Obesity, Insulin resistance, and

type 2 DM in children and

adolescents
 Obesity
Metabolic syndrome

First consequence of weight increase:

insulin resitance, leads to:
Glucose intolerance
Dyslipidemia
Hypertension
Polycystic Ovary Sundrome(PCOS)
Result: type 2 DM
 25% of obese children showed glucose
intolerance
Sinha et al. NEJM 2002;346:802-10
 Tracking for overweight and obesity in
Indonesia (Julia et al. 2007)
• Prevalence of obesity > 5 times higher in urban
than rural area
• Longitudinal study of 6-8 yrs to 11-13 yrs
children (2001-6)
 Obesity in childhood is risk to be obese in
adolescence
 All obese children are obese in adolescence
 84.6% overweight is still overweight
 Prevalence of overweight and obesity increases from
childhood to adolescence from 6.1% to 12.0%
 Prevalence of underweight decreased from 27.3%
in childhood to 18.8% in adolescence
Hormone Res pedtr,2008
 Indonesia??
RISKESDAS 2007:
 Main causes of deaths in adults: stroke, DM
 Prevalence of DM (type 2): 5.7% (unDx:
4.2%)
 By age: 10.5% (45-54y), 13.5% (55-64y),
14% (65-74y)
No data of obesity in Indonesian children
and adolescent
IDAI Role
Pediatric DM in Indonesia
•Total ( SENSUS 2010) : 237,556,363
Population in • 83 millions of them are children
Indonesia

DM prevalence • 5.7% based on blood glucose

examination in 24,417 respondent
(Riskesdas age > 15th years
2007)

• 0.3 per 100,000 children/year

Estimated type • 240 new cases/year
1 DM incidence
CAUSES?
HOW WE
GOT FAT?

Time magazine, 2004

We inherited our ancestor’s
appetite
Time magazine, 2004
 Etiology of Obesity
Genetic and environment:
– multifactorial (250 genes)
Monogenetic causes:
– rare but relevant for understanding
mechanism and role of genes
The “Thrifty” Gene Hypothesis

Nature 2000;404:631
Endocrine and Biochemical disorders
with the obesity phenotype
Classical endocrine disorders:
hypothyroidism, Cushing syndrome, GH
Deficiency
Prader-Willi and other syndrome with
obesity
Hypothalamic Obesity and Insulin
hypersecretion
Insulin resistance
Leptin Resistance
 Fetal origin of adult disease
Barker hypothesis ?

Low birth weight is associated with an increased risk to obesity,

type 2 diabetes, hypertension and cardiovascular diseases
Infancy weight gain and overweight in adulthood
(Stetller et al, Circulation 2005.)

Rapid
infancy
weight gain +

+ Adulthood
overweight
Infant +
formula
feeding
 What About Breast Milk?

Does breast
feeding make a
difference?
 COMPLICATIONS OF OBESITY

Endocrine
Insulin resistance
Type 2 diabetes

Xanthakos et.al, Adolesc medModified

Clinics from2006;17
Ebbeling CB et al, Lancet 2002
OBESITY INDUCED INSULIN RESISTANCE
 Pathophysiology Genetic +
Glucotoxicity
Lipotoxicity
Enivironment
of T2DM Latent
autoimmunity

Hyperinsuline Hyperinsuline
-mia + -mia +
Insulin ↓β –cell
normal postpandrial
resistance function
glucose hyperglycemi
tolerance a
Risk factor and
markers:
• Obesity
Type 2 DM:
• Family history
•↑ insulin resistance
• Puberty
•↓β –cell function
• Minority population
•↑hepatic glucose
• PCOS
production
• Acanthosis nigricans
• Intrauterine Arslanian, Horm Res2002
programming
 Familial, clinical, and physical features
as risk factors for IR in children and
adolescent
Family history Patient’s history Physical examination
Glucose intolerance of Birth weight (small or Acanthosis nigricans
T2DM larger for gestational age) Striae
Overweight or obesity Precocious pubarche Centripetal obesity
Hypertension Evolution of obesity Adipomastia
Metabolic syndrome Dietary habits Hypertension
Hyperuricemia or gout Physical activity Acne
Coronary heart disease Medication/drugs which Hirsutism
Stroke affect appetite, glucose Tall Stature
Gestational diabetes or lipid metabolism Precocious puberty
Polycystic ovary syndrome Genu valgum
or hirsutism
Nonalcoholic fatty liver
disease

Eyzaguirre F, et al. Horm Res 2009

 Acanthosis nigricans

Di
tengkuk Di ketiak
Di tangan

Screen for insulin resistance

The IDF definition of the at-risk group and
Metabolic syndrome in children and
adolescents
Age Obesity Triglyce- HDL-C Blood Glucose or
group (WC) rides pressure known
(yr0 T2DM
6 to < 10 ≥ 90 percentile
10 to < ≥ 90 ≥ 1.7 < 1.03 Systolic ≥ ≥ 5.6
16 percentile mmol/L (≥ mmol/L 130 mmHg mmol/L (100
Or adult 150 (< 40 or diastolic mg/dL) or
cut- off if mg/dL) mg/dL) ≥ 85 mmHg known
lower T2DM , if
glucose ≥
5.6 mmol/L
recommend
OGTT
≥ 16 Use existing IDF criteria for adults
IDF Task Force l. Lancet 2007
 Childhood obesity and
premature death
Obesity, glucose intolerance, and
hypertension in childhood were strongly
associated with increased rates of
premature death
In contrast, childhood
hypercholesterolemia was not a major
predictor of premature death
Franks, et al. NEJM, 2010
Treatment of overweight and
obesity
Goal: normalisation of BMI and
prevention of complications
Lifestyle
– healthy food intake in combination with
increase of physical activity.
– Education program
Medication: no evidence in the young
 Treatment of impaired
glucose tolerance and T2DM
in obesity
Goal:
– metabolic control, no progression T2DM, and
improved BMI
Lifestyle
Medication: no evidence in the young(IGT)
(T2DM: metformin)
Insulin treatment when HbA1C is high
 Screening guidelines fot T2DM
in Children and adolescent
BMI > 85th perentile
Body weight for height > 85th perentile
Body weight . 120% of ideal for height
Plus any 2 of the following risk factors
Family history of T2DM in 1st or 2nd degree
relatives
Race/Ethnicity: American Indian, African
American, Hispanic, Asian
Signs/symptoms of insulin resistance ADA 2000
 When to Screen
Age 10 or at onset of puberty
Frequency of screening: every 2 years
Screening test : Fasting plasma glucose
Clinical judgment should be used to test for
DM in high risk patients who do not meet
these criteria. OGTT is recommended.
HbA1C?

ADA , Diabetes care 2000

 CONCLUSIONS
Still dramatic increase of prevalence of
overweight/obesity
Inequalities in Data and treatment
Indonesia: double burden
– Obesity and its long term consequences
– Undernutrition
 Conclusion
T2DM has emerged as a serious public
health problem in the pediatric population,
with its escalating rates paralleling the
epidemic of childhood obesity
High index of suspicion is important to
prompt screening in the clinical setting of
high-risk youth
Screening help early diagnosis
 CONCLUSIONS
Interventions: Normal life style (food intake
and physical activity)
– Support of parents ; Schools programs
prevention
• APPLES: UK; Trim and Fit: Singapore
• 1st Lady-White house: USA
– IDAI: Consensus
– KEMENKES, KEMDIKNAS