Slide 1

Lecture:
T2DM : PATHOGENESIS, CLASSIFICATION,
TREATMENT
 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
 Normoglycemia
Beta cell
produces Muscle and fat
insulin
Islet

Glucose Homeostasis

Liver

Alpha cell
produces
glucagon FASTING INPUT NUTRISI

NORMAL 5
 Normoglycemia
Hyperglycemia
Beta cell
produces Muscle and fat
insulin
Islet

Glucose Homeostasis

Liver

Alpha cell
produces
glucagon INPUT NUTRISI

TYPE 1 DM 6
 Diminished
insulin
Beta cell
Normoglycemia
Hyperglycemia
produces Muscle and fat
insulin

Insulin resistance
(decreased glucose uptake)
Glucose Homeostasis

Liver
Alpha cell
produces
glucagon Excess glucose output
INPUT NUTRISI

TYPE 2 DM 7
 Slide 8

Type 2 diabetes is a progressive disease

HOMA: homeostasis model assessment

Lebovitz. Diabetes Reviews 1999;7:13953 (data are from the UKPDS population: UKPDS 16.
Diabetes 1995;44:124958)
 Slide 9

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 10

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 11

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 12

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 13

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 14

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 15

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 16

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 17

The Importance of treating Type 2 Diabetes

Type 2 diabetes is a progressive disease

Postprandial glucose

Diagnosis

Glucose Fasting glucose

Insulin Insulin resistance

Inadequate
-cell function Insulin secretion
Microvascular changes
Macrovascular changes

Prediabetes
NGT Diabetes
(IFG/IGT)

Adapted from Type 2 Diabetes BASICS. International Diabetes Center 2000

 Slide 18

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 19

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 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

Practical Monitoring Scheme

Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan
Diabetes Melitus Terpadu. 2009
 Slide 22

Practical Monitoring Scheme Cont

Source: Konsensus Pengelolaan dan Pencegahan DMT2 di Indonesia. PERKENI. 2011. Diabetes Care 2012. Penatalaksanaan
Diabetes Melitus Terpadu. 2009
 Slide 23

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: 239244

Slide 24
 Slide 25

Factors to Consider when Choosing an Anti-

hyperglycemic agent

Effectiveness in lowering glucose

Extraglycaemic effects that may reduce long-term complications

Safety profile

Tolerability

Cost

Effect on body weight

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Slide 26

OADs a quick summary of the different mechanism of

actions

Incretins :GLP-1 analogue(exen-

atide)/DPP-4 inhibitors Improves Thiazolidinediones
glucose-dependent insulin Increase glucose uptake in
secretion from pancreatic -cells, skeletal muscle and
suppresses glucagon secretion decrease lipolysis in
from -cells, slows gastric emptying adipose tissue

Meglitinides
Increase insulin secretion from
pancreatic -cells

Sulfonylureas
Increase insulin secretion
from pancreatic -cells
-Glucosidase inhibitors
Delay intestinal carbohydrate
absorption
GLP = glucagon-like peptide.
Adapted from Cheng and Fantus. CMAJ. 2005;172:213226.
 Slide 27

EAT FOR LIFE OR LIFE FOR EAT ???

2.5 million years 50 years