Diabetes Care, Vol 21, Issue 11 1990-1996, Copyright © 1998 by American Diabetes Association
Influence of puberty on endothelial dysfunction and oxidative stress in young patients with type 1 diabetes
TA Elhadd, F Khan, G Kirk, M McLaren, RW Newton, SA Greene and JJ Belch
University Department of Medicine, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
OBJECTIVE: To examine the influence of puberty on endothelial dysfunction
and oxidative stress in children and young people with type 1 diabetes.
RESEARCH DESIGN AND METHODS: There were 51 young patients with type 1
diabetes, including 12 prepubertal children, 16 adolescents, and 23 young
adults who had no clinical diabetic angiopathy, studied; none had
microalbuminuria. The three groups were matched for glycemic control, and
systolic and diastolic blood pressures and cholesterol levels were not
significantly different between the groups. Endothelium-dependent
vasodilatation was assessed by laser Doppler flowmetry after iontophoresis
of acetylcholine (ACh) to the skin of the dorsum of the right foot. Soluble
E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), von Willebrand
factor (vWF), plasma thiol (PSH), red cell glutathione (GSH), and red cell
superoxide dismutase (SOD) were measured in blood samples obtained in the
early morning. RESULTS: Skin vascular responses to ACh were significantly
reduced in the young adult group compared with the prepubertal group (P
< 0.05, analysis of variance). The levels of soluble ICAM-1 and
E-selectin were significantly higher in the adolescent group compared with
the young adult group: 338 (267-415) and 89 (64-106) ng/ml (median
[interquartile range]), respectively, versus 255 (222-284) and 58 (54-71)
ng/ml (P < 0.01 and P < 0.005, Mann-Whitney U test). SOD levels were
significantly higher in the prepubertal group at 250 (238-282) micro/ml,
when compared with the adolescent, 217 (171-249) micro/ml (P < 0.04),
and young adult, 217 (157-244) micro/ml (P < 0.02), groups. GSH tended
to be lower in the adolescent group, 1,192 (1,047-1,367) micromol/l, when
compared with the young adults, 1,286 (1,145-1,525) pmol/l, and levels of
vWF tended to be higher in the adolescent group, but these failed to reach
statistical significance (both P = 0.09). PSH was not different between the
three groups. CONCLUSIONS: These results suggest that puberty modulates
endothelial function and antioxidant mechanisms in childhood diabetes,
which may have implications for therapy and intervention.