Much interest has recently focused on the effects in adulthood of an altered in utero environment. We have previously shown that the adult offspring of diabetic rats show reduced urinary calcium output and re-modelling of bone (Hamilton et al 1998, Proc. 3rd Europ. Kidney Res. Forum). Here we tested the hypothesis that changes in renal handling of calcium are the primary in utero effect of diabetes mellitus and are present immediately after birth.
Sprague Dawley female rats were injected with 60mg/kg Streptozotocin or vehicle. Half the STZ rats then received insulin implants to normalise blood glucose. Rats were then mated with normal males. Immediately after birth pups were sexed, weighed and the bladder emptied by gentle perineal stroking. On average 4 male and 4 female pups from each litter were then separated from the mother for 2 hours and kept at 37°C. The bladder was again emptied and urine collected. Calcium and magnesium were measured by atomic absorption spectrophotometry. Results are shown as means±S.E.M. with (n) being the number of litters sampled. Since no difference was seen between sexes data were pooled for comparisons between offspring of control (OC, n=15), diabetic (ODM, n=8) or insulin-treated diabetic (OIDM, n=8) mothers. Statistics were by Kruskal-Wallis with Dunn's post-hoc test.
As expected, rats born to diabetic dams were significantly lighter than those born to controls (OC 6.33±0.15; ODM 5.01±0.15; OIDM 5.80±0.35g; p<0.01, OCvsODM p<0.001). Urine volume was not affected by the in utero environment (OC 8.62±0.71; ODM 7.99±1.04; OIDM 9.45±0.84µl/2h/g body weight; ns). Both calcium and magnesium outputs were lower in the ODM than OC pups although this was not significant at the 5% level. OIDM pups exhibited significantly higher calcium and magnesium outputs than both ODM and OC pups (calcium output as µmol/2h/g body weight; OC 11.3±1.77; ODM 8.1±1.99; OIDM 24.91±6.06; p<0.01, ODMvsOIDM p<0.01: magnesium output as µmol/2h/g body weight; OC 34.89±4.83; ODM 20.95±3.53; OIDM 73.15±12.92, p<0.01, OCvsOIDM p<0.05, ODMvsOIDM p<0.01).
We conclude that the reduced urinary calcium output seen in adult offspring of diabetic dams is an in utero effect which is apparent immediately after birth and persists into adult life. Supported by the Sir Jules Thorn Charitable Trust.
03 - 04 Dec 2001
Society for Endocrinology