Ann M. Spungen

Disorders of carbohydrate and lipid metabolism in veterans with paraplegia or quadriplegia: a model of premature aging.

One hundred veterans with paralysis due to spinal cord injury (SCI), equally divided between those with paraplegia and quadriplegia, and 50 able-bodied veteran controls underwent a 75-g oral glucose tolerance test (OGTT). In subjects with SCI, 22% were diabetic by criteria established by the World Health Organization (WHO), whereas only 6% of the control group were diabetic. Eighty-two percent of the controls had normal (NL) oral glucose tolerance, compared with 38% of those with quadriplegia and 50% of those with paraplegia. Subjects with diabetes mellitus (DM) were older in both the SCI and control groups, but those with SCI developed carbohydrate disorders at younger ages than did the control group. SCI subjects had significantly higher mean glucose and insulin values at several points during the OGTT when compared with controls, suggesting an accentuated state of insulin resistance in those with SCI. Mean fasting plasma glucose (FPG) values for both SCI and control groups were significantly higher in subjects with DM compared with those with NL glucose tolerance. When the FPG value was compared between SCI or control subjects with abnormalities in glucose tolerance, the subgroups with SCI and NL or impaired glucose tolerance (IGT) had significantly lower FPG levels than the respective control subgroups, suggestive of decreased hepatic glucose output in SCI.(ABSTRACT TRUNCATED AT 250 WORDS)

Invited Review Carbohydrate And Lipid Metabolism In Chronic Spinal Cord Injury

Abstract Background: Abnormalities of carbohydrate and lipid metabolism are more common in the spinal cord injury (SCI) population than in the able-bodied population. This is an important consideration in the long-term care of individuals with SCI. Design: Literature review. Findings: When compared with the able-bodied population, people with SCI are more likely to have oral carbohydrate intolerance, insulin resistance, elevated low-density lipoprotein cholesterol, and reduced high-density lipoprotein cholesterol, associated with increased prevalences of diabetes mellitus and cardiovascular disease. Conclusions: Because of increased risk factors for diabetes mellitus and heart disease in individuals with SCI, modifiable risk factors should be addressed, eg, obesity, inactivity, dietary factors, and smoking. To reduce mortality and morbidity associated with these risk factors, periodic screening for carbohydrate and lipid abnormalities is recommended, with appropriate therapeutic interventions.

Depressed serum high density lipoprotein cholesterol levels in veterans with spinal cord injury

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 percent 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 160mg/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 VO2 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.

Continuous Loss of Bone During Chronic Immobilization: A Monozygotic Twin Study

Abstract: Acute immobilization is associated with rapid loss of bone. Prevailing opinion, based on population cross-sectional data, assumes that bone mass stabilizes thereafter. In order to address whole-body and regional skeletal mass in long-term immobilization, monozygotic twins were studied, one of each twin pair having chronic spinal cord injury (SCI) of a duration ranging from 3 to 26 years. The research design consisted of the co-twin control method using 8 pairs of identical male twins (mean ± SD age, 40 ± 10 years; range 25–58 years), one of each set with SCI. The twins were compared by paired t-tests for total and regional bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry. Linear regression analyses were performed to determine the associations of age or duration of injury with the differences between twin pairs for total and regional skeletal bone values. In the SCI twins, total-body BMC was significantly reduced (22%± 9%, p<0.001), with the predominant sites of reduction for BMC and BMD being the legs (42%± 14% 35%± 10%, p<0.0001), and pelvis (50%± 10% and 29%± 9%, p<0.0001). Duration of SCI, not age, was found to be linearly related to the degree of leg bone loss in SCI twins (BMC: r2= 0.60, p<0.05; BMD: r2= 0.70, p<0.01). Our findings suggest that pelvic and leg bone mass continues to decline throughout the chronic phase of immobilization in the individual with SCI, and this bone loss appears to be independent of age.

Risk factors for atherogenesis and cardiovascular autonomic function in persons with spinal cord injury

Risk factors for atherogenesis and cardiovascular autonomic function in persons with spinal cord injury

Pulmonary function and spinal cord injury

Injury to the cervical and upper thoracic spinal cord disrupts function of inspiratory and expiratory muscles, as reflected by reduction in spirometric and lung volume parameters and static mouth pressures. In association, subjects with tetraplegia have decreased chest wall and lung compliance, increased abdominal wall compliance, and rib cage stiffness with paradoxical chest wall movements, all of which contribute to an increase in the work of breathing. Expiratory muscle function is more compromised than inspiratory muscle function among subjects with tetraplegia and high paraplegia, which can result in ineffective cough and propensity to mucus retention and atelectasis. Subjects with tetraplegia also demonstrate heightened vagal activity with reduction in baseline airway caliber, findings attributed to loss of sympathetic innervation to the lungs. Significant increase in airway caliber following inhalation of ipratropium bromide, an anticholinergic agent, suggests that reduction in airway caliber is not due to acquired airway fibrosis stemming from repeated infections or to abnormal hysteresis secondary to chronic inability of subjects to inhale to predicted total lung capacity. Reduced baseline airway caliber possibly explains why subjects with tetraplegia exhibit airway hyperresponsiveness to methacholine and ultrasonically nebulized distilled water. While it has been well demonstrated that bilateral phrenic nerve pacing or stimulation through intramuscular diaphragmatic electrodes improves inspiratory muscle function, it remains unclear if inspiratory muscle training improves pulmonary function. Recent findings suggest that expiratory muscle training, electrical stimulation of expiratory muscles and administration of a long-acting beta(2)-agonist (salmeterol) improve physiological parameters and cough. It is unknown if baseline bronchoconstriction in tetraplegia contributes to respiratory symptoms, of if the chronic administration of a bronchodilator reduces the work of breathing and/or improves respiratory symptoms. Less is known regarding the benefits of treatment of obstructive sleep apnea, despite evidence indicating that the prevalence of this condition in persons with tetraplegia is far greater than that encountered in able-bodied individuals.

Is immobilization associated with an abnormal lipoprotein profile? Observations from a diverse cohort.

Objective: The potential effects of ethnicity, gender, and adiposity on the serum lipid profile in persons with spinal cord injury (SCI) were determined. Subjects: Subjects with SCI were recruited during their annual physical examination from Rancho Los Amigos Medical Center, Downey, California. Sedentary able-bodied controls were Bridge and Tunnel Officers of the Triboro Bridge and Tunnel Authority of the New York City metropolitan area. Methods: Serum lipid profiles were investigated in 320 subjects with SCI and compared to those obtained from 303 relatively sedentary able-bodied controls. Serum lipid studies were obtained in the fasting state. Data were collected between 1993 and 1996. All lipid determinations were performed by the same commercial laboratory. Main outcome measures: The dependent variables were the values from the lipid profile analysis. The independent variables consisted of study group, gender, ethnic group, age, duration of injury, and anthropometric measurements. Results: The serum high-density lipoprotein cholesterol (HDL-c) level was reduced in the SCI compared with the control group (mean±SEM) (42±0.79 vs 47±0.67 mg/dl, P<0.0005). The serum HDL-c level was significantly lower in males with SCI than males in the control group (39±0.83 vs 45±0.70 mg/dl, P<0.0001), but not for females (51±1.54 vs 54±1.52 mg/dl, n.s.). Within the subgroups for whites and Latinos, HDL-c values were also lower in subjects with SCI than in controls (whites: 41±1.02 vs 46±0.86 mg/dl, P<0.0001; Latinos: 37±1.53 vs 42±1.59 mg/dl, P<0.05), but not for African Americans (49±1.56 vs 51±1.27 mg/dl, n.s.). African Americans had higher HDL-c values than whites or Latinos (SCI: 49±1.56 vs 41±1.02 or 37±1.53 mg/dl, P<0.0001; controls: 51±1.27 vs 46±0.86 mg/dl, P<0.01 or 42±1.59 mg/dl, P<0.0005). In persons with SCI, the serum HDL-c values were inversely related to body mass index and estimated per cent body fat (r=0.27, P<0.0001). Conclusion: In white and Latino males, but not in females or African Americans, immobilization from SCI appears to be associated with lower HDL-c values than in controls.

The effect of residual neurological deficit on serum lipoproteins in individuals with chronic spinal cord injury

Subjects with spinal cord injury (SCI) have been shown to have an adverse lipid profile. Prior studies performed with smaller numbers of subjects have not been able to demonstrate any relationship between the level and degree of the neurological deficit and plasma lipid levels. Over a 2 year period we investigated the lipid profiles in 541 subjects from Rancho Los Amigos Medical Center, Downey, California. Subjects were grouped by tetraplegia (Tetra; n=247) or paraplegia (Para; n=294) and by subgroup for degree of neurological deficit: complete Tetra (n=156), incomplete Tetra (n=91), complete Para (n=206) and incomplete Para (n=88). The serum high-density lipoprotein (HDL) cholesterol level was lower in the Tetra than in the Para group (38±0.7 vs 45±0.8, P<0.01). The group with Tetra had a higher percentage of subjects with serum HDL cholesterol values <35 mg/dL [an independent risk factor for coronary heart disase (CHD)] than those with Para (38% vs 21%, P<0.0001). A significant inverse relationship was found for degree of neurological deficit and mean serum HDL cholesterol level (r=0.19, P<0.001), with the greater the deficit, the lower the serum HDL cholesterol level. Serum total cholesterol levels were higher in the Para group than in the Tetra group (198±2.6 vs 184±2.6, P<0.01). However, the ratio of total cholesterol to HDL cholesterol (a discriminator of risk for CHD) was significantly lower in the Para group than the Tetra group (4.8 vs 5.2%, P<0.01). Thus, in persons with SCI a spectrum of depressed serum HDL cholesterol levels and increased cardiovascular risk occur, with the most adverse lipid changes correlating with the severity of neurological deficit.

Metabolic and Endocrine Changes in Persons Aging with Spinal Cord Injury

Persons with spinal cord injury (SCI) have secondary medical disabilities that impair their ability to function. With paralysis, dramatic deleterious changes in body composition occur acutely with further adverse changes ensuing with increasing duration of injury. Lean mass, composed of skeletal muscle and bone, is lost and adiposity is relatively increased. The body composition changes may be further exacerbated by associated reductions in anabolic hormones, testosterone, and growth hormone. Individuals with SCI also have decreased levels of activity. These body composition and activity changes are associated with insulin resistance, disorders in carbohydrate and lipid metabolism, and may be associated with premature cardiovascular disease. Although limited information is available, upper body exercise and cycle ergometry of the lower extremities by functional electrical stimulation (FES) have been reported to have a salutary effect on these body composition and metabolic sequelae of paralysis. Perhaps other innovative, externally mediated forms of active exercise of the paralyzed extremities will result in an increased functional capacity, metabolic improvement, and reduction of atherosclerotic vascular disease.

Resistive inspiratory muscle training in subjects with chronic cervical spinal cord injury

OBJECTIVE To determine whether pulmonary function, respiratory muscle strength, and dyspnea can be improved in individuals with chronic cervical spinal cord injury (SCI). STUDY DESIGN Ten subjects participated in an 8-week resistive inspiratory muscle training (IMT) program for 15 minutes twice daily. Spirometry, lung volumes, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and dyspnea were measured at baseline, week 4, and week 8. Six months after the study, spirometry, MIP, and MEP were re-measured in a subgroup of the original participants. RESULTS We found that regular IMT in subjects with cervical SCI significantly improved forced vital capacity (means +/- SE) (11% +/- 2.82% increase), forced inspiratory vital capacity (21% +/- 6.91%), vital capacity (8% +/- 4.36%), total lung capacity (12% +/- 3.23%), functional residual capacity (15% +/- 5.96%), and MIP (24% +/- 6.98%) (p < .05). Furthermore, although no statistical differences were observed for the dyspnea scale, the fact that subjects reported decreased levels (43% +/- 21.30% reduction) of perceived difficulty breathing may be of greater importance. No significant differences from baseline values were found in the seven subjects whose spirometry and respiratory muscle strength were measured 6 months after the study. CONCLUSIONS Our findings suggest that in individuals with cervical SCI regular resistive IMT may result in decreased restrictive ventilatory impairment and reported dyspnea and, thus, reduced incidence of chronic respiratory complaints, respiratory infection, and other pulmonary complications.