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DIABETES MELLITUS IN

CHILDREN
A S R I P U R WA N T I
DIVISION OF ENDOCRINOLOGY
D E PA R T M E N T O F P E D I AT R I C
DIPONEGORO UNIVERSITY
D R . K A R I A D I H O S P I TA L
SEMARANG

CURRICULLUM VITAE
Nama Lengkap
Tempat/TanggalLahir

S1
Sp.1
S2
Sp.2
S3

1
2
3
4

DR. dr. Asri Purwanti SpA(K), MPd


:

Yogyakarta, 06-11-1955

RIWAYAT PENDIDIKAN
FK Universitas Diponegoro (S1)
Spesialis Anak FK UNDIP
Magister Bimbingan Konseling Universitas Negeri Semarang
Kolegium Kesehatan Anak Indonesia /
Pediatric Endocrinologi Konsultan (Sp2)
S3 univesitas Negeri Semarang

1982 Kedokteran
1994 Ilmu Kesehatan Anak
2002
2007

SpA(K)

2014 DR

Pendidikan Lanjutan Klinik di Klinik Tumbuh Kembang Khusus dan Genetika 1995
Klinis (dismorfologi) RSAB Harapan Kita Tempat di Jakarta
Kursus Genetika Klinis NUH Singapore Tempat di Singapore
1996
Orientasi di Sub Bidang Endokrinologi Anak FKUI Tempat di Jakarta
2005
Fellowship APPES Pediatric Endocrinologi Tempat di Wuhan, Cina
2005

No
Dari
1 Mendiknas
2 Presiden RI
3 Presiden RI

Penghargaan
Mahasiswa Teladan Universitas Diponegoro
Satya Lencana KARYA SATYA 20 tahun
Satya Lencana KARYA SATYA 30 tahun

Tahun
1981
2004
2013

CURRICULLUM VITAE
Tahun
2 Januari 1996
1996- Sekarang
2008- Sekarang
2008 - sekarang
2005- sekarang
2005 - sekarang
2002- Sekarang
1996-1999
1999-2002
2002-sekarang
1998-2001
2002- sekarang
2008-sekarang
2009-sekarang
2008-sekarang
1997-sekarang
1997-sekarang
2008-sekarang

Riwayat Pekerjaan
Dokter Spesialis Anak di RS dr. Kariadi
SK Pengajar Luar Biasa FK UNDIP di Bagian Ilmu Kesehatan Anak
SK Pengajar S2 Biomedik FK UNDIP
SK pengajar S2 Genetik Konseling / Biomedik
SK Pengajar SP.1 PPDS.1.Kesehatan Anak. FK UNDIP RSDK
SK pengajar S2 (MKIA) Magister Kesehatan Ibu dan Anak UNDIP
Ketua POKJA KIPI JATENG
Sekretaris IDAI JATENG
Wakil ketua IDAI JATENG
Anggota IDAI JATENG
Seksi Organisasi IDI cab Semarang
Anggota Satgas Imunisasi Nasional
Anggota MKEK IDI Jateng
Sekertaris SMF Bagian Anak FK UNDIP / RSUP. Dr Kariadi
SEmarang
Tim GAKI FK UNDIP
Tim Pelayanan Genetik RS Kariadi FK UNDIP
Tim DSD (Disosder of sexual Development)/
Tim Penyesuaian Kelamin RS Kariadi FK UNDIP
Tim Stem cell RS Kariadi FK UNDIP

OUTLINE PRESENTATION
Epidemiology
Classification

Diagnosis
Etiology
Patogenesis

Clinical Manifestation
Complication

EPIDEMIOLOGY
In 2007, the total child population of the world
(014 yr) was estimated to be 1.8 billion, of whom
0.02% had diabetes. (ISPAD 2014)
Every years the type 1 DM occurs in 80 000
children (Craig et al. 2014)
Every year increasing type 1 DM in adults in 3%
and in 4.8% in children (EURODIAB)
Type 2 DM is becoming higher prevalence In
geographical areas where T1DM occurs with
Lower incidence, there is a higher rate of diabetic
ketoacidosis (DKA)

DEFINITION OF DIABETES MELLITUS


The term diabetes mellitus describes
a complex metabolic disorder characterized by
chronic hyperglycemia
resulting from defects in insulin secretion,
insulin action, or both.

ETIOLOGIC CLASSIFICATION
I. Type 1 diabetes
(b-cell destruction, usually leading to absolute insulin deficiency)
A. Immune mediated
B. Idiopathic

II. Type 2 diabetes


(may range from predominantly insulin resistance with relative insulin
deficiency to a predominantly secretory defect with insulin resistance)

III. Other specific types


A. Genetic defects of b-cell functions
B. Genetic defects in insulin action
C. Diseases of the exocrine pancreas
D. Endocrinopathies
E. Drug or chemical induced
F. Infections
G. Uncommon forms of immune-mediated diabetes .
H. Other genetic syndromes sometimes associated with diabetes

IV. Gestational diabetes mellitus

DIAGNOSIS OF DIABETES
Diabetes in children --. Most characteristic symptoms
polyuria, polydipsia, blurring of vision, and weight loss, in
association with glycosuria and ketonuria.
most severe form, ketoacidosis, or rarely a non-ketotic
hyperosmolar state, stupor, coma, death.
hyperglycaemia incidentally-or under conditions of acute
infective, traumatic, circulatory, or other stress may be
transitory and should not in itself be regarded as diagnostic
of diabetes.

The diagnosis of diabetes should not be based on a single


plasma glucose concentration. require continued
observation with fasting and/or 2-h postprandial blood
glucose levels and/or an oral glucose tolerance test (OGTT).

IMPAIRED GLUCOSE TOLERANCE (IGT) AND


IMPAIRED FASTING GLYCAEMIA (IFG)
IFG and IGT are INTERMEDIATE STAGES in the natural history of
disordered carbohydrate metabolism between normal glucose
homeostasis and diabetes (E ).
IFG is a measure of disturbed carbohydrate metabolism in the
basal state, while IGT is a dynamic measure of carbohydrate
intolerance after a standardized glucose load.

Patients with IFG and/or IGT - pre-diabetes, indicating the


relatively high risk for development of diabetes (A)
IFG and IGT associated with the METABOLIC SYNDROME (MS),
which includes obesity (especially abdominal or visceral
obesity), dyslipidaemia of the high-triglyceride and/or low-high
density lipoprotein (HDL) type, and hypertension.

CRITERIA FOR THE DIAGNOSIS OF DIABETES


A1C 6.5%
OR
Fasting plasma glucose (FPG)
126 mg/dL (7.0 mmol/L)
OR
2-h 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. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S9;


Table 2.1

Categories of Increased Risk for Diabetes


(Prediabetes)*
FPG 100125 mg/dL (5.66.9
mmol/L): IFG
OR

2-h plasma glucose in the 75-g OGTT


140199 mg/dL (7.811.0 mmol/L):
IGT
OR

A1C 5.76.4%
*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. 2. Classification and Diagnosis. Diabetes Care
2015;38(suppl 1):S10; Table 2.3

Clinical Characteristic of Type 1 and Type 2 DM

GENETICS:
Several alleles of HLA-DQB1 are
associated with an increased risk of
developing type 1 diabetes.
The locus also has the genetic name IDDM1
as it is the highest genetic risk for type 1
diabetes.
The strongest gene, IDDM1, is located in
the HLA Class II region on chromosome
6, at staining region 6p21.
Certain variants of this gene increase the
risk for decreased histocompatibility
characteristic of type 1.
Such variants include DRB1 0401, DRB1
0402 etc.

Race.
White people have a
greater risk for
developing type 1
diabetes than black,
Asian, or Hispanic
people.

Type 1 Diabetes Mellitus


(T1DM)

TYPE 1 DIABETES MELLITUS (T1DM)

Formerly called insulin-dependent diabetes mellitus (IDDM)


or juvenile diabetes

T1DM is characterized by low or absent levels of

endogenously produced insulin

The onset occurs predominantly in childhood, with median


age of 7-15 yr, but it may present at any age.

Indian data suggest an incidence of 10.5/100,000/yr .

India would have 79 million diabetes by 2030, the highest

for any country in the world.

PATHOGENESIS & NATURAL HISTORY


The natural history includes distinct
stages
1) Initiation of autoimmunity
2) Preclinical autoimmunity with progressive
loss of -cell function
3) Onset of clinical disease
4) Transient remission( Honeymoon
period)
5) Established disease
6) Development of complications

PRECLINICAL DIABETES
Preclinical diabetes (stages 13) refers to the months
or years preceding the clinical presentation of type
1 diabetes when islet antibodies can be detected as
markers of -cell autoimmunity :

Glutamic acid decarboxylase 65 autoantibodies (GAD)


Tyrosine phosphatase-like insulinoma antigen 2(IA2)
Islet cell antibody 512 (ICA512)
Insulin autoantibodies (IAA)
-cell-specific zinc transporter 8 autoantibodies( ZnT8)

MANAGEMENT THERAPY OF T1DM


Insulin

Exercise

Metabolic
control

Education

Diet

GOAL OF TREATMENT
Optimal metabolic control
Optimal growth and development
Prevent short and long term complication
Normal physchosocial function
Self management depends on their development

PURPOSE OF INSULIN THERAPY


Prevent and treat fasting and postprandial hyperglycemia
Permit appropriate utilization of glucose and other nutrients
by peripheral tissues
Suppress hepatic glucose production

Prevent acute complications of uncontrolled diabetes


Prevent long term complications of chronic diabetes

24

THE BASICS OF INSULIN: 4 TYPES


Rapid-acting insulin
Regular or short-acting insulin

Intermediate-acting insulin
Long-acting insulin

DIFFERENT TYPES OF INSULIN PREPARATIONS:


Type

Appearance

Onset (hr)

Peak (hr)

Duration (hr)

Insulin lispro

Clear

0.2-0.3

1-1.5

3-5

Insulin aspart

Clear

0.2-0.3

1-1.5

3-5

Insulin glulisin

Clear

0.2-0.4

1-2

3-5

Clear

0.5-1

2-3

6-8

Insulin zinc suspension


or Lente

Cloudy

1-2

8-10

20-24

NPH or isophane
Insulin

Cloudy

1-2

8-10

20-24

Clear

Glargine: 2-4
Detemir: 1-4

RAPID ACTING

SHORT ACTING
Regular (soluble)
insulin
INTERMEDIATE
ACTING

LONG ACTING
Insulin glargine and
Insulin detemir

_
_

Glargine: 24
Detemir: 20-24

INSULIN THERAPY in Diabetes Mellitus


Insulin Profiles schematic (duration)
ASAspart, Lispro (45 hr)
Plasma Insulin Levels

Regular (68 hr)


NPH (1216 hr)
Ultralente (~1620 hr )
Detemir (~20 hr)
Glargine (~22 hr)

6 8

10 12

Hours

14

16

18

20 22 24

DR. MASHFIQ - ENDOCRINE - BSMMU

27

INSULIN REGIMEN
MDI (multiple daily injection) Basal Bolus
CSII ( continouos subcutaneous insulin
infusion) Pump insulin
Premixed Insulin

Whatever insulin regimen is chosen, it must be supported by


comprehensive education appropriate for the age, maturity,
and individual needs of the child and family

1. INSULIN
Type of Insulin
Dose of insulin : Total daily dose in children at initial
treatment approximately 0,5-1unit/kg
Regimen of insulin
Injection site

Adjusment dose depends on blood glucose


monitoring,, diet, exercise, puberty , stress, illness

INJECTION SITE

MONITORING
Metabolic
target
Preprandial
Postpandrial

Urine
reduction
HbA1c

Very good

Good

Moderate

Poor

< 120
mg/dl
< 140

< 140

< 180

>180

< 200

< 240

>240

+-

>+

<7%

7 -7,9
%

8-9%

>10%

2. TARGET METABOLIK

GLYCEMIC TARGETS: GRADUATE WITH AGE


(CANADIAN DIABETES ASSOCIATION)
2013

Age

Target A1C

<6 years of age

<8.0%

6 to 12 years of age

7.5%

Adolescents

7.0%

ADVERSE EFFECTS OF INSULIN


Hypoglycemia
Lipoatrophy

Lipohypertrophy
Obesity
Insulin allergy

Insulin antibodies
Insulin induced edema

MONITORING KOMPLIKASI

3. NUTRITION

Smart CE, 2014

4. EXERCISE
Tailor insulin regimen to activity
Discuss the percentage reductions in insulin
before exercise
Any exercise is dangerous and should be
avoided if pre-exercise blood glucose levels
are high (> 14 mmol/L, 250 mg/dL)
with ketonuria / ketonemia (> 0.5 mmol/L).

EDUCATION
At the diagnosis : overview diabeter for family

Including :
- hyperglycaemia, hypoglycaemia
- the dos and donts life with diabetes

- Insulin (type, injection site, adverse effect etc)


- Blood glucose monitoring
- Glucose monitoring Target

SELF-CARE
Patients should be educated to practice self-care. This allows the
patient to assume responsibility and control of his / her own
diabetes management. Self-care should include:

Blood glucose monitoring


Body weight monitoring
Foot-care
Personal hygiene
Healthy lifestyle/diet or physical activity
Identify targets for control
Stopping smoking

FUTURE PROMISES

The cure for IDDM is successful islet cell transplantation,

which will be available in the near future.

Primary prevention by a vaccine or drug will be offered


to at risk subjects identified by genetic studies.

Gene modulation therapy for susceptible subjects is a


promising preventive measure.

TYPE 2 DIABETES MELLITUS

Differentiating between type 1 and type 2 diabetes


at diagnosis
Features suggesting the diagnosis of type 2 diabetes rather than
type 1 diabetes at diagnosis include :
Overweight or obesity
Age above 10
Strong family history of type 2 diabetes
Acanthosis nigricans
High-risk racial or ethnic group
Undetectable islet autoantibodies
Elevated C-peptide (since there is considerable overlap in insulin or
C-peptide measurements between type 1 and type 2 diabetes in the
first year after diagnosis)

RISK FACTORS FOR T2DM


Obesity (BMI 95th %ile for age and gender)
Member of a high-risk ethnic group
Family history of T2DM and/or exposure to
hyperglycemia in utero
Signs or symptoms of insulin resistance
Acanthosis nigricans
Hypertension
Dyslipidemia
Non alcoholic fatty liver disease (ALT > 3X ULN or fatty liver on
ultrasound
Polycystic ovarian syndrome

CLINICAL FEATURES AT DIAGNOSIS OF TYPE 2 DM


(T2DM)
Clinical feature

Proportion (%)

Asymptomatic

35%

Acanthosis nigricans

73%

Obesity

95%

Ketosis

44%

Diabetic ketoacidosis

10%

PCOS

12.1%

Dyslipidemia

44.8%

Hypertension

28.3%

ALT > 90 IU/L or FLD

22.2%

Micro-/macroalbuminuria

14.2%

Amed S et al. Diabetes Care 2010;33:786-791.

GOAL OF MANAGEMENT T2 DM
Education for diabetes self-management
Normalization of glycemia

Weight loss
Reduction in carbohydrate and calorie intake
Increase in exercise capacity

Control of comorbidities, including hypertension,


dyslipidemia, nephropathy, sleep disorders, and
hepatic steatosis.

MANAGEMENT THERAPY OF T2DM


Metformin
& or
Insulin

Exercise

Metabolic
control

Education

Diet

INITIAL TREATMENT
Lifestyle change should be initiated at the time of
diagnosis of T2D .
Initial pharmacologic treatment of youth with T2D
should include metformin and insulin alone or in
combination
Initial treatment is determined by symptoms, severity
of hyperglycemia, and presence or absence of
ketosis/ketoacidosis.

APPROACH OF INITIAL TREATMENT OF


YOUTH WITH T2DM

Zeitler et al 2014

GLP

ORAL HYPOGLYCAEMIC MEDICATIONS

RECOMMENDATION MANAGEMENT
In children with type 2 diabetes and an A1C 9.0%,
and in those with severe metabolic decompensation
(e.g. DKA), insulin therapy should be initiated, but
may be successfully weaned once glycemic targets
are achieved, particularly if lifestyle changes are
effectively adopted [Grade D, Level 4].

SCIENTIFIC FOUNDATION FOR INSULIN


THERAPY IN TYPE 2 DIABETES
Why is insulin needed?

To achieve glycemic targets

When is insulin needed?

Earlier in the treatment plan

Is insulin therapy effective?

Yes if regimen matched to patients


glucose profile and lifestyle

Is insulin therapy safe?

Used effectively the benefits of


glycemic control out weight risks

Weight Gain

Minimize by lifestyle advice & matching glycemic profile

Hypoglycemia Minimize by lifestyle advice & matching glycemic profile


Cancer

Not clear risk of exogenous insulin and cancer


established likely some increased risk of
cancer with diabetes

COMPLICATIONS OF DIABETES
Acute:
Diabetic keto acidosis (DKA)
Hypoglycemia
Late-onset:
Retinopathy
Neuropathy
Nephropathy
Ischemic heart disease & stroke

COMPLICATIONS OF DIABETES
Microvascular1,2
Cognitive impairment3
Diabetic retinopathy

Macrovascular1,2
Cerebrovascular disease
Coronary disease
Coronary heart disease

Diabetic nephropathy
Diabetic neuropathy
Cardiac autonomic
neuropathy

Atherosclerosis

Skin infection

Gastro-intestinal and
bladder dysfunction

Peripheral vascular
disease

Sexual dysfunction

Peripheral sensory
dysfunction
Diabetic foot

Adapted from: 1. International Diabetes Foundation. Time to Act: Type 2 diabetes, the metabolic
syndrome and cardiovascular disease in Europe. 2006. 2. International Diabetes Federation. Time to Act.
2001. 3. Seaguist ER. Diabetes. 2010;59:4-6.

Tight Glycaemic Control Reduces


Complications
Epidemiological extrapolation showing benefit of a 1% reduction in mean HbA1c

21%

Deaths related
to diabetes *

37%

Microvascular
complications e.g.
kidney disease and
blindness *

14%

Heart attack *

43%

Amputation or fatal
peripheral blood
vessel disease *

HbA1c

1%

* p<0.0001
** p=0.035

12%
Stratton IM et al. UKPDS 35. BMJ 2000; 321: 405412

Stroke **

Take Home Message


Diabetes is one of the main chronic diseases in children and
adolescent
Multidisciplinary approach are important
The role of parent or caregiver is key success factors on
management of treatment

THANK YOU FOR YOUR ATTENTION