Intrauterine programming of urinary calcium and magnesium excretion in children born to mothers with insulin dependent diabetes mellitus

Abstract

Background: Offspring of diabetic rats have reduced urinary calcium and magnesium excretion compared with offspring of controls; these differences persist up to16 weeks after birth, a time equivalent to young adulthood in humans. Objectives: To test the hypothesis that urinary calcium and magnesium excretion would be lower in children born to mothers with insulin dependent diabetes mellitus (ChMIDDM) than those born to nondiabetic mothers. Methods: Concentrations of calcium, magnesium, sodium, and creatinine were measured in first void spot urine samples collected from 45 (28 male; median age 9.6 years) ChMIDDM and 127 (58 male; median age 11.3 years) controls. Analysis of covariance was used to test for differences in urinary calcium to creatinine ratios (UCa/Cr), magnesium to creatinine ratios (UMg/Cr), and log sodium to creatinine ratios (logUNa/Cr) between controls and ChMIDDM after allowing for the effects of sex and age. Results: UCa/Cr (difference 20.10, 95% confidence interval (CI) 20.19 to 20.01; p = 0.03) and UMg/ Cr (difference 20.15, 95% CI 20.22 to 20.08; p,0.0001) were lower in ChMIDDM than controls. However, logUNa/Cr did not differ between ChMIDDM and controls (difference 20.14, 95% CI 20.33 to 0.05; p = 0.1). The daily estimated intake of magnesium, sodium, and protein were significantly higher and that of calcium non-significantly higher in ChMIDDM than controls. In ChMIDDM, UCa/Cr and UMg/ Cr were not related to diabetic control of mothers. Conclusions: Results of this study provide the first evidence that in humans, as in rats, there is modification of renal Ca and Mg handling in ChMIDDM, which persists well into childhood.

Increased Renal Tubular Reabsorption of Calcium and Magnesium by the Offspring of Diabetic Rat Pregnancy

“…Hypomagnesemia and hypocalcemia have been widely reported in the neonatal offspring of human diabetic pregnancy (2,(7)(8)(9), despite recent observations that show a reduction in urinary calcium and magnesium excretion by children who are born to diabetic mothers (24). This study has demonstrated that offspring that are born to mothers with diabetes maintain altered renal function, in particular enhanced tubular reabsorption of calcium and magnesium, under the conditions of renal clearance analysis used herein.…”

“…These observations suggest that not only the renal tubular reabsorptive mechanism(s) for magnesium and calcium transport but also their sensitivity to PTH action may be programmed in utero. Preliminary data suggest that there may be similar effects on renal function in children who are born to women with diabetes in pregnancy (24). The mechanisms by which maternal diabetes induces these alterations in renal divalent ion handling now require attention.…”

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

“…Similarly, there may be long-term implications for renal function in adults whose mothers were diabetic. Indeed, we have recently reported the results of a preliminary study showing decreased urinary calcium and magnesium excretion by children born to mothers with type 1 diabetes [31].…”

Prenatal programming of adult mineral metabolism: Relevance to blood pressure, dietary prevention strategies, and cardiovascular disease

“…Such a restriction in birth weight, then, may also be associated with impaired kidney growth (Schmidt et al, 2005;Simonetti et al, 2008) and increased salt sensitivity of blood pressure in children and adults (de Boer et al, 2008;Simonetti et al, 2008). Prenatal programming of essential mineral metabolism, however, has also been observed without a reduction of birth weight, i.e., a lower urinary calcium and magnesium excretion rate in children born to mothers with insulin dependent diabetes mellitus (Mughal et al, 2005). Alternatively, there is evidence from animal studies that salt intake itself may be influenced by perinatal androgens which are differentially effective in male and female rats, resulting in an epigenetically programmed sexual dimorphism of sodium intake later on in adulthood (Chow et al, 1992;Krecek, 1973).…”