Health Organisation and the American Diabetes Association [3]. Patients frequently
present with typical symptoms, such as elevated blood glucose level,
polyuria, polydipsia and unexplained weight loss. Also other, less-specific
symptoms such as acanthosis nigricans and hyperandrogenism may represent
clinical indicators for the presence of type 2 diabetes in an individual [24].
A simple algorithm will help to establish the diagnosis (fig. 2).
Screening
The population with a special risk to develop type 2 diabetes mellitus
should be screened already at a young age of life: obese children with a family
history of type 2 diabetes and particularly African-Americans, native Americans
and Hispanic children. Other than in adults, in children and adolescents with
newly diagnosed diabetes, type 2 diabetes counts for 5–45% of cases [32].
In some cases it might be advisable to determine autoantibodies, for example
to IA-2 and GAD65, to define or rule out autoimmunity or even to carry out
molecular analysis for differentiation of MODY types in order to clearly classify
diabetes in a patient [3, 31, 36, 37]. However, autoantibodies to IA-2 and
GAD65 might be found in patients with type 2 diabetes as well. Thus, they are
not specific for type 1 diabetes mellitus [31].
Data on glucose metabolism in children and adolescents (i.e. glucose production,
gluconeogenesis, and insulin sensitivity) have been published recently
by Sunehag et al. [38], which will be valuable helping to interpret metabolic
studies in obese children and children at risk to develop type 2 diabetes.
Co-Morbidity
Among the most common sequelae of primary childhood obesity are hypertension,
dyslipidemia and psychosocial problems [10, 11, 12, 14], predisposing
for additional co-morbidity such as cardiovascular disease in early adulthood
[39]. For this reason, obese children and, even more important, children and
adolescents with diabetes mellitus should be carefully examined with regard to
blood pressure monitoring and check of lipid status [25, 27, 33, 39, 40]. It is
mandatory to involve orthopedic surgeons and child psychiatrists into the treatment
regimen of those patients. In adulthood, it has been shown that alcohol and
illicit drug use are associated with an earlier onset of type 2 diabetes [30]. As a
consequence of the epidemic of overweight and obesity, a new epidemic of
childhood hypertension has also been recognized in children. Ambulatory
blood pressure monitoring is a helpful tool to investigate children and adolescents
at an early stage of the disorder [39, 40].
Treatment
For the treatment of diabetes mellitus, several therapeutic strategies have
to be included and taken into consideration: psychological and family therapy
interventions, lifestyle/behavior modification and nutrition education. Regular
exercise is especially emphasized [11, 39, 41–43]. Multidisciplinary outpatient
treatments are considered to be the most effective [44]. Health insurance
providers and policy-makers should strongly support obesity prevention programs
as the most cost-effective therapy of type 2 diabetes. Both exercise and
physical activity have a significant effect on body weight reduction as well as
on insulin sensitivity and a reduction of serum interleukin-6 concentrations
[45]. Any comprehensive treatment protocol for type 2 diabetes should therefore
include exercise programs and physical training. Most importantly, lifestyle
intervention programs have turned out to be more effective and more
efficient than pharmacotherapy for the prevention of progression from impaired
glucose tolerance to overt type 2 diabetes in obese adults [3, 45].
However, for long-term treatment of very obese adolescents as well as
individuals with type 2 diabetes, pharmacotherapy may be necessary [28]. The
clinical picture in children with type 2 diabetes and the fact that most affected
patients come from families with type 2 diabetes mellitus have led physicians
to conclude that affected children will respond to the same treatments used in
adults and that clinical courses will be similar to those described in adults.
However, data is very limited about experience in children with most of the
drugs that are being frequently used for glycemic management in adults with
type 2 diabetes.
At present, metformin is being studied as therapy for both type 2 diabetes
and obesity in children and adolescents. Metformin has been shown to decrease
hyperinsulinemia and insulin resistance in adults, but also to reduce plasma
leptin, cholesterol and free fatty acids [46, 47]. Since metformin also seems to
reduce appetite in obese children with type 2 diabetes, it may be beneficial and
prove to be the drug of choice in the long term. However, side effects include
gastrointestinal problems and should not be neglected [45–47].
In the acute state of type 2 diabetes, children are treated with insulin. Some
of these children will have to be transitioned to oral antidiabetic agents. Very
recently, multicenter trials of metformin used in children with type 2 diabetes
mellitus have been completed in the United States. Metformin was found to significantly
improve glycemic control in 82 subjects with type 2 diabetes aged
10–16 years. Doses of up to 1,000 mg twice daily were reported to be safe and
efficacious [47]. At present, metformin is a safe and effective treatment option
for type 2 diabetes mellitus in pediatric patients [2, 5, 47].
With regard to therapy of co-morbidities which frequently accompany type 2
diabetes mellitus in children, such as hyperlipidemia and hypertension, there
are no evidence-based guidelines as to what therapy should be used.
Prevention
The financial and societal consequences of the emerging epidemic of
obesity and type 2 diabetes are substantial and demand a prompt public health
response. Emphasis must be placed upon preventive strategies [26]. As prevention
has to start very early in life and perhaps even before extrauterine life [11],
a population and community approach for prevention of obesity and hence type 2
diabetes in childhood and adolescence seems to be the most promising and
reasonable treatment strategy available at the moment. A multidisciplinary team
approach is asked for to develop and secure preventive strategies. Good nutrition
and modest exercise for pregnant women as well as monitoring of intrauterine
growth of the child are mandatory. After birth, rapid weight gain should be
avoided and principles of good nutrition and physical activities should be taught
at all ages [42]. Breast-feeding should strongly be recommended. Children’s
food choice can be influenced by early intervention and guidance. The costeffectiveness
of group and mixed family-based treatments for childhood
obesity has been tested and proven. It is therefore to be concluded that familybased,
behavioral treatment of obesity is the best strategy to prevent type 2
diabetes [45, 48].
Perspectives
Obesity is the most common chronic disorder in the Western World [10, 11].
Childhood obesity is associated with substantial co-morbidity and late sequelae
[11, 14]. While diagnostic strategies are clear and straight forward, treatment
remains difficult. In our opinion, much more attention should be given to prevention
and the development of preventive strategies early in life. Physicians
should make the public aware of both the childhood obesity epidemic and its
serious consequences and among them most importantly of type 2 diabetes. In
conclusion, it is becoming increasingly clear, that very obese children above the
age of 10 years should be screened for the presence of impaired glucose tolerance
or overt type 2 diabetes. Prevention and treatment of type 2 diabetes should
finally become one of the prime targets of public health intervention programs
[3, 17, 19–22, 24].
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