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DIABETES MELLITUS

Classification and Diagnosis


Djoko Wahono Soeatmadji

Division of Diabetes and Endocrinology,


Department of Medicine, Dr. Saiful Anwar
Hospital
Medical Faculty, Brawijaya University
Malang

CLASSIFICATION

Diabetes Mellitus
A group of metabolic diseases
Characterized by hyperglycemia
Resulting from defects in insulin secretion , insulin
action, or both

Classification of Diabetes and Allied


Categories of Glucose Intolerance
(WHO, 1985; PERKENI, 1993)

A. Clinical Classification
1. Diabetes Mellitus
IDDM
NIDDM Obese
Non-obese
Secondary Diabetes
MRDM
2. Gestational Diabetes
3. Impaired Glucose Tolerance
B. Statistical Risk Classification

ETIOLOGIC CLASSIFIACTION
I.

Type 1 (-cell destruction leading to absolut deficiency)


A. Immune mediated
B. Idiopathic

II. Type 2
Predominantly insulin resistance + relative insulin
deficiency
Predominantly secretory defect + insulin resistance
III. Other specific types
IV. Gestasional diabetes mellitus
Type 1 + Type 2 = 70 95% of diabetes
The Expert Committee,1997

Controversies in Classification
=
Controversies in Management

Type 1 diabetes = Insulin dependent DM


(Dependency on insulin for life)
Type 2 diabetes = Non Insulin Dependent DM
= Not requiring insulin ??

Clinical Features
Age at onset
Onset
Weight
Spontaneous ketosis
Chronic complication
Epidemiology
Prevalence
Sex
Insulin (C-petide) level
Genetics
Concordance in twins
HLA asoociation
Pathology
Islet cell mass
Insulitis at onset
Immunology
Associated with other endocrinopathy
Anti-islet ell immunity
Humoral
Cell mediatedl

Type 1

Type 2

Usually < 30
Acute
Non obese
Common
(++)

Usually > 40
Insidious
Obese
Rare
(++)

0,5%
Male prepdominancece
/ (-)

2%
Female predominance
/N/

40%
(+) (DR3/DR4)

70 90%
(-)

Severely reduced
Present

Moderately reduced
?

Frequent

Frequent

60 80% at onset
35 50% at onset

5 20%
< 5%

Many diabetic individuals do not easily fit


into a single class

10 20 % of subjects with NIDDM show (+)


ICA and/or anti GAD65Abs

Type 1 Diabetes
(-cell destruction leading to
absolut deficiency)

100
80
60
40
20

II

III

IV

Hypothetical stages and loss of beta cells in an individual progressing to


type 1A diabetes (Eisenbarth. N Eng J Med 1986; 314: 1360-1368) (16)

Clinical Subtypes of Type 1 Diabetes

Slowly progressive Type 1 (SP type 1) diabetes


(Diabetes Care 16: 780 788, 1993)
1. ICA and/or GAD ab (+)
2. Non-insulin dependent at onset
3. Non-insulin requiring period more than 13 months
after the onset or diagnosis
Regular
Fulminant Type 1 diabetes ( N Eng J Med 342: 301,
2000)
1. Ketosis/ketoasidosis within a week after the onset of
hyperglycemic symptoms
2. Serum C-peptide < 0.3 ng/ml (fasting) and
< 0.5 ng/ml (after meal or iv.
Glucagon)
3. AIC < 5.5% on first visit

The destruction of -cells and the appearance of type 1 diabetes according to


the age of onset and the putative pathogenetic mechanism (Paolo Pozzilli and
Umberto Di Mario : Diabetes Care 2001 24: 1460-1467)

Natural History of Type 1 DM


-cell function
100%

GAD65 antibodies
ICA antibodies
IAA antibodies
IA2 and IA-2
Abnormal -cell function test
Tolerance reestablished
T-cell tests (+)

T-cell tests ()

Clinical onset

5-10%

Time (months to years)

(Mehta,1996)

Type 2 Diabetes

Pathogenesis of Type 2 Diabetes

Insulin resistance
?

vs
-cell dysfunction

Pathogenesis of Type 2 Diabetes


Impaired -Cell function
Enzymatic defects
Reduced mass
Premature aging

Sine qua none


(and sufficients )

Genetic

Insulin resistance

Obesity (Genetic ?)
Inactivity
Hyperglycemia
Hyperinsulinemia
Drugs

Secondary and
facilitative

Environmental

Insulin Resistance
Normal -cells

Abnormal -cells

Compensatory
Hyperinsulinemia

Inadequate Insulin
Response

Isulin Resistance
Syndrome

Type 2 Diabetes

Hypertension
Dyslipidemia Obesity

CVD

Retinopathy
Neuropathy
Nephropaty

Hidden dangers of the


metabolic syndrome iceberg

Hyperglycemia
Hypertension
Atherogenic
dyslipidemia

Insulin resistance
+
Hyperinsulinaemia

Abdominal obesity

Impaired
fibrinolysis

Pro-inflammatory
profile

Natural History of Type 2


Diabetes
Glucose
350
300
mg/dL 250
200
150
100

Post-prandial glucose
Fasting glucose

Relative to normal

(%)

Insulin resistance
250
200
150
100
50 At risk for Beta-cell dysfunction
Insulin level
diabetes
0
30
0
5
10 15 20 25
-10 -5

Years
R.M. Bergenstal, International Diabetes Center

Disdorders of Gycemia

Etiologic types and Stages


Hyperglycemia

Stages Normoglycemia
Types

Type 1
Type 2
Other
types
Gestational
diabetes

Normal glucose
regulation

Diabetes Mellitus

IGT or

Insulin requiring

IFG

No

For control

Insulin requirement

+++

For survival

+++++

Many diabetic individuals do not easily fit


into a single class

10 20 % of subjects with NIDDM show (+)


ICA and/or anti GAD65Abs

F
A
M
I
L
Y
S
T
U
D
Y

F
E
N
O
T
Y
P
E
VS
G
E
N
O
T
Y
P
E

CASE STUDY
A 56 y-old Javanese man presented 7 years
ago with type 2 DM; BMI was 22 kg/m2. He
was taking glybenclamide 2.5 mg b.i.d., with
HbA1c level of 7.8%. Her diet is high in rice
and other complex cbh.
During the subsequent 6 year, his HbA1c
level rose to 10% and body weight decreased
12 kg despite increasing glybenclamide to 10
mg twice daily and combination with
metformin 500 mg three times daily.

Diagnosis: Type 2 (?) diabetes with secondary


failure of two combination of oral agent

CASE
Female 56 y.o, diagnosed as NIDDM 7 years ago, BMI 22
kg/m2, addhere to diet, routine exercise, Tx. Glibenclamide
15 mg/day + metformin 1500 kg, Blood sugar : fasting 230
mg ; 2 h pp 324 mg%
Past medical history : good controlled with 2 mg
glibenclamide but gradually needs higher dose and finally
needs combined oral hypoglycemic drugs

DIAGNOSIS

Criteria Diagnosis of Diabetes Mellitus


1.. Symptoms (+) & casual plasma glucose > 200 mg%
(11.1 mmol/L)
or
2. FPG 126 mg% (7.0 mmol/L)
or
3. 2hPG 200 mg/dl during OGTT

(The Expoert Committee,1997)

Prevalence of retinopathy by
deciles of the distribution of FPG,
2-h PG, and HbA1c

126
200

Casual is defined as any time of day without


regard to time since last meal.
.

The classic symptoms of diabetes include


polyuria, polydipsia, and unexplained weight
loss
Glucose load described by WHO (75 g
anhydrous glucose dissolved in water)
In the absence of unequivocal hyperglycema
with acute metabolic decompensation, these
criteria should be confirmed by repeat
testing on a different day
(The Expoert Committee,1997)

Symptoms and signs of diabetes

Linked to osmotic diuresis


Polyuria
Increased thirst and polydipsia
Blurred vision
Drowsiness, dehydration

Linked to lacked of insulin


Hyperglyceaemia with massive glucosuria
Extreme fatigue
Muscle wasting
Weight loss
Ketosis, ketoasidosis

Symtoms of decreased resistance to infections


Skin infection
Genital pruritus

Linked to caloric depletion


Increased appetite
Weight loss

Slama, 2003

CATEGORIES WHEN THE


OGTT IS USED
Glucose load described by WHO (75 g
anhydrous glucose dissolved in water)

Categories of 2 hours after glucose


loading (2 hPG) values
Normal: 2 hPG 140 mg%
IGT

: 2 hPG 140 mg% and 200 mg%

DM

: 2 hPG 200 mg%*

Provisional diagnosis of diabetes (the diagnosis must be confirmed, as


described above).

The Expert Committee,1997

Categories of fasting plasma


glucose values
Normal: <100 mg/dl (6.1 mmol/l)
IFG
: 100 - 125 mg/dl (6.1 - mmol/l 7.0 mmol/l)
Diabetes: 126 mg/dl (7.0 mmol/l)*

ADA, 2004

Diagnostic Criteria for epidemiological


studies estimates of prevalence and
incidence should be based on FPG 126
mg%

The Expert Committee,1997

CRITERIA FOR TESTING FOR DIABETES


(SCREENING)
1. All individuals at age 45 - repeat every 3 years
2. Considered at a younger age or be carried more
frequently :
- Obese > 120% or BMI 27kg/m2
- First degree relative with diabetes (+)
- Members of a high-risk ethnic population
- Delivered a baby weighing 9 lb (Indonesia ?) or
have been diagnosed with GDM
- Hypertensive ( 140/90)
- HDL-chol < 35 mg% and/or TG > 250 mg%
- On previous testing had IGT or IFG

The Low-risk Group


Age < 25
Normal weight
No family history of diabetes
Not members of and ethnic/racial group with a high
prevalence of diabetes

The Expert Committee,1997

GESTATIONAL DIABETES

SCREENING AND DIAGNOSTIC SCHEME


FOR GDM (24 28 week of gestation)
Plasma glucose 50-g
screening test

100-g
diagnostic test

Fasting
1-h
2-h
3-h

105
190
165
145

140 mg/dl
-

mg/dl
mg/dl
mg/dl
mg/dl

The Expert Committee,1997

Diagnosis of GDM with a 100-g or 75-g


glucose load
mg/dl

mmol/l

100-g Glucose load


Fasting
1-h
2-h
3-h

95
180
155
140

5.3
10.0
8.6
7.8

75-g Glucose load


Fasting
1-h
2-h

95
180
155

5.3
10.0
8.6

Two or more of the venous plasma concentrations must be met or exceeded


for a positive diagnosis

Hospital Admission Guidelines For


Diabetes Mellitus
Life-threatening acute metabolic complications of
diabetes
Newly diagnosis diabetes in children and adolescents
Substantial poor metabolic control (Etiology of control
problems ? Modification of therapy ?)
Severe chronic complications that require intensive
treatment
Severe condition unrelated to diabetes that
significantly affects its control or complicated by
diabetes
Uncontrolled or newly discovered insulin-requiring
diabetes during pregnancy
Institution of intensive insulin regimens