among children and adolescents with particular impact in minority groups
[1–10]. The incidence of T2DM is steadily escalating throughout the world in
people from a wide range of ethnic groups and all social and economic levels
[11–14]. According to the WHO ‘an apparent epidemic of diabetes has occurred
which is strongly related to lifestyle and economic change’. This warning was
already sounded in 1991 [15]. Matters have definitely gotten worse since then.
Recent projections suggest now that by the year 2010 there will be more than
230 million diabetic individuals in the world [16].
The first description of T2DM in youth was probably described already by
Elsa Paulsen [17] in 1968. She studied 66 obese children with an oral GTT and
found 5 to have an impaired GTT and 7 with diabetes mellitus by GTT applying
current criteria. Four of the children with DM and 5 with impaired glucose
tolerance (IGT) were from families with diabetes in parents and/or grandparents.
Until recently, pediatricians were taught T2DM did not exist in children and
atypical diabetes in children was classified as MODY, a monogenic, insulinopenic
class of diabetes [18, 19]. Subsequently, an increased occurrence of
T2DM was reported in children among the Pima Indians [1]. This was followed
by alarming reports of an increased occurrence of T2DM in Mexican-American
children from California, Texas, African-American children from Ohio,
Arkansas, New York, Caribbean-Hispanic children from New York and from
First Nation children from Canada [1–10].
This nearly epidemic rise of T2DM in youth is, however, not limited to the
Americas; it has now been reported from many countries around the globe from
both developed and less-developed nations [13, 20–23].
The occurrence of T2DM has been attributed to the rising rate of childhood
obesity and an increasingly sedentary lifestyle in genetically predisposed
individuals. Several studies report a steady increase in obesity in the past
30 years among American children [24–26].
There are currently no nationwide epidemiological data focusing on T2DM.
The prevalence has been established at between 2 and 50 per 1,000 in various
populations; rates have been increased as much as 10-fold over the past 2 decades
[3, 14]. In 3 studies conducted in the past decade among adolescents aged less
than 19 years, T2DM accounted for 33–50% of all diabetes in that age group.
These figures may actually underestimate the actual magnitude of the problem
because T2DM is more likely to be misclassified, misdiagnosed as T1DM or simply
go unreported [14]. Up to 50% of persons with T2DM are currently undiagnosed,
yet are at risk for all the long term sequelae of T2DM (hypertension,
hyperlipidemia, microalbuminuria). More than 40% of the children of those with
T2DM have an increased lifetime risk for also developing T2DM [27]. Within the
United States African-Americans have a 2-fold increase in risk, Hispanics a
2.5-fold increase and native Americans (First Nation Americans) a 5-fold increase
compared to Whites. The risk is slightly higher for females and those living in
poverty, probably secondary to the added risk of higher rates of obesity [27, 28].
Epidemiology
The clinical spectrum of T2DM in children forms a wide spectrum from
incidental diagnosis to severe clinical symptomatology. In its mildest form the
diagnosis is made incidentally in obese children during routine evaluation with
detection of glycosuria and hyperglycemia. Some patients present with severe
insulin deficiency, weight loss and even ketoacidosis [29, 30]. Often these
patients are initially diagnosed as having T1DM with negative autoimmune
studies. Initial insulin requirements decline usually when glucose toxicity is
controlled. There is no specific laboratory test for T2DM, though absence of
immune markers is often helpful. Jones et al. [30] documented that obese children
of all ethnicities can be antibody positive. In an efficacy study of metformin
in multi-ethnic adolescents referred with a diagnosis of T2DM, of 481 patients
screened, 10% were antibody positive.
Recently, a component of immune destruction of beta cells has been
documented in a subset of T2DM patients – latent autoimmune diabetes of
adults (LADA). There is every reason to assume that LADA can also occur in
adolescents [19].
Unstimulated C-peptide values are often diagnostic and are distinctly higher
at diagnosis in T2DM as compared to T1DM at diagnosis [18, 19, 30].
Even the clinical signs for T2DM lose some of their discriminating power:
as children’s BMI increases across the board even T1DM children may present
now more frequently as obese children [30, 31, 32].
The majority of T2DM children and adolescents in the US present with:
• obesity
• acanthosis nigricans
• are prepubertal in age (range 6–18 years, mean 14 2.3 years)
• have a strong family history of T2DM
• and belong to a minority population
(see also table 1).
In the series described and followed in the Bronx, 48% had polyuria and
polydipsia at the time of diagnosis, 13% complained of fatigue and 22% of
weight loss. The mean BMI at diagnosis was 34.7 9.0kg/m 2. Upto 20% had a
BMI within 1 SD of the mean for age. Particularly the non-obese patients were
more often symptomatic at time of diagnosis with polyuria, polydipsia and weight
loss. These systems may have led to their near normal BMI at diagnosis [8].
It should be stressed that 30% were completely asymptomatic at the time
of diagnosis and were found to be hyperglycemic after glucosuria had been
detected by routine urinalysis performed by the primary care physician.
The patients with acanthosis nigricans (AN) had higher insulin levels at
diagnosis than those without AN. Nine of the 50 females had mild hirsutism
and 2 had polycystic ovarian syndrome. Birth weight by history was normal.
The biochemical data at time of presentation again underscore the heterogeneity
of adolescents with T2DM. Although the majority of the patients were
hyperinsulinemic at the time of diagnosis, nearly 17%, had insulin levels under
10mU/ml. Girls had higher mean insulin levels than did boys. Mean blood
sugar at the time of presentation was 321 184 mg/dl. The mean HbgA1c at
time of diagnosis was 10.9% 3.3 (normal less than 6.45). Less than 7% had
a normal HgbA1c at time of presentation. Five patients presented in DKA and
ketonuria was present in 31 patients.
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