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Betts
and colleagues presented anthropometric data on 168 children diagnosed
with type 1 diabetes (T1DM) between the years 1980 and 2002 in an
attempt to provide data to support the “Accelerator
Hypothesis”. This hypothesis, originally proposed in 2001 by
Wilkin (co-author of the current study), postulates that T1DM and T2DM
are a single disease rather that 2 distinct disorders with a common
final biochemical abnormality - hyperglycemia. The argument is that
the 2 types of diabetes differ only by the rate of beta cell loss and
the accelerator responsible. Three accelerators are proposed: a
potential for B-cell death, insulin resistance, and a genetic
predisposition to develop beta cell autoimmunity. The researchers
examine the relationship between body mass index (BMI) with
associated visceral obesity and the earlier onset and rising
incidence of T1DM in children.
The
study population included all children under 16 years of age
diagnosed with DM between 1980 and 2002 in Southampton, UK for whom
records of height, weight, age of diagnosis, duration of disease, and
the presence of ketoacidosis were available. Height and weight at
diagnosis were those recorded at the first outpatient visit after
treatment began (<3 weeks from presentation). It is assumed that
these data reflected pre-onset measurements since weight loss from
dehydration, etc. had been restored at that time. Height and weight
were also recorded 6, 12, and 24 months post-diagnosis. Pre-diagnosis heights and weights were measured at 3 years
of age and at school entry were abstracted from a child health
community database. BMI was calculated at each visit and converted to
SDS scores using 1990 UK standards. Waist circumference, a surrogate
indicator of insulin resistance, was measured in each child at their
outpatient visits. (Waist circumference SDS charts for children have
been published in the UK.) A local control group of 254 primary
school children was available for anthropometric measurements.
The
study group included 87 boys and 81 girls, with similar ages at
diagnosis (1.1 to 15.7 years). Mean height, weight and BMI SDS were
not different from population means and specifically not different
from the comparison group. However, there were significant positive
correlations between weight SDS and BMI SDS, and the year of
diagnosis. Those diagnosed more recently tended to be heavier.
Substantial weight SDS gain and BMI SDS increase occurred during the
first 6 months after diagnosis, but no further significant changes in
these parameters were observed over the next 18 months. There were
significant positive correlations between weight SDS and BMI SDS at 6
months and the year of diagnosis; significant inverse correlations
were noted between weight SDS and BMI SDS and age at diagnosis. The
heavier the child, the younger the age of onset.
There
were 91 of the 111 children who were positive for islet cell
autoimmunity. Their anthropometric determinations were not different
from those without autoimmunity. Likewise there were no differences
between children who presented with ketoacidosis and those who did
not. There were no significant differences between birth weights of
the study population and those of the comparison group. A subset of
younger children (n=62) who had been born more recently had been
routinely measured at ages 3 or 5 years, (0.1 to 9.8 years prior to
diagnosis). There was a significant inverse relationship between age
of diagnosis and pre-diagnostic BMI SDS suggesting that children who were heavier pre-diagnosis developed diabetes earlier. Waist measurements
were available for 90 children; 90% had waist circumferences above
the 50th centile, but there was no correlation between
waist circumference and duration of diabetes.
The
authors stated that their data showed that heavier children develop
diabetes at an earlier age, and that these children were heavier even
in their pre-school years. These data confirmed previous reports.1
They suggested that the increase in the incidence of T1DM seen in the
UK and throughout the world, especially in younger children has
occurred too rapidly to be explained by genetic changes and must
therefore be explained by environmental factors. Early weight gain
and increased BMI in young children may pre-dispose them to early
insulin resistance and early beta cell destruction. The implications
for prevention of T1DM (and T2DM) are obvious. Lifestyle
interventions must be encouraged. Of note, the authors report that
although there is an increase in the incidence of childhood onset
T1DM among several registries, this may be at the expense of adult
incidence. Obtaining documentation of a shifting incidence of T1DM
may be difficult, as many registries of T1DM do not include
information regarding adult onset T1DM
Betts P, Mulligan J, Ward P, Smith B, Wilkin T. Increasing body weight predicts the earlier onset of insulin-dependant diabetes in childhood: testing the 'accelerator hypothesis' . Diabet Med. 2005; 22:144-151.
Editor’s
Comment: This is a very provocative paper. Indeed many pediatric
endocrinologists are reporting an increase in the incidence of T1DM
in young children. Some registries however, suggest that there may be
a shift in the age of diagnosis but not a total increase in
incidence. Of course, as noted by the authors, many registries don’t
track adults along with children. If the age of diagnosis is becoming
lower, there must be a reason; hence, the Accelerator Hypothesis.
Early weight gain and increasing BMI SDS of young children may lead
to increased insulin resistance and an earlier destruction of
pancreatic beta cells in a person who may be genetically
predetermined to develop T1DM. It’s an interesting hypothesis.
In
an accompanying editorial by Daneman2 the arguments for
and against the Accelerator Hypothesis are logically presented.
Daneman suggests that there are 4 areas of the hypothesis that
warrant further scrutiny. The first area is a better study of the impact
of the epidemic of obesity on childhood diabetes. The other 3
areas relate to the 3 potential accelerators described by the
authors. Clearly this manuscript and the editorial should stimulate
lots of interest, discussion, and future studies.
William
L. Clarke, MD
References - (linked to  )
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Kibirige M, Metcalf B, Renuka R, Wilkin TJ. Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of type 1 diabetes. Diabetes Care. 2003;26:2865-2870.
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Daneman D. Is the 'Accelerator Hypothesis' worthy of our attention? Diabet Med. 2005;22:115-117.
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Current GGH - Vol. 24 No. 1
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