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Biomedical subjects

J Verhaeghe

Publications and source records attributed to J Verhaeghe.

At least 19 recordsLinked to original sources
PubMed1994

Brittle bones in spontaneously diabetic female rats cannot be predicted by bone mineral measurements: studies in diabetic and ovariectomized rats.

Spontaneously diabetic BB rats were sham operated (SO) or ovariectomized (OVX) within days after onset and studied after 4, 8, and 12 weeks. Analyses included histomorphometry of proximal tibial metaphyses, biochemical analyses of humeri, DXA analyses, and biomechanical testing of femora. In SO diabetic rats, no osteoblasts, osteoid tissue, or osteoclasts were present on the trabecular bone surface, but trabecular bone volume (TBV) remained normal compared with control BB rats. The concentration of IGF-I per dry weight of humerus was decreased after 12 weeks of diabetes, whereas the concentrations of calcium and osteocalcin did not change. DXA analysis showed normal bone mineral density (BMD) at both diaphyseal and metaphyseal femoral areas. On biomechanical testing, angular deformation, energy absorption, and torsional strength of the femora were decreased after 8-12 weeks of diabetes, but stiffness was normal. Ovariectomy in diabetic rats caused a decrease in femoral BMD especially at the metaphysis, and there was a trend toward decreased TBV in the tibial metaphysis; TBV loss was less marked than in control OVX rats, however. The increase in BMD at the femoral diaphysis, measured after 12 weeks of OVX in control rats, was absent in diabetic rats. Multiple-regression analysis indicated that the presence of diabetes but not ovariectomy, weight, and mineral content correlated with decreased energy absorption, angular deformation, and strength of the femora. The data infer that the (near) absence of unmineralized bone matrix in severely diabetic rats alters bone microarchitecture and ultimately results in brittle bones, which is not predicted by BMC or BMD measurements.

Absorptiometry, Photon↗
PubMed1994

1,25-Dihydroxyvitamin D3 and osteocalcin in maternal and fetal guinea pigs.

Maternal and fetal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and osteocalcin were measured in guinea pigs, to examine their potential use as animal models for fetal bone development and calcium homeostasis. Measurements were performed on days 42, 57 and 63 of gestation. Maternal serum total 1,25(OH)2D3 concentrations were increased only at the end of gestation (day 63). However, because the vitamin D binding protein (DBP) and albumin levels were decreased by 35-50% from day 42 onwards, the unbound 1,25(OH)2D3, calculated as the 1,25(OH)2D3/DBP molar ratio, was increased before day 63. Osteocalcin concentrations during gestation were 50-54% of levels found in nongravid animals. Fetal serum total 1,25(OH)2D3 concentrations were 20% of those in maternal guinea pigs. Since DBP levels were only 9-15% of maternal levels, the unbound 1,25(OH)2D3 was consistently higher in fetuses, from day 42 onwards. There was a rise in total and unbound 1,25(OH)2D3 between days 57 and 63 of fetal life. Osteocalcin concentrations were higher in fetal than in adult guinea pigs, and reached peak values on day 57 (1023 micrograms/l, i.e. 4.2 times higher than in adult female guinea pigs). Fetuses of guinea pigs that had received a restricted food supply for 14 days (days 49-63) had normal 1,25(OH)2D3 concentrations, but decreased osteocalcin concentrations compared with normal fetuses. The data obtained in fetal guinea pigs are comparable with those found in human fetuses, and suggest that the guinea pig may be a suitable model for studies on fetal bone and mineral development.

Animals↗
PubMed1993

C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in umbilical cord serum: correlations with birth weight.

OBJECTIVE: Our purpose was to determine the correlation between birth weight and hormones or growth factors believed to be involved in fetal growth: insulin, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1. STUDY DESIGN: Five hundred thirty-eight cord serum samples were analyzed for insulin-like growth factor-I, insulin-like growth factor-II, C-peptide, and insulin-like growth factor binding protein-1 by immunoassay. Samples included all gestational ages in the third trimester and a large range of birth weights. RESULTS: Cord serum insulin-like growth factor-I concentrations increased until 39 weeks (+84% from 28 to 29 weeks), followed by a 21% decline at 41 weeks. Insulin-like growth factor-I levels were decreased by 40% in small-for-gestational-age (< 10th percentile) newborns and were increased by 28% in large-for-gestational-age (> 90th percentile) newborns in the absence of diabetes. Insulin-like growth factor-I levels were best correlated with birth weight (R = 0.48, p < 0.001). Cord serum insulin-like growth factor-II concentrations were sixfold to tenfold higher than those of insulin-like growth factor-I and were 8% to 10% (p < 0.001) higher in large-for-gestational-age than in average-weight and small-for-gestational-age newborns. Cord serum C-peptide concentrations were 28% and 34% higher in large-for-gestational-age than in average-for-gestational-age and small-for-gestational-age newborns, respectively. Insulin-like growth factor binding protein-1 levels were increased in preterm average-for-gestational-age and in term small-for-gestational-age newborns compared with term average-for-gestational-age newborns and showed a negative correlation with birth weight (R = -0.43, n = 131, p < 0.001). Insulin-like growth factor binding protein-1 was not correlated with C-peptide concentrations. CONCLUSIONS: Insulin-like growth factors I and II and insulin are all related to fetal growth and weight gain, and insulin-like growth factor-I correlates best with birth weight. Insulin is mainly related to fetal overgrowth (macrosomia). Insulin-like growth factor binding protein-1 may be a growth inhibitor in the fetus.

Adult↗
PubMed1992

Calciotropic hormones during reproduction.

This review summarizes the reported effects of the menstrual cycle, pregnancy and lactation on serum concentration of the calciotropic hormones PTH and 1,25(OH)2D. A midcycle rise in PTH and 1,25(OH)2D has been observed, but in the majority of studies there was no change in PTH and 1,25(OH)2D concentrations throughout the menstrual cycle. Both total and free 1,25(OH)2D levels are increased during pregnancy. The renal 1,25(OH)2D production is stimulated, and there is some evidence of 1,25(OH)2D production by decidua/placenta and fetal kidney in vitro; the decidual/placental production should not be overestimated in vivo. The increased renal 1 alpha-hydroxylase activity is possibly mediated by estrogens and PTH, although the effect of pregnancy on PTH remains uncertain. Increased serum 1,25(OH)2D concentrations probably result in a rise of intestinal calcium absorption during pregnancy. There is a postdelivery drop in PTH and 1,25(OH)2D levels, but they are increased when lactation is prolonged, or in mothers nursing twins. The l alpha-hydroxylase activity during lactation may be stimulated by PTH, but also by prolactin.

Animals↗
PubMed1992

The effects of systemic insulin, insulin-like growth factor-I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats.

Spontaneously diabetic BB rats have a markedly depressed longitudinal bone growth and bone formation/turnover. In this study, male diabetic BB rats were infused intraperitoneally or subcutaneously for 2 weeks with hormones that are believed to stimulate skeletal growth and/or trabecular bone formation: insulin (3 or 4 U/day), human GH (hGH; 400 mU/day), recombinant human insulin-like growth factor-I (rhIGF-I; 300 or 600 micrograms/day) and testosterone (80 micrograms/100 g body weight per day). Saline-treated diabetic BB rats had decreased plasma concentrations of IGF-I and osteocalcin (OC) (OC, 3.7 +/- 0.3 vs 13.1 +/- 0.8 (S.E.M.) nmol/l in controls); bone histomorphometry showed decreased epiphyseal width, osteoblast surface (0.04 +/- 0.04 vs 1.5 +/- 0.3%) and osteoid surface, and mineral apposition rate (MAR) (1.8 +/- 0.5 vs 7.9 +/- 0.6 microns/day). Testosterone and hGH infusions had no effect on weight loss or on decreased skeletal growth and bone formation of diabetic rats, nor did they increase plasma IGF-I concentrations. Insulin infusions into diabetic rats resulted in hyperinsulinaemia and accelerated weight gain. The epiphyseal width, osteoblast/osteoid surfaces and OC levels of insulin-treated rats were normalized or stimulated well above control values (osteoblast surface, 4.3 +/- 0.8%; plasma OC, 16.1 +/- 1.4 nmol/l); the MAR (4.0 +/- 0.9 microns/day) was only partly corrected after the 2-week infusion. Infusions of rhIGF-I into diabetic rats doubled but did not restore plasma IGF-I levels to normal; weight gain, however, was similar to that in control rats. IGF-I treatment had no effect on epiphyseal width, osteoblast/osteoid surfaces and OC concentrations, but improved the decreased MAR (4.6 +/- 1.2 microns/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Platelet count and liver function tests in proteinuric and chronic hypertension in pregnancy.

Platelet counts and plasma enzyme estimations were performed in 207 pregnant patients with proteinuric hypertension and in 60 patients with chronic hypertension. Patients with abruptio placentae were excluded. In the proteinuric hypertensive patients a low platelet count (less than 150,000/mm3) was found in 63 (30%) and elevated transaminase levels in 50 (24%) and both abnormalities were present in 47 patients (23%). The serum lactate dehydrogenase (LDH) value was mildly elevated in most proteinuric hypertensive women, but a markedly elevated LDH level (greater than 400 IU/l) was usually associated with other evidence of liver necrosis. Raised plasma alkaline phosphatase and gamma-glutamyltransferase levels were not related to the occurrence or severity of liver necrosis. In proteinuric hypertensive patients a low platelet count or elevated transaminase level was associated with deteriorating renal function, increased maternal morbidity, increased incidence of low-birth-weight babies and a raised perinatal mortality rate (149/1,000). In patients with chronic hypertension, 1 had a low platelet count but none had elevated transaminase, LDH or other enzyme levels and there was no recorded perinatal mortality.

Adolescent↗
PubMed1990

Osteoporosis and diabetes: lessons from the diabetic BB rat.

The spontaneously diabetic BB rat was used to study the effect of diabetes on bone. Short-term diabetes (3-4 weeks) resulted in a state of low bone turnover, characterized by a severe decrease in osteoblast/osteoid surface and bone mineral apposition rate on histology, and in serum osteocalcin concentrations. If diabetes was long-term (12 weeks), the parameters of low bone formation were associated with histological evidence of osteoporosis and a decreased bone strength; the relative bone calcium concentration remained normal in diabetes. We conclude that long-standing diabetes results in a low-turnover osteoporosis.

Animals↗
PubMed1990

Bone and mineral metabolism in BB rats with long-term diabetes. Decreased bone turnover and osteoporosis.

The effect of long-term diabetes mellitus on bone and mineral metabolism was studied in BB rats. Diabetic rats were treated with 1 U of long-acting insulin every other day for 12 wk and compared with nondiabetic littermates. Urinary calcium excretion was increased greater than 10-fold, but serum total and diffusible calcium remained normal. Serum concentrations of both 1 alpha, 25-dihydroxyvitamin D3 and vitamin D-binding protein were significantly decreased in diabetic rats. The intestinal calbindin-D 9K concentration was decreased by nearly 50%, and active duodenal calcium absorption was totally abolished. Trabecular bone volume measured in the tibial metaphysis was decreased by 44%, and the osteoblast and osteoid surfaces were less than 10% of values observed in control rats, whereas the osteoclast surface was unchanged by diabetes. The daily bone formation (bone mineral apposition rate) measured by labeling twice with calcein was decreased by 86% in diabetic rats. The serum concentration of osteocalcin, a biochemical marker of osteoblast function, was similarly decreased (mean +/- SE 23 +/- 3 and 62 +/- 4 micrograms/L in diabetic [n = 15] and nondiabetic [n = 15] rats, respectively). Serum osteocalcin was significantly correlated with the serum concentration of insulinlike growth factor I (r = 0.89, P less than 0.001). Bone strength measured as the energy needed to fracture the femur was markedly decreased (5.3 +/- 1.4 and 8.4 +/- 1.3 N.m.degree in diabetic and nondiabetic rats, respectively; P less than 0.01). These histological, chemical, and biomechanical data clearly indicate that long-standing diabetes in BB rats results in severe low-turnover osteoporosis probably related to decreased osteoblast recruitment and/or function.

Animals↗
PubMed1990

Osteocalcin is vitamin D-dependent during the perinatal period in the rat.

The vitamin D-dependence of renal calbindin D-28K and osteocalcin during the perinatal period was studied in fetuses (days 18 and 21) and neonates (days 2, 12, 17 and 22) of rats fed either a standard diet (0.85% Ca-0.7% P; "high Ca-P diet" rats) or a mildly Ca-P restricted diet (0.2% Ca-0.2% P; "low Ca-P diet" rats). Body weight and plasma calcium levels were identical in both groups. Plasma 1,25(OH)2D concentrations were markedly higher in the low Ca-P diet rats at all stages of fetal and neonatal life (in 22-day-old neonates: 536 +/- 58 pg/ml versus 126 +/- 12 pg/ml). 1,25(OH)2D concentrations increased between day 18 and 21 of fetal life, remained constant between day 21 of fetal and day 12 of neonatal life, and increased sharply between day 12 and 17 in both groups; after day 17, 1,25(OH)2D concentrations increased further in pups fed the low Ca-P diet. Renal calbindin D-28K reached peak concentrations on day 12 of neonatal life; calbindin D-28K levels were similar in the high and low Ca-P diet rats at all stages of perinatal development. Plasma osteocalcin levels increased steadily during the perinatal period; at most stages of perinatal life, and already from the fetal period was osteocalcin higher in the low Ca-P diet rats than in the high Ca-P diet rats (in 22-day-old pups: 1106 +/- 47 ng/ml versus 429 +/- 14 ng/ml). Femoral osteocalcin concentrations were also increased in fetal and early neonatal (days 2 and 12) low Ca-P diet rats, while the femoral calcium content and concentration of these rats were decreased in the late neonatal period (days 12, 17 and 22). These studies indicate that osteocalcin is vitamin D-dependent in the fetal and neonatal rat.

Animals↗
PubMed1989

Maternal and fetal endocrine pancreas in the spontaneously diabetic BB rat.

The maternal and fetal endocrine pancreas were investigated in the diabetic BB rat on day 21 of pregnancy. The maternal pancreas of the diabetic rat contained practically no insulin-positive B cells. The A and D cell mass were also decreased, while plasma glucagon and somatostatin levels were normal or increased, confirming previous data. Six of 11 diabetic rats had B-cell-specific surface antibodies (ICSA), whereas only 1 of 10 nondiabetic rats was ICSA-positive. The volume density of insulin-positive cells was decreased in the fetal pancreas of diabetic BB rats compared to fetuses of nondiabetic rats, but the volume density of glucagon- and somatostatin-positive cells remained normal. The B cells of these fetuses were ultrastructurally less granulated and showed signs of increased cellular activity. Plasma insulin levels were decreased while plasma glucagon and somatostatin concentrations were normal. ICSA were not detected in fetuses of nondiabetic and diabetic rats. There were no differences in the histology of the spleen and thymus between both groups of fetuses. Metabolic characterization of the growth-retarded fetuses of diabetic rats revealed, besides lower plasma insulin concentrations, increased branched chain amino acid levels, and normal plasma Sm/IGF-I levels. The main conclusions from this study are: (1) Severe maternal diabetes decreases the pancreatic insulin-positive cell mass and plasma insulin levels in the fetus, but not the A and D cell mass and function; (2) ICSA are not detectable in fetal plasma; (3) the influence of maternal BB rat diabetes on fetal endocrine pancreas and metabolic environment resembles that of severe streptozotocin-induced diabetes.

Animals↗
PubMed1989

Bone mineral homeostasis in spontaneously diabetic BB rats. I. Abnormal vitamin D metabolism and impaired active intestinal calcium absorption.

Calcium homeostasis was investigated in male BB rats with a diabetes duration of 3-4 weeks and compared with that in nondiabetic littermates either fed ad libitum or receiving selective semistarvation or an oral Ca supplement to obtain additional weight-matched and Ca intake-matched control groups. Diabetic rats had markedly increased food and Ca intake, so that their net Ca balance remained positive despite a 13-fold increase in urinary Ca excretion and a disappearance of active duodenal Ca absorption. Decreased duodenal Ca uptake correlated with decreased 1,25-(OH)2D3 levels (89 +/- 15 vs. 160 +/- 13 pg/ml in nondiabetic rats), decreased duodenal 9K Ca-binding protein concentrations (10 +/- 1 vs. 21 +/- 2 micrograms/mg protein), and decreased number of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-binding sites in duodenum, although the binding affinity was above normal. Nondiabetic Ca-supplemented rats exhibited a similar response: decreased 1,25-(OH)2D3 (95 +/- 8 pg/ml) and 9K Ca-binding protein (7 +/- 0.5 micrograms/mg protein) concentrations, decreased active duodenal Ca uptake, increased urinary Ca excretion, and a normal net Ca balance. Plasma vitamin D-binding protein levels were decreased by 62% in diabetic rats, due to a marked decrease in production rate, while the plasma half-time remained normal. The free 1,25-(OH)2D3 index was highest in diabetic rats, suggesting partial vitamin D resistance at the duodenal level. In semistarved rats, 1,25-(OH)2D3 levels and active Ca uptake remained normal, and the free 1,25-(OH)2D3 index was increased, together with suppressed vitamin D-binding protein levels. These studies indicate that nutritional abnormalities may contribute to but cannot totally explain the disturbances in vitamin D metabolism, transport, or action at the intestinal level.

Animals↗
PubMed1989

Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis.

Bone morphology and function were studied in male spontaneously diabetic BB rats after 3-4 weeks of diabetes. The tibia and lumbar vertebrae weights were decreased, but the bone calcium percentage remained normal. Bone volumes in the tibial metaphysis and the first lumbar vertebra were normal on quantitative histomorphometry. Osteoclast, osteoblast, and osteoid surface percentages, however, and the calculated daily mineral apposition rate in the tibia (1.0 +/- 0.4 vs. 5.6 +/- 0.6 microns/day) and vertebra (0.2 +/- 0.1 vs. 2.3 +/- 0.2 microns/day) were all severely decreased in diabetic rats. Plasma osteocalcin concentrations were also markedly decreased in diabetic rats (24 +/- 2 vs. 108 +/- 10 ng/ml); the half-times of [125I]osteocalcin were similar in diabetic and nondiabetic rats, indicating that decreased plasma osteocalcin was due to decreased synthesis. Plasma osteocalcin levels were more decreased than expected from their suppressed 1,25-dihydroxyvitamin D3 levels, and 1,25-dihydroxyvitamin D3 injections did not increase plasma osteocalcin in diabetic rats as they did in nondiabetic rats. Bone osteocalcin content was normal in diabetic rats. Photon absorptiometry of tibiae showed a similar bone mineral content in diabetic and nondiabetic rats. Biomechanical properties of diabetic rat femora were all in the normal range. Nondiabetic semistarved rats with the same body weight as diabetic rats exhibited a similar delay in bone growth as diabetic rats, but the osteoblast and osteoid surfaces were normal, and the mineral apposition rate was normal (tibia) or slightly decreased (vertebra). Plasma osteocalcin concentrations were also normal in semistarved rats. Thus, the number and/or function of osteoblasts are severely suppressed in diabetes, and this results in decreased osteoid surface, mineral apposition rate, and plasma osteocalcin levels; moreover, these changes cannot be explained by simple weight loss.

Animals↗
PubMed1989

Osteocalcin during the reproductive cycle in normal and diabetic rats.

Concentrations of osteocalcin were measured in plasma and bone of normal and diabetic rats during the reproductive cycle and compared with plasma 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) concentrations. The age-dependence of osteocalcin was also examined. Plasma concentrations of osteocalcin levels were low but detectable in 21-day-old fetuses (3.7 +/- 0.3 nmol/l); osteocalcin concentrations were highest in weaning rats (104 +/- 9 nmol/l) and decreased thereafter. In adult rats, plasma concentrations of both osteocalcin and 1,25-(OH)2D3 increased during the last days of normal pregnancy, and even more so in rats fed a diet low in calcium and phosphate. After an early post-partum decline, osteocalcin concentrations in plasma remained at non-pregnant levels in lactating rats fed a high calcium/phosphate diet while their 1,25-(OH)2D3 concentrations were higher than in non-pregnant rats; however, lactating rats fed a low calcium/phosphate diet showed increasing osteocalcin concentrations. In spontaneously diabetic BB rats, plasma osteocalcin concentrations were severely decreased compared with those in non-diabetic rats, more than would have been expected from their decreased 1,25-(OH)2D3 concentrations. Moreover, plasma osteocalcin did not increase during pregnancy or lactation in diabetic rats, even when fed a low calcium/phosphate diet. Fetuses of diabetic rats also had lower plasma osteocalcin levels than fetuses from non-diabetic rats or than weight-matched fetuses from semistarved rats. In contrast to plasma osteocalcin concentrations, bone osteocalcin concentrations and content were not altered by pregnancy, lactation, low calcium/phosphate diet or diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1988

Diabetes and low Ca-P diet have opposite effects on adult and fetal bone mineral metabolism.

The effect of diabetes on maternal bone mineral metabolism and fetal mineralization was studied in nonpregnant and pregnant BB rats fed two diets (0.85% calcium-0.7% phosphorus and 0.2% calcium-phosphorus). Non-pregnant female diabetic rats had normal total bone mineral content (BMC), despite decreased trabecular bone volume density (TBVD). Nondiabetic rats on the low calcium-phosphorus diet showed decreased TBVD, signs of increased bone turnover, and decreased BMC; plasma 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3] was increased and urinary calcium excretion was decreased. A similar response was observed in diabetic rats with a further decrease in TBVD. Nondiabetic 21-day pregnant rats on high and low calcium-phosphorus diets had higher 1,25(OH)2D3 than nonpregnant rats (98 vs. 58 and 328 vs. 147 pg/ml, respectively). Maternal BMC did not change during pregnancy but was decreased by the low calcium-phosphorus diet; fetal mineral content was not influenced by the low calcium-phosphorus regime. No increase in 1,25(OH)2D3 was observed in pregnant diabetic rats (57 vs. 52 and 112 vs. 128 pg/ml in high and low calcium-phosphorus diet groups). Fetal mineralization was severely impaired in diabetes but was not further decreased by the low calcium-phosphorus diet. Thus nonpregnant diabetic rats respond normally to a low calcium-phosphorus diet, but pregnant diabetic rats do not show increased 1,25(OH)2D3 levels due to impairment of fetal mineralization.

Amniotic Fluid↗
PubMed1988

1,25(OH)2D3 and Ca-binding protein in fetal rats: relationship to the maternal vitamin D status.

The autonomy and functional role of fetal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH)2D3 were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH)2D3 levels were correlated (r = 0.80; P less than 0.001). The vitamin D-dependent calcium-binding proteins (CaBP9K and CaBP28K) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP9K and CaBP28K in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH)2D3 levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP9K and renal CaBPs, but placental CaBP9K was not different. In diabetic pregnant rats, duodenal CaBP9K tended to be lower, while renal CaBPs were normal; placental CaBP9K was decreased. No significant changes in CaBP levels were observed in fetuses of low calcium-phosphorus diet rats or fetuses of diabetic rats. The results indicate that in the rat fetal 1,25(OH)2D3 depends on maternal 1,25(OH)2D3 or on factors regulating maternal 1,25(OH)2D3. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH)2D3 levels confirms earlier data showing that 1,25(OH)2D3 has a limited hormonal function during perinatal development in the rat.

Animals↗
PubMed1986

Vitamin D and bone mineral homeostasis during pregnancy in the diabetic BB rat.

Vitamin D and bone mineral metabolism during pregnancy were studied in 17 diabetic and 13 control BB rats. On day 21 of pregnancy, reduced mean levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; 56.9 vs. 97.9 pg/ml; P less than 0.0001] and vitamin D-binding protein (304 vs. 482 micrograms/ml; P less than 0.0001) were found in the diabetic rats, while the free 1,25-(OH)2D3 concentration was not different from the control level. Total plasma calcium and total plasma protein concentrations were also significantly decreased in the diabetic group, but the calculated diffusible calcium was not significantly lower. Calcium and phosphorus urinary excretion were increased in the diabetic rats. There was no difference in bone mineral content. The fetuses of the diabetic BB rat had a lower body weight and were hypoinsulinemic. Both 1,25-(OH)2D3 (41.3 vs. 54.7 pg/ml; P less than 0.01) and vitamin D-binding protein (80 vs. 123 micrograms/ml; P less than 0.001) were decreased in the fetuses of diabetic rats, but the free 1,25-(OH)2D3 concentration was slightly but significantly (6.96 vs. 5.54; P less than 0.05) increased. We observed that the fetuses of diabetic rats had fewer ossification centers, counted with the Alizarin Red S staining method. The fetal ash weight was lower in the diabetic group (16.7 vs. 26.9 mg; P less than 0.0001). In addition, the relative calcium and phosphorus, but not magnesium, content of ash was lower in the fetuses of diabetic rats. This reduced mineral content in fetuses of diabetic mothers could be implicated in the pathogenesis of early neonatal hypocalcemia in infants of diabetic mothers.

Animals↗