Slide 1

Early Detection, Diagnosis and

Management of Diabetes
 Slide 2

Some Definitions before we start…

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)

IFT Impaired Fasting Glucose (Gula Darah Puasa Terganggu)

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

HbA1c
period
 Slide 3

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 4

Difference between Type 1 and Type 2 Diabetes

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 Insulin Low or absent Normal, decreased or increased

Prevalence Less prevalent More prevalent, typically 90-95%

of all people with diabetes
 Slide 5

Type 2 diabetes is 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 6

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 7

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 8

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 9

4 Simple Steps from Screening to Diagnosis

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

4
Inform Patient and
Initiate treatment
 Slide 10

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 >250 • 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 11

Step 2: Conduct 1st Blood Test

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

FBG >126 <126 FBG >126 100-125 <100

RBG >200 <200 RBG >200 140-199 <140

Repeat FBG or RBG

2 Hour Post loading

Plasma Glucose

Diabetes Mellitus IGT IFG Normal

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Slide 12

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

RBG >200 <200 RBG >200 140-199 <140

Repeat FBG or RBG

>126 <126 2 Hour Post loading

Plasma Glucose
>200 <200

PPG >200 140-199 <140

Diabetes Mellitus IGT IFG Normal

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Slide 13

Step 4: Inform Patient and Initiate Treatment

Diabetes Mellitus IGT IFG

• Evaluation of Nutritional Status • Education

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

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Slide 14

Cut-points: Diabetes, IGT and IFG

mg/dL
Fasting Plasma Glucose (FPG)

Diabetes

126

IFG (Impaired
Fasting Glucose

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

140 200 mg/dL

2-hour Plasma
Glucose (PPG)
 Slide 15

Diagnosis of Type 2 Diabetes

KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

1. Symptoms of Diabetes
• Random plasma glucose concentration > 200 mg/dl

Or
2. Fasting Plasma Glucose:
• FBG > 126 mg/dl. No calorie intake for at least 8 hours
• Need to be repeated twice in two independent days

Or
3. 2-hour post-OGTT
• OGTT > 200 mg/dl. 75 g. of glucose dissolved in water
 Slide 16

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

 Slide 17

Treatment therapies for Type 2 diabetes

When and How to start treatment

START TREATMENT OAD TREATMENT START INSULIN INSULIN INTENSIFICATION

Basal
+-other OAD Basal +
Lifestyle + Basal Premix
or GLP-1 Bolus
Metformin Insulin Insulin
agonists Insulin

HbA1c ≥7.0%

Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.

 Slide 18

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 19

Risk of Complications increases as Hb1Ac

increases and that’s why diabetes must be treated

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 20

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.
 Slide 21

ABCD Strategy to guide Diabetes Treatment

ABCD Strategy

Age (older) • Increased risk for hypoglycemia & comorbidities

• Less stringent therapy
• Reduce the use of kidney-excreted drugs if possible

Body Weight • BW neutral (gliptins, acarbose, DPPIV inhibitors,

long-acting insulin analogues),
• BW gain (human insulin, sulphonylureas, TZDs)
• BW loss (metformin, GLP1 analogues)

Complications • Major macro- & microvascular complication  less

stringent
• Consider renal or heart failure

Duration of Disease • Strict glycemic control at the early period of the

disease  better prevention of macro &
microvascular complications

Source: Diabetes Metab Res Rev 2010; 26: 239–244

 Slide 22

Individualized Treatment based on several criteria

to control blood glucose

Inzucci SE, et al. Diabetologia. 2012

 Slide 23

Practical Initiation of Diet Programs for diabetes

patients
Food Mapping Systems
Food Mapping System can be used for patient education to increase patient
compliance with diet scheme

Beras Merah
Nasi Putih Nasi Goreng
Kukus

Ayam Goreng
Ayam Bakar Ayam Goreng
Tepung

Ikan Bakar /
Ikan Goreng Udang Goreng
Kukus

Dim Sum
Sayur Kukus Kukus Dim Sum
Goreng
 Slide 24

Practical Initiation of Diet Programs for diabetes

patients
Healthy Plate Models
Portion Control Plate was effective in inducing weight loss and decreased use
of hypoglycemic medications in obese patients with type 2 diabetes mellitus

Protein
Carbo-
hydrate /
Starch
Vegetables
Carbo-
hydrate / Vegetables
Protein Starch

T-shaped plate Y-shaped plate

model to loose model to
weight maintain weight

Pedersen DE et al. Arch Intern Med. 2007; 167

 Slide 25

Practical Initiation of Exercise Programs for diabetes

patients
CRIPE Pricnciple

CRIPE: Continuous, Rhytmic, Interval, Progressive, Endurance

• Exercises should be done continuously without

Continuous
rest (e.g. 30 minutes of jogging without rest)

• Choose more rhythmical sports where regular

Rhythmic contraction and relaxation are possible (e.g.
walking, jogging, running and swimming)

• Exercises with both quick and slower actions

Interval
(e.g. running followed by jogging)

• Increase intensity according to abilities (heart

Progressive
rate target: 75-85% from maximum heart rate)

• Exercise for endurance to improve

Endurance cardiorespiratory abilities (e.g. walking,
jogging, swimming, cycling)
 Slide 26

Properties of available glucose-lowering agents

that may guide treatment choice in Type 2
Diabetes
Class Compounds(s) Cellular Primary Advantages Disadvantages
mechanism Physiological
action(s)
Biguanides Metformin Activates Hepatic Glucose Extensive Gastrointestinal side
AMP-kinase Production  Experience effects
No weight gain Lactic acidosis risk
No hypoglycemia (rare)
Likely CVD Events  Vitamin B12
deficiency
Multiple
contraindications:
CKD, acidosis,
hypoxia,
dehydration etc.
Sulfonylureas Glibenclamide / Closes KATP Insulin secretion  Extensive Hypoglycemia
glyburide channels on experience Weight gain
Glipizide beta cell Microvascular Risk  Blunts myocardial
Gliclazide plasme (UKPDS) ischaemic
Glimepiride membranes preconditioning ?
Low durability
Meglitinides Repaglinide Closes KATP Insulin secretion  Postprandial Hypoglycemia
Nateglinide channels on glucose excursions  Weight gain
beta cell Dosing flexibility Blunts myocardial
plasme ischaemic
membranes preconditioning ?
Frequent dosing
schedule

Inzucci SE, et al. Diabetologia. 2012

 Slide 27

Properties of available glucose-lowering agents

that may guide treatment choice in Type 2
Diabetes cont.
Class Compounds(s) Cellular Primary Advantages Disadvantages
mechanism Physiological
action(s)
Thiazolidinedi Pioglitazone Activates the Insulin Sensitivity  No hypoglycemia Weight Gain
ones Rosiglitazone nuclear Durability Oedema / Heart
transcription HDL-C  Failure
factor PPAR-y Triacylglycerols  Bone Fractures
(pioglitazone) LDL-C 
CVD Events ? (rosiglitazone)
Mn  (meta-
analyses,
rosiglitazone)
Bladder Cancer ?
(pioglitazone)
a-Glucosidase Acarbose Inhibits Slows intestinal No hypoglycemia Modest HbA1c
Inhibitors Migitol intestinal a- carbohydrate Postprandial efficacy
Voglibose glucosidase digestions / glucose Gastrointestinal side
absorption excursions  effects (flatulence,
CVD Events  diarrhoea)
Non-systemic Frequent dosing
schedule
DPP-4 Sitagliptin Inhibits DPP-4 Insulin secretion  No hypoglycemia Modest HbA1c
Inhibitors Vildagliptin activity, (glucose-dependent) Well tolerated efficacy
Saxagliptin increasing Glucagon secretion  Urticardia/Angio-
Linagliptin postprandial (glucose-dependent) oedema
Alogliptin active incretin Pancreatitis ?
(GLP-1, GIP)
concentrations

Inzucci SE, et al. Diabetologia. 2012

 Slide 28

Properties of available glucose-lowering agents

that may guide treatment choice in Type 2
Diabetes cont.
Class Compounds(s) Cellular Primary Advantages Disadvantages
mechanism Physiological
action(s)
GLP-1 Exenatide Activates GLP- Insulin secretion  No hypoglycemia Gastrointestinal side
Receptor Liraglutide 1 receptors (glucose-dependent) Weight reduction effects (nausea /
Agents Glucagon secretion  Improved beta vomiting)
(glucose-dependent) cell mass / Acute pancreatitis ?
Slows gastric function ? C cell hyperplasia /
emptying Cardiovascular medullary thyroid
Satiety  protective tumours
actions ? Injectable
Training
Requirements

Insulin Human NPH Activates Glucose disposal  Universally Hypoglycemia

Human Regular insulin Hepatic glucose effective Weight gain
Lispro receptors production  Theoretically Mitogenic effects ?
Aspart unlimited Injectable
Gluisine efficacy Training
Glargine Microvascular Requirements
Determir Risk  (UKPDS) ‘Stigma’ for patients
Pre-mixed
(several types)

Inzucci SE, et al. Diabetologia. 2012