Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring.
OBJECTIVE
We tested the hypothesis that diabetes in pregnancy can result in the in-utero reprogramming of renal calcium and magnesium handling and of bone formation in the offspring, which persists into adulthood.


METHODS
Male offspring of streptozotocin-treated diabetic rats (OD rats) and of control non-diabetic animals (OC rats) were investigated as neonates and at 8, 12 and 16 weeks of age.


RESULTS
Compared with OC rats, urinary calcium and magnesium output was significantly reduced in OD rats at every age studied; Na+ and K+ outputs were unaffected. The renal expression of proteins involved in the tubular reabsorption of calcium (calcium ATPase, calbindin-D28k and epithelial calcium channel) was increased in OD animals compared with that in OC animals. Additionally, we observed that adult OD rats had lower trabecular and higher cortical femoral bone volumes, explained by deposition of bone on the endosteal surface.


CONCLUSIONS
These data show that diabetes in pregnancy has profound effects on male offspring in terms of renal tubular calcium and magnesium reabsorption and the normal pattern of bone formation. These effects persist into adulthood. Such long-lasting effects of diabetes on kidney and the skeleton were not suspected and could have important implications for the health of children born to diabetic women.
Bond
H
H
Academic Unit of Child Health, St Mary's Hospital, University of Manchester, Hathersage Road, Manchester, M13 OJH, UK.
Hamilton
K
K
Balment
R J
RJ
Denton
J
J
Freemont
A J
AJ
Garland
H O
HO
Glazier
J D
JD
Sibley
C P
CP
D000375:Aging / Q000502:physiology; D000818:Animals; D001846:Bone Development / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D007668:Kidney / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D008274:Magnesium; D002118:Calcium