Consequences of low birthweight on urinary excretion of DNA markers of oxidative stress in young men.
OBJECTIVE
Low birthweight (LBW) has been associated with an increased risk of development of type 2 diabetes in adult life. Both type 1 and type 2 diabetes mellitus are characterized by increased oxidative stress. The purpose of this study was to investigate whether young healthy adults born with LBW showed differences in oxidative stress under normal conditions and during the added challenge of a physiological Intralipid infusion.


METHODS
Urinary excretion of DNA markers of oxidative stress were analyzed by LC-MS/MS in 19 men (aged 19 years) with LBW and in 19 age matched, normal birthweight (NBW) controls pre- and post a 3-fold increase of plasma free fatty acids.


RESULTS
Mean excretion rates of 8-oxo-guanine (8oxoGua), 8-oxo-guanosine (8oxoGuo), 8-oxo-2'deoxyguanosine (8oxodG), and 1,N6-ethenodeoxyadenosine (epsilon dA) did not statistically differ between subjects with LBW and NBW (66.9 versus 73.9 nmol/15 h, 17.8 versus 18.5 nmol/15 h, 11.9 versus 14.4 nmol/15 h and 44.0 versus 43.2 pmol/15 h, respectively). Furthermore, Intralipid infusion did not affect excretion of DNA adducts in LBW or NBW subjects. Statistically significant correlations were found between body mass index and urinary excretion of 8oxoGua (r = 0.64, p = 0.003) and 8oxoGuo (r = 0.64, p = 0.003) in the LBW group only.


CONCLUSIONS
These findings suggest that oxidative stress may be a consequence of diabetes and is not, or at least only partly, involved in the early pathogenesis of type 2 diabetes.
Hillestrøm
P R
PR
Department of Clinical Pharmacology Q7642, Rigshospitalet, University Hospital Copenhagen, Denmark.
Weimann
A
A
Jensen
C B
CB
Storgaard
H
H
Vaag
A A
AA
Poulsen
H E
HE
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001724:Birth Weight / Q000502:physiology*; D015992:Body Mass Index; D004247:DNA / Q000652:urine*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D018384:Oxidative Stress
D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D006151:Guanosine; C046215:8-hydroxyguanosine; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA