Slide 1

DMT2 :
Early Detection
&
Standardized Management

Prof Dr dr Asman Manaf SpPD KEMD

Sub bagian Endokrin Metabolik, Bagian I P Dalam, FK Univ.Andalas
 Slide 2

References

• AACE : American Association of Clinical Endocrinologists;

• ACE : American College of Endocrinology;
• ADA : American Diabetes Association
• IDF : International Diabetes Federation
• PERKENI : Konsensus Pengelolaan Dan Pencegahan DM Type 2
 Slide 3

Early Detection and Standardized

Diabetes Management
Main Learning Points

• Understand the process from

screening to diagnosis and the
associated national guidelines

•Understand the importance of

treating diabetes and intensify
treatment on diabetes via blood
glucose- and HbA1c monitoring

•Understand the reason and need for

routine follow-up and reaching
individual targets to avoid complications
 Slide 4

Common Definitions
Abbreviation Definition

NGT Normal Glucose Tolerance (Gula Darah Normal)

FPG Fasting Plasma Glucose (Gula Darah Puasa)

PPG Post-Prandial Plasma Glucose (Gula Darah Post Prandial)

IGT Impaired Glucose Tolerance (Toleransi Glukosa Terganggu)

IFG Impaired Fasting Glucose (Gula Darah Puasa Terganggu)

Average amount of glucose in the bloodstreams over a 3-month

HbA1c
period
 Slide 5

Classification of Diabetes

• Type 1 diabetes
• Absolute insulin deficiency due to the destruction of pancreatic
beta-cells
• Type 2 diabetes
• Type 2 is characterized by insulin resistance with relative
insulin deficiency to a predominately secretary defect with
insulin resistance
• Other specific types
• Gestational diabetes
• Glucose intolerance first detected in pregnancy that often
resolves after the birth of the baby

Diabetes Care 1997; 20: 1183-1197

 Slide 6

Comparison of Type 1 and Type 2 Diabetes

Features Type 1 Diabetes Type 2 Diabetes

Onset Sudden Gradual

Age at Onset Any age (mostly young) Mostly in adults

Body Habitus Thin or normal Often obese

Ketoacidosis Common Rare

Autoantibodies Usually present Absent

Endogenous Low or absent Normal, decreased or increased

Insulin

Prevalence Less prevalent More prevalent, typically 90-

95% of all people with
diabetes
 Slide 7

Type 2 Diabetes :
a Progressive Disease

HOMA: homeostasis model assessment

Lebovitz. Diabetes Reviews 1999;7:139–53 (data are from the UKPDS population: UKPDS 16.
Diabetes 1995;44:1249–58)
 Slide 8

Diabetes : elevated blood glucose

due to insufficient insulin secretion
Normal glucose and insulin Early Type 2 Diabetes Glucose
excursions and insulin excursions

Glucose Insulin Glucose Insulin

400 120 400 120

100 100
Glucose mg/dL

Glucose mg/dL
Insulin U/mL

Insulin U/mL
300 300
80 80

200 60 200 60

40 40
100 100
20 20

06:00 10:00 14:00 18:00 22:00 02:00 06:00 06:00 10:00 14:00 18:00 22:00 02:00 06:00

Breakfast
Time of Day Time of Day
Breakfast

Dinner
Lunch

Dinner
Lunch
 Slide 9

The Importance of treating Type 2 Diabetes

Type 2 diabetes is a progressive disease

Postprandial glucose

Diagnosis

Glucose Fasting glucose

Insulin Insulin resistance

Inadequate
β-cell function Insulin secretion
Microvascular changes
Macrovascular changes

Prediabetes
NGT Diabetes
(IFG/IGT)

Adapted from Type 2 Diabetes BASICS. International Diabetes Center 2000

 Environmental
factors
inactivity
sedentary
calori
obese

ß R
normal Complication ?

G
pre-diabetes ß L R
Complication
U
C
diabetes O
Hyper Complica
(early )
ß glycemia R tion ↑
L
I
diabetes P Complica
( late) ß O R tion ↑↑

toxicity
diabetes Complica
(terminal) ß ß R R
tion ↑↑↑

Diabetes progression
 Slide 11

Classical Diabetes Symptoms

Polyuria • Excessive Urination at night

Polyphagia • Excessive Hunger

Polydipsia • Excessive Thirst

Unexplained weight
• Weight Loss even if food in-
loss
take is normal
 Slide 12

Other Diabetes Symptoms

Blurred Vision • Damaging blood vessels in the eyes

Numbness and/or • Numbness and tingling in hands, legs

Tingling and feet

Fatigue • Frequent fatigue regardless of

exercise

Itchy Skin • affects legs, feet, and hands

Impotence • Physical and Physiological

 Slide 13

Diagnosis of Type 2 Diabetes

KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

■ Classical symptoms of Diabetes +

Random plasma glucose concentration ≥ 200 mg/dl
Or

■ Classical symptoms of Diabetes +

Fasting Plasma Glucose ≥ 126 mg/dl.
Or
■ Classical symptoms of Diabetes +
2-hour post-OGTT ≥ 200 mg/dl.

Note:
• Classical symptom of diabetes (+), only need 1 abnormal BG
• No classical symptom of diabetes, need 2 x abnormal BG level in a different days
 Slide 14

Cut-points: Diabetes, IGT and IFG

mg/dL
Fasting Plasma Glucose (FPG)

Diabetes

126

IFG (Impaired Diabetes

Fasting Glucose

100
IGT (Impaired
Glucose Tolerance)
NGT (Normal
Glucose
Tolerance)

140 200 mg/dL

2-hour Plasma
Glucose (PPG)
 Slide 15

Four Simple Steps

from Screening to Diagnosis

1 2 3
Screen patients with Conduct 1st Blood Test Conduct 2nd Blood
diabetes risk factors Test (if required) and
establish Diagnosis

4
Inform Patient and
Initiate treatment
 Slide 16

Step 1: Risk Factors

( PERKENI screening risk factor guideline )

Diabetes Associated
Unmodifiable Risk Modifiable Risk Risk

• Race and Ethnic • Overweight (BMI >23) • Polycystic Ovary

• Family History of • Hypertension > Syndrome (PCOS) or
Diabetes 140/90 mmHg another clinical
• History of Gestational • Dyslipidemia (HDL < condition related to
Diabetes 35 mg/dl and/or insulin resistance
• History of delivery a triglycerides >150 • Metabolic Syndrome
baby more than mg/dl (IGT, IFG, History of
4.000g • Unhealthy Diet Coronary Artery
• History of low birth • Limited Physical Disease , stroke
weight <2.500g Activity and/or PAD)

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Slide 17

Step 2: Conduct 1st Blood Test

Clinical Test
(+) Classic (-) Classical
Symptoms Symptoms

FBG ≥126 <126 FBG ≥126 100-125 <100

or or
RBG ≥200 <200 RBG ≥200 140-199 <140

Repeat FBG or RBG

Repeat

2 Hour
Post Fasting
loading Plasma
Plasma Glucose
Glucose

Diabetes Mellitus IGT IFG Normal

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Slide 18

Step 3: Conduct 2nd Blood Test (if required)

and Establish Diagnosis

Clinical Test
(+) Classic (-) Classical
Symptoms Symptoms

FBG ≥126 <126 FBG ≥126 100-125 <100

or or
RBG ≥200 <200 RBG ≥200 140-199 <140

Repeat FBG or RBG

2 Hour
Post
≥126 <126 loading Fasting
PG Plasma
Glucose
≥200 <200

PPG ≥200 140-199 100-125

Diabetes Mellitus IGT IFG Normal

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Slide 19

Step 4: Inform Patient and Initiate Treatment

Diabetes Mellitus IGT IFG

• Education • Education
• Evaluation of Nutritional Status • Food Regulation
• Evaluation of Diabetes • Physical Exercise
Complications • Ideal Body Weight
• Evaluation of Required Food • OADs are unnecessary
Regulation at this stage
• Decision on medicines

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Slide 20

What is good glycemic control?

• Overall aim to achieve glucose levels as close to normal as

possible
• Minimise development and progression of microvascular
and macrovascular complications

ADA1 FPG HbA1c PPG

<130 mg/dL < 7.0% <180 mg/dL

IDF2 FPG HbA1c PPG

<110 mg/dl < 6.5% <145 mg/dL

PERKENI3 FPG HbA1c PPG

<100 mg/dl < 7% <140 mg/dl

1. American Diabetes Association Diabetes Care 2009;32 (Suppl 1):S1-S97

2. IDF Clinical Guidelines Task Force. International Diabetes Federation 2005. 3. PERKENI 2011 Konsensus .
 Slide 21

Type 2 Diabetes Treatment Algorithm

Updated PERKENI

Diabetes STEP 1 STEP 2 STEP 3

Healthy life style Healthy life style

+
Mono therapy Healthy life style
Note:
+ Healthy life style
1. Therapy failed if
target of HbA1c < 2 OAD Combination +
7% is not achieved
Combination 2 OAD
within 2-3 months Alternative option, if :
for each step +
• No insulin is available
2. In case of no • The patient is objecting insulin Basal insulin
HbA1c test, the • Blood glucose is still not optimally
use of blood controlled
glucose level is
also permitted.
Average blood Healthy life style
Insulin
glucose level for a +
Intensification*
few BG test in one
day can be 3 OAD Combination
converted to
HbA1c (ref: ADA
2010)
*Intensive Insulin: use of basal insulin together with insulin prandial
 Slide 22

HbA1c correlation with blood glucose level

The relationship between A1C and eAG is described by the formula 28.7 X
A1C – 46.7 = eAG

David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, David Schoenfeld, and Robert J. Heine, for the A1c-Derived
Average Glucose (ADAG) Study Group. Diabetes Care 2008
 Slide 23

Risk of complications increases

as Hb1Ac increases
Blood glucose must be controlled
80

60 Microvascular disease
Incidence per 1.000
patient-years

40 Myocardial infarction

20

0
5 6 7 8 9 10 11 Mean HbA1c (%)
97 126 154 183 212 240 269 Mean mg/dl

Adjusted for age, sex, and ethnic group. The relationship between A1C and mg/dl is described
by the formula 28.7 X A1C – 46.7 = mg/dl.

Stratton IM et al. BMJ 2000;321:405–12

 Slide 24

The benefits of good blood glucose control are

clear

Myocardial
Good control is infarction
≤ 7.0% HbA1c
-14%
HbA1c measures
the average
blood glucose Microvascular
level over the HbA1c complications
last three
-1% -37%
months

Deaths related
to diabetes

-21%
Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM
et al. BMJ. 2000;321(7258):405-412.
 UKPDS: Observational data for a
1% decrease in HbA1c
Any Diabetes- All Peripheral
diab-related related cause Myocardial vascular MicrovascularCataract
endpoint death mortality infarction Stroke disease* disease extraction
0
Percentage reduction in relative risk
corresponding to a 1% fall in HbA1c

–5
21% 21% 14% 14% 12% 43% 37% 19%
–10
–15
–20
†
† ‡
–25 †
†
–30 †

–35
–40
†
–45
*Lower extremity amputation or fatal
–50 PVD
†P < 0.0001; ‡P = 0.035
–55 †
Error bars = 95% CIs
Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000;321:405–412.
 Effect of diet on insulin resistance
Insulin resistance (mean HOMA-IR)*

Quintile 1Quintile 2Quintile 3Quintile 4Quintile 5 P for trend

Dietary fibre
( IR) 7.0 6.7 6.7 6.7 6.4 < 0.001

Cereal fibre
6.8 6.9 6.8 6.6 6.5 0.02
( IR)

Fruit fibre
7.0 6.8 6.8 6.6 6.5 < 0.001
( IR)
Whole grains
( IR) 6.8 6.9 6.7 6.6 6.6 0.05

Glycaemic index
( IR) 6.4 6.7 6.8 6.8 7.0 < 0.001

Glycaemic load
( IR) 6.7 6.5 6.7 6.8 7.0 0.03

Framingham Offspring Cohort. *Insulin resistance measured as multivariate adjusted

geometric mean homeostasis model assessment (HOMA-IR) across quintiles of
carbohydrate-related dietary factors
Adapted from McKeown NM, et al. Diabetes Care 2004;27:538–546.
 Aerobic exercise
improves insulin sensitivity

*
Insulin sensitivity as measured by

200 Pre-training
Post-training
glucose clamp (mg/m2.min)

150

100

50 †

0 Total body glucose uptake Hepatic glucose production

Error bars = SE
n = 7, moderately obese patients following a 6-week exercise training programme
*P < 0.01 vs. pre-training; †P < 0.05 vs. pre-training

Adapted from DeFronzo RA, et al. Diabetes 1987; 36:1379–1385.

 Short-term weight loss improves
insulin sensitivity
Total glucose disposal during insulin clamp

45 *

40
35
(mol/kg LBM/min)

30
25
20
15
10
5
0
Before weight loss After weight loss

Subjects received a 6-week very low calorie diet n = 12; BMI at baseline 33.4 ± 1.1 kg/m2
*P < 0.05 compared with before weight loss Error bars = SE

Adapted from Franssila-Kallunki, et al. Am J Clin Nutr 1992;55:356–361.

 Oral Antidiabetic Agents

Effects on
Effects on insulin Reduction of
insulin action secretion HbA1C

Sulfonylurea 0/+ ++++ 1% to 2%

Glinides 0 ++ 0.9 to 1.7%

Biguanides ++++ 0 1% to 2%

0.5% to
Glitazones +++ 0
1.3%
Penghambat enzim
 glucosidase
0 0 0.5% to 1%

Data from Henry. Endocrinol Metab Clin. 1997;26:553-573 - Gitlin, et al. Ann Intern Med. 1998;129:36-38 - Neuschwander-Tetri, et al. Ann Intern Med. 1998;129:38-41
Medical Management of Type 2 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 1998:1-139 - Fonseca, et al. J Clin Endocrinol Metab. 1998;83:3169-3176
Data from Bell & Hadden. Endocrinol Metab Clin. 1997;26:523-537 - De Fronzo, et al. N Engl J Med. 1995;333:541-549 - Bailey & Turner. N Engl J Med. 1996;334:574-579
Medical Management of Type 2 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 1998:1-139 - Goldberg, et al. Diabetes Care 21:1897-1903
 Slide 30

Practical Monitoring Scheme

Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan
Diabetes Melitus Terpadu. 2009
 Slide 31

Practical Monitoring Scheme Cont…

Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan
Diabetes Melitus Terpadu. 2009
 Slide 32

Individualized Treatment based on several criteria

to control blood glucose

Inzucci SE, et al. Diabetologia. 2012

Majority of patients with type 2 diabetes
remain far above glycaemic goals

10.1% have HbA1c > 10%2

10.0

20.2% have HbA1c > 9%1

9.0

37.2% have HbA1c > 8%1

8.0
63.0% of patients
with type 2 diabetes 7.0 ADA target (< 7%)3
have HbA1c > 7.0%1*
AACE/ACE target (≤ 6.5%)4
6.0

HbA1c

AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; ADA = American Diabetes Association
* Adapted from Saydah SH, et al. JAMA. 2004;291:335-342.
1. Saydah SH, et al. JAMA. 2004;291:335–342; 2. Oluwatowoju I, et al. Diabet Med. 2010;27:354–359; 3. ADA. Diabetes Care. 2003;26:S33–S50; 4.
AACE/ACE. Endocr Pract. 2009;15:540–559.

Early Detection and
Standardized Diabetes Management
Summary
• Diabetes is a progressive disease
that must be treated in order to avoid
long-term complications
• Good glycemic control according to
PERKENI is:
• HbA1c <7%
• FPG: <100 mg/dl
• PPG: <140 mg/dl
• Patient treatment need to be
individualized according to the
characteristics of each particular
patients
Slide 34
Main Learning Points
• Understand the importance of
treating diabetes and reaching
individual targets to avoid
complications
• Understand the process from
screening to diagnosis and the
associated national guidelines
• Understand the reason and
need for routine follow-up and
intensify treatment on diabetes
via blood glucose- and HbA1c
monitoring
Assalamu ’alaikum