Nonalcoholic fatty liver, nonalcoholic steatohepatitis, ectopic fat, and the glycemic index.
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Biomedical subjects
Publications and source records attributed to Livia S A Augustin.
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Strategies that decrease postprandial glucose excursions, including digestive enzyme inhibition, and low glycemic index diets result in lower diabetes incidence and coronary heart disease (CHD) risk, possibly through lower postprandial oxidative damage to lipids and proteins. We therefore assessed the effect of decreasing postprandial glucose excursions on measures of oxidative damage. Fifteen healthy subjects ate 2 bread control meals and 3 test meals: almonds and bread; parboiled rice; and instant mashed potatoes, balanced in carbohydrate, fat, and protein, using butter and cheese. We obtained blood samples at baseline and for 4 h postprandially. Glycemic indices for the rice (38 +/- 6) and almond meals (55 +/- 7) were less than for the potato meal (94 +/- 11) (P < 0.003), as were the postprandial areas under the insulin concentration time curve (P < 0.001). No postmeal treatment differences were seen in total antioxidant capacity. However, the serum protein thiol concentration increased following the almond meal (15 +/- 14 mmol/L), indicating less oxidative protein damage, and decreased after the control bread, rice, and potato meals (-10 +/- 8 mmol/L), when data from these 3 meals were pooled (P = 0.021). The change in protein thiols was also negatively related to the postprandial incremental peak glucose (r = -0.29, n = 60 observations, P = 0.026) and peak insulin responses (r = -0.26, n = 60 observations, P = 0.046). Therefore, lowering postprandial glucose excursions may decrease the risk of oxidative damage to proteins. Almonds are likely to lower this risk by decreasing the glycemic excursion and by providing antioxidants. These actions may relate to mechanisms by which nuts are associated with a decreased risk of CHD.
The glycemic index concept owes much to the dietary fiber hypothesis that fiber would reduce the rate of nutrient absorption and increase the value of carbohydrate foods in the maintenance of health and treatment of disease. However, properties and components of food other than its fiber content contribute to the glycemic and endocrine responses postprandially. The aim of the glycemic index classification of foods was therefore to assist in the physiological classification of carbohydrate foods which, it was hoped, would be of relevance in the prevention and treatment of chronic diseases such as diabetes. Over the past two decades low glycemic index diets have been reported to improve glycemic control in diabetic subjects, to reduce serum lipids in hyperlipidemic subjects and possibly to aid in weight control. In large cohort studies, low glycemic index or glycemic load diets (glycemic index multiplied by total carbohydrate) have also been associated with higher levels of high-density lipoprotein cholesterol, reduced C-reactive protein concentrations and with a decreased risk of developing diabetes and cardiovascular disease. More recently, some case-control and cohort studies have also found positive associations between the dietary glycemic index and the risk of colon, breast and other cancers. While the glycemic index concept continues to be debated and there remain inconsistencies in the data, sufficient positive findings have emerged to suggest that the glycemic index is an aspect of diet of potential importance in the treatment and prevention of chronic diseases.
Dietary carbohydrates have different glycemic and insulinemic potentials depending on type (glycemic index, GI) and amount (glycemic load, GL) of carbohydrate consumed or both. Insulin in turn has been implicated as a risk factor for several cancers, including that of the prostate. We assessed the relationship of GI and GL with prostate cancer risk in a multicenter case-control study. Cases and controls were recruited between 1991 and 2002 in the network of major teaching and general hospitals in 4 Italian areas. Cases were 1,204 men (age range 46-74 years) admitted for incident, histologically confirmed prostate cancer. Controls were 1,352 men (age range 46-74 years) admitted for acute, nonmalignant conditions unrelated to long-term modifications of diet. ORs of prostate cancer and the corresponding 95% CIs were derived using unconditional multiple logistic regression, including terms for age, study center, education, family history of prostate cancer, smoking, body mass index, physical activity, alcohol consumption, intake of energy, fiber and lycopenes. Compared to the lowest quintile of GI, the ORs were 1.23, 1.24, 1.47 and 1.57 for subsequent levels of GI. The corresponding values for GL were 0.91, 1.00, 1.20 and 1.41. No heterogeneity was found among strata of selected covariates. We found direct relations between dietary GI and GL and prostate cancer risk. Correcting for potential confounding factors did not substantially modify these associations.
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BACKGROUND: The apparent favorable effect of alcohol on the risk of acute myocardial infarction (MI) may be related to its hypoinsulinemic effect when consumed with meals. We studied how the timing of alcohol consumption in relation to meals might affect the risk of MI in a population with relatively high regular alcohol consumption. METHODS: We conducted a case-control study between 1995 and 1999 in Milan, Italy. Cases were 507 subjects with a first episode of nonfatal acute MI, and controls were 478 patients admitted to hospitals for other acute diseases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression models. RESULTS: Compared with nondrinkers, an inverse trend in risk was observed when alcohol was consumed during meals only (for > or =3 drinks per day: OR = 0.50; 95% CI = 0.30-0.82). In contrast, no consistent trend in risk was found for subjects drinking outside of meals (for > or =3 drinks per day: 0.98; 0.49-1.96). The pattern of risk was similar when we considered people who drank only wine. CONCLUSIONS: Alcohol drinking during meals was inversely related with risk of acute MI, whereas alcohol drinking outside meals only was unrelated to risk.
OBJECTIVE: The insulin-like growth factor (IGF) system has been related to cell proliferation, obesity, diabetes, hyperinsulinemia and endometrial cancer risk. We used data from a case-control study conducted in Italy to provide additional information on the relation between the IGF system and endometrial cancer. METHODS: A case-control study was conducted between 1999 and 2002 in Italy, including a total of 73 women with incident, histologically confirmed endometrial cancer and 108 controls admitted to the same hospital network for acute, nonneoplastic diseases. All subjects were interviewed using a validated questionnaire. RESULTS: The odds ratios for endometrial cancer comparing the highest versus the lowest tertile of various IGF components were as follows: 0.5 [95% confidence interval (CI) 0.2-1.2] for free IGF-I, 1.1 (95% CI 0.5-2.6) for total IGF-I, 1.2 (95% CI 0.6-2.6) for total IGF-II, 2.4 (95% CI 1.0-5.9) for IGF binding protein (IGFBP)-1 and 0.8 (95% CI 0.4-2.0) for IGFBP-3. Further allowance for all IGF components in the model did not modify the results. The direct relation with IGFBP-1 was stronger and limited to heavier and older women. CONCLUSIONS: The present findings suggest a limited effect of the IGF system on endometrial cancer risk. Increasing IGFBP-1 levels seem to be associated with endometrial cancer risk in older women and in women with a higher body mass index.
BACKGROUND: Components of the insulin-like growth factor (IGF) system have been associated with several cancers, but very few studies are available for ovarian cancer. METHODS: A case-control study conducted between 1999 and 2003 in Italy, including a total of 59 women with incident, histologically confirmed ovarian cancer and 108 controls admitted to the same hospital network as cases, for acute non-neoplastic diseases. All subjects were interviewed using a validated questionnaire. RESULTS: After adjustment for potential confounders, the multivariate odds ratios for the highest versus the lowest tertile of various IGF components were 0.6 (95% confidence interval, CI: 0.2-1.4) for free IGF-I, 0.4 (CI: 0.1-1.5) for total IGF-I, 2.6 (CI: 0.9-6.9) for IGF-binding protein (IGFBP)-1, and 0.2 (CI: 0.0-0.6) for IGFBP-3. CONCLUSIONS: This study suggests a protective role of IGFBP-3 and a positive association of IGFBP-1 with ovarian cancer. The complex role of the IGF system in ovarian carcinogenesis deserves further clarification.
Circulating levels of adiponectin, a hormone with insulin-sensitizing properties, are decreased in conditions related to obesity and hyperinsulinemia, which are recognized risk factors for endometrial cancer. Eighty-seven cases with incident, histologically confirmed endometrial cancer and 132 controls admitted for acute, nonneoplastic diseases were interviewed in northeastern Italy between 1999 and 2002, and blood samples were collected. Levels of adiponectin were evaluated in samples by means of a RIA. An inverse association with endometrial cancer risk emerged for plasma adiponectin levels [odds ratio (OR), 0.42; 95% confidence interval, 0.19-0.94] when comparing the highest vs. the lowest tertiles. Similar results emerged for serum adiponectin (OR, 0.30; 95% confidence interval, 0.14-0.68). The association was stronger in pre- than in postmenopausal women, but no significant heterogeneity was observed across strata of body mass index (BMI) or parity. BMI and adiponectin showed independent effects on the risk of endometrial cancer according to a multiplicative model (OR, 6.45 in the highest level of BMI and in the lowest one of adiponectin).
Glycemic index (GI) and glycemic load (GL) are measures of the metabolic effects of dietary carbohydrates. The higher their value, the greater the glucose and insulin responses. Raised insulin levels are associated with endometrial cancer and with its risk factors including obesity, diabetes and hypertension. To study the role of the GI and GL we analyzed the data of two hospital-based case-control studies on endometrial cancer conducted between 1988-98 in Italy and Switzerland, including a total of 410 women with incident, histologically confirmed endometrial cancer and 753 controls admitted for acute, non-neoplastic diseases. A food frequency questionnaire was used to assess the subjects usual diet and to derive estimates of dietary GI and GL. The odds ratios (OR) of endometrial cancer, after adjustment for major risk factors, for the highest versus the lowest quintile of dietary GI and GL were 2.1 (95% confidence interval [CI] = 1.4-3.2) and 2.7 (95% CI = 1.8-4.2), respectively. The associations were stronger in older women, in those with higher body mass index and in hormone replacement therapy users. Our study supports the hypothesis of a direct association between GI and endometrial cancer risk.
BACKGROUND: The ability of dietary carbohydrates to affect blood glucose and insulin levels by dietary carbohydrates is best measured by the glycemic index (GI) and glycemic load (GL) which have been directly associated with risk of several chronic conditions, including cancer. PATIENTS AND METHODS: Three case-control studies were conducted between 1992 and 2000 in Italy. The first one included 598 hospital patients with incident, histologically confirmed oral and pharyngeal cancer and 1491 controls admitted to the same hospital networks for acute, non-neoplastic diseases; the second study included 304 subjects with squamous cell oesophageal cancer and 743 controls; the third one included 460 cases with laryngeal cancer and 1088 controls. All subjects were interviewed using a validated food frequency questionnaire. RESULTS: The odds ratios (OR) of upper aero-digestive tract neoplasms for the highest versus the lowest quintile of dietary GI and GL were 1.5 (95% confidence interval [CI]: 1.1-2.0) and 1.8 (95% CI: 1.1-2.9), respectively. The associations were in the same direction for various cancer sites. The ORs were apparently stronger in women, in those with high body mass index and reporting low alcohol consumption. CONCLUSIONS: This study supports the hypothesis that high dietary GI and GL are associated with cancers of the upper aero-digestive tract.
Based on what is known of the components of plant-based diets and their effects from cohort studies, there is reason to believe that vegetarian diets would have advantages in the treatment of type 2 diabetes. At present there are few data on vegetarian diets in diabetes that do not in addition have weight loss or exercise components. Nevertheless, the use of whole-grain or traditionally processed cereals and legumes has been associated with improved glycemic control in both diabetic and insulin-resistant individuals. Long-term cohort studies have indicated that whole-grain consumption reduces the risk of both type 2 diabetes and cardiovascular disease. In addition, nuts (eg, almonds), viscous fibers (eg, fibers from oats and barley), soy proteins, and plant sterols, which may be part of the vegetarian diet, reduce serum lipids. In combination, these plant food components may have a very significant impact on cardiovascular disease, one of the major complications of diabetes. Furthermore, substituting soy or other vegetable proteins for animal protein may also decrease renal hyperfiltration, proteinuria, and renal acid load and in the long term reduce the risk of developing renal disease in type 2 diabetes. The vegetarian diet, therefore, contains a portfolio of natural products and food forms of benefit for both the carbohydrate and lipid abnormalities in diabetes. It is anticipated that their combined use in vegetarian diets will produce very significant metabolic advantages for the prevention and treatment of diabetes and its complications.
Current dietary guidelines of the American Diabetes Association emphasize the importance of minimizing risk factors for cardiovascular disease while maximizing diabetes control. Potential advantages are seen for increased monounsaturated fat intake, but only the quantity rather than the quality of the carbohydrate is considered important. However, review of the carbohydrate issue suggests that many cultures now at high risk of diabetes originally consumed starchy staples higher in fiber and with a lower glycemic index than eaten currently. Furthermore, diets high in cereal fiber have been associated with improved glycemic control, and low glycemic index diets resulted in reduction in glycosylated proteins in type 1 and 2 diabetes. Finally, large cohort studies have demonstrated beneficial effects of cereal fiber and low glycemic index carbohydrate foods in reducing the risk both for diabetes and cardiovascular disease. The effect of insoluble cereal fiber is not readily explained, but a low glycemic index may result from a slower rate of carbohydrate absorption. Increased meal frequency as a model for reducing the rate of carbohydrate absorption has been shown to reduce day-long glucose and insulin levels in type 2 diabetes and reduce serum lipids in nondiabetic subjects. Therefore, there appears to be a potential role for low glycemic index, high-cereal fiber foods for prevention and treatment of diabetes. Both the nature of the dietary fat and the carbohydrate should be considered as potentially modifiable factors that together with weight control and exercise may play a role in diabetes and cardiovascular disease prevention and treatment.
The glycemic index concept is an extension of the fiber hypothesis, suggesting that fiber consumption reduces the rate of nutrient influx from the gut. The glycemic index has particular relevance to those chronic Western diseases associated with central obesity and insulin resistance. Early studies showed that starchy carbohydrate foods have very different effects on postprandial blood glucose and insulin responses in healthy and diabetic subjects, depending on the rate of digestion. A range of factors associated with food consumption was later shown to alter the rate of glucose absorption and subsequent glycemia and insulinemia. At this stage, systematic documentation of the differences that exist among carbohydrate foods was considered essential. The resulting glycemic index classification of foods provided a numeric physiologic classification of relevant carbohydrate foods in the prevention and treatment of diseases such as diabetes. Since then, low-glycemic-index diets have been shown to lower urinary C-peptide excretion in healthy subjects, improve glycemic control in diabetic subjects, and reduce serum lipids in hyperlipidemic subjects. Furthermore, consumption of low-glycemicindex diets has been associated with higher HDL-cholesterol concentrations and, in large cohort studies, with decreased risk of developing diabetes and cardiovascular disease. Case-control studies have also shown positive associations between dietary glycemic index and the risk of colon and breast cancers. Despite inconsistencies in the data, sufficient, positive findings have emerged to suggest that the dietary glycemic index is of potential importance in the treatment and prevention of chronic diseases.
OBJECTIVE: Cohort studies indicate that cereal fiber reduces the risk of diabetes and coronary heart disease (CHD). Therefore, we assessed the effect of wheat bran on glycemic control and CHD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 23 subjects with type 2 diabetes (16 men and 7 postmenopausal women) completed two 3-month phases of a randomized crossover study. In the test phase, bread and breakfast cereals were provided as products high in cereal fiber (19 g/day additional cereal fiber). In the control phase, supplements were low in fiber (4 g/day additional cereal fiber). RESULTS: Between the test and control treatments, no differences were seen in body weight, fasting blood glucose, HbA(1c), serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin. LDL oxidation in the test phase was higher than that seen in the control phase (12.1 +/- 5.4%, P < 0.034). Of the subjects originally recruited, more dropped out of the study for health and food preference reasons from the control phase (16 subjects) than the test phase (11 subjects). CONCLUSIONS: High-fiber cereal foods did not improve conventional markers of glycemic control or risk factors for CHD in type 2 diabetes over 3 months. Possibly longer studies are required to demonstrate the benefits of cereal fiber. Alternatively, cereal fiber in the diet may be a marker for another component of whole grains that imparts health advantages or a healthy lifestyle.
It was initially hypothesized that resistant starches, i.e., starch that enters the colon, would have protective effects on chronic colonic diseases, including reduction of colon cancer risk and in the treatment of ulcerative colitis. Recent studies have confirmed the ability of resistant starch to increase fecal bulk, increase the molar ratio of butyrate in relation to other short-chain fatty acids, and dilute fecal bile acids. However the ability of resistant starch to reduce luminal concentrations of compounds that are damaging to the colonic mucosa, including fecal ammonia, phenols, and N-nitroso compounds, still requires clear demonstration. As such, the effectiveness of resistant starch in preventing or treating colonic diseases remains to be assessed. Nevertheless, there is a fraction of what has been termed resistant (RS1) starch, which enters the colon and acts as slowly digested or lente carbohydrate in the small intestine. Foods in this class are low glycemic index and have been shown to reduce the risk of chronic disease. They have been associated with systemic physiological effects such as reduced postprandial insulin levels and higher HDL cholesterol levels. Consumption of low glycemic index foods has been shown to be related to reductions in risk of coronary heart disease and Type 2 diabetes. Type 2 diabetes has in turn been related to a higher risk of colon cancer. If carbohydrates have a protective role in colon cancer prevention this may lie partly in the systemic effects of low glycemic index foods. The colonic advantages of different carbohydrates, varying in their glycemic index and resistant starch content, therefore, remain to be determined. However, as recent positive research findings continue to mount, there is reason for optimism over the possible health advantages of those resistant starches, which are slowly digested in the small intestine.