the mid nineties, although the occurrence of type 2 diabetes mellitus used to be
very rare in children and adolescents until recently. A striking increase in both the
prevalence and the degree of obesity in children and adolescents in many populations
around the world is causing this phenomenon. For example, investigators in
Cincinnati, USA, reported an increase of type 2 diabetes in a review of 1,027 children
diagnosed with diabetes from 1982 to 1994. In Germany, only 70 patients
below an age of 15 years have been identified in the systematic, nationwide ‘dpv’
diabetes survey, while it has been suggested that more than 5,000 youths would
meet the diagnostic criteria of type 2 diabetes. The prevalence of type 2 diabetes
mellitus is also very high in Australasia, depending on ethnicity and the degree of
obesity [1–7]. The relation between type 2 diabetes and obesity is referred to as
one of the most challenging health issues at present. The presently available data
on type 2 diabetes in children and adolescents are summarized in order to show
preventive and therapeutic strategies against type 2 diabetes in this age group.
Definition and Epidemiology
At present, obesity is the most common chronic disease in the developed
countries and even in developing countries around the world [8–14]. The prevalence
of impaired glucose tolerance among children and adolescents with marked
obesity has been reported to be as high as 25%, and type 2 diabetes mellitus
could be detected in 4% of those children [8].
The number of obese children and adolescents is increasing worldwide,
and it has been estimated that about 22 million children younger than 5 years
of age are affected [15]. In addition, the prevalence of overweight at a young
age is increasing [16]. In the United States overweight prevalence among children
aged 4–12 years had increased by 1998 to 21.8% in Hispanics, 21.5% among
African-Americans and 12.3 among non-Hispanic whites [16]. In addition,
screening for abnormal glucose tolerance in adolescents with polycystic ovary
syndrome also yields a high number of affected individuals with impaired carbohydrate
metabolism. Of 27 subjects with polycystic ovary syndrome 8 had
impaired glucose tolerance and 1 had previously undiagnosed diabetes when
the group was screened with a 75-gram glucose challenge and glucose was
measured after 2 h. The metabolic abnormalities were seen among lean and
obese subjects [17, 18].
Type 2 diabetes mellitus in children was first reported in white UK
teenagers [19–21], Japanese youths [22], Indian adolescents [23] and young
adults and teenagers in Central Europe [4] (table 1). Most of these individuals
had marked obesity (body mass index more than 3 SDS or 99th percentile)
[19–21].
In all ethnic groups in the Unites States, the incidence of type 2 diabetes
has increased substantially over the past several years [17, 19]. In fact, in the
United States, in some populations, type 2 diabetes is now the predominant
form of diabetes in children and adolescents [2, 5, 6, 15]. Varying biological
responses to overweight in different racial/ethic groups differently contribute to
the development of type 2 diabetes during adolescence (fig. 1). Type 2 diabetes
is usually associated with significant obesity and is only very rarely diagnosed
in lean subjects. In the USA, children as young as 8 years are now being
diagnosed with the disease [19, 24–29].
Pathogenesis
Both genetic and environmental/exogenous factors play in concert in
the pathogenesis of type 2 diabetes [2, 3, 5, 19, 21, 30–32]. Family histories,
ethnicity and the concordance in monozygotic twins all point to inheritance of
the disease. Possible candidate genes putatively implicated in the regulation of
glucose homeostasis in man and hence in the pathogenesis of type 2 diabetes
are listed in table 2.
However, the striking increase of the number of individuals being affected
over a short period of time point to exogenous factors as very strong pathogenetic
candidates. Changes in life style which might be contributable to the global
epidemic of type 2 diabetes are listed in table 3.
Pancreatic beta- and alpha-cell dysfunctions have by now been described
in children with type 2 diabetes (table 4), and insulin insensitivity seems to be
an early marker for the onset of type 2 diabetes [25].
Adipocytes which expand in obesity synthesize and secrete several factors
and signaling proteins (table 5). These factors are known to alter insulin secretion,
insulin sensitivity and even cause insulin resistance under experimental and
clinical conditions. Thus, the adipose tissue seems to play a role of major significance
in the pathogenesis of type 2 diabetes.
Genetics Factors
Candidate genes that may be involved in the pathogenesis of type 2 diabetes
are listed in table 2. However, those factors are not yet as well defined as the
role of HLA genes in the pathogenesis of type 1 diabetes. At present, several
rare mutations explain less than 5% of all cases of type 2 diabetes.
Ethnic factors seem to play an important role as basal and post-challenge
insulin are significantly higher in African-American, Mexican-American and
Pima Indian children compared to Caucasian children. These ethnic differences
are independent of adiposity, while adiposity is associated with greater insulin
levels in all ethnic groups examined. African-American children are more likely
to develop type 2 diabetes at the same degree of adiposity, while Mexican-
American children may be more likely to develop syndrome X due to greater
obesity-related hyperinsulinemia and dyslipidemia [27].
Environmental Factors
The global epidemic of obesity and type 2 diabetes mellitus is contributable
to alterations in life style during the past decades (table 3). Without any
doubt, obesity is the major risk factor for the worldwide increase of type 2
diabetes in children and adolescents. Juvenile obesity may be defined as body
mass index 97th percentile corrected for age and sex [9, 11–15, 29–33].
Changes in specific eating patterns as well as alterations of the level of physical
activity at a young age may explain the increase in adiposity among children.
Increases have for example occurred in respect to the number of meals
eaten at restaurants, food availability, portion sizes, snacking and meal-skipping
as well as in regards to hours spent in front of the TV set [34, 35].
0 komentar:
Posting Komentar