OBJECTIVE: Our purpose was to investigate a possible ionic basis linking pregnancy and gestational diabetes with the vascular disorders associated with them. STUDY DESIGN: We used phosphorus 31 nuclear magnetic resonance spectroscopy and magnesium-and calcium-specific ion electrodes to measure erythrocyte intracellular free magnesium, plasma ionized magnesium, and ionized calcium in fasting nonpregnant (n = 26), normal pregnant (n = 20), and diet-controlled (class Al) gestational diabetic women (n = 13). RESULTS: Compared with nonpregnant controls (total magnesium 0.91 +/- 0.07 mmol/L, ionized magnesium 0.51 +/- 0.03 mmol/L), total and ionized magnesium were significantly lower in both normal pregnant (total magnesium 0.72 +/- 0.07 mmol/L, ionized magnesium 0.46 +/- 0.02 mmol/L, significance < 0.0001) and gestational diabetic (total magnesium 0.74 +/- 0.05 mmol/L, ionized magnesium 0.46 +/- 0.02 mmol/L, significance < 0.0001) subjects. Gestational diabetic women had significantly lower intracellular free magnesium values compared with nonpregnant and normal pregnant individuals (140 +/- 20 mu mol/L vs 169 +/- 27 mu mol/L, significance = 0.007). Ionized calcium values were similar in all groups, resulting in significant elevation (significance < 0.0001) of ionized calcium/ionized magnesium ratios in both pregnant groups. CONCLUSIONS: These results support the presence of magnesium depletion in pregnancy itself acid to a greater extent in gestational diabetes. We suggest that magnesium depletion, or relative calcium excess, may predispose to vascular complications of pregnancy.