Associations between intake of specific nutrients and disease cannot be considered primary effects of diet if they are simply the result of differences between cases and noncases in body size, physical activity, and metabolic efficiency. Epidemiologic studies of diet and disease should therefore be directed at the effect of nutrient intakes independent of total caloric intake in most instances. This is not accomplished with nutrient density measures of dietary intake but can be achieved by employing nutrient intakes adjusted for caloric intake by regression analysis. While pitfalls in the manipulation and interpretation of energy intake data in epidemiologic studies have been emphasized, these considerations also highlight the usefulness of obtaining a measurement of total caloric intake. For instance, if a questionnaire obtained information on only cholesterol intake in a study of coronary heart disease, it is possible that no association with disease would be found even if a real positive effect of a high cholesterol diet existed, since the caloric intake of cases is likely to be less than that of noncases. Such a finding could be appropriately interpreted if an estimate of total caloric intake were available. The relationships between dietary factors and disease are complex. Even with carefully collected measures of intake, consideration of the biologic implications of various analytic approaches is needed to avoid misleading conclusions.
Integrated insulin secretion rates calculated from peripheral venous C-peptide measurements by two-compartment kinetic analysis were measured in six young normal subjects after increasing oral glucose loads of 25, 50, and 100 g and respective isoglycemic glucose infusions. The differences in B-cell secretory responses between oral and iv glucose challenges were attributed to factors other than glycemia itself (incretin effect). Both insulin and C-peptide concentrations as well as calculated integrated insulin secretion rates increased with increasing oral glucose loads. Due to the similarity in the glucose profiles after all oral loads, almost identical amounts of iv glucose (approximately 20 g) were infused in all "isoglycemic" infusion experiments, with resulting similar hormone profiles and insulin secretion rates. The percent contribution of incretin factors to total immunoreactive insulin responses after 25, 50, and 100 g glucose (85.6%, 74.9%, and 93.0%; response to oral load, 100%) was significantly higher than their contribution to integrated C-peptide responses (27.6-62.9%) or calculated integrated insulin secretion rates (19.2-61.0%). These findings indicate that the degree of incretin stimulation of insulin secretion depends on the amount of glucose ingested. A discrepancy between the estimates of the incretin effect derived from peripheral venous insulin responses, on the one hand, and C-peptide responses or calculated insulin secretion rates, on the other hand, exists. Inasmuch as peripheral insulin values reflect both insulin secretion and hepatic insulin removal, this discrepancy suggests that elimination kinetics of insulin differ between oral and iv glucose administration. This difference can be related to a significantly reduced fractional hepatic insulin extraction after oral (46.9-54.6%) compared to iv (63.4-76.5%) glucose administration when calculated by a three-compartment kinetic model. This reduction in fractional hepatic insulin extraction could be caused by gastrointestinal factors (hormones or nerves) stimulated in the course of glucose ingestion.
This paper studies the optimal timing of investment in an irreversible project where the benefits from the project and the investment cost follow continuous- time stochastic processes. The optimal investment rule and an explicit formula for the value of the option to invest are derived, assuming that the option is valued by risk-averse investors who are well diversified. The same analysis is applied to the scrapping decision. Simulations show that this option value can be significant, and that for reasonable parameter values it is optimal to wait until benefits are twice the investment costs.
The effects of essential fatty acids on cell proliferation and cell viability of 3 human tumor and 4 normal cell lines were tested in vitro. It was found that n-3 and n-6 fatty acids supplemented at 20 micrograms/ml killed human breast, lung, and prostate cancer cells selectively. Normal human fibroblasts and other normal cells were not killed, but their rate of division was lowered. The most selective cytotoxic effects were obtained with fatty acids containing 3, 4, and 5 double bonds. The degree of inhibition of growth and/or loss of viability depended on a given fatty acid, on cell density, on fatty acid concentration, and on the type of cell. When eicosapentaenoate, gammalinolenate, or arachidonate was added to cocultures made of human cancer cells with normal fibroblasts, the cancer cells were selectively eliminated. These results, combined with the observation that certain fatty acids coupled to cytotoxic agents may enhance the cytotoxic activity, suggest that treatment of cancer with polyunsaturated fatty acids containing 3, 4, and 5 double bonds has potential clinical usefulness.
Four hundred and ninety pancreas cancer patients representative of confirmed cases in Los Angeles County residents of working age were compared to healthy controls individually matched by age, sex, race, and neighborhood. Home interviews were conducted on occupation, smoking, food and beverage consumption, and medical history. Cigarette smoking was a strong and consistent predictor of pancreas cancer occurrence; the effect disappeared after a decade of nonsmoking, and there was no increase in risk among current smokers as daily dose increased. There was no link between pancreas cancer and past consumption of tea, carbonated beverages, beer, or spirits; and an association with coffee consumption was inconsistent. A strong association between pancreas cancer and history of subtotal gastrectomy at any past time could not be explained by chance or any other factor. Pancreas cancer patients had experienced fewer allergies of any kind.
Blacks in the United States have the highest prostate cancer rate in the world and nearly twice that of whites in the United States. The 2:1 black-to-white ratio in prostate cancer rates is already apparent at age 45 years, the age at which the earliest prostate cancer cases occur. This finding suggests that the factor(s) responsible for the difference in rates occurs, or first occurs, early in life. Testosterone has been hypothesized to play a role in the etiology of prostate cancer, because testosterone and its metabolite, dihydrotestosterone, are the principal trophic hormones that regulate growth and function of epithelial prostate tissue. This report gives the results of assays of circulating steroid hormone levels in white and black college students in Los Angeles, CA. Mean testosterone levels in blacks were 19% higher than in whites, and free testosterone levels were 21% higher. Both these differences were statistically significant. Adjustment by analysis of covariance for time of sampling, age, weight, alcohol use, cigarette smoking, and use of prescription drugs somewhat reduced the differences. After these adjustments were made, blacks had a 15% higher testosterone level and a 13% higher free testosterone level. A 15% difference in circulating testosterone levels could readily explain a twofold difference in prostate cancer risk.
An association between hyperinsulinemia and hypertension has been suggested by epidemiological surveys. To assess whether this association is independent of the presence of other hyperinsulinemic states, such as obesity and glucose intolerance, we measured the insulin response to oral glucose in a group of middle-aged moderately obese [144 +/- 4% overweight (mean +/- SEM)] patients (n = 18) with essential hypertension (174 +/- 5/104 +/- 2 mm Hg) and normal glucose tolerance. Normotensive subjects (n = 17) with normal glucose tolerance, matched for age and degree of overweight, served as the control group. The mean insulin response to glucose was twice as high in the hypertensive patients (25.8 +/- 0.2 mU/ml X 2 h) as in the normotensive subjects (11.3 +/- 0.2; P less than 0.001), yet the glucose incremental area was 3-fold higher in the former (10.9 +/- 1.0 g/dl X 2 h) than in the latter (3.5 +/- 0.7; P less than 0.001), thus indicating more severe insulin resistance. In the hypertensive group, systolic blood pressure levels were directly correlated with the 2-h plasma insulin values (r = 0.75; P less than 0.001). Furthermore, the 2-h plasma insulin value and the degree of overweight accounted for 65% of the variation in the systolic blood pressure in a multiple regression model (r = 0.81; P less than 0.001). We conclude that in obesity, the occurrence of hypertension marks the presence of additional hyperinsulinemia and insulin resistance, independent of any impairment of glucose tolerance.
In 1979-81, 419 patients with incident cases of colon and rectal cancer and 732 controls were questioned regarding diet and alcohol. Cancer cases were a population-based series reported to the South Australian Central Cancer Registry, were 30-74 years of age, and were residing in Metropolitan Adelaide. Controls were selected from the electoral roll and individually age- and sex-matched to cancer cases. The most consistent risk factor for colorectal cancer was dietary protein, which was associated with a twofold-to-threefold relative risk for colon cancer and for rectal cancer in women for all levels of consumption above the base line (i.e., the lowest consumption quintile). For male colon cancer the corresponding relative risk was similar; but for male rectal cancer, risk was elevated only at old ages. Total energy intake and, less clearly, meal frequency were also positively associated with increased risk. Total alcohol intake (but not specifically beer) was associated with increased risk of both colon and rectal cancer in women; in both sexes, there was an increased risk of colon and rectal cancer associated with spirits consumption. A reduced risk of rectal cancer was associated with vitamin C but not with vitamin A. The increased risk associated with high protein and total energy was confined to those consuming a low fiber diet, particularly among women; but some other aspects of the relationship between fiber consumption and risk of colorectal cancer were more complex. Some modifications and extensions of the current fat-to-bile acid-to-fiber theory of bowel carcinogenesis were suggested.