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

Tempat/TanggalLahir : Yogyakarta, 06-11-1955

RIWAYAT PENDIDIKAN
S1 FK Universitas Diponegoro (S1) 1982 Kedokteran
Sp.1 Spesialis Anak FK UNDIP 1994 Ilmu Kesehatan Anak
S2 Magister Bimbingan Konseling Universitas Negeri Semarang 2002
Kolegium Kesehatan Anak Indonesia /
Sp.2 2007 SpA(K)
Pediatric Endocrinologi Konsultan (Sp2)
S3 S3 univesitas Negeri Semarang 2014 DR

Pendidikan Lanjutan Klinik di Klinik Tumbuh Kembang Khusus dan Genetika 1995
1
Klinis (dismorfologi) RSAB Harapan Kita Tempat di Jakarta
2 Kursus Genetika Klinis NUH Singapore Tempat di Singapore 1996
3 Orientasi di Sub Bidang Endokrinologi Anak FKUI Tempat di Jakarta 2005
4 Fellowship APPES Pediatric Endocrinologi Tempat di Wuhan, Cina 2005

No Dari Penghargaan Tahun


1 Mendiknas Mahasiswa Teladan Universitas Diponegoro 1981
2 Presiden RI Satya Lencana KARYA SATYA 20 tahun 2004
3 Presiden RI Satya Lencana KARYA SATYA 30 tahun 2013
CURRICULLUM VITAE
Tahun Riwayat Pekerjaan
2 Januari 1996 Dokter Spesialis Anak di RS dr. Kariadi
1996- Sekarang SK Pengajar Luar Biasa FK UNDIP di Bagian Ilmu Kesehatan Anak
2008- Sekarang SK Pengajar S2 Biomedik FK UNDIP
2008 - sekarang SK pengajar S2 Genetik Konseling / Biomedik
2005- sekarang SK Pengajar SP.1 PPDS.1.Kesehatan Anak. FK UNDIP RSDK
2005 - sekarang SK pengajar S2 (MKIA) Magister Kesehatan Ibu dan Anak UNDIP
2002- Sekarang Ketua POKJA KIPI JATENG
1996-1999 Sekretaris IDAI JATENG
1999-2002 Wakil ketua IDAI JATENG
2002-sekarang Anggota IDAI JATENG
1998-2001 Seksi Organisasi IDI cab Semarang
2002- sekarang Anggota Satgas Imunisasi Nasional
2008-sekarang Anggota MKEK IDI Jateng
2009-sekarang Sekertaris SMF Bagian Anak FK UNDIP / RSUP. Dr Kariadi
SEmarang
2008-sekarang Tim GAKI FK UNDIP
1997-sekarang Tim Pelayanan Genetik RS Kariadi FK UNDIP
1997-sekarang Tim DSD (Disosder of sexual Development)/
Tim Penyesuaian Kelamin RS Kariadi FK UNDIP
2008-sekarang 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.
Race.
The locus also has the genetic name IDDM1 White people have a
as it is the highest genetic risk for type 1 greater risk for
developing type 1
diabetes. diabetes than black,
The strongest gene, IDDM1, is located in Asian, or Hispanic
people.
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.
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

Metabolic
Exercise control
Diet

Education
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)
RAPID ACTING
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
SHORT ACTING
Regular (soluble) Clear 0.5-1 2-3 6-8
insulin
INTERMEDIATE
ACTING
Insulin zinc suspension Cloudy 1-2 8-10 20-24
or Lente
NPH or isophane Cloudy 1-2 8-10 20-24
Insulin
LONG ACTING
Insulin glargine and Clear Glargine: 2-4 _ Glargine: 24
Insulin detemir Detemir: 1-4 _ Detemir: 20-24
INSULIN THERAPY in Diabetes Mellitus
Insulin Profiles schematic (duration)
ASAspart, Lispro (45 hr)
Regular (68 hr)
Plasma Insulin Levels

NPH (1216 hr)


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

0 2 4 6 8 10 12 14 16 18 20 22 24
Hours 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 Very good Good Moderate Poor
target

Preprandial < 120 < 140 < 180 >180


mg/dl
Postpandrial < 140 < 200 < 240 >240

Urine - - +- >+
reduction
HbA1c <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

Metabolic
Exercise control
Diet

Education
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 Macrovascular1,2

Cognitive impairment3 Cerebrovascular disease

Diabetic retinopathy Coronary disease


Coronary heart disease
Diabetic nephropathy

Diabetic neuropathy
Cardiac autonomic Atherosclerosis
neuropathy

Skin infection

Gastro-intestinal and Peripheral vascular


bladder dysfunction 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

Deaths related
21%
to diabetes *

Microvascular
37% complications e.g.
HbA1c kidney disease and
blindness *

1% 14% Heart attack *

Amputation or fatal
43% peripheral blood
* p<0.0001 vessel disease *
** p=0.035
Stroke **
12%
Stratton IM et al. UKPDS 35. BMJ 2000; 321: 405412
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