Clinical Briefs
July 30, 1999 3 minutes read
Acute Hyperhomocysteinemia and Reversal by Antioxidant Vitamins
Elevated levels of homocysteine (> 15 micromoles/L) are associated with increased risk of atherosclerotic cardiovascular disease. The mechanisms for this association are not fully understood, but endothelial dysfunction is felt to be a likely culprit.
Homocysteine levels rise after a load of oral methionine in healthy individuals. This study evaluated healthy young men, age 25-45 (n = 20), for the effect of an acute elevation of homocysteine upon endothelial function, as measured by vascular response to L-arginine (the immediate precursor to nitric oxide); endothelial responses were also measured after administration of antioxidants (vitamin E 800 IU and vitamin C 1000 mg) to see whether pretreatment with antioxidants affected outcomes. In addition to vascular responsiveness, plasma lipids, glucose, coagulation profiles, and adhesion molecules were monitored.
Methionine loading produced a change of mean plasma homocysteine from 10.5 to 27.1, unaltered by administration of antioxidants. Coagulation parameters increased significantly upon homocysteine elevation, but this increase was abolished by pretreatment with antioxidant vitamins; the same profile was seen with adhesion molecules. L-arginine normally produces a reduction in blood pressure, platelet aggregation, and blood viscosity. Elevation of homocysteine significantly altered these responses, and the deleterious alterations seen were favorably modified by pretreatment with antioxidant vitamins.
Nappo and associates conclude that acute elevations of homocysteine produce adverse changes in cardiovascular risk profiles, including blood pressure, coagulation parameters, and response to L-arginine. Antioxidant vitamins prevent acute endothelial dysfunction produced by elevation of homocysteine.
Nappo F, et al. JAMA 1999;281: 2113-2118.
Inflammation and Prediction of Diabetes Mellitus in Adults
Macrovascular disease remains the no. 1 cause of mortality in diabetics. Inflammatory processes are felt to play a role in atherosclerosis, and mediators of inflammation such as tumor necrosis factor alfa and interleukin-6 are elevated in type 2 diabetes. The purpose of this study was to determine whether inflammatory markers predict the development of type 2 diabetes in nondiabetic participants in the Atherosclerosis Risk in Communities study (n = 15,792). In this study group, approximately 80% were caucasian and 20% African-American. Inflammatory markers surveyed included fibrinogen, white blood cell count (WBC), sialic acid, orosomucoid, alpha-1-antitrypsin, and haptoglobin, at levels below that which would be considered indicative of an acute inflammatory reaction.
Individuals in the highest WBC quartile had 50% higher odds of developing diabetes. Persons with sialic acid, orosomucoid, and haptoglobin levels higher than the median also had a 1.7-7.9-fold odds ratio for developing diabetes.
Proinflammatory cytokines (e.g., tumor necrosis factor alpha) may affect insulin sensitivity or secretion; it has been theorized that tumor necrosis factor alpha produces insulin resistance by decreasing autophosphorylation of the insulin receptor, in addition to other mechanisms.
Schmidt and colleagues believe that although the pathophysiologic mechanism remains incompletely explained, inflammatory mediators are etiologically involved in the development of type 2 diabetes.
Schmidt MI, et al. Lancet 1999; 353:1649-1652.
Coffee Consumption and the Risk of Symptomatic Gallstone Disease in Men
Numerous aspects of the physiologic effects of coffee and caffeine suggests that coffee ingestion might have some effect on gallstones. Stimulation of cholecystokinin release and enhanced gallbladder contraction are effects of coffee; bile cholesterol concentrations may be affected by cafestol, a component of coffee beans. Caffeine affects bile flow, gallbladder fluid absorption, and tendency to bile crystallization all in an anti-stone-forming fashion.
The cohort evaluated were participants in the Health Professionals Follow-up Study (n = 51,529). Coffee consumption was evaluated on the basis of a 131-item questionnaire in 1986. At the same time, a baseline assessment for presence or absence of gallstones was performed, and surveillance continued through 1996.
More than 1000 cases of gallstone disease were discovered. Intake of regular coffee had a strong inverse relationship with gallstones. For instance, men who drank at least four cups of coffee daily had a 33% lower relative risk of gallstones than those who drank no coffee. No statistically significant relationship was found between consumption of tea, decaffeinated coffee, or caffeinated soft drinks and gallstones. In this population, higher intake of regular coffee in men older than age 40 is associated with reduced incidence of gallstone disease.
Leitzmann MF, et al. JAMA 1999; 281:2106-2112.
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