Advanced Glycation End products in Children with Obesity and Children with Diabetes Mellitus type 1

Advanced glycation endproducts (AGEs) are known to accumulate in collagen in
human skin. AGEs can be measured invasively in plasma and non-invasively in
skin. AGEs in skin can be measured with skin auto-fluorescence (sAF) due to
their fluorescent characteristics. Chronic hyperglycemia and oxidative stress
result in elevated AGEs levels. Therefore, patients with obesity or diabetes
are known to develop elevated levels of AGEs.

Even though glycemic control in patients with diabetes mellitus type 1 (T1DM)
is measured by HbA1c levels, AGEs levels also provide information on chronic
glycemic control. AGEs, measured as sAF levels are known to be significantly
higher in adults with T1DM compared to non-T1DM adults. It has also been shown
that sAF levels in adults with T1DM correlate with duration of diabetes and
levels of glycated hemoglobin. One study in children demonstrates a correlation
between HbA1c and AGEs measured in plasma. However, until today, very little
data has been published regarding these correlations with AGEs measured with
sAF in children and young adults with T1DM.

In adult patients with central obesity, significantly higher levels of AGEs
have been measured compared to non-obese adults. So far, there are some data on
AGEs measured in plasma in children and young adults. However, data on AGEs
measured non-invasively with sAF in obese children are scarce.

Correlation between AGEs measured with sAF and HbA1c in adults have been
published, but very little data on this correlation is known in children and
young adults with T1DM. In addition in obese adults elevated levels of AGEs
have been demonstrated, whereas data on level of AGEs in obese children are
scarce.

Therefore, the rational of the current study is to generate data on levels of
AGEs measured with sAF in children and young adults with T1DM and in obese
children with or without T2DM.

The primary aim of the GLYCOD study is to determine sAF levels in children and
young adults with T1DM and in children with obesity with or without T2DM and
determine the correlation between sAF levels and HbA1c. In the current study
sAF levels will be measured with the AGE reader.

Primary objective:
To determine sAF levels in children and young adults with T1DM and in children
with obesity with or without T2DM and determine the correlation between sAF
levels and HbA1c in children and young adults with T1DM and in children with
obesity with or without T2DM.

Secondary objectives:
To determine the correlation between sAF levels and age, body mass index,
duration of T1DM, duration of obesity, duration of T2DM, cardiovascular
parameters, lipid profile, renal function and use of medication for
co-morbidities.

Tertiary objectives (exclusively applicable in obesity with or without
T2DM-group):
To determine the correlation between sAF levels and fasting plasma glucose
(FPG), fasting plasma insulin (FPI), insulin resistance (IR) and impaired
glucose tolerance (IGT).

cross-sectional observational study.

Burden
The AGEs will be measured non-invasively with sAF during the regular
anthropometric measurements at the out-patient clinic. The measurement will
prolong the time of measurements with approximately five minutes. No extra
hospital visits are needed, since the measurement will be done during the
regular visits at the out-patient clinic. Additional determinants will be
collected from medical charts, preferable at the day of the sAF measurement or
at the most nearest date to the sAF measurement, with a maximum of 90 days from
the sAF measurement.


Risks
Up to date no risks are known from sAF measurement with the AGE reader in
children with diabetes. The AGE reader has been used safely in adult studies in
patients with T1DM, T2DM or obesity.1,8

Benefit
The participants will gain no benefit from participating in this study.

Group relatedness
Until today very little data exist on sAF levels in children with T1DM and in
children with obesity with or without T2DM and the correlation between sAF
levels and glycemic control; duration of T1DM and T2DM, and duration of obesity
in children. Therefore, it is essential to obtain sAF levels in these specific
paediatric populations.