidinedione - Avandia, Actos

DPP - 4 inhibitor (Galvus –October 2007)

GLP-1 Agonis (Liraglutide/Victosa)
GLP-1 Receptor agonis (Exenatide)
Class Oral Agent Target Organ FBG, A1c Reduction Adverse Reaction Precautions

SU Glyburide, Pancreas ↓ FBG 50-60 mg/dl Hypoglycemia. Use caution in elderly pts,
Glipizide, ↓ A1c 1,5-2 weight gain, renal or hepatic
Glimepiride, hyperinsulinemia impairments
Chlorpropamide
Tolbutamide

Biguanide Metformin Liver ↓ FBG 50-60 mg/dl Diarrhea; metallic Contraindicated if SrCr>1.5
↓ A1c 1,5-2 taste mg/dl in men; >1.4 in
women or if CrCl <60-75
ml/min; use caution in
patients with CHF, renal or
hepatic disease

TZD Rosiglitazone Peripheral tissue ↓ FBG 30-60 mg/dl Weight gain, edema Contraindicated if ALT>2.5
Pioglitazone ↓ A1c 0,8-1,5 ULN; use caution in pts
with CHF or hepatic
disease

Meglitinide Repaglinide Pancreas ↓ PPG 40-50 mg/dl Hypoglycemia.

Nateglinide ↓ A1c 0,4-1,7 weight gain, Use caution in renal or
hyperinsulinemia hepatic impairments

AGI ACARBOSE Intestine ↓ PPG 50 mg/dl Flatulence, diarrhea Avoid if SrCr>2.0 mg/dl;
↓ A1c 1,5-2 avoid in pts with GI
disorders

DPP IV Inh Sitagliptin DPP IV / ↓ PPG 25mg/d/ ↓ angioedema Avoid if CKD moderate,
Pankreas severe; avoid in pts with
Vildagliptin ↓ A1c 0,9 – 1,5 CHF

Source: Adapted from Zettervall. Cornell and Briggs, Journal of Pharmacy Practice 2004, 17; 1: 49-54
SrCr= serum creatinine, CrCl= creatinine clearance, ALT = alanine transferase, PPG= post prandial glucose, FBG= fasting bl. gluc.
 COMMON ORAL HYPOGLYCEMIC AGENTS
AND THE SITE OF ACTION

Meglitinides Thiazolidinediones
Increase insulin Increase glucose
secretion from uptake in skeletal
pancreatic -cells muscle and decrease
lipolysis in adipose
Insulin secretagogue tissue

Sulfonylureas
Increase insulin Biguanide (metformin)
secretion from Decreases hepatic
pancreatic -cells production and
increases uptake

DPP – 4 inhibitor
Increase insulin -Glucosidase inhibitors
secretion from β-cells, Delay intestinal
suppress glucagon carbohydrate absorption
secretion from α-cells

DPP-4 = Dipeptidyl peptidase – 4 inhibitior

Adapted from Cheng and Fantus. CMAJ. 2005;172:213–226
Insulin
Sejarah Perkembangan
insulin

 1921 : penemuan insulin

 s/d 1983 : era insulin hewan
Menggunakan ekstrak pankreas hewan (sapi / babi)
 1983 : era Human insulin
Menggunakan rDNA manusia untuk menghasilkan insulin
 1999 : era insulin modern (analog) dimulai
Menggunakan teknologi bioengineering untuk memodifikasi
rantai DNA human insulin untuk membuat insulin baru yang
lebih baik dalam hal farmakologi
Saccharomyces cerevisiae
TIPE INSULIN
Tipe Insulin Onset Peak/Puncak Duration Duration
(Jam) (Jam) Efektif Maksimal
Rapid Acting
Human Lyspro 0,25-0,5 0,5 – 2,5 <5 4–5
Human Aspart <0,20 1–3 3–5
Short Acting
Human Regular 0,5 – 1,0 2–3 4–6 5–7

Intermediate Acting
Human NPH 2–4 4 – 10 10 – 16 14 – 18
Human Lente 3–4 4 – 12 12 – 18 16 – 20
Long Acting
Human Ultralente 6 – 10 14 – 24 18 – 20 20 - 36
Insulin Glargine 2-4 Peakless 20 -24
Combinations
Mixtard
Novomix
Indications of Insulin Treatment
Indication for the use of insulin in
Type 2 DM
• In severe metabolic decompensation
• Ketoacidosis
• Hyperosmolar non ketotic coma
• Lactic acidosis
• Severe stress :
Systemic infection
Major surgery
• Weight loss within a short period of time
• Pregnancy if diet does not succeed to control
glycemia
• OHA failure or contra-indication of OHA
 How to Start
Insulin Therapy ?
1.If Fasting BG is elevated, start for basal insulin
with long acting insulin (Levemir)

2. If Prandial BG is elevated, start for prandial

/bolus insulin with rapid acting insulin
(NovoRapid)
3. If Fasting and Post Prandial are elevated :
- Oral agent with basal insulin
- premix insulin (NovoMix)
- basal/bolus as in multiple daily injection (MDI)
TREATMENT ALGORITHM FOR
TYPE 2 DIABETES ( s/d 2006)

Aim Diet, exercise, health education

Sulphonylurea, metformin
Glucosidase Inhibitors
Glinides
Thiazolidinediones
Oral combinations

Oral agents plus insulin

Improved Control Insulin

 Conservative management of glycemia:
traditional stepwise approach

OAD OAD +
Diet and OAD* monotherapy OAD OAD + multiple daily
exercise monotherapy up-titration combination basal insulin insulin injections
10

9
HbA1c (%)

HbA1c = 7%
7
HbA1c = 6.5%

6
Duration of diabetes *OAD = oral antidiabetic

Campbell IW. Br J Cardiol 2000; 7:625–631.

 PENATALAKSANAAN
DIABETES MELITUS SEJAK TAHUN
2006
Terjadi perubahan setelah
diperkenalkan algoritme baru ADA -
EASD
 TYPE 2 DIABETES MELLITUS
ALGORITHM FOR THE INITIATION
AND ADJUSMENT OF THERAPY

From 2006 to 2009,

two consensus /algorithms
has been introduced by the same associations
the ADA and EASD:

August 2006, and January 2009

 ADA/EASD: Metabolic Management of Type 2 Diabetes 2006
STEP 1 Lifestyle Intervention + Metformin
(Reinforce at every visit)

No A1C ≥ 7% Yes*

Add Basal Insulin Add Sulfonylurea Add Glitazone

STEP 2 (Most effective) (Least expensive) (No hypoglycemia)

No A1C ≥ 7% Yes* No A1C ≥ 7% Yes* No A1C ≥ 7% Yes*

Intensive Add Glitazone† Add Add

STEP 3 Insulin Basal Insulin Sulfonylurea†

No A1C ≥ 7% Yes* No A1C ≥ 7% Yes*

*Check A1c every 3 month until < 7% and then at Add Basal or Intensive Insulin
least every 6 month
†although 3 oral agents can be used,
initiation an intensification of insulin
therapy is preferred based
on effectiveness and expense Intensive Insulin+ Metformin + Glitazone
Nathan DM et al. Diabetes Care. 2006; 29: 1963-1972
 Tier 1: Well validated core therapies

At diagnosis:
Lifestyle + Metformin Lifestyle + Metformin
+ +
Basal insulin Intensive insulin
Lifestyle
+ Lifestyle + Metformin
Metformin +
Sulfonylurea*

STEP 1 STEP 2 STEP 3

Tier 2: Less well validate therapies
Lifestyle +Metformin
Lifestyle +Metformin +
+ Pioglitazone
Pioglitazone +
Nohypoglycemia Sulfonylurea
Oedema/CHP
Boneless

Lifestyle+ Metformin Lifestyle+Metformin

+ +
GLP-1 agonist b Basal insulin
Nohypoglycemia
Weight loss
Nausea / vomiting Nathan DM, et al. Diabetes Care
* Not glybenclamide
2009, ADA-EASD 2009
 Tier 1: Well validated core therapies

Lifestyle + Metformin Lifestyle + Metformin

At diagnosis: +
Basal insulin +
Lifestyle Intensive insulin
+ Lifestyle + Metformin
Metformin +
Sulfonylurea*

STEP 1 STEP 2 STEP 3

Nathan DM, et al. Diabetes Care

* Not glybenclamide
2009, ADA-EASD 2009
 AACE/ACE DIABETES ALGORITHM For Glycemic Control
LIFESTYLE MODIFICATION

A1c 6.5-7.5%** A1c 7.6-9.0% A1c > 9.0%

Drug Naive Under treatment

Symptoms No Symptoms
Monotherapy Dual therapy8
MET† DPP41 GLP-1 TZD2 AGI3 GLP-1 or DPP4 GLP-1
MET + or TZD INSULIN or DPP41 + SU7 INSULIN
2-3 Mes ***
SU or Glinide4,5 + Other MET + TZD2 + Other
Dual therapy Agents(s)6 GLP-1 Agents(s)6
2-3 Mes ***
GLP-1 or DPP41 or DPP41 + TZD2
MET + TZD2
Triple therapy9 * May not be appropriate for all pateints
Glinide or SU5 ** For patients with diabetes and A1c < 6.5%
GLP-1 + TZD2 pharmacologic Rx may be considered
TZD + GLP-1 or DPP41 or DPP41 *** If A1C goal not achieved safety
MET + GLP-1 † Preferred initial agent
MET + Colesevelam
1 DPP4 if ↑PPG and ↑FPG or GLP-1 if ↑↑ PPG
or DPP41 + SU7
AGI3 2 TZD if metabolic syndrome and or monalcoliolic
TZD2 fatty liver disease (NAFLD)
2-3 Mes *** 3 AGI if †PPG
2-3 Mes ***
Triple therapy 4 Glinide if †PPG or SU if †FPG
5 Low-dose ancreragogua recommanded
MET* TZD2 INSULIN 6 a) Discontinue insulin secretagogue with multidose
+ Other
GLP-1 or + insulin
Agents(s)6 b) Can use pranilinlide with praundial insulin
DPP4 Glinide or SU4,7
7 Decreases secretagogue by 50% after added to
2-3 Mes *** GLP-1 or DPP-4
8 If A1c < 8.5%, combination Rx with agents that
INSULIN cause hypoglycemia should be used with caution
+ Other 9 If A1c > 8.5%, in patients on dual therapy, insulin
should be considered
Agents(s)6

AACE December 2009 update.

Algoritme Pengelolaan DM tipe-2
Algoritme Pengelolaan DM tipe-2 Tanpa Dekompensasi

DM Tahap-I Tahap-II Tahap-III

GHS
GHS
+
monoterapi
GHS
Catatan :
1. GHS = Gaya hidup sehat +
2. Dinyatakan gagal bila Kombinasi 2 OHO
terapi selama 2-3 bulan
pada tiap tahap tidak
GHS
mencapai target terapi Jalur pilihan alternatif, bila: +
HbA1c <7% -Tidak terdapat insulin Kombinasi 2 OHO
3. Bila tidak ada -diabetisi betul-betul menolak
pemeriksaan HbA1c +
insulin
dapat dipergunakan
-kendali glukosa belum optimal Basal Insulin
pemeriksaan glukosa
darah
Rata-2 hasil pemeriksaan
beberapa kali glukosa GHS
darah sehari yang +
dikonversikan ke HbA1c
Insulin Intensif*
menuntut kriteria ADA, Kombinasi 3 OHO
2010 *insulin intensif: penggunaan insulin basal bersamaan dengan insullin prandial
PROBLEM WITH THESE ALGORYTHMS

AACE / ACE :
- easy to apply need not fasting but
- A1C should be standardized,
- not always available especially in the develop-
ing countries such as Indonesia
- expensive
 PROBLEMS WITH THESE ALGORYTHMS

ADA / EASD
- most developing countries only glibenclamide
and metformin are available in the tertiary hos-
pitals (PUSKESMAS)
- for private practice
- Tier 2 is more complicated
 GLYCEMIC GOAL FOR DIABETES
ADA IDF AACE PERKENI

HbA1C% <7.0 <6.5 <6.5 <6.5

FBS/Pre 80-120 <100 <110 <100

prandial
Mg/dl
Plasma
2hr post 185 <135 <140 <144
prandial
 Current ADA treatment targets

• HbA1c < 7%
• Blood pressure < 130/80 mmHg
• LDL-cholesterol < 100 mg/dl (2.6 mmol/l)
• HDL-cholesterol
Men > 40 mg/dl (1.1 mmol/l)
Women > 50 mg/dl (1.3 mmol/l)
• Triglycerides < 150 mg/dl (1.7 mmol/l)

American Diabetes Association. Diabetes Care 2004; 27 (Suppl 1): S15–35.

How can we be more successful
in achieving glycemic goals?
Paradigm for early combination
treatment

If HbA1c  9%
at diagnosis
Initiate combination
therapy† or insulin
in parallel with
diet/exercise
Treat to goal of
HbA1c < 6.5%*
If HbA1c < 9% If HbA1c > 6.5%* by 6 months
at diagnosis at 3 months
Initiate monotherapy Initiate combination
in parallel with therapy† in parallel
diet/exercise with diet/exercise

0 1 2 3 4 5 6
Months from diagnosis
*Or fasting/preprandial plasma glucose < 110 mg/dL (6.0 mmol/L) where assessment of HbA1c is not possible
†Combination therapy should include agents with complementary mechanisms of action

Del Prato S, et al. Int J Clin Pract 2005; 59:1345–1355.

Combination therapy should include agents
with complementary mechanisms of action
 Proactive management of glycemia:
early combination approach

Diet
and exercise
OAD
monotherapy
10 OAD
combinations OADs
uptitration
HbA1c (%)

9 OAD
+ basal insulin OAD + multiple daily
insulin injections
8

HbA1c = 7%
7

HbA1c = 6.5%
6
Duration of diabetes

*OAD = oral antidiabetic Del Prato S, et al. Int J Clin Pract 2000; 7:625–631.
 CURRENT TREATMENT PARADIGM (USA):
Physicians tolerate higher levels of hyperglycemia

134 mg/dl 152 mg/dl 168 mg/dl 220 mg/dl

Diet/Exercise Oral Combinations Insulin +

monotherapy oral agents

Morris,et al.Diabetes,2000;49 Suppl 1:A76.

Which drug partnership offers the
strongest potential to control
hyperglycaemia?
Primary sites of action of oral anti-diabetic agents

-glucosidase inhibitors Sulfonylureas and

Stomach
meglitinides

Gut

Glucose (G)
Pancreas
Insulin

Biguanides

Adipose tissue

Liver
metformin
Thiazolidinediones
primarily sup - Muscle
press hepatic
glucose output
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.
Choice of agents in current use

Glipizide
Acarbose
Gliclazide
Miglitol
Glimepiride
Glibenclamide
Sulphonylureas Voglibose

Metformin -glucosidase
TZDs
inhibitors

Meglitinides
Rosiglitazone Repaglinide
Pioglitazone Nateglinide
Blood glucose monitoring is a
cornerstone of diabetes
management
Self-Monitoring of Blood Glucose
(SMBG) - ADA Recommendations

Type 1 Diabetes : 3 x daily

Type 2 Diabetes: optimal frequency and timing not known;
“sufficient to facilitate reaching glucose goals”
Postprandial BG may be necessary to reach A1C goals
and/or reduce risk of hypoglycemia
Self-management training: how to use the data to adjust
food intake, exercise or pharmacologic therapy
• Diabetes Care 2006
Diabetes is Managed

GOAL:
To maintain target
blood glucose
 Complications :

Acute : Chronic :

Microangiopathy Macroangiopathy

Ketoacidosis Retinopathy CAD

Nonketotic Nephropathy PVD
Hyperosmolar syndrome Neuropathy Stroke
Hypoglycemia
Infection
Komplikasi Akut
• Koma hiperglikemia
KOMPLIKASI KRONIK
Type 2 diabetes is NOT a mild disease
Stroke
2- to 4-fold increase
Diabetic in cardiovascular
retinopathy mortality and stroke3
Leading cause
of blindness
in working-age
adults1
Cardiovascular
disease
8/10 diabetic patients
die from cardiovascular
events4
Diabetic
nephropathy Diabetic
Leading cause of neuropathy
end-stage renal Leading cause of
disease2 non-traumatic lower
extremity amputations5

1. Fong DS et al. Diabetes Care 2003; 26 (Suppl 1): S99–102; 2. Molitch ME et al. Diabetes Care 2003; 26 (Suppl 1): S94–8;
3. Kannel WB et al. Am Heart J 1990; 120: 672–6; 4. Gray RP, Yudkin JS. In: Pickup JC, Williams G, eds. Textbook of
Diabetes. 2nd Edn. Oxford: Blackwell Science, 1997; 5. Mayfield JA et al. Diabetes Care 2003; 26 (Suppl 1): S78–9.
KOMPLIKASI KRONIK
RINGKASAN

• Diabetes adalah masalah global

• Diperlukan deteksi dini untuk menurunkan morbiditas
dan mortalitas
• Skrining dilakukan pada orang dewasa dengan faktor
risiko / usia > 45 tahun
• Pemeriksaan untuk menegakkan diagnosis DM
meliputi GDP dan TTGO (diulangi tiap tahun), HbA1C
• Untuk mencegah komplikasi diabetes diperlukan
kontrol kadar gula darah yang baik dengan olahraga,
diet, obat/ insulin, edukasi
• HbA1c untuk pemantauan keberhasilan terapi , target
< 7/< 6,5
Komplikasi Kronik

Kronik
Hiperglikemia

Makrovaskuler
Mikrovaskuler