Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring

Abstract

Aims/hypothesis: 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 streptozotocintreated 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-D 28k 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/interpretation: 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.

The effect of a low-protein diet in pregnancy on offspring renal calcium handling

“…2B). The monoclonal anti-PMCA antibody detected a broad protein band at ϳ140 kDa (ϳ133 to 147 kDa), as well as a smaller band at 92 kDa, consistent with previous observations (7). These bands were absent from negative control blots (data not shown).…”

“…Kidneys were harvested from a separate group of control (n ϭ 5 from 5 litters) and LP (n ϭ 5 from 5 litters) rats. Tissue was homogenized, and renal calcium transporter expression was determined according to the method of Bond et al (7). The antisera used were mouse monoclonal anti-calbindin-D28K (1:2,500 dilution; Sigma), mouse monoclonal anti-PMCA 5F10 (1:1,500 dilution; Cambridge Bioscience, Cambridge, UK), affinity-purified rabbit polyclonal anti-ECaC1 (1:1,000 dilution; Alpha Diagnostic International, San Antonio, TX), and polyclonal rabbit anti-NHE3 [Na ϩ /H ϩ exchanger 3 (NHE3), 1:300 dilution; Alpha Diagnostic International].…”

Body composition and bone status of children born to mothers with type 1 diabetes mellitus

“…This distribution of bone mass further away from the central axis of the bone in CDM resulted in higher axial moment of inertia, which is likely to increase the bending bone strength 3738. In contrast to these findings, Bond et al 3 found that in comparison to controls, adult offspring of streptozotocin-induced diabetic rats had thicker long bone (femoral and tibial) cortical shells, arising from deposition of bone on the endosteal surface but not the periosteal surface. At the distal ends of long bones, these animals had reduced trabecular volume compared with the adult offspring of nondiabetic rats 3.…”

“…Abnormalities of skeletal mineralisation have also been reported in infants born to mothers with type 1 diabetes mellitus and in offspring of streptozotocininduced diabetic rats 3. Mimouni et al 4 reported a 10% reduction in the radial bone mineral content (BMC), measured by single photon absorptiometry, in infants born to mothers with type 1 diabetes mellitus compared with controls.…”

“…However, Lapillonne et al 5 found that the total body BMC measured by dual-energy x-ray absorptiometry (DXA) was normal in infants born to mothers with type 1 diabetes mellitus. Adult offspring of streptozotocin-induced diabetic rats have lower trabecular and higher cortical femoral bone volumes compared with controls,3 with the latter arising from increased deposition of bone on the endosteal surface of the femoral cortical shell. To the best of our knowledge, the bone geometry and bone mineral status of children and adolescents born to mothers with type 1 diabetes mellitus has not previously been studied.…”