Epidemiology,

Pathogenesis, Classification
& Diagnosis of Diabetes
Mellitus
dr. Pande Dwipayana, SpPD-KEMD
dr. Pande Dwipayana, SpPD-KEMD
Divisi Endokrin dan Metabolik
Divisi Endokrin dan Metabolik
Bagian/SMF Ilmu Penyakit Dalam
Bagian/SMF Ilmu Penyakit Dalam
Fakultas Kedokteran Universitas Udayana
Fakultas Kedokteran Universitas Udayana
RSUP Sanglah Denpasar
RSUP Sanglah Denpasar

Mataram 18-19 juni 2015

Objectives
Definition of type 2 diabetes mellitus

(type 2 DM)
Epidemiology of diabetes mellitus
Glucose homeostasis and pathogenesis
Classification and diagnosis of diabetes

mellitus

Definition
The term diabetes mellitus describes a metabolic

disorder of multiple etiology characterized by

chronic hyperglycemia with disturbances of
carbohydrate, fat, and protein metabolism
resulting from defect in insulin secretion, insulin
action, or both.
The effects of diabetes mellitus include long-term

damage, dysfunction and failure of various organs

World Health Organization., http://www.who.int/ncd/dia/

Top 10 Countries For Number Of People

Age 20-79 Years With Diabetes In 2011
and 2030
2011

2030

Country

Million

Country

Million

China

90.0

China

129.7

India

61.3

India

101.2

U.S.A

23.7

U.S.A

29.6

Russian
Federation

12.6

Brazil

19.6

Brazil

12.4

Bengladesh

16.8

Japan

10.7

Mexico

16.4

Mexico

10.3

Russia
Federation

14.1

Bangladesh

8.4

Egyp

12.4

Egyp

7.3

Indonesia

11.8

Indonesia

7.3

Pakistan

11.4

Whiting DR et al. Diabetes Research And Clinical Practice.2011 94: 311-321

POPULATION OF DIABETES
IN THE WORLD

Estimation: 285 million

diabetision in 2010
Increasing > 150% during
20 years.
Sumber: http://www.diabetesatlas.org/content/prevalence

Diabetes prevalence in several selected provinces of Indonesia

(based on OGTT measurement)
12

10

Prevalence
6
10.4
4

8.5

6.2

5.3
2

11.1

8.6
4.1

6.6
4.2

Province

Indonesia prevalence= 5.7%

Riskesdas,2007

11.1

7.8
5.4

8.1

6.8
5
3

7.7

6
4.6

Estimation of Type 2 Diabetes in

Indonesia

Known DM

Undiagnose
d DM

Total DM

IGT

1,5 %

4,2 %

5,7 %

10,2 %

National Health Survey 2007

24417 subjects, >15 years old, from 33 provinces in Indonesia.

Undiagnosed Diabetes in Indonesia

Prevalence of Diabetes 5.7%

26.3
73.7

Undiagnosed

Diagnosed

National Health Survey 2007

24417 subjects from 33 provinces in Indonesia.

PREVALENCE OF DIABETES
IN INDONESIA (WHO)

Estimation: 8,4 million

diabetision in 2000
Increasing become:
21,3 million in 2030

Source: Konsensus Pengelolaan & Pencegahan DM tipe 2 di Indonesia, Perkeni 2011

Epidemiology DM in
Bali

Sangsi
t
Pedawa

Pengelipur
an

Tengana
n

Ubud

Legian
Ceninga
n

Sangsit (sea area,

471 subjects)
Pedawa (mountain,
294 subjects)
Ubud (tourism area,
301 subjects)
Tenganan (highland
area, 81 subjects)
Ceningan (seasore
area, 305 subjects)
Legian (tourism
area, 288 subjects)
Pengelipuran
(highland area, 100
subjects)

The prevalence of metabolic syndrome by sex and village

The prevalence of impaired fasting glycemia (IFG) and diabetes mellitus (DM), by village

The prevalence of central obesity, impaired fasting glycemia (IFG), diabetes

mellitus (DM), and metabolic syndrome (MS,) by village

Classification of Diabetes

Type 1

Type 2

Cells
destruction
leading to
absolute
insulin
deficiency

Progressive
insulin
secretory
defect on
background
of insulin
resistance

Other specific
type of
diabetes due to
other causes

Genetic defect
on cell
function
Genetic defects
in insulin
action
Disease of the
exocrine
pancreas
Drug or
chemical
induced
ADA, Diabetes Care 2012;35(suppl 1):S11-S63
diabetes

Gestation
al
Diabetes
diagnosed
during
pregnancy

Basic Pathophysiology of Diabetes

Mellitus
(3 main defects)
Islet

Insulin
deficiency

Pancreas
Excess
glucagon
Diminished
Insulin

Hyperglycemia

Alpha cell
produces
excess
glucagon

Beta cell

produces
less
insulin
Diminished
Insulin

Muscle and fat

Liver
Insulin resistance
(decreased glucose
Adapted from Buse JB et al. In Williams Textbook of Endocrinology. 10th ed. Philadelphia, Saunders, 2003:14271483; Buchanan TA Clin
uptake)
Ther 2003;25(suppl B):B32B46; Powers AC. In: Harrisons Principles of Internal Medicine. 16th ed. New
York: McGraw-Hill, 2005:21522180;
Excess glucose
output

Rhodes CJ Science 2005;307:380384.

(mg/100ml)

360
330
300
270
240
110
80

(U/ml)

150
120
90
60
30
0

(g/ml)

Glucagon

Insulin

Glucose

Insulin and Glucagon Respon to

Carbohydrate in Type 2 Diabetes Mellitus

140
130
120
110
100
90

Type 2 diabetes mellitus (n=12)*

Nondiabetic controls (n=11)

Meal

Depressed/delayed insulin response

Nonsuppressed glucagon

60
*Insulin measured in five patients

60

Time (minutes)

Adapted from Mller WA et al N Engl J Med 1970;283:109115.

120

180

240

Pregresive Declining of Beta Cell

Pancreas in Diabetes

HOMA: homeostasis model assessment

Lebovitz. Diabetes Reviews 1999;7:13953 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:124958)

The Ominous Octet

Decreased
Incretin Effect

Islet-cell

Increased
Lipolysis

Impaired
Insulin Secretion

Islet-cell

Increased Glucose
Reabsorption

Increased
Glucagon Secretion

Increased
HGP
DeFronzoRA.Diabetes2009;58:773-795

Neurotransmitter
Dysfunction

Decreased Glucose
Uptake

Criteria for the Diagnosis of

Diabetes
A1C 6.5%
OR
Fasting plasma glucose (FPG)
126 mg/dl (7.0 mmol/l)
OR
Two-hour plasma glucose 200 mg/dl (11.1
mmol/l) during an OGTT
OR
A random plasma glucose 200 mg/dl
(11.1 mmol/l)
ADA, Diabetes Care 2012;35(suppl 1):S11.

Criteria for the Diagnosis of

Diabetes
A1C 6.5%
The test should be performed in a laboratory
using an NGSP-certified method
standardized to the DCCT assay*
*In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing
NGSP : National Glycohemoglobin Standardization Program

ADA, Diabetes Care 2012;35(suppl 1):S11-S63.

Criteria for the Diagnosis of

Diabetes
Two-hour plasma glucose 200 mg/dl
(11.1 mmol/l) during an OGTT
The test should be performed as described by
the World Health Organization, using a
glucose load containing the equivalent of 75 g
anhydrous glucose dissolved in water*
*in the absence of unequivocal hyperglycemia, result should be
confirmed by repeat testing.
ADA, Diabetes Care 2012;35(suppl 1):S11-S63.

Criteria for the Diagnosis of

Diabetes

In a patient with classic symptoms of

hyperglycemia or hyperglycemic crisis,
a random plasma glucose 200
mg/dl (11.1 mmol/l)
ADA, Diabetes Care 2012;35(suppl 1):S11-S63.

Prediabetes: IFG, IGT, Increased

A1C
Categories of increased risk for diabetes
(Prediabetes)*
FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG
or
2-h plasma glucose in the 75-g OGTT
140-199 mg/dl (7.8-11.0 mmol/l): IGT
or
A1C 5.7-6.4%
*For all three tests, risk is continuous, extending below the lower limit of a range and
becoming disproportionately greater at higher ends of the range.

ADA, Diabetes Care 2012;35(suppl 1):S11-S63.

Asymptomatic Adult Individuals

(1)
1.Testing should be considered in all adults who are

overweight (BMI 25 kg/m2*) and have additional risk

factors:
HDL cholesterol level

Physical inactivity

First-degree relative with

diabetes
High-risk race/ethnicity (e.g.,

African American, Latino,

Native American, Asian
American, Pacific Islander)

A1C 5.7%, IGT, or IFG on

previous testing

baby weighing >9 lb or were

diagnosed with GDM
mmHg or on therapy for
hypertension)

Women with polycystic ovarian

syndrome (PCOS)

Women who delivered a

Hypertension (140/90

<35 mg/dl (0.90 mmol/l)

and/or a triglyceride level
>250 mg/dl (2.82 mmol/l)

Other clinical conditions

associated with insulin

resistance (e.g., severe
obesity, acanthosis nigricans)
History of CVD

ADA, Diabetes Care 2012;35(suppl 1):S11-S63.

Glucose levels for

diagnosis of diabetes and prediabetes (impaired glucose
tolerance)
Fasting plasma glucose
(FPG)

2-hour postprandial
glucose
(PPG)
Diabetes mellitus

Diabetes mellitus
126 mg/dL

100 mg/dL

Impaired fasting
glucose (IFG)
Normal

7.0 mmol/L

5.6 mmol/L

ADA. Diabetes Care. 2009;32:S62-S67.

200 mg/dL

140 mg/dL

Impaired glucose
tolerance (IGT)
Normal

11.1 mmol/L

7.8 mmol/L

Criteria for the diagnosis of diabetes ( ADA

2015)

OR

OR

OR

Recommendations: A1C
Perform A1C test at least twice yearly in patients

meeting treatment goals (and have stable

glycemic control)
Perform A1C test quarterly in patients whose

therapy has changed or who are not meeting

glycemic goals
Use of point-of-care testing for A1C allows for

timely decisions on therapy changes, when

needed

ADA. Diabetes Care 2012;35(suppl 1):S11-S63.

Glycemic Recommendations for

Non-Pregnant Adults with Diabetes
(1)
A1C
Preprandial capillary
plasma glucose

<7.0%*

Peak postprandial
capillary plasma
glucose

<180 mg/dl*
(<10.0 mmol/l)

70130 mg/dl*80-130
(3.97.2 mol/l)

*Postprandial glucose measurements should be made 12 h after the

beginning of the meal, generally peak levels in patients with diabetes.
ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S11

Approach to the management

of hyperglycemia
PATIENT / DISEASE FEATURES

HbA1c

more
stringent

7%

Risks potentially associated

low
with hypoglycemia and
other drug adverse effects
Disease duration

Life expectancy

Important comorbidities

Established vascular
complications

Patient attitude and

expected treatment efforts

Resources and support

system

less
stringent
high

newly diagnosed

long-standing

Usually not
modifiable
long

short

absent

few / mild

severe

absent

few / mild

severe

highly motivated, adherent,

excellent self-care capacities

Readily available

less motivated, non-adherent,

poor self-care capacities

Potentially
modifiable

limited

DiabetesCare2015;38:140149;Diabetologia2015;58:429-442

Summary
Diabetes mellitus is a metabolic disorder characterized by

chronic hyperglycemia with resulting from defect in insulin

secretion, insulin action, or both.
Prevalence of type 2 DM tend to increase from 6% (2007) to

7.3% (2025)
National Data of the prevalence diabetes: 5.7% , whereas

74% of them are newly diagnosed.

Most of the cases are type 2 diabetes.
The main factors of type 2 diabetes are insulin resistance

and insulin deficiency

Matur

Case
Laki-laki berusia 43 tahun datang dengan keluhan sering lelah. Dia seorang
eksekutif, sering makan di restaurant, jarang berolahraga, perokok, tidak konsumsi
alkohol, dan tidak mempunyai riwayat hipertensi. Ibunya penyandang diabetes,
ayahnya hipertensi.

TB= 170cm, BB=88 kg, Lingkar perut = 112cm. TD =140/80 mmHg, lain-lain dalam
batas normal.

Faktor risiko apa saja yang ditemukan pada kasus ini?

Pemeriksaan penunjang apa yang diperlukan pada pasien ini?
Bagaimana pengelolaan pasien ini sesuai dengan sumber daya yang ada di
tempat anda?

Case
Seorang pasien pria berusia 55 tahun, datang ke klinik mengeluhkan
penurunan berat badan yang terjadi selama 8 minggu terakhir walaupun
selera makannya tetap. Pasien tersebut juga mengeluhkan rasa lelah dan
lemas selama jam kerja dan selalu merasa haus. Pada malam hari, pasien
tersebut terbangun 3-4 kali untuk BAK. Saat ini BB pasien 70 kg, dengan
tinggi badan 165cm. Pasien tersebut bekerja di bank, dengan gaya hidup
santai / kurang aktif. Pasien tersebut memiliki ibu yang menderita diabetes,
dan ayahnya meninggal dunia 5 tahun yang lalu karena serangan jantung pada
usia 75 tahun. Pasien tersebut belum pernah melakukan medical check-up
dalam 5 tahun terakhir.
Pemeriksaan laboratorium apa yang akan anda sarankan untuk
mendiagnosis pasien tersebut?
Apa kriteria diagnosis untuk diabetes melitus?
Apa rekomendasi anda untuk pengelolaan pasien tersebut?
Slide 35