INTRODUCTION

Diabetes mellitus (DM) is a common, chronic, metabolic syndrome characterized

by hyperglycemia as a cardinal biochemical feature. The major forms of
diabetes are classified according to those caused by of insulin secretion due to
pancreatic cell damage (type1 DM or T1DM) and those that are a consequence
of insulin resistance occurring at the level of skeletal muscle, liver, adipose
tissue, with various degree of -celll impairment (type2 DM or T2DM). 1Type 2
diabetes mellitus (T2DM) was once thought to be a disease exclusive to adults.
However, as rates of obesity in children have risen, the prevalence of pediatric
T2DM has also increased.2
Currently, in the United States, up to 1 in 3 new cases of diabetes
mellitus diagnosed in youth younger than 18 years is T2DM with a
disproportionate representation in ethnic minorities and occurring most
commonly among youth between 10 and 19 years of age. 3T2DM is caused by
the combination of insulin resistance (IR), defined as dysfunctional cellular
response to insulin combined with pancreatic beta-cell insufficiency. Insulin
resistance thought to be the initial defect, also underlies the metabolic
syndrome. 2
Multiple factors play a role in the progression frominsulin resistance to
T2DM in youth. It is well known that insulin sensitivity decreases in puberty due
to increases in growth hormone, testosterone, and estrogen secretion, and
increases fat mass. Our modern, sedentary, high-calorie lifestyle has contributed
to the increase in obesity rates overall, but the youth who develop insulin
resistance or T2DM seem to store this excess lipid in different locations than
obese youth who remain insulin sensitive.4It may also be that this alternate lipid
storage is affected by fetal exposure to maternal obesity or diabetes, and early
neonatal feeding patterns. 5,6
The following report is a case of a child With Type 2 Diabetes Mellitus
and Overweight who controlledat outpatient clinic of Prof. Dr. R. D. Kandou
General Hospital Manado.

1
CASE REPORT
GK, 9 years 4 months old girl, Christian, Minahasanese,controlled at outpatient
clinic Prof. Dr. R.D. Kandou General Hospital Manado on June22nd, 2015 at
12.00 p.m.She diagnosed as type 2 diabetes mellitus.

PATIENT IDENTITY
Registry number : 450245
Name : GK
Date of Birth : February 13rd, 2006
Age : 9 years and 4 months
Place of Birth : Bethesda General Hospital
Gender : Female
Nationality : Indonesia
Tribe : Minahasanese
Religion : Christian
Address :JlWakan Oki no 26 Matani II Lk ITomohon

History of illness
(alloanamnesis with patient’s parents)
Patient came to outpatientclinic due to control her diabetes. The patient was
diagnosed as type 2 diabetes mellitus since 1 month prior to admission. She
complained that she often urinate every night since 6 months ago, twice a night.
But she never complains about always hungry and thirsty.She never snores
when she is sleeping. She has no blurred vision and no paresthesia.
Herrandom plasma glucose was high,it was found incidentally in blood
routine examination when she was admitted at Bethesda Hospital due to fever.
Then she was referred to endocrinology pediatric consultant. After examination,
she was diagnosed as type 2 diabetes mellitus and started her therapy with
metformin 2 x 500 mg and calcium supplementation oncedaily. She took the
drugs routine and her random plasma glucose was controlled, so her mother
decreased the dose to 2x 250 mg by herself.
She was overweight since childhood. Prior diagnosed as type 2 diabetes
mellitus, she ate 4 times a day, 2 plates each. She exercised only at school. She
never gets menstruation before.
2
History of prenatal care and birth
Patient was born at Bethesda General Hospital by caesarean section due to
macrosomia. She immediately cried after birth. It was a term pregnancy. Birth
weight was 5150 gram and birth length was 56 cm. During pregnancy, her
mother had regular antenatal care, had tetanus toxoid immunization twice, and
was in good health.

History of past illness

Patients had been treated in Endocrinology Consultant Pediatrician on May
13rd 2015 with diagnosis of Type II Diabetes Mellitus. Since then, she is
routinely taking Metformin 2x 500 mgfor 1 month and then the drug
decreased to 2x 250 mg.

Developmental milestones
Social smile : 3 months
Turning in prone position : 4 months
Sitting : 8 months
Crawling : 9 months
Standing : 10 months
Walking : 12 months
Calling mama/papa : 12 months
Walking :12 months

History of feeding
Breast feeding : Birth – 2 years
Milk porridge : 6-8 months
Soft rice porridge : 9-10 months
Steam rice : 10-12 months
Rice : 12 months- now

Immunization Status
She received basic immunization completely as recommended.
BCG : 1 time
3
Polio : 4 times
DTP : 3 times
Measles : 1 times
Hepatitis B : 3 times

Family History
Her mother diagnosed as type 2 diabetes mellitus since 5 years ago and
diagnosed as acute coronary syndrome since 2,5years ago.

Pedigree

Social, Economic and Environmental conditions

She is the last child of three children in the family. His father was47 years old, a
university graduation, a civil servant, while his mother was47 years old,
university graduation, a pastor. Her parents were nonsmoker.
She lived with her parents in a permanent house with 3 rooms, occupied
by 2 adults and 3 children. Restroom was located inside the house. They had
electrical source from the electrical company of government and water supply
from local state water company. The rubbish was collected and thrown
away.She usedgovernment social health insurance 1st class.

Physical examination (June 22nd, 2015)

Antropometric status
Body weight : 47 kg
4
Body height : 148 cm
BMI : 21,46
Nutritional status :overweight (body weight / body heightpercentile was
117,5% based on CDC2000 growth chart and based on
BMI for age : percentile 85-95 )
General condition : Looked well
Consciousness : Compos mentis
Vital signs : Blood pressure : 100/60 mmHg
Pulse rate : 88 times/minutes, regularly
Respiratory rate : 24 times/minutes
Temperature : 36.5°C
Random Plasma Glucose : 120 mg/dL
Head : Normocephaly, black colour hair, not easily pulled out
Eyes : Conjunctiva was not anemic, sclera was not icteric. Pupil
was round, isocoria, 3-3 mm, light reflex was normal
Ears : Clear meatus acusticus externus, normal ear drums, no
discharge
Nose : There was no discharge and no flare.
Mouth : There was no cyanosis, tonsils T1/T1 without inflammatory
sign, pharynx without inflammatory sign
Neck : There was no lymph node enlargement
Chest :
Heart :
- Inspection : no visualization of ictus cordis
- Palpation : ictus cordis was palpable
- Percussion : left margin : linea midclavicularis sinistra
right margin : linea parasternalis dextra
upper margin : 2nd – 3th intercostals spaces
- Auscultation : no murmur

Lung :
- Inspection : symmetrical respiration movement on the both side
hemithorax
5
 - Palpation : vocal fremitus right=left
- Percussion : sonor percussion right=left
- Auscultation : bronchovesicular breath sound, rales -/-,
wheezing -/-
Abdomen :
- Inspection : no distended abdomen wall
- Auscultation : normal bowel sound
- Palpation : liver and spleen were not palpable
- Percussion : tympanic percussion, no sign of ascites
Extremities :warm, capillary refill time (CRT) ≤2”, no deformity, no
cyanosis, normal muscle tone, physiological reflexes
normal, no pathological reflexes, edema -/-
Genitalia : female, no abnormality
Puberty stage : A1M2P1
Lymph node : no lymph node enlargement
Skin : no petechiae, no cyanosis, acanthosisnigricans (+)

Laboratory findings ( May 13rd , 2015)

Fasting Plasma Glucose: 303 mg/dL (N: <100 mg/dL)
HbA1c : 13,9% (N < 8%)
Fasting Insulin : 5,1IU/mL (N 3,2-38,5 IU/mL)
AST : 16 U/L (N: <51 U/L)
ALT :16 U/L (N: <39 U/L)
Ureum : 11 mg/dL (N : 5-18 mg//dL)
Creatinine : 0.39 mg/dL (N: <1 mg/dL)
LFG : 119 ml/min/m2
Total Cholesterol : 156 mg/dL (N : 110-230 mg/dL)
LDL Cholesterol : 89 mg/dL (N: 58-143 mg/dL)
HDL Cholesterol : 24 mg/dL (N: 32-74 mg/dL)
Vitamine D 25-OH : 30,7ng/mL (N: 30-100 ng/mL)
C-peptide : 3,7ng/mL

June 22nd, 2015

6
Random Plasma Glucose :120 mg/dL
Consult to Pediatric Ophthalmology Department : No diabetic retinopathy.
Working Diagnosis :
Type II Diabetes Mellitus
Treatment
Lifestyle Intervention including nutrition intervention, moderate- vigorous
physical activity minimal 60 minutes daily and reduce screen time less than 2
hours.
Pediatric Nutritional care (consultation results from Nutrition and Metabolic
division):
1. Nutritional assessment :
Actual Body weight : 47 kgs
Ideal Body Weight : 40 kgs
Actual Body Height : 148 cm
BMI : 21,46
Nutritional Status based on CDC 2000 Growth Chart : 117,5% (overweight)
BMI for age Chart : persentile 85-95 (overweight)
2. Nutritional requirement : based on Recommended Daily Allowance (RDA)
Calorie needed : 1880 kkal/day (47 kkal/kgBW)
Divided to 50% carbohydrate, 20% protein, 30% fat.
3. Adminitration route : oral
4.Given As: polimeric food:
Breakfast (20%= 376 kkal) : ¾ cup of rice, 50 g fried meat/ fish/ 1 egg ,100g
vegetable
Snack (15%=282 kkal) : 5 crackers/ biscuits
Lunch (30%= 564kkal) : 1 cup of rice, 50 g fried meat/ fish/ 1 egg, 2
pieces tofu, 100 g vegetable, 1 pieces fruits.
Snack (15%=282 kkal) : 5 crackers/ biscuits
Dinner (20%= 376 kkal) : ¾ cup of rice, 50 g fried ,100g vegetable
5. Monitoring and evaluation : random plasma glucose, body weight reduction.

Medical treatment:
Metformin 2x 250 mg p.o
Planning :
7
 - Complete blood count
- Urinalysis

FOLLOW UP
June 26th, 2015
Complaint : no complaint
General conditions : Looked well, compos mentis
Body weight : 47 kgs
Vital signs : Blood pressure : 90/60 mmHg
Pulse rate : 96 times/minutes, regularly
Respiratory rate : 24 times/minutes
Temperature : 36.7°C
Random Plasma Glucose : 116 mg/dL
Physical examination
Head : Conjunctiva anemic (-), sclera icteric (-), pupil isocoria, Ø 3mm-3mm,
light reflex +/+
Chest : Symmetrical respiratory movements, no retraction
Heart : Normal rate, regular rhythm, no thrill, no murmurs
Lung : Bronchovesicular breath sound, rales -/-, wheezing -/-
Abdomen : non-distended, soft and non-tender, normal bowel sound, liver and
spleen: not palpable
Extremities: warm, CRT ≤2”, cyanosis (-), acanthosisnigricans (+)
Laboratory :
Complete Blood count:
Hemoglobine : 12,8g/dL
Hematocrite : 39,5%
Leucocyte : 11.900/mm3
Trombocyte : 359.000/mm3
Fasting plasma glucose : 89/mm3

Urinalysis :
pH :5
Spesific gravity : 1.007
8
 Epithel : 2-5/High Power Field [HPF]
Leukocyte : 0-1/HPF
Erythrocyte : negative
Albumin : (-)
Glucose : (-)
Nitrite : (-)
Ketone : (-)

Diagnosis :
Type II Diabetes Mellitus

Treatment
Metformin 2x 250 mg p.o
Lifestyle intervention same like before.

June 29th, 2015

Complaint :no complaint
General conditions : looked well, compos mentis
Body weight : 47 kgs
Vital signs : Blood pressure : 100/60 mmHg
Pulse rate : 100 times/minutes, regularly
Respiratory rate : 24 times/minutes
Temperature : 36.8°C
Random Plasma Glucose : 109 mg/dL
Physical examination
Head : Conjunctiva anemic (-), sclera icteric (-), pupil isocoria, Ø 3mm-3mm,
light reflex +/+
Chest : Symmetrical respiratory movements, no retraction
Heart : Normal rate, regular rhythm, no thrill, no murmurs
Lung : Bronchovesicular breath sound, rales -/-, wheezing -/-
Abdomen : non-distended, soft and non-tender, normal bowel sound, liver and
spleen: not palpable
Extremities : warm, CRT ≤2”, cyanosis (-), acanthosisnigricans (+)

9
Diagnosis :
Type II Diabetes Mellitus

Treatment
Metformin 2x 250 mg p.o
Lifestyle intervention same like before

July 06th, 2015

Complaint : no complaint
General conditions : looked well, compos mentis
Body Weight : 46,5 kg
Vital signs : Blood pressure : 100/60 mmHg
Pulse rate : 104 times/minutes, regularly
Respiratory rate : 24 times/minutes
Temperature : 36,6°C
Random Plasma Glucose : 112 mg/dL
Physical examination
Head : Conjunctiva anemic (-), sclera icteric (-), pupil isocoria, Ø 3mm-
3mm, light reflex +/+
Chest : Symmetrical respiratory movements, no retraction
Heart : Normal rate, regular rhythm, no thrill, no murmurs
Lung : Bronchovesicular breath sound, rales -/-, wheezing -/-
Abdomen : non-distended, soft and non-tender, normal bowel sound, liver and
spleen: not palpable
Extremities : warm, CRT ≤2”, cyanosis (-), acanthosisnigricans (+)

Diagnosis :
Type II Diabetes Mellitus

Treatment
Metformin 2x 250 mg p.o
Lifestyle intervention same like before

10
Prognosis :
Ad vitam : ad bonam
Ad functionam : ad bonam
Ad sanatitionam : dubia ad bonam

DISCUSSION

Diabetes mellitus (DM) is a common, chronic, metabolic syndrome characterized

by hyperglycemia as a cardinal biochemical feature. The major forms of
diabetes are classified according to those caused by of insulin secretion due to
pancreatic cell damage (type1 DM or T1DM) and those that are a consequence
of insulin resistance occurring at the level of skeletal muscle, liver, adipose
tissue, with various degree of -celll impairment (type2 DM or T2DM).1
T2DM was once thought to be a disease exclusive to adults. However, as
rates of obesity in children have risen, the prevalence of pediatric T2DM has
also increased.2According to the most recent estimates, the prevalence of T2DM
in 2009 was estimated at more than 20,000, an increase of 30% over estimates
in 2001.3 The average age of onset is 13.7 years.7
Based on a national survey of T2DM children in Indonesia was conducted
in April 2009-March 2012, there are 38 children with T2DM (16 boys, 22 girls).
Twenty two children are diagnosed at >10 years old. Cases come spreadly from
11 provinces, the most cases are from Jakarta (16), Central Java (7) and West
Java (6). Twenty children are obese. Only 10 children had weight loss and 1
child had ketoasidosis. Mean BMI at diagnosis is 24 (+2.2) kg/m2. Mean of A1c
at diagnosis is 11.5% (+ 1.9). Therapy at diagnosis are oral hypoglycemic only
(4), insulin only (11), combination of insulin and oral hypoglycemic (1). Diabetes
family histories are found in 16 subjects, (1 T1DM and 15 T2DM); 4 subjects
have no family history.8
Childhood T2DM is a disease in the child who typically is overweight or
obese (BMI ≥85th–94th and >95th percentile for age and gender, respectively),
has a strong family history of T2DM, has substantial residual insulin secretory
capacity at diagnosis (reflected by normal or elevated insulin and C-peptide
concentrations), has insidious onset of disease, demonstrates insulin resistance

11
(including clinical evidence of polycystic ovarian syndrome or acanthosis
nigricans), lacks evidence for diabetic autoimmunity (negative for autoantibodies
typically associated with T1DM). These patients are more likely to have
hypertension and dyslipidemia than are those with T1DM.3
The major risk factors for type 2 diabetes in young persons are as
follows:9
 Obesity and inactivity, which are important contributors to insulin
resistance.
 Native American, black, Hispanic, Asian, or Pacific Islander descent
 Family history of type 2 diabetes
 Age of 12-16 years, the mean age range of onset of type 2 diabetes
in youths. These ages coincide with the relative insulin resistance
that occurs during pubertal development.
 High birth weight
 Maternal gestational diabetes or type 2 diabetes
 Not breastfed during infancy
Factors contributing to insulin resistance include obesity/sedentary
lifestyle, race/ethnicity, and family history. The Bogalusa Heart Study looked at
>6500 kids aged 4-17 years, with and without parental diabetes mellitus (DM)
from childhood to adulthood. This study showed that children with parental DM
had a higher body mass index (BMI) and increased systolic blood pressure
(SBP) from childhood, increased fasting insulin and glucose and insulin
resistance index from puberty, increased Triglycerides (TGs) and low density
lipoprotein, and decreased high-density lipoprotein (HDL) in adulthood.10
A family history of type 2 diabetes increases the risk of developing the
disease. Moreover, the high concordance of type 2 diabetes in identical twins
and the aggregation of type 2 diabetes in families support the existence of
genetic determinants for type 2 diabetes in families. The risk for developing type
2 diabetes increases when one or both parents are affected. 11 Some studies
have suggested that adult offspring whose mothers have diabetes are more
likely to develop the disease themselves than are offspring whose fathers have
diabetes.12
Assuming that maternal influences are important in the transmission of
type 2 diabetes, several possible genetic mechanisms have been suggested.
12
These include the role of mitochondrial DNA (mtDNA), gene imprinting, and the
effect of maternally determined environments (intrauterine influences). Although
several mutations have been implicated, the strongest evidence suggests a
point substitution at nucleotide position 3,243 (A to G) in the mitochondrial
tRNA gene. Apart from severe, pathogenic mtDNA mutations, common
polymorphisms in mtDNA may contribute to variations of insulin secretory
capacity in normal individuals. 13
Puberty is another important factor leading to the development of
Type2DiabetesMellitus.Glucose clearance was30% lower in children between
Tanner stage 2 and Tanner stage 4 compared with prepubertal children or
adults. Greater fat mass, sex steroids and higher concentrations of growth
hormone/ Insulin like Growth Factor -1 (IGF-1) have variously been proposed to
explain the difference.10
Pubertal maturation of the hypothalamopituitary-gonadal axis reportedly
begins with a rise in luteinizing hormone (LH) around 8–9 years in girls, and 1–2
years later in boys, although longitudinal data are few. The insulin resistance
(IR) of early adolescence is usually attributed to puberty, but Jeffryet al suggest
that it emerges well before the rise in LH that initiates puberty and before any
discernible physical changes. 12
The prepubertal increase in IR was partially accounted for by increases
in adiposity, with percent fat alone explaining 25 and 30% of the variation in IR
in boys and girls, respectively. Type 2 diabetes is increasingly common in
childhood, and the majority of diabetic children are female, consistent with their
greater adiposity and IR. However, even when accounting for increases in
percent fat, IGF-1, and age, over half of the total variance in IR remained
unexplained.12
In addition to the effect of childhood diet and activity, the development of
Insulin resistance (IR) and obesity may also be influenced by the in utero
environment, and by feeding patterns and weight gain in the first year of life. It is
known that both low and high birth weight predict metabolic abnormalities later
in life. In children exposed to gestational diabetes mellitus (GDM) in utero, the
BMI velocity from ages 6–12 is increased.14
The risk of metabolic syndrome by age 11 years in children born large for
gestational age to GDM mothers was 3.6 times greater than those born average
13
for gestational age to GDM mothers, and maternal obesity, regardless of birth
size, increased the risk twofold. Increased maternal BMI prior to conception was
also associated with increased neonatal hepatic fat content. 15At 1 year of age,
infants whose mothers had GDM had higher plasma triglycerides, and glucose
area under the curve during an Oral Glucose Toleration Test (OGTT) compared
with infants from mothers without GDM. IR in these infants was associated with
increased weight gain in the first year of life. Furthermore, children who were
breastfed at least 6 months in infancy were more likely to be in to be lean and
have lower percentages of visceral and subcutaneous adipose tissue.16
Increased ectopic fat storage may also be related to increased levels of
plasma free fatty acids (FFA) which can also directly decrease insulin sensitivity.
Excessive processing of nutrients, including FFA by mitochondria may result in
an increase of reactive oxygen species (ROS) due to uncoupling of oxidative
phosphorylation which in turn leads to altered mitochondrial function and to
production of more ROS.17 These ROS can then lead to endoplasmic reticulum
dysfunction and thus defective insulin secretion in pancreatic beta cells. ROS,
and/or lipid byproducts may also impair insulin signaling cascades. 18
Obese children are reported to have increased FFA concentrations,
related to their degree of IR.18 Muscle mitochondrial dysfunction in individuals
with T2DM has been shown to be associated with muscle IR. Muscle and
hepatic IR is also mediated by peroxisome proliferator-activated receptor
(PPAR)- receptors, as evidenced by the use of PPAR- agonists for the
treatment of T2DM. In some individuals with T2DM, there may be genetic
alterations in PPAR- expression, mitochondrial function, and/or inflammation
related to IR, arguing that obesity-induced FFA elevations in genetically
predisposed individuals are a primary cause of pediatric T2DM.19
Part of the variability in insulin sensitivity in obese adolescents is likely
related to hormonal changes in puberty. Growth hormone, estrogen, and
androgens can all affect insulin sensitivity.2 Studies have monitored the changes
in insulin sensitivity in healthy children throughout the progression of puberty.
These studies show that IR starts prior to puberty, even before rises in pituitary
gonadotropin secretion, and is partly explained by the accumulation of fat and
rising insulin-like growth factor 1 (IGF-1).12IR peaks when children are in mid-

14
puberty, equivalent to Tanner stage 3–4, and decreases at the conclusion of
puberty, at least in normal-weight youth. These unique, fluctuating influences on
IR, which can vary by time of day and time during menstrual cycle in girls,
maybe a large reason that the diagnosis of IR, impaired glucose tolerance, and
impaired fasting glucose can be so challenging to reproduce in adolescents.2
Studies show that time spent at a BMI greater than the 85th percentile is
associated with an increased risk of diabetes. Pubertal IR requires additional
insulin secretion to maintain normoglycemia, and superimposed obesity may
create too large of a demand on the pancreas in susceptible individuals.A
sedentary lifestyle is also critical to development of T2DM in youth. There has
been a dramatic recent decrease in overall physical activity level, especially in
girls, during the transition from childhood to adolescence, the time at which
overweight youth are at great risk for developing T2DM. 20

The average age of T2DM diagnosis in youth is around 13.5 years, with
female predominance. This age of presentation is likely to be related to a time of
puberty-mediated insulin resistance in combination with increased weight.The
clinical presentation can be diverse. T2DM can be detected while screening
asymptomatic youth because of belonging to a high-risk population.21These risk
factors include being overweight (BMI ≥ 85th percentile) or obese (BMI ≥ 95th
percentile), family history in a first or second degree relative of T2DM, being
from certain ethnic groups known to have higher risk of T2DM (Aboriginal, South
Asian, Asian, African, and Hispanic), and history of in-utero exposure to obesity
or hyperglycemi. Screening in high-risk groups is recommended to start at the
age of 10 years or when puberty starts if it is sooner than that, using fasting
plasma glucose every 2 years. Oral glucose tolerance test can also be used but
has poor reproducibility and is more expensive.21,22
Some children and adolescents present with diabetes-related symptoms
including polyuria, polydipsia, tiredness, blurred vision, vaginal moniliasis, and
weight loss. They may also present with acute metabolic
decompensationincluding ketosis, diabetic ketoacidosis, and hyperglycemic
hyperosmolar nonketotic state.20
Patient is a 9 years and 4 months old girl. She was born by caesarean
section due to macrosomia with birth weight 5150 grams dan birth length 56 cm.
Her mother diagnosed as type 2 diabetes mellitus since 5 years ago and
15
diagnosed as acute coronary syndrome at 2,5 years ago. She was overweight
since childhood. She ate 4 times daily, 2 plates each. She not yet has
menstruation.She never complains about hungry and thirsty. She only
complained that she often urinate every night since 6 months ago, twice a night.
Her random plasma glucose was high, it was found incidentally in blood routine
examination when she was admitted at Bethesda Hospital due to fever.
Antropometric measurement showed that she was overweight (body
weight / body height =117,5% based on CDC 2000 growth chart appropriate to
age and gender and based on BMI for age : percentile 85-95). Her puberty
status was A1M2P1, and there was insulin resistance clinical evidence such as
acanthosisnigricans.
The laboratory diagnosis of T2DM in children uses the blood glucose cut-
offs that are identical to adults and involves measuring fasting or random plasma
glucose or a formal oral glucose tolerance test.21,22 HbA1c is not recommended
in the pediatric age group as a diagnostic test as is the case in adults but is used
for follow-up in established T2DM to determine glycemic control.22
Diabetesaccording to the American Diabetes Association criteria, defined
as :
1. HbA1c ≥6.5% (test performed in an appropriately certified laboratory); or
2. Fasting (defined as no caloric intake for at least 8 hours) plasma glucose
≥126 mg/dL (7.0 mmol/L); or
3. 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an oral glucose
tolerance test performed as described by the World Health Organization by
using a glucose load containing the equivalent of 75 g anhydrous glucose
dissolved in water; or
4. A random plasma glucose ≥200 mg/dL (11.1 mmol/L) with symptoms of
hyperglycemia.
Screening for type 2 diabetes should be performed every 2 years using
an fasting plasma glucose test in children with any of the following:22
1. 3 risk factors in nonpubertal or2 risk factors in pubertal children:
a. Obesity (BMI95th percentile for age and gender)
b. Member of a high-risk ethnic group (e.g. Aboriginal, African,Asian,
Hispanic or South Asian descent)

16
 c. Family history of type 2 diabetes and/or exposure to hyperglycemia in
utero
d. Signs or symptoms of insulin resistance (including
acanthosisnigricans,hypertension, dyslipidemia, Non
AlcoholicFattyLiverDisease(ALT>3X upperlimit of normal or fatty liver on
ultrasound), Polycystic Ovarian Syndrome
2. Impaired fasting glucose or impaired glucose tolerance
3. Use of atypical antipsychotic medications
With rising obesity rates in children, it is increasingly difficult to
differentiate between T1DM and T2DM on clinical grounds alone. DM
classification in clinical cases depends on age, clinical symptoms, ketonic acid
presence in urine, obesity, family history, evidence of autoimmune disease, and
serum C-peptide level. The patients with (1) younger age of onset, (2) clinical
symptoms, (3) DKA presence, and (4) suspected autoimmune disease tend to
be classified as T1DM. On the other hand, patients who (1) are obese, (2) have
a family history of T2DM, (3) have few or no diabetic symptoms, (4) have insulin
resistance tend to be classified as T2DM. However, it is difficult to classify DM in
some cases, even though there are significant differences in each type. 23
C-peptide reflects insulin secretion from pancreatic β cells, and the
amount of insulinsecreted reflects the metabolic needs of the body. One of the
major roles for measuring C-peptide in pediatric populations is to assist in the
correct diagnosis of diabetes subtypes, which in turn determines appropriate
management. C-peptide levels are usually elevated in children with T2DM at
diagnosis in contrast to children with T1DM. Katz et al. identified that a fasting
C-peptide level at 0.85 ng/mL had 83% of sensitivity and 89% specificity for
distinguishing pediatric T1DM from T2DM at diagnosis.24
The patient diagnosed as type 2 diabetes mellitus because she had some
risk factors such as family history of type 2 diabetes mellitus,large birth weight,
puberty but only has few of diabetic symptoms. Antropometric status was
overweight. Physical examination there was clinical evidence of insulin
resistance such as acanthosisnigricans. Her laboratorium results showedher
fasting plasma glucose was 303 mg/dL and HbA1c was 13,9% but normal range
of insulin and C-peptide.Ureum, creatinine, AST and ALT was normal showed
there was no complication on kidney and liver. Urinalysis showed there was no
17
urine glucose and ketone. Consult to pediatric ophthalmology department
showed there wa no diabetic retinopathy.
The current management plans for T2DM involve lifestyle intervention
and pharmacotherapy.The treatment of T2DM requires a family-focused plan
and delivered by a multidisciplinary team. The multidisciplinary team includes a
combination of physicians, diabetes nurse educators, dietitians, physical activity
specialists, social workers, psychologists, and behavioral therapists and may
also require the involvement of additional medical subspecialties to address its
comorbidities and complications.25
The management plan should be intensive with frequent contacts with
family and teen and personalized to the individual patient taking into account the
family’s financial resources and being receptive and respectful of ethnic and
cultural attributes of the family. Engaging the patient and family early and
frequently is critical to minimize attrition, which is a common problem in this
populatio. The goals of T2DM management include:20
1. achieving and maintaining glycemic control
2. weight maintenance or weight loss if possible
3. acquisition of healthy lifestyle habits and skillsets
4. management of comorbidities
5. prevention of complications
The above goals can be met with establishing an education plan and the
introduction of lifestyle intervention program (LSI) including nutrition
interventions and increased physical activity, along with the use of
pharmacotherapy.20Regarding nutrition, focus should be on formulating a
nutrition plan that involves food composition and eating behaviors that drive
excess food intake.3,26 Recommendations regarding controlling portion size and
setting up regular meal and snack times are important. Equally important is
eating meals as a family and elimination of distractions during meal times
including TV, computers, or other disturbances to slow down eating and improve
social interactions.26,27
Other recommendations include avoiding snacking especially while
watching TV, using the computer, and late at night. 25,26 In addition, the
elimination of sugary drinks and foods with high fat or caloric content is also
critical to reducing caloric intake to promote weight maintenance or weight loss.
18
Parents, caregivers, and teens need to be taught how to read food labels to
understand the nutritional value of consumed foods and to emphasize the
importance of consuming less fat including saturated fatty acids, increasing fiber
intake, and reducing sugar intake and eating out.20
The Academy of Nutrition and Dietetics recommends that protein-sparing,
modified-fast (ketogenic) diets be restricted to children who are >120% of their
ideal body weight and who have a serious medical complication that would
benefit from rapid weight loss. Specific recommendations are for the intervention
to be short-term (typically 10 weeks) and to be conducted under the supervision
of a multidisciplinary team specializing in pediatric obesity.3
Common dietary recommendations to reduce calorie intake and to
promote weight loss in children include the following: (1) eating regular meals
and snacks; (2) reducing portion sizes; (3) choosing calorie-free beverages,
except for milk; (4) limiting juice to 1 cup per day; (5) increasing consumption of
fruits and vegetables; (6) consuming 3 or 4 servings of low-fat dairy products per
day; (7) limiting intake of high-fat foods; (8) limiting frequency and size of
snacks; and (9) reducing calories consumed in fastfood meals.3
The Dietary Intervention Study in Children (DISC) evaluated the effects of
a low fat, high fiber diet during adolescence and showed benefit in both glycemic
control and blood pressure.28 A ketogenic very low calorie diet sustained for 60
days can also improve BMI and blood glucose control in children with T2DM.2
Diet intervension methods for overweight and obese children is
consuming nutrition acording to Recommended Dietary Allowances (RDA).
Decreased of calories up to 200-500 cal per day, with target of weight loss 0.5
kg per week. Targeting weight loss until 20% above ideal body weight quite
enough to be the ideal target, considering linier growth is still continuous.
Composition of diet with 50-60% carbohydrates, 30% fats, and 15-20% proteins,
is ideal for daily nutrition.Give a stabil diit based on requirement daily
allowances. Give with food rules methods.29
1. Eat pattern should be scheduled with 3x/day for maincourse and 2x/day for
snack (prior with fresh fruit), give water between eat schedule for
maincourse and snack.
2. The procedure to give food suit with calori needed based on requirement
daily allowences from height age with ideal body weight based on height.
19
 For food alternative, use the traffic light diet. Traffict light diet contain with
green food (food with low calori < 20 calori per set and fat can consume freely),
yellow food (food with low fat but with moderate calori which can consume
limited only), red food (food with high fat and high calori which not to consume or
only once a week).29
Physical activity is an integral part of weight management for prevention
and treatment of T2DM. At present, moderate to-vigorousvigorous exerciseof at
least 60 minutes daily is recommended for reduction of BMI and improved
glycemic control in patients with T2DM.Moderate-to-vigorousvigorous exercise is
defined as exercise that makes the individual breathe hard and perspire and that
raises his or her heart rate. An easy way to define exercise intensity for patients
is the “talk test”; during moderate physical activity a person can talk but not sing.
During vigorous activity, a person cannot talk without pausing to catch a
breath.3It is most helpful to recommend an individualized approach that can be
incorporated into the daily routine, is tailored to the patients’ physical abilities
and preferences, and recognizes the families’ circumstances. It is also important
to recognize that the recommended 60 minutes of exercise do not have to be
accomplished in 1 session but can be completed through several, shorter
increments (10–15 minutes). Patients should be encouraged to identify a variety
of forms of activity that can be performed both easily and frequently. 30
Reducing screen time contributes to a sedentary lifestyle, especially
when the child or adolescent eats while watching television or playing computer
games. The US Department of Health and Human Services recommends that
individuals limit “screen time” spent watching television and/or using computers
and handheld devices to less than 2 hours per day unless the use is related to
work or homework. Physical activity may be gained either through structured
games and sports or through everyday activities, such as walking, ideally with
involvement of the parents as good role models.3
In pediatric patients, lifestyle change is most likely to be successful when
a multidisciplinary approach is used and the entire family is involved.
Unfortunately, efforts at lifestyle change often fail for a variety of reasons,
including high rates of loss to follow-up; a high rate of depression in teenagers,
which affects adherence; and peer pressure to participate in activities that often
center on unhealthy eating. Expert consensus is that fewer than 10% of pediatric
20
T2DM patients will attain their blood glucose goals through lifestyle interventions
alone. 3
While LSI is important to provide the basis for acquiring healthy behaviors
in T2D, the success rates of maintaining glycemic targets based on LSI alone
are low and starting pharmacotherapy at diagnosis is appropriate. 3 Metformin is
the first line therapy for youth with T2DM. It is a biguanide that lowers blood
glucose levels via several mechanisms including (i) reducing hepatic glucose
output by inhibiting gluconeogenesis, (ii) increasing insulin-stimulated glucose
uptake in muscle and adipose tissue, (iii) inhibiting inflammation in cells by
inhibiting the NF𝜅B pathway which, when active, interferes with insulin
signaling, (iv) increasing fatty acid oxidation in muscle and inhibiting fatty acid
synthesis in fat and liver by upregulating AMPK activity, (v) enhancing the
secretion of GLP-1 from gut.20
Because gastrointestinal adverse effects are common with metformin
therapy, the committee recommends starting the drug at a low dose of 500 mg
daily, increasing by 500 mg every 1 to 2 weeks, up to an ideal and maximum
dose of 2000 mg daily in divided doses. It should be noted that the main
gastrointestinal adverse effects (abdominal pain, bloating, loose stools) present
at initiation of metformin often are transient and often disappear completely if
medication is continued. Generally, doses higher than 2000 mg daily do not
provide additional therapeutic benefit.31 In addition, the use of extended-release
metformin, especially with evening dosing, may be considered, although data
regarding the frequency of adverse effects with this preparation are scarce.
Metformin is generally better tolerated when taken with food.20
Metformin is recommended as the initial pharmacologic agent in
adolescents presenting with mild hyperglycemia and without ketonuria or severe
hyperglycemia. In addition to improving hepatic insulin sensitivity, metformin has
a number of practical advantages over insulin: 20
- Potential weight loss or weight neutrality.
- Because of a lower risk of hypoglycemia, less frequent finger-stick Blood
glucose measurements are required with metformin, compared with
insulin therapy or sulfonylureas.
- Improves insulin sensitivity and may normalize menstrual cycles in
females with polycystic ovary syndrome.
21
 - Taking pills does not have the discomfort associated with injections.
- Less instruction time is required to start oral medication, making it is
easier for busy practitioners to prescribe. Adolescents do not always
accept injections, so oral medication might enhance adherence.
There are slow release preparations (e.g., Glucophage XR, Glumetza)
that have less gastrointestinal side effects and are taken once daily, which may
improve compliance, and pediatric trials are ongoing to evaluate their efficacy.
Importantly, metformin use is rarely associated with hypoglycemia. The usual
maintenance dose is 1000 mg twice daily, with a starting dose of 250–500 mg,
to be increased every few days to reach full dose within 3-4 weeks. If side
effects develop, the patient can be reassured that these are transient and to
continue titration with lower dose increments. 20
There are limited data on the use of additional medications to treat T2DM
in youth compared to adults. There are ongoing studies to evaluate their role
alone or in combination to treat youth.20Drug Administration (FDA) for use in
children, both thiazolidinediones and incretins are occasionally used in
adolescents younger than 18 years.3
There are limited data on the use of additional medications to treat T2DM
in youth compared toadults.There are ongoing studies to evaluate their role
alone or in combination to treat youth. Rosiglitazone binds to peroxisome
proliferator-activated receptor gamma (PPAR-𝛾) in metabolic cells. This is a
transcription factor and master regulator of fat and carbohydrate metabolism and
is an insulin sensitizer. In adults, rosiglitazone reduces HbA1c by 0.5–1.3%.
Recently, an FDA panel voted to ease the restrictions for rosiglitazone use in
adults with T2DM, as previous reports that suggested a possible association
with adverse cardiovascular outcomes were felt to be exaggerated. This may
result in increased use in the adult population and may offer further basis for its
use in children.20
IncretinMimetics,this class of drugs includes glucagon-like peptide-1
(GLP-1) receptor agonist, which is a peptide secreted by the L cells of the small
intestine in response to food, and has a half-life of 2 minutes. It enhances insulin
secretion in response to glucose, suppresses glucagon production, delays
gastric emptying, prolongs satiety, and reduces HbA1c and weight. It is given
subcutaneously twice daily, which may limit compliance in teens. Some of its
22
side effects include nausea, vomiting, diarrhea, dyspepsia, and headache.
Pediatric studies are ongoing to validate its use in T2D teens.32,33
Insulin reduces islet glucotoxicity and has a paradoxical effect on
improving insulin sensitivity in the context of insulin resistance. Insulin is used at
presentation if the patient is hyperglycemic (blood glucose > 11.1 mmol/L),
ketotic, or ketoacidotic or if the HbA1c is ≥9%. The goal of insulin therapy is to
reverse the acute metabolic decompensation noted in some patients at
presentation and may be used for few weeks at diagnosis along with metformin
and then is withdrawn gradually. Insulin may be the only prescribed agent in
adolescents with T2DM in several institutions. The main side effects of insulin
include weight gain and hypoglycemia.20
Once treatment goals are met, the frequency of monitoring can be
decreased; however, the committee recommends some continued blood
glucose testing for all youth with T2DM, at a frequency determined within the
clinical context (e.g. medication regimen, HbA1c, willingness of the patient, etc.).
For example, an infrequent or intermittent monitoring schedule may be adequate
when the patient is using exclusively an oral agent associated with a low risk of
hypoglycemia and if HbA1c concentrations are in the ideal or non-diabetic
range. A more frequent monitoring schedule should be advised during times of
illness or if symptoms of hyperglycemia or hypoglycemia develop.3
The committee suggests that clinicians monitor HbA1c concentrations
every 3 months.HbA1c provides a measure of glycemic control in patients with
diabetes mellitus and allows an estimation of the individual’s average blood
glucose over the previous 8 to 12 weeks. No RCTs have evaluated the
relationship between glycemic control and the risk of developing microvascular
and/or macrovascular complications in children and adolescents with T2DM.20
It is generally recommended that HbA1c concentrations be measured
every 3 months. For adults with T1DM, the American Diabetes Association
recommends target HbA1c concentrations of less than 7%; the American
Association of Clinical Endocrinologists recommends target concentrations of
less than 6.5%. Although HbA1c target concentrations for children and
adolescents with T1DM are higher.Several review articles suggest target HbA1c
concentrations of less than 7% for children and adolescents with T2DM.3

23
 The treatment to this patient was lifestyle intervention (including nutrition
intervention and physical activity) and pharmacotherapy. The nutrition given
acording to Recommended Dietary Allowances (RDA) with composition of diet
with 50% carbohydrates, 30% fats, and 20% proteins.We recommend to
decrease calories up to 200-500 cal per day, with target of weight loss 0.5 kg
per week.
Eat pattern scheduled 3x/day for maincourse and 2x/day for snack. We
recommendto avoid snacking especially while watching TV, using the computer,
and late at night. In addition, we recommend to eliminate of sugary drinks and
foods with high fat or caloric content. For food alternative, we use the traffic light
diet. Traffict light diet contain with green food (food with low calori < 20 calori per
set and fat can consume freely), yellow food (food with low fat but with moderate
calori which can consume limited only), red food (food with high fat and high
calori which not to consume or only once a week).
The patients also was recommended to have moderate to-
vigorousvigorous exercise of at least 60 minutes daily and reduce screen time,
spent watching television and/or using computers and handheld devices to less
than 2 hours per day. Because of the success rates of maintaining glycemic
targets based on lifestyle intervention alone are low, we started the
pharmacotherapy together with lifestyle intervention. Metformin was chosen
because of its mechanism improving hepatic insulin sensitivity, with starting
dose 2x 500 mg. The parents were advised to control her random plasma
glucose routine and HbA1c every 3 months. Family’s support is important in
lifestyle interventions.
It is important to note that T2DM is associated with other comorbidities
that are related to insulin resistance, and some of these comorbidities are
present at diagnosis. T2DM is a more aggressive disease than T1D, with
complications occurring early in the course of the disease. Over the past few
years, the term “metabolic syndrome” emerged as a unifying description of
insulin resistance-related conditions and includes abdominal obesity,
dysglycemia, dyslipidemia, and hypertension. Insulin resistance is also
associated with hyperandrogenism and polycystic ovarian syndrome (PCOS)
and non-alcoholic fatty liver disease (NAFLD).

24
 Hypertension (Blood pressure ≥ 95th percentile for age, sex, and height
and confirmed on two readings) is present in 20–30% at initial presentation.
Bloodpresure should be checked at diagnosis and with e1very encounter
afterwards. When hypertension is associated with proteinuria, it can progress to
end-stage renal disease (ESRD) and requires aggressive
treatment.34Hypertension may account for 35– 75% of micro- and
macrovascular problems in T2DM. Treatment involves using angiotensin
converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB).35
Dyslipidemia present in 50–65% of T2DM teens with established T2DM,
with hypertriglyceridemia and low high density lipoprotein (HDL) being the most
common abnormalities seen. In children who have family history of dyslipidemia
or early cardiovascular disease and after 3–6 months of unsuccessful LSI, statin
therapy is recommended.The goals of therapy are to maintain low density
lipoprotein (LDL) below 2.6 mmol/L, triglycerides below 1.7 mmol/L, and HDL
above 0.9 mmol/L. Statins are the first line of therapy in these patients.27
Deposition of fat in the liver is a common association with T2DM, with
22.2% of children havingNon-Alcoholic Fatty Liver Disease at diagnosis. Fatty
liver is related to increased visceral fat mass and insulin resistance and
components of the metabolic syndrome and is twice as common in boys.36 This
condition is first suspected with elevated transaminases (×3 times normal
levels), and the diagnosis is confirmed on a liver ultrasound. The treatment for
Non-Alcoholic Fatty Liver Disease is Life Style Intervention including weight loss
and exercise. 37
PCOS is seen in obese and T2DM women, including adolescents. The
diagnosis criteria are not fully formalized in teens because several features of
PCOS are seen during the course of normal puberty. However, emphasis on
using more rigorous criteria for teen PCOS diagnosis has gained more support,
including the recently revised Rotterdam criteria and others; these involve
having oligo- or anovulation or primary amenorrhea at 16 years of age, clinical
and biochemical hyperandrogenism, and ovarian volume of ≥10 cm3 on
ultrasound (need 3 of 3).Patients with PCOS require an oral glucose tolerance
test as there is a higher rate of dysglycemia associated with the diagnosis. The
treatment of PCOS involves lifestyle intervention; in addition, combined oral

25
contraceptive pills, antiandrogens (e.g., spironolactone), and insulin sensitizers
including metformin all play a role in different patients. 20
There is evidence that obstructive sleep apnoe is associated with the
metabolic syndrome. In adults, OSA patients have higher rates of Non-Alcoholic
Fatty Liver Disease The diagnosis is suspected clinically and confirmed on
sleep studies. In some cases, OSA is treated with CPAP. 20
So far, no population-based follow-up study has been conducted to
determine the long-term prognosis of type 2 diabetes among children and
adolescents. Complications of T2DM Youth with T2DM have a more aggressive
disease than adult T2DM and pediatric T1DM, with complications noted early in
the course of the disease. Young adults aged 18–44 years with type 2 diabetes
develop microalbuminuria and cardiovascular disease more rapidly than
individuals diagnosed after age 45 and have a 14-fold relative increase in
myocardial infarction risk compared with age-matched and gender-matched
controls without diabetes.38
The incidence of nephropathy in Pima Indians, a population with the
highest rate of T2DM in the world, is the same across different age groups, and
retinopathy was more common when T2DM is diagnosed at an older age. In
another study, retinopathy was noted in 4% of T2DM, proteinuria and
hypertension in 36%. In the latter study, 6 International Journal of Pediatrics
peripheral and autonomic neuropathy occurred at 21 and 57% of T2D teens,
respectively.39 Limited data suggest that rates of peripheral and autonomic
neuropathy do not differ among adolescents with type 1 and type 2 diabetes;
however, adolescents with type 2 diabetes appear to develop neuropathy at a
more rapid rate.38
It has also been shown that renal disease and retinopathy may occur
early in the course of the disease, and, by early adulthood, many of these
complications were already causing morbidities.This indicates the need for
aggressive screening for complication in T2DM youth at diagnosis and regularly
afterwards, and collaboration with nephrology, ophthalmology, and neurology
services is a must.20
As the number of obese children increases, pediatric providers must be
aware of the higher rates of vitamin D deficiency seen in obese children.
Lifestyle factors such as skipping breakfast, increased soda intake, and
26
increased juice intake appear to contribute to the lower 25(OH)D levels seen in
obese children. In our study, 25(OH)D levels in obese children were negatively
correlated with both insulin resistance (as measured by Homeostatic Model
Assessment-Insulin resistance/ HOMA-IR) and 2-hours glucose levels from an
OGTT. Thus, low 25(OH)D levels may play a role in the pathophysiology of
impaired glucose tolerance in obese children.40
The prognosis of this patient is ad vitam ad bonam and ad functionam ad
bonam because there were only few symptoms at this patient and there was no
complication found at this patient, but ad sanationam is dubiaadbonam because
patient takes the drugs routine now and her family support her. But, diabetes
mellitus is a long term disease, there is possibility that she will fail to change life
style for a variety of reasons, including a high rate of depression in teenagers,
which affects adherence; and peer pressure to participate in activities that often
center on unhealthy eating. The patient is advised to check her random plasma
glucose routine and HbA1c every 3 months to monitor her glicemic control.

27