No abstract

Cardiovascular diseases are the most frequent cause of death among persons with spinal cord injury (SCI), and these diseases are reported to occur prematurely in the disabled compared to the able bodied population. The mechanism of accelerated coronary heart disease (CHD) in persons with SCI may be partially explicable on the basis of the lipoprotein profile. We performed fasting lipoprotein determinations on 100 veterans with SCI, 50 with paraplegia and 50 with quadriplegia, and 50 veteran controls. The mean age of the subjects with SCI was 47.8 ± 1. 4 years with a duration of injury of 16.3 ± 1.2 years. The mean serum high-density lipoprotein (HDL) cholesterol was depressed in subjects with paraplegia or quadriplegia compared to controls (37 ± 1 or 40 ± 1 versus 48 ± 2 mg/dL, p < 0.0001). Although serum total cholesterol was lower (p < 0. 01) in subjects with SCI than in controls, there was no significant difference in mean serum low-density lipoprotein (LDL) cholesterol. Thirty seven p ercent of subjects with SCI have serum HDL cholesterol levels less than 35 mg/dL with no significant difference in lipoprotein distribution between high and low cord lesions. Eighteen percent of individuals with SCI have an absolute elevation of LDL cholesterol (greater than 160 mg/dL). About 40% of those with SCI and LDL cholesterol levels between 130 and 160 mg/dL also have serum HDL cholesterol values below 35 mg/dL, all of whom would have their serum HDL cholesterol level undetected if lipoprotein profiles were performed according to· present recommendations -that is, only if the serum total cholesterol is elevated. The ratio of serum total cholesterol to HDL cholesterol and serum LDH cholesterol to HDL cholesterol, commonly used ratios for risk of CHD, were calculated and are elevated in groups with SCI. In a subgroup of 12 subjects with paraplegia, a linear correlation is noted between serum HDL cholesterol values and cardiopulmonary fitness by determination of V02 max by upper body ergometry. Also, a linear correlation (p = 0. 02) is found between serum HDL cholesterol and insulin sensitivity as determined by the minimal model method.

Augmented fetal hemoglobin synthesis during diabetic pregnancy increases fetal iron demand. To study the effect of increased fetal iron demand on placental transferrin receptor (TR), we utilized a monoclonal antibody to localize placental TR immunoreactivity and 125I-labeled transferrin to study TR binding characteristics in 10 placentas from poorly controlled diabetic mothers with increased fetal iron demand and 10 placentas from nondiabetic mothers. The infants born to the diabetics had higher cord serum C-peptide, erythropoietin, and hemoglobin concentrations, indicating fetal hyperinsulinemia and hypoxia, with augmented erythropoiesis and iron demand. TR immunoreactivity was localized to the syncytiotrophoblast in both groups, was greater in the diabetic group, and was inversely correlated with fetal storage iron (r = -0.75; P < 0.001). Scatchard analysis of 125I transferrin binding data confirmed greater receptor number (Bmax 17.9 +/- 2.2 vs. 12.6 +/- 1.3 pM/mg protein, P = 0.05), but reduced binding affinity [dissociation constant (Kd) 7.6 +/- 0.9 vs. 5.4 +/- 0.4 nM/l, P = 0.03] in the diabetic group. The TR staining intensity, Bmax, and Kd were each correlated with cord C-peptide, suggesting either a primary or secondary role for fetal hyperinsulinemia in TR expression. This study provides in vivo evidence that fetal factors, such as iron demand or hyperinsulinemia, influence regulation of placental TR in humans. The increase in placental syncytiotrophoblastic TR expression associated with reduced cord serum ferritin concentration suggests that the fetus utilizes both increased placental iron transport and mobilization of fetal iron stores to support augmented fetal erythropoiesis.

No abstract