Current Obesity Reports

https://doi.org/10.1007/s13679-019-00357-x

METABOLISM (M DALAMAGA, SECTION EDITOR)

Metabolic Syndrome in Children and Adolescents: Diagnostic Criteria,

Therapeutic Options and Perspectives
Paul Weihe 1 & Susann Weihrauch-Blüher 1

# Springer Science+Business Media, LLC, part of Springer Nature 2019

Abstract
Purpose of Review This review summarizes our current understanding of the metabolic syndrome (MetS) in children and
adolescents. Special emphasis is given towards diagnostic criteria and therapeutic options.
Recent Findings Consistent diagnostic criteria to define MetS in childhood and adolescence are not available to date. There is
common agreement that the main features defining MetS include (1) disturbed glucose metabolism, (2) arterial hypertension, (3)
dyslipidemia, and (4) abdominal obesity. However, settings of cut-off values are still heterogeneous in the pediatric population.
Additional features that may define cardiometabolic risk, such as non-alcoholic fatty liver disease (NAFDL) or hyperuricemia,
are not considered to date.
Summary Prevalence of childhood obesity has more than doubled since 1980, and 6–39% of obese children and adolescents
already present with MetS, depending on the definition applied. There is common agreement that a consistent definition of MetS
is urgently needed for children to identify those at risk as early as possible. Such definition criteria should consider age, gender,
pubertal stage, or ethnicity. Additional features such as NAFDL or hyperuricemia should also be included in MetS criteria.
Lifestyle modification is still the main basis to prevent or treat childhood obesity and MetS, as other therapeutic options
(pharmacotherapy, bariatric surgery) are not available or not recommended for the majority of affected youngster.

Keywords Obesity . Childhood . Adolescence . Metabolic syndrome . Definition . Therapy

Introduction transaminases and nonalcoholic fatty liver disease

The prevalence of childhood and adolescent obesity has
reached dramatic dimensions globally and still remains one
of the most challenging problems in the western civilization.
Many affected children already present with one or more
cardiovascular risk factors or metabolic disturbances such as
dyslipidemia, disturbed glucose tolerance and even type 2
diabetes, hyperuricemia, arterial hypertension, and others
[1]. As associated comorbidities increase with severity of obe-
sity already at a young age, a significant number of obese
children and adolescents already suffer from elevated
This article is part of the Topical Collection on Metabolism
* Susann Weihrauch-Blüher
susann.weihrauch-blueher@uk-halle.de
1
Department of Pediatrics I/Pediatric Endocrinology, University
Hospital of Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle
(Saale), Germany
(NAFLD), orthopedic problems, psychological comorbidity
(depression or attention deficit disorders), and sleep disorders.
In addition, there is significantly increased risk for malignan-
cies later in life [2–4].
The Global Burden of Disease Study has presented data
that prevalence of childhood obesity has doubled in more than
70 countries since 1980. It is estimated that up to 115.1 million
children are obese, accounting to a global prevalence of 5%
[5, 6••]. Overall prevalence of overweight and obesity was as
high as 23% in 2015, corresponding to 603.7 million adults.
This is the more alarming since obesity has been made respon-
sible for about 4 million deaths worldwide in 2015 which were
mainly attributable to cardiovascular disease (nearly 70% of
the deaths) [5].
Therapeutic interventions to treat childhood obesity (i.e., to
reduce BMI or standard deviation score of body mass index,
BMI-SDS) have only shown modest success to date, with an
achievable reduction in BMI-SDS between 0.05 and 0.42 [7].
However, results of therapeutic interventions are the better the
earlier they are initiated and show the best effects in younger
 Curr Obes Rep

Table 1 Comparison of suggested diagnostic criteria for the MetS in childhood and adolescence. Definition of MetS in the pediatric population as proposed by different groups. MetS can be diagnosed if

AHD anti-hypertensive drug, BMI body mass index, DBP diastolic blood pressure, FG fasting glucose, GI glucose intolerance, HDL-C high-density lipoprotein cholesterol, HOMA-IR homeostatic model
Monitoring level (action level)
children (kindergarten- or early school age), whereas effects are
limited during puberty [8]. A recent study has shown that obesity

Prevalence in overweight
that has started before the onset of puberty is associated with a

FG or HOMA-IR > 90th

≥ 90th (95th) percentile
≥ 90th (95th) percentile
≥ 90th (95th) percentile
≥ 90th (95th) percentile
Ahrens et al., 2014:

prevalence in obese
≤ 10th (5th) percentile

adolescents: 13.2%
adolescents: 4.5%;
significantly increased risk to develop type 2 diabetes and car-

(95th) percentile
diovascular disease in midlife [9]. All these aspects underline the
importance to identify children at increased risk for cardiometa-
bolic comorbidity as early in life as possible. Consistent and
internationally validated criteria should be applied so that preven-

–
–
tive or therapeutic measures can be initiated before concomitant
disease has manifested. The aim of this review is to give a con-

Zimmet et al. 2007 [15]

cise and critical overview regarding our current understanding of

Prevalence in overweight
the metabolic syndrome in childhood and adolescence and to

prevalence in obese
adolescents: 0.4%;
Taking LLD or AHD

adolescents: 3.6%
discuss available therapeutic options.

FG ≥ 5.6 mmol/L
≥ 90th percentile

≤ 1.03 mmol/L
≥ 1.7 mmol/L
≥ 130 mmHg
≥ 85 mmHg
Definition of Metabolic Syndrome in Children
and Adolescents

–
There is no international consensus how to define the meta-

assessment of insulin resistance, LLD lipid-lowering drug, SBP systolic blood pressure, TG triglycerides, WC waist circumference
de Ferranti et al., 2004 [14]
bolic syndrome (MetS) in children and adolescents so far.

1 metabolic abnormality,
Since 2003, several definitions have been proposed by several

two-thirds had at least

adolescents: 31.2%;
≤ 1.17 mmol/L(girls),

Overall prevalence in

and nearly 1 in 10
groups, and most authors have adapted criteria from the adult

≤ 1.3 mmol/L (boys)

overweight/obese
FG ≥ 6.11 mmol/L
≥ 75th percentile
≥ 90th percentile
≥ 90th percentile
population. However, definitions differ in terms of cut-off

≥ 1.1 mmol/L

had MetS
values. There is common agreement that four main compo-
nents should be included: (1) hyperinsulinemia/disturbed glu-
cose metabolism/insulin resistance, (2) arterial hypertension,

–
–
(3) dyslipidemia, and (4) abdominal obesity. According to the
most commonly used MetS definitions for the pediatric pop-

subjects: none met the criteria

ulation, as suggested by Cook et al. [10] as well as the

Prevalence in moderately obese

subjects: 38.7%; prevalence
in (severly) obese subjects:
International Diabetes Federation (IDF) [11], MetS can be

overweight or nonobese
Weiss et al., 2004 [13]

49.7%; prevalence in
diagnosed with abdominal obesity and the presence of two
or more other clinical features. Abdominal obesity is defined
GI (ADA criteria)
≥ 95th percentile
≥ 95th percentile
≥ 95th percentile

for the MetS

≤ 5th percentile

as elevated waist circumference (WC), based on age- and

z–score ≥ 2

gender-specific percentile curves. Additional anthropometric,

clinical, and metabolic parameters to define MetS in children
and adolescents should also be based on age- and sex-specific
–

reference curves or values.

An overview of proposed definitions is presented in
in adolescents at risk (BMI 85th
prevalence in overweight/obese
Overall prevalence in adolescents

Table 1.
percentile): 8.7%; prevalence

to < 95th percentile): 6.8%

Available definitions for the MetS in children and adolescents

adolescents (BMI > 95th
aged 12–19 years: 4.2%;
Cook et al., 2003 [12]

have several limitations: (1) Additional parameters that are sig-

nificantly associated with increased cardiometabolic risk, such as
FG ≥ 6.11 mmol/L
≥ 90th percentile
≥ 90th percentile
≥ 90th percentile

steatosis hepatis/NAFDL or hyperuricemia, have not been con-

≥ 1.24 mmol/L
≤ 1.03 mmol/L

sidered so far. (2) There is ongoing discussion about which

criteria are to use. Among these criterions are some marked
differences to the setting of cut-off values, which may lead to
–
–

underestimation of affected children [16]. And, (3) available def-

≥ 3 criteria are fulfilled

initions only refer to peri- or postpubertal children, and criteria or

according to study
Glucose homeostasis

cut-offs for prepubertal children are lacking so far. Therefore,

Prevalence of MetS
Pharmaco-therapy

Ahrens et al. proposed a new definition of MetS, which also

includes criteria for prepubertal children [17]. The German
Variables

HDL-C

Leibnitz Institute for Prevention Research and Epidemiology

DBP

BMI
SBP
WC

TG

(BIPS) has established an online tool to assist pediatricians and

Curr Obes Rep
general practitioners in assessing the risk of MetS in children
aged 3–10 years. Data from the IDEFICS study were applied
to validate and implement this tool [18]. First analyses have
shown that this tool has led to a higher number of children/
adolescents that are considered “at risk to develop MetS” and
are therefore under observation.
In summary, cardiometabolic disease is a major health risk
already in young children with obesity. Prevalence of MetS in
childhood and adolescence has been estimated to differ be-
tween 6 and 39%, depending on which diagnostic criteria
are applied [19].
Diagnostic Criteria
To define cardiometabolic risk in obese children and adolescents,
a detailed clinical examination is essential. Anthropometric mea-
sures should include standardized determination of body height,
weight, waist, and hip circumferences, applying age- and gender-
specific centiles. The degree of overweight or obesity should be
determined, applying age-and gender-specific BMI-centiles. The
clinical examination should also include the determination of
pubertal stage according to Tanner, clinical signs for cardiomet-
abolic risk factors such as acanthosis nigricans, hirsutism, or
striae distensae. To exclude rare syndromal diseases associated
with obesity, it is proposed to investigate for syndromic symp-
toms like dysmorphia, mental retardation, and growth retardation
[20].
Although the BMI does not allow to distinguish between
fat and muscle mass, it is the most useful marker and the “gold
standard” to define obesity in childhood and adolescence. In
addition, it shows strong correlations to different cardiometa-
bolic risk factors such as dyslipidemia, hyperinsulinemia, or
elevated blood pressure [13, 21].
As abdominal obesity is significantly associated to cardio-
metabolic risk, the anthropometric index waist-to-height-ratio
(WHtR) has been established and provides a useful tool to
define abdominal obesity in childhood. A WHtR < 0.5 is
regarded as normal in both, children and adults. The clustering
of BMI and WHtR could identify more patients with cardio-
metabolic risk factors [22]. The index WHtR reflects the de-
gree of abdominal obesity or visceral fat depots and may thus
define cardiometabolic risk associated with obesity [23].
Blood pressure in the daily routine is mostly accessed by
point of care measurements. This can lead to misinterpreting
of the obtained values. Thus, blood pressure should be mea-
sured at rest and in the lying position, and the mean value of
three measurements should be documented. The risk of arte-
rial hypertension is still underestimated and underdiagnosed
in children. To assess a potential risk for arterial hyperten-
sions, age- and sex-specific centile curves should be applied
in children and adolescents. A systolic or diastolic blood pres-
sure higher than the 95 percentile suggests arterial
hypertension in children. To confirm the diagnosis, a 24-h
blood pressure measurement should be performed [24].
When cardiometabolic complications or the presence of
MetS are suspected, a fasting blood sample should be obtained
and a basal checkup should be performed, including fasting
glucose and insulin, transaminases, lipids, uric acid, and addi-
tional parameters if appropriate (see Table 2).
In addition to fasting glucose and fasting insulin, the
HOMA-IR (homeostatic model assessment of insulin resis-
tance) should be assessed [15]. It has to been emphasized that
the HOMA-IR could not be strictly transferred from adulthood
to adolescents: A marked increase in insulin concentrations and
in HOMA-IR values was observed in 13- and 16-year-olds
compared with 9-year-olds, which is attributable to decreased
insulin sensitivity associated with the onset of puberty [25].
Uric acid is a product of the purine metabolism. The uric
acid plays an important role in the pathophysiology of arterial
hypertension, kidney function, congestive heart failure, and
the development of type 2 diabetes. This could be explained
through the fact that a high purine intake (animal protein,
meat, and seafood) and fructose (processed food) intake lead
to elevated uric acid levels [26]. Many obese children already
present with marked hyperuricemia.
Steatosis hepatis or non-alcoholic fatty liver disease
(NAFLD) has meanwhile been regarded as the hepatic mani-
festation of MetS. It presents the most common form of chron-
ic hepatic disease in childhood, and it is estimated that up to
20% of obese children already suffer from steatosis hepatis or
NAFDL. Alanine-aminotransferase (ALAT) and gamma-
glutamyl-transferase (GGT) are two liver function parameters
that are strongly associated with an elevated waist circumfer-
ence or BMI [21, 27].
The adipose tissue is meanwhile regarded an endocrine organ
that secretes a variety of different factors such as pro-
inflammatory cytokines (e.g., TNF-α, IL-6) and adipokines
(e.g., adiponectin, leptin, chemerin). These factors are significant-
ly correlated to metabolic and cardiovascular risk factors [28].
Most of these adipokines are not yet implemented into a routine
laboratory checkup [29]. Although Reinehr et al. [30] did not
find an association between markers of MetS (i.e., triglycerides,
HDL-cholesterol, LDL-cholesterol, blood pressure, HOMA-IR)
and several adipocytokines, it has been suggested by several
groups to include the measurement of distinct adipokines and
pro-inflammatory markers into the basal checkup of obese chil-
dren and adolescents to evaluate the risk for cardiometabolic
comorbidities.
According to the current recommendations of the
American Diabetes Association (ADA), an oral glucose toler-
ance test with 1.75 g glucose per kilo/maximum to 75 g should
be performed in obese children older than 10 years with a first-
or second-degree relative with type 2 diabetes [31].
Suggested diagnostic workup is summarized and pre-
sented in Table 2.
 Curr Obes Rep

Table 2 Suggested diagnostic workup in overweight/obese children and adolescents if MetS is suspected

Step 1: Patient’s history: Chronic disease, medication, SGA or LGA

Family history: Gestational diabetes (mother), first or second degree relatives
with obesity, type 2 diabetes or other features of the MetS

Step 2: Anthropometric data: Body weight, body lengths (calibrated scales), WC:
Calculation of BMI and WHtR to define the degree of general and visceral obesity.

Step 3: Clinical examination: Signs for syndromal obesity; acanthosis nigricans, signs
for virilization, striae distensae
3 blood pressure measurements at rest in the lying position if elevated, perform a 24-
hour blood pressure measurement

Step 4: Fasting blood sample: glucose, insulin, HbA1c, cholesterol, HDL-C, LDL-C,
triglycerides, ASAT, ALAT; GGT, uric acid,

Additional parameters, if clinically relevant: Cortisol, TSH, fT4, gonadotropines, steroid

hormones

Step 5: Oral glucose tolerance test

(according to ADA criteria)

Step 6: Additional diagnostic procedures if appropriate:

- Abdominal ultrasound (stetatosis hepatis; degree of NAFLD?)
- Ultrasound of the genital organs (polycystic ovaries?)
- Intima media thickness
- BIA measurement
Abbreviations: ASAT: aspartate aminotransferase; ALAT: alanine aminotransferase; BIA measurement: bioelectrical
impedance analysis; BMI: body mass index; fT4: free tetraiodothyronine; GGT: gamma glutamyl transferase; HDL-C:
high-density lipoprotein cholesterol; LGA: large for gestational age; NAFLD: nonalcoholic fatty liver disease; SGA:
small for gestational age; TSH: thyroid stimulating hormone; WC: waist circumference; WHtR: waist to height ratio

ASAT aspartate aminotransferase, ALAT alanine aminotransferase, BIA measurement bioelectrical impedance analysis, BMI body mass index, fT4 free
tetraiodothyronine, GGT gamma glutamyl transferase, HDL-C high-density lipoprotein cholesterol, LGA large for gestational age, NAFLD nonalcoholic
fatty liver disease, SGA small for gestational age, TSH thyroid stimulating hormone, WC waist circumference, WHtR waist to height ratio

Therapeutic Options for MetS in Childhood
and Adolescence
Many studies have shown that the weight status in early
childhood is a significant predictor for the weight status
and associated cardiometabolic comorbidities later in life.
Thus, prevention or treatment of childhood obesity should
start as early in life as possible. If any possible, it should
start with preventive measures already in kindergarten- or
young school age.
As far as therapeutic options are concerned, a recent
systemic review has confirmed what we have known be-
fore: A multidisciplinary lifestyle intervention provides
the strongest evidence of effectiveness [32]. Some studies
have suggested that a more personalized intervention may
be beneficial for an effective therapy [8, 33].
The hallmarks to treat obesity in childhood and adoles-
cence are presented as follows:
Lifestyle Intervention
Lifestyle intervention provides the basis for obesity therapy in
children and adolescents and is to date the “gold standard” or
major therapeutic option for the majority of pediatric patients.
It should include a balanced diet with reduction in energy-
dense, sugar-, and fat-rich products, an increase in daily phys-
ical activity, as well as behavioral treatment [2].
Curr Obes Rep
According to Foster et al., lifestyle intervention can be
divided into four stages: (1) “prevention plus” which focusses
on healthy eating and activity habits; (2) “structured weight
management” which is based on monthly visits to provide
structured approaches to diet counselling and regular physical
activity; (3) “comprehensive multidisciplinary intervention”
which is similar to stage 2 but includes weekly visits and
additional structured behavioral intervention; and stage (4)
“tertiary care intervention” which includes a structured pro-
gram addressing all modules of stage 3, but which is in addi-
tion considering concomitant disease, medications, severe di-
etary restrictions, or surgical intervention [8].
As pharmacotherapy and bariatric surgery are treatment
options only for an absolute minority of adolescent pa-
tients (see below), lifestyle intervention is the “gold stan-
dard” and the basis for the majority of obese children and
adolescents to date.
The four stages of lifestyle intervention suggested by
Foster and colleagues are widely accepted and applied to
prevent or treat childhood obesity and cardiometabolic
comorbidities: While most programs are based on stage
2 or 3, most of the available and validated programs differ
in duration, frequency of consultation, type and intensity
of intervention, and after-care programs. Most of the pro-
grams have a duration between 6 and 18 months. To guar-
antee short- as well as long-term success, the multidisci-
plinary team should consist of pediatricians, nutrition
counselors, psychologists, and exercise physiologists.
However, the average achievable reduction in BMI-SDS
is rather low after 18–24 months of follow-up (mean re-
duction in BMI-SDS (z-score) of − 0.34, see above) [32].
Although these effects may be regarded as very small,
a decrease in BMI-SDS of − 0.125 is capable of reducing
multiple cardiovascular risk factors (CRF) such as
systolic/diastolic blood pressure, triglycerides, insulin re-
sistance measured by HOMA-Index, and increasing HDL
cholesterol. In addition, a decrease in BMI-SDS of more
than − 0.25 was significantly associated with an improve-
ment of all CRFs except fasting glucose and LDL [34•].
In general, an intervention may be regarded as successful
if BMI-SDS is reduced by ≥ 0.2 which is almost equiva-
lent to 1 kg/m2 [35]. In accordance with all these studies
presented above, Weiss and colleagues have shown that a
reduction in BMI-SDS (z-score) of greater than 0.09 is
already associated with improvements of almost all car-
diovascular risk factors [36]. Even weight stabilization in
obese children may be regarded as success: a stabilization
of body weight in a child growing 5 cm/year equals to a
reduction of BMI-SDS of − 0.5 [34•].
In summary, these results underline the importance of
weight stabilization or (even small) weight loss induced by
lifestyle interventions to reduce or minimize the risk of
obesity-associated cardiometabolic comorbidity later in life.
Rehabilitation
To date, it is discussed controversially, which type of re-
habilitation is most favorable and most effective in child-
hood obesity. Inpatient rehabilitation approaches have
shown rapid short-term effects to reduce BMI-SDS after
an intervention of 26 weeks (− 18%) compared to ambu-
lant rehabilitation (− 10.5%). In addition, nearly all car-
diometabolic risk factors improved [37]. However, inpa-
tient rehabilitation is not the most appropriate form of
rehabilitation for many obese youngsters due to obliga-
tions in schools, fears to be away from the family for
several weeks, and other reasons. In addition, many obese
children show a rapid rebound in weight gain as soon as
they return home. Therefore, the focus for future ap-
proaches should be shifted towards ambulant rehabilita-
tion with settings addressing the entire family and which
also include aftercare programs.
As the most significant reduction in BMI-SDS can be
achieved in prepubertal children compared to obese adoles-
cents, rehabilitation approaches should generally be initiated
as soon as possible [38].
Pharmacotherapy
While various drugs for weight reduction have been released
to the market during the past years, most of them were with-
drawn again due to limited effectiveness and/or severe side
effects, and none of them was approved for children and ad-
olescents [39].
To date, there is only one medication that has been
approved by the US Food and Drug Administration
(FDA) to be used in children and adolescents: metformin.
However, this antihyperglycemic drug has only been ap-
proved so far to treat type-2 diabetes (and not disturbed
glucose tolerance or insulin resistance) in children 10
years or older. While its safety profile is quite favorable
and it is capable of improving glucose metabolism and of
reducing cardiometabolic risk profile in obese children
and adolescents, its effects on weight loss or BMI reduc-
tion, respectively, are rather limited [2, 40].
Another group of medications which is under develop-
ment and is tested in clinical trials to be used in obese
children and adolescents is incretin hormones such as
glucagon-like peptide 1 (GLP-1). However, none of these
medications has been approved for the use in the pediatric
population so far. These group of agents are described in
more detail in another study [2].
Obese children and adolescents with dyslipidemia should
be treated in first line with lifestyle modification (diet counsel-
ling and elevated physical activity). If this treatment approach
fails and if LDL levels are higher than 160 mg/dl, treatment
with statin may be considered [41].

If obese children present with arterial hypertension, first-
line treatment again should focus on lifestyle modification and
increased physical activity. Only if this has failed, pharmaco-
therapy might be considered in the second line and should be
started with an ACE inhibitor [24, 42]. β-Blockers should, if
possible, not be used in the pediatric population because of
their negative effect on energy metabolism and other side
effects [43].
If obese adolescents have already manifested type 2
diabetes, pharmaceutic intervention will depend on the
HbA1c level. If they present HbA1c > 6.5% and an im-
paired fasting glucose > 7 mmol/l, they should be treated
with metformin in the first line, in addition to a lifestyle
intervention. Insulin is to be considered if HbA1c levels
are higher than 9% [44]. The intake of metformin is also a
therapeutic option if a polycystic ovary syndrome (PCOS)
has been diagnosed [41]. In summary, there is common
agreement that first-line treatment of MetS in children and
adolescents should be lifestyle modification. The use of
medications should be limited to those who have failed to
respond after 6 months.
Bariatric Surgery
Bariatric surgery in (extreme) obese children and adoles-
cents is the last therapeutic option when all other inter-
ventions have failed. To date, bariatric surgery has been
suggested to be a therapeutic option only for extreme
obese adolescents (BMI > 35 kg/m2) with cardiometabolic
disease, if all conservative approaches including lifestyle
intervention, rehabilitation, and pharmacotherapy have
failed [45]. Although a rapid weight loss after surgery
can be achieved, it is not a therapeutic option for the
majority of adolescent patients due to certain risks like
dumping syndrome, difficulties in post-operative care,
risk of a poor supply in fat soluble vitamins and electro-
lytes, and others. In addition, there are only limited data
so far for long-term results and long-term safety [7, 40].
Prevention of MetS in Children
and Adolescents
Due to the fact that therapeutic approaches often only show
modest effects in obese children and adolescents (see above),
prevention of childhood obesity should be the primary goal
and should include both, behavioral and community-based
approaches.
In order to reach this goal, the report of the WHO
commission on ending childhood obesity suggests differ-
ent measures with six key points: (a) promotion of heathy
food; (b) promotion of physical activity; (c) focus on pre-
conception and pregnancy care; (d) starting diet and
Curr Obes Rep
physical activity in early childhood; (e) special care of
health, nutrition, and physical activity for school-aged
children; and (f) perform a proper weight management.
More detailed information is available in the Report of
the World Health Organization (WHO) [46••].
There are additional four measures that have been
demanded in the Global Action Plan of the WHO in order to
prevent and control noncommunicable diseases such as obe-
sity in children and adolescents: These measures include (1)
restriction of the advertisement of unhealthy foods to children,
(2) improving school meals by development of binding qual-
ity standards for the catering offers in kindergartens and
schools, (3) implementation of a sugar—or fat tax to reduce
consumption of unhealthy foods, and (4) increase in daily
physical activity by offering more physical activity/sports in
schools and kindergartens [47].
There is common agreement in the scientific community
that a shift from individual, behavioral-oriented obesity pre-
vention towards environment- or community-based preven-
tion strategies are mandatory to fight the obesity epidemic.
Summary and Future Perspectives
Obesity still remains one of the global burdens in medicine
especially because of its remaining high prevalence in chil-
dren and adolescents and associated cardiometabolic sequalae
of the MetS that often start early in life [5]. Obese children and
adolescents often stay obese adults, leading to markedly in-
creased morbidity and mortality. As obesity induces major
changes in the cytokine and adipokine profile of the growing
organism, there is significantly increased risk for the develop-
ment of type 2 diabetes, cardiometabolic disease, and different
types of cancer [2].
Consistent and internationally validated diagnostic
criteria to define MetS in the pediatric population are
not available and are urgently needed. Most definitions
of the MetS in children are adapted from adults.
Common agreement has been made to include abdominal
obesity, arterial hypertension, dyslipidemia, and disturbed
glucose metabolism as main features. However, there are
certain limitations in the clinical use of these proposed
definitions due to different criteria applied, heterogeneous
cut-off values, and missing values for prepubertal chil-
dren. In addition, gender and ethnic origin should also
be considered and clinically relevant disturbances such
as NAFDL or hyperuricemia which may significantly de-
fine cardiometabolic risk later in life are not yet consid-
ered in available definitions of the MetS.
Many obese children and adolescents already present with
two or more features of the MetS, and therapeutic options are
mainly based on lifestyle intervention so far. Depending on
which definition of the MetS is applied, the percentage of
Curr Obes Rep
affected children and adolescents as well the number of in-
volved components (low grade vs. high grade MetS) may vary
widely. In addition, obese children may also present with a
“healthy” phenotype, and underlying factors of the so-called
metabolically healthy obesity (MHO) are poorly understood
so far and need further investigations [48]. Prevalence for the
MHO phenotype has been estimated to be between 4 and 68%
in overweight and obese children, depending on criteria ap-
plied [48]. In a pediatric cohort from central Europe, preva-
lence for MHO has been found to be 16% [49]. On the other
hand, elevated waist circumference as marker of abdominal
obesity and increased cardiometabolic risk profile is common-
ly seen in the first line in the majority of children affected by
MetS, followed by altered lipid profile. In the third line, ele-
vated blood pressure can be frequently found [19]. However,
steatosis hepatis/NAFDL and increased liver enzymes affect
up to 50% of obese children and adolescents and should thus
be included into the diagnostic criteria defining MetS.
Intervention strategies for overweight and obese chil-
dren and adolescents have been shown only limited ef-
fects to date and cannot prevent long-term consequences
and cardiometabolic sequalae later in life in the most
countries of the world. Thus, prevention of obesity should
be the major goal and should start as early in life as
possible. Puberty seems to be a critical period for the
development of hyperinsulinemia, insulin resistance, and
other features of the metabolic syndrome, and
hyperinsulinemia and subclinical inflammation are sug-
gested to be key players for the development of concom-
itant disease of obesity later in life.
Conclusions
Common and internationally validated diagnostic criteria to
define MetS in childhood and adolescence are urgently need-
ed. Such criteria should also consider additional factors such
as age, gender, pubertal stage, or ethnicity and should also
include additional components which may define cardiovas-
cular risk such as NAFDL/elevated liver enzymes or hyper-
uricemia. To date, treatment of MetS in childhood and adoles-
cence is mainly based on lifestyle intervention, as pharmaco-
therapy or bariatric surgery is only recommended for a small
minority of patients so far.
Compliance with Ethical Standards
Conflict of Interest All authors declare that they have no conflicts of
interest.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.
References
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