ACCUMULATION OF SKIN ADVANCED

GLYCATION END-PRODUCTS ARE

ASSOCIATED WITH EARLY RETINOPATHY
IN YOUTH WITH TYPE 1 DIABETES
Yoon Hi Cho1,2, Maria E Craig1,2,3, Andrzej Januszewski4, Stephen Hing1,
Alicia Jenkins4, Kim C Donaghue1,2
1. Institute of Endocrinology and Diabetes, The Children's Hospital at
Westmead
2. Discipline of Paediatrics and Child Health, The University of Sydney
3. School of Women's and Children's Health, University of New South Wales
4. NHMRC Clinical Trials Centre, The University of Sydney

BACKGROUND
Advanced glycation end products
Advanced glycation end-products (AGEs) are proteins

or lipids glycated after exposure to sugars

AGEs accumulate with age, age-related diseases such

as atherosclerosis and Alzheimers disease, chronic

renal failure
AGE accumulation also accelerated in diabetes;

enhanced by elevated glucose and oxidative stress

and so implicated in pathogenesis of diabetes
complications

AGEs
AGE measurement: plasma and skin biopsies
Non-invasive measure of skin autofluorescence (AF) - correlates well

with skin biopsy quantification

AGEs can be fluorescent (e.g. pentosidine) and non-fluorescent AGE

(e.g. N-(carboxymethyl)lysine [CML]).

Fluorescent AGEs: a characteristic fluorescence spectrum at 440 nm.
Skin AF associated with microvascular complications in adults with

type 1 and 2 diabetes. No data in adolescents.

AIMS
1. To compare AGE accumulation, as measured by skin

autofluorescence (AF), in young people with type 1

diabetes (T1D) vs controls
2. To examine putative association between skin

autofluorescence (AF) and diabetic retinopathy

METHODS
100 Participants recruited through the Diabetes Complications

Assesment Service, The Childrens Hospital at Westmead (age

range 8-28 yrs, mean age 17.3 yrs 3.6)
77 Controls non-diabetic siblings and staff members/families
Performed skin autofluorescence using the Diagnoptics AGE

reader
Retinal photography: 7-field stereoscopic retinal photography

Skin Autofluorescence
Diagnoptics AGE Reader
A light source illuminates the

skin of the forearm

This light excites fluorescent
moieties in the tissue
Fluorescent AGEs will emit light
with a specific wavelength
Skin AF: ratio of average
fluorescence per nm over the
entire emission spectrum 420
600 nm: 300420-nm range

Controls vs T1D: Age-adjusted mean skin AF

2.00
1.80

p=0.002

1.60

Skin AF (AU)

1.40
1.20
1.00

0.80
0.60
0.40
0.20
0.00

Controls

T1D

Skin autofluorescence: controls vs

T1D retinopathy free vs retinopathy

Age-adjusted skin autofluorescence:

Controls vs T1D retinopathy free vs retinopathy
2.00
1.80

1.60

p<0.00001
p<0.001

Skin AF (AU)

1.40
1.20
1.00

0.80
0.60
0.40
0.20
0.00

Controls

T1D Ret[-]

T1D Ret[+]

Skin AF relationship to age and diabetes status

2.5

Skin Fl (AU)

2.0
1.5
1.0
Controls; y=0.031+0.69
T1D Ret[-]; y=0.040+0.61
T1D Ret[+]; y=0.049+0.66

0.5
0.0

10

20

Age (yrs)

30

ROC curve AUC 0.77

100

Sensitivity (%)

80
60
40
20
0
0

20

40

60

100-Specificity (%)

80

100

Retinopathy
Retinopathy
N=23

No retinopathy
N=77

p-value

Age (yrs)

19.8 [17.4-22.2]

16.9 [16.0-17.8]

0.002

Skin autofluorescence

1.65 [1.46-1.85]

1.37 [1.24-1.50]

0.03

HbA1c (%)

10.0 [8.9-11.1]

8.5 [8.2-8.9]

0.001

Duration (yrs)

12.6 [11.4-13.8]

8.9 [7.8-10.0]

<0.001

Cholesterol (mmol/L)

4.7 [4.2-5.2]

4.5 [4.2-4.7]

0.31

No differences in blood pressure, BMI SDS

Skin AF highest quartile and retinopathy

Univariate
OR

Model 1
OR

Model 2
OR

Quartile 4 skin AF

5.9

6.7

3.9

Age (years)

1.2

Duration (years)

1.3

HbA1c (%)

1.7

Model 3
OR

1.2
1.2
1.5
R2=0.21

1.7
R2=0.18

R2=0.18

Conclusions
Accumulation of skin AGE in youth with diabetes is

higher than age-matched controls.

Skin AF is associated with age , duration and
longitudinal glycaemic control in diabetes
Skin AF was associated with retinopathy independent
of HbA1c, but age remains a significant confounder.
FUTURE STUDIES
Skin autofluorescence as potential measure of
"metabolic memory" in diabetes complications

Acknowledgements
CHW Diabetes Complications Assessment Service: Ms Janine

Cusumano, Ms Alison Pryke, Ms Tracey Jopling, Dr Paul BenitezAguirre, Dr Myra Poon

Collaborators: University of Sydney Clinical Trials Centre
Funding: Australian Postgraduate Award, University of Sydney
Patients and families who participated in the study

Retinopathy
Highest quartile skin AF

5.9, 2.1-16.0; p=0.001

Age 1.2, 1.5-1.4; p=0.005
Duration 1.3, 1.1-1.5;
p=0.001
HbA1c 1.7, 1.2-2.5;
p=0.003

Model 1: R2=0.21
Highest quartile SAF 6.7, 2.022.1; p=0.002
HbA1c 1.5, 1.0-2.2; p=0.04

Model 2: R2=0.18
Highest quartile SAF 3.9, 1.311.5; p=0.01
Duration 1.2, 1.1-1.4; p=0.008
Model 3: R2=0.18
Age 1.2, 1.0-1.4; p=0.01
HbA1c 1.7, 1.2-2.6; p=0.006

HYPOTHESIS
Skin AF is higher in young people with T1D than

controls
Skin AF is higher in young people with retinopathy

compared to those retinopathy-free, independent of

glycaemic control