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Association between markers of

endothelial dysfunction and early signs


of renal dysfunction in pediatric obesity
and type 1 diabetes
M. Loredana Marcovecchio, Tommaso de Giorgis, Simone Franchini,
Daniela Caniglia, Francesco Chiarelli, Angelika Mohn
Department of Paediatrics,
University of Chieti, Chieti, Italy

Presenter Disclosure Information

M. Loredana Marcovecchio
Disclosed no conflict of interest.

Background
Obesity and type 1 diabetes (T1D) are two dysmetabolic
conditions that are increasing in prevalence among children
and adolescents.
Ogden CL et al., JAMA 2014; Patterson CC et al., Lancet 2009

Both conditions are recognized to be associated with an


increased risk of developing cardiovascular disease and
microvascular complications.
Shay CM et al., Circulation 2013; Franchini S et al., Pediatr Diabetes 2014

Common mechanisms implicated in vascular disease in


obesity and T1D are inflammation and oxidative stress,
which both contribute to endothelial dysfunction.
Ceriello A et al., Arterioscler Thromb Vasc Biol 2004

Background
Increased levels of inflammatory and oxidative stress
markers, such intercellular adhesion molecule-1 (ICAM-1)
and myeloperoxidase (MPO), have been associated with the
development of endothelial dysfunction.
Szimiko PE et al., Circulation 2003; Lau D et al., Pharmacol Ther 2006

Data on the potential role of these markers in the


pathogenesis of obesity- and diabetes-related vascular
disease in the pediatric population are limited, and they
have not been compared between youth with obesity and
those with T1D.

Study Aims
To evaluate and compare circulating levels of
intercellular adhesion molecule-1 (ICAM-1) and
myeloperoxidase (MPO) in children and adolescents
affected with obesity or with T1D.

To assess whether ICAM-1 and MPO levels are


associated with markers of renal function.

Study Population
and
Methods
Methods
2
Study population
Obese group:
N = 60

T1D group:
N = 30

Control group:
N = 30

618 yr
BMI >95th percentile
Normal glucose tolerance
No medications
No chronic diseases

Clinical examination: height, weight, BMI, Pubertal stage, blood pressure


Blood samples: to measure ICAM-1 and MPO (ELISA method)
24-hour urine collection: to measure albumin excretion rate (AER)
Glomerular filtration rate (GFR) was calculated from serum creatinine using the
Schwartz formula.

618 yr
BMI: 5-85th percentile
No other chronic diseases
No medications apart from
insulin

618 yr
BMI: 5-85th percentile
No chronic diseases
No medications

Study Results

General characteristics of the study population


Obese group
(n= 60)

T1D group
(n=30)

Control group
(n= 30)

Sex (M/F)

30/30

15/15

15/15

0.44

Age (years)

12.5 2.8

12.9 2.4

12.4 3.3

0.72

Puberty stage
(pre/pub)

12/48

7/23

7/23

0.99

BMI (kg/m2)

31.4 5.2

21.3 2.6

18.7 2.5

<0.001

BMI z-score

2.26 0.46

0.45 0.77

-0.25 0.56

<0.001

Systolic BP (mmHg)

116.9 9.6

107.4 12.5

110.6 9.7

<0.001

Diastolic BP (mmHg)

67.5 6.0

65.4 8.7

62.7 6.6

0.001

HbA1c (%)
HbA1c (mmol/mol)

5.0 [4.5-5.0]
31 [26-37]

7.6 [7.1-8.4]
60 [54-68]

4.2 [4.0-4.5]
22 [20-26]

<0.001

Data are mean SD or median [interquartile range]; P values are from one-way ANOVA test

Study results

Markers of Renal function

Controls
Controls
Obese
AER
(ug/min)
e-GFR
(ml/min/1.73m2)

7.948.92
7.94
(5.35-8.13)
(6.53-10.84)
(5.35-8.13)

Obese

T1D

8.92
9.00
8.92
9.00
9.00
(6.53-10.84)
(7.75-12.40)
(6.53-10.84)
(7.75-12.40)
(7.75-12.40)

P P

0.314
0.001
<0.001

134.50
142.82
134.50
142.82
145.50
142.82
145.50 145.50
0.485
0.007
0.002
0.005
(119.00-142.25)
(124.31-160.32)
(119.00-142.25)(124.31-160.32)
(130.75-156.00)
(124.31-160.32)
(130.75-156.00)
(130.75-156.00)

Data are median [interquartile range]


P values are from one-way ANOVA test and Bonferroni Post hoc test

Study results

Obese
T1D
T1D

Markers of Endothelial dysfunction


ICAM-1
P for trend < 0.001
p = 0.001

P= 0.716

p < 0.001

P values are from one-way ANOVA and Bonferroni Post hoc test
Study results

Markers of Endothelial dysfunction


Myeloperoxidase (MPO)
P for trend < 0.001
p = 0.001

P= 0.905

p < 0.001

P values are from one-way ANOVA test and Bonferroni Post hoc test
Study results

Independent associations between markers of renal


function and markers of endothelial dysfunction

ICAM-1

GFR
AER

0.23
0.26

P
0.012
0.004

MPO

0.18
0.05

Results are adjusted for age, sex, pubertal stage, BMI, HbA1c

Study Results

P
0.08
0.60

Summary and Conclusions (1)


Children and adolescents with T1D and those with
obesity showed increased levels of inflammatory and
oxidative stress markers compared to healthy peers.
No differences were found between T1D and obese
youth in the investigated markers.

These findings suggest a similar increased cardiovascular


risk in youth with obesity and T1D.

Summary and Conclusions (2)


Children and adolescents with T1D and those with
obesity also showed early signs of renal dysfunction,
as indicated by increased GFR and AER, compared to
healthy peers.
ICAM-1 was independently associated with GFR and
AER.

This suggests a potential role of inflammation-mediated


endothelial dysfunction in the pathogenesis of early
renal alterations in the context of obesity and T1D.

Final conclusions
Further studies are required to confirm a
pathophysiological role of these markers in vascular
complications of T1D and obesity:
Further assessments in additional cohorts of
youth with T1D and with obesity.
Longitudinal studies to assess their potential
predictive role for the development of vascular
complications.