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Background: Inflammation may be a mechanism by which high postprandial insulin and glucose responses increase the risk of type 2 diabetes mellitus. Objective: We hypothesized that dietary carbohydrates characterized by different postprandial insulin responses may differentially modify cytokine concentrations in plasma and gene expression in subcutaneous adipose tissue. Design: Individuals (n = 47) with the metabolic syndrome were randomly assigned to a 12-wk diet with oat and wheat bread and potato (high postprandial insulin response) or rye bread and pasta (low postprandial insulin response). Postprandial glucose and insulin responses to the oat and wheat bread meal and to the rye bread meal were determined in 19 individuals before intervention. Results: During the 12-wk diet, the change in the gene expression of interleukin (IL)-10 receptor [alpha] and tumor necrosis factor-[alpha] in subcutaneous adipose tissue differed between the groups (P = 0.002 and P = 0.083, respectively). Moreover, the change in fasting plasma concentrations of IL-1 [beta] and IL-6 differed between the groups (P = 0.020 and P = 0.055, respectively). In the postprandial challenge, the insulin response to the rye bread meal was lower than that to the oat and wheat bread meal (P < 0.001), whereas there were no differences in the mean blood glucose response. In contrast, plasma glucose concentrations decreased more below fasting concentrations 2.5-3 h after the oat and wheat bread meal than after the rye bread meal. A late postprandial rebound of free fatty acids was detected after the oat and wheat bread meal (P = 0.048). Conclusions: Long-term intake of cereal foods with differing postprandial insulin responses may be a factor that modulates the inflammatory status in individuals with the metabolic syndrome. KEY WORDS Gene-nutrient interactions, adipose tissue, inflammation, cytokines, postprandial response

Background: Diets rich in whole-grain cereals and foods with a low glycemic index may protect against type 2 diabetes, but the underlying molecular mechanisms are unknown. Objective: The main objective was to test whether 2 different carbohydrate modifications--a rye-pasta diet characterized by a low postprandial insulin response and an oat-wheat-potato diet characterized by a high postprandial insulin response--affect gene expression in subcutaneous adipose tissue (SAT) in persons with the metabolic syndrome. Design: We assessed the effect of carbohydrate modification on SAT gene expression in 47 subjects [24 men and 23 women with a mean ([+ or -] SD) age of 55 [+ or -] 6 y] with the features of the metabolic syndrome in a parallel study design. The subjects had a mean ([+ or -] SD) body mass index (kg/[m.sup.2]) of 32.1 [+ or -] 3.8 and a 2-h plasma glucose concentration of 8.0 [+ or -] 2.3 mmol/L. Adipose tissue biopsies were performed, and oral-glucose-tolerance tests and other biochemical measurements were conducted before and after the intervention. Results: We detected 71 down-regulated genes in the rye-pasta group, including genes linked to insulin signaling and apoptosis. In contrast, the 12-wk oat-wheat-potato diet up-regulated 62 genes related to stress, cytokine-chemokine--mediated immunity, and the interleukin pathway. The insulinogenic index improved after the rye-pasta diet (P = 0.004) but not after the oat-wheat-potato diet. Body weight was unchanged in both groups. Conclusions: Dietary carbohydrate modification with rye and pasta or oat, wheat, and potato differentially modulates the gene expression profile in abdominal subcutaneous adipose tissue, even in the absence of weight loss. KEY WORDS Gene-nutrient interactions, metabolic syndrome, insulin resistance, microarray, adipose tissue, diet intervention, insulinemic response, rye, oat, wheat

Background: Carbohydrate modification based on rye bread and pasta enhances early insulin secretion in subjects with the metabolic syndrome. Objective: Because the actions of insulin and cholesterol metabolism are interrelated, the question is raised of whether it is possible to alter cholesterol metabolism by means of dietary carbohydrate modification. Design: We investigated the 12-wk effects of dietary carbohydrate modification on cholesterol synthesis and absorption by measuring the ratios of surrogate markers of precursor (cholestenol, desmosterol, and lathosterol) and absorption (cholestanol and plant sterols) sterols to cholesterol and their association to glucose metabolism in 74 subjects with the metabolic syndrome. The subjects were randomly assigned to diets with rye bread and pasta (RPa) or oat, wheat bread, and potato (OWPo) as the main carbohydrate source (34% and 37% of energy intake, respectively). Results: During the study, serum cholesterol concentrations remained unchanged. Cholesterol synthesis was lower (6-10% for cholestenol and lathosterol; P < 0.05) and absorption higher (9%; P < 0.05 for sitosterol) with the OWPo diet than at baseline. With the RPa diet, cholesterol absorption was lower and synthesis higher than with the OWPo diet. The increment in the glucose area under the curve with the RPa diet was positively related to baseline cholesterol synthesis (eg, lathosterol; r = 0.480, P < 0.05) and negatively to absorption (for cholestanol; r = -0.520, P < 0.05). In the combined group, the changes in the cholestanol ratio and the insulinogenic index were interrelated (r = -0.464, P < 0.001). Conclusions: Carbohydrate modifications had dissimilar effects on cholesterol metabolism. Consumption of RPa, as compared with OWPo, may be clinically more favorable because it seems to inhibit the absorption of cholesterol, a factor crucial in the development of arterial atherosclerosis. KEY WORDS Rye, oat, wheat, metabolic syndrome, glucose metabolism, cholesterol metabolism, sitosterol, campesterol, lathosterol, randomized controlled trial

Background: Methodologic choices affect measures of the glycemic index (GI). The effects on GI values of blood sampling site, reference food type, and the number of repeat tests have been insufficiently determined. Objective: The objective was to study the effect of methodologic choices on GI values. Comparisons were made between venous and capillary blood sampling and between glucose and white bread as the reference food. The number of tests needed for the reference food was assessed. Rye bread, oatmeal porridge, and instant mashed potato were used as the test foods. Design: Twelve healthy volunteers were served each test food once and both reference foods 3 times at 1-wk intervals in a random order after they had fasted overnight. Capillary and venous blood samples were drawn at intervals for 3 h after each study meal. Results: GIs and their CVs based on capillary samples were lower than those based on venous samples. Two tests of glucose solution as the reference provided stable capillary GIs for the test foods. The capillary GIs did not differ significantly when white bread was used as the reference 1, 2, or 3 times, but the variation was lower when tests were performed 2 and 3 times. Capillary GIs with white bread as the reference were 1.3 times as high as those with glucose as the reference. The capillary GIs of rye bread, oatmeal porridge, and mashed potato were 77, 74, and 80, respectively, with glucose as the reference. Conclusions: Capillary blood sampling should be used in the measurement of GI, and reference tests with glucose or white bread should be performed at least twice. KEY WORDS Glycemic index, capillary blood, venous blood, methods, reference food, rye bread, oatmeal porridge, mashed potato

Background: In vitro and in vivo studies suggest that selected strains of probiotic bacteria can form tight complexes with aflatoxin [B.sub.1] and other carcinogens. Objective: The aim of the present study was to determine whether administration of probiotic bacteria could block the intestinal absorption of aflatoxin [B.sub.1] and thereby lead to reduced urinary excretion of aflatoxin [B.sub.1]-[N.sup.7]-guanine (AFB-[N.sup.7]-guanine), a marker for a biologically effective dose of aflatoxin exposure. Elevated urinary excretion of this aflatoxin-DNA adduct is associated with an increased risk of liver cancer. Design: Ninety healthy young men from Guangzhou, China, were randomly assigned to 2 groups; one group received a mixture of Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii subsp, shermanii strains 2 times/d for 5 wk, and the other group received a placebo preparation. The subjects provided 4 urine samples: at baseline, at 3 and 5 wk after starting the supplementation, and at the end of the 5-wk postintervention period. Results: The percentage of samples with negative AFB-[N.sup.7]-guanine values tended to be higher in the probiotic group than in the placebo group during the 5-wk intervention period (odds ratio: 2.63, P = 0.052), and a statistically significant decrease in the concentration of urinary AFB-[N.sup.7]-guanine was observed in the probiotic group. The reduction was 36% at week 3 and 55% at week 5. The geometric means for the probiotic and placebo groups were 0.24 and 0.49 ng AFB-[N.sup.7]-guanine/mL, respectively, during the intervention period (P = 0.005). Conclusion: A probiotic supplement reduces the biologically effective dose of aflatoxin exposure and may thereby offer an effective dietary approach to decrease the risk of liver cancer. KEY WORDS Probiotic bacteria, aflatoxins, aflatoxin [B.sub.1]-[N.sup.7]guanine, supplementation, young men, liver cancer

Background: The metabolic syndrome markedly increases the risk of type 2 diabetes and cardiovascular disease, but the influence of dietary modification on insulin and glucose metabolism independent of weight loss is still poorly understood. Objective: Our aim was to test whether carbohydrate dietary modifications improve insulin sensitivity and secretion and glucose tolerance in overweight or obese persons with the metabolic syndrome, even in the absence of weight loss. Design: We assessed the effect of carbohydrate modification on insulin and glucose metabolism in 72 overweight or obese men and women with the metabolic syndrome, as determined according to the National Cholesterol Education Program criteria. The subjects were randomly assigned to 12-wk diets in which either rye bread and pasta or oat and wheat bread and potato were the main carbohydrate sources (34% and 37% of energy intake, respectively). Results: Body weight did not significantly change in either group during the trial. No significant difference was observed in the changes in fasting glucose and insulin concentrations or in glucose and insulin areas under the curve between the groups during a 2-h oral-glucose-tolerance test. The insulinogenic index (an index of early insulin secretion) increased more in the rye bread and pasta group than in the oat and wheat bread and potato group (33.2% compared with 5.5%; P = 0.026). In the combined groups, an enhanced insulinogenic index was associated with improved glucose tolerance, whereas weight gain worsened glucose tolerance. Moreover, even modest weight gains abolished the relative improvement in the insulinogenic index in the rye bread and pasta group compared with the oat and wheat bread and potato group (P for the interaction between weight change and group = 0.019). Conclusions: Rye bread and pasta-based carbohydrate modification enhances early insulin secretion in persons with the metabolic syndrome, which may lower the risk of deteriorating glucose tolerance and development of type 2 diabetes. KEY WORDS: Rye. oat, wheat, insulin secretion, glucose tolerance, metabolic syndrome, randomized controlled trial

Background: Rye bread has a beneficial effect on the postprandial insulin response in healthy subjects. The role of rye fiber in insulin and glucose metabolism is not known. Objective: The aim of the study was to determine the effect of the content of rye fiber in rye breads on postprandial insulin and glucose responses. Design: Nineteen healthy postmenopausal women aged 61 [+ or -] 1 y, with a body mass index (in kg/[m.sup.2]) of 26.0 [= or -] 0.6, and with normal glucose tolerance participated in the study. The test products were refined wheat bread (control), endosperm rye bread, traditional rye bread, and high-fiber rye bread; each bread provided 50 g available carbohydrate and was served with breakfast. Plasma glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and serum C-peptide were measured in fasting and 8 postprandial blood samples. In vitro starch hydrolysis and the microscopic structure of the breads were also determined. Results: Postprandial insulin, glucose-dependent insulinotropic polypeptide, and C-peptide responses to the rye breads were significantly lower than the response to the control; no significant differences in insulin and C-peptide responses to the rye breads were found. Glucose and glucagon-like peptide 1 responses to the rye breads were not significantly different from those to the control, except at 150 and 180 min. In vitro starch hydrolysis was slower in all rye breads than in the control, and the structure of continuous matrix and starch granules differed between the rye and control breads. Conclusion: Total fiber content does not explain the lower postprandial insulin response to rye bread than to wheat bread, but structural differences between rye and wheat breads might. KEY WORDS: Rye, wheat, cereal fiber, postprandial, blood glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, postmenopausal women

Background: Fiber and whole-cereal intakes may protect against hyperinsulinemia and the risk of type 2 diabetes. Objective: The aim was to study whether the long-term use of high-fiber rye bread and white-wheat bread modifies glucose and insulin metabolism in healthy postmenopausal women. Design: The study was a randomized crossover trial consisting of 8-wk test and 8-wk washout periods. The subjects were 20 postmenopausal women [[bar]x [+ or -] SD age: 59 [+ or -] 6.0 y; body mass index (in kg/[m.sup.2]): 27.5 [+ or -] 2.9; baseline fasting serum cholesterol: 6.5 [+ or -] 0.8 mmol/L], of whom 3 had impaired glucose tolerance as determined by a 2-h oral-glucose-tolerance test. The test breads were high-fiber rye and white-wheat breads, planned to make up [greater than or equal to] 20% of energy. Fasting blood samples were collected for the measurement of plasma glucose and insulin at the beginning and at the end of both bread periods. The frequently sampled intravenous-glucose-tolerance test was performed at the run-in and at the end of both bread periods. The acute insulin response, insulin sensitivity, and glucose effectiveness were calculated. Results: The rye bread made up 23.4 [+ or -] 4.3% and wheat bread 26.7 [+ or -] 8.2% of total energy intake. Compared with that during the run-in period, the acute insulin response increased significantly more during the rye bread period (9.9 [+ or -] 24.2%) than during the wheat bread period (2.8 [+ or -] 36.3%; P = 0.047). Other measured variables did not change significantly during the study. Conclusions: Modification of carbohydrate intake by high-fiber rye bread did not alter insulin sensitivity in postmenopausal, hypercholesterolemic women. High-fiber rye bread appears to enhance insulin secretion, possibly indicating improvement of b cell function. KEY WORDS Rye, wheat, fiber, insulin sensitivity, insulin secretion, glucose, women

Background: Various botanical and structural characteristics of starchy food modify the postprandial glucose and insulin responses in humans. Objective: We investigated what factors in grain products affect human glucose and insulin responses and elucidated the mediating mechanisms. Design: Ten men and 10 women [mean age: 28 [+ or -] 1 y; mean body mass index (in kg/[m.sup.2]): 22.9 [+ or -] 0.7] with normal glucose tolerance were recruited. The test products were whole-kernel rye bread, whole-meal rye bread containing oat [beta]-glucan concentrate, dark durum wheat pasta, and wheat bread made from white wheat flour. Paracetamol, a marker of the rate of gastric emptying, was added to the breads during baking. Each product provided 50 g available carbohydrate and was served in random order with breakfast (except for the [beta]-glucan rye bread, which was served at the last visit). Fasting and 8 postprandial blood samples were collected at intervals of 15-30 min for 3 h to determine plasma glucose, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), serum insulin, and paracetamol concentrations. The in vitro starch hydrolysis, the structural characteristics (by light microscopy), and the molecular weight of [beta]-glucan in the test products were analyzed. Results: Glucose responses and the rate of gastric emptying after consumption of the 2 rye breads and pasta did not differ from those after consumption of white wheat bread. However, insulin, GIP, and GLP-1 responses, except for GLP-1 responses to the rye bread containing oat [beta]-glucan concentrate, were lower after the consumption of rye breads and pasta than after consumption of white wheat bread. Conclusions: Postprandial insulin responses to grain products are determined by the form of food and botanical structure rather than by the amount of fiber or the type of cereal in the food. These effects may be mediated through GIP and GLP-1. KEY WORDS Rye, wheat, dietary fiber, postprandial period, blood glucose, insulin, incretin, glucose-dependent insulinotropic polypeptide, glucagon-like-peptide 1, gastric emptying

To study the potential beneficial effects of a vegan diet on biomarkers of chemoprevention, a cross-sectional study was performed and several biomarkers of chemoprevention were measured in a population of female 'living food' eaters (vegans, n = 20) and compared with matched omnivorous control subjects (n = 20). White blood cells obtained from fresh blood samples were subjected to the single-cell gel-electrophoresis assay and the number of binucleated lymphocytes with micronuclei were calculated before and after treating the fresh cells with mitomycin C. The content of glutathione S-transferase in plasma was measured using radioimmunoassay. There were no significant differences between the vegans and control subjects in any of the indexes studied. However, the 'tail moment' was significantly lower in a subset of the vegans (ie, in those who did not use any health supplements), and a significant negative correlation (r = -0.64, P [is less than] 0.01) between the number of mitomycin C-induced micronuclei and the activity of erythrocyte superoxide dismutase was found in the vegans. The present data indicate only minor differences in biomarkers of chemopreventive potential in strict vegans compared with matched omnivores. This finding may be because the 'living food' diet has both beneficial (eg, high supply of antioxidants) and harmful characteristics (eg, low supply of vitamin B-12) with regard to the chemopreventive potential.

The effect of phosphate on the intestinal absorption of lead (203Pb2+) was examined in chicks. Absorption was determined by the in situ ligated duodenal loop technique. In one approach, diets differing in phosphate content were fed to 2-week-old chicks for a period of 7 days. With respect to the control group (1.06% P), a severe phosphate deficiency (0.16% P) decreased growth, CaBP synthesis and 203Pb absorption; a moderate phosphate deficiency (0.33% P) resulted in an increase in CaBP production and 203Pb absorption; and the high phosphate diet (2.12%) gave mean values for CaBP synthesis and 203Pb absorption intermediate between those from the chicks fed the 0.33 and 1.06% diets. 203Pb absorption was highly correlated with CaBP concentrations. In another approach, phosphate in varying concentrations was added directly to the dosing solution. In one study, phosphate addition (0.1 mM) depressed 203Pb absorption in rachitic and cholecalciferol-treated chicks. When the data were expressed in terms of absorption of the soluble 203Pb present in the intestinal lumen at the end of the absorption period, an effect of phosphate in addition to the precipitation of the insoluble lead salt was uncovered. In an experiment with normal chicks, it was observed that phosphate in the dosing solution at concentrations of 1 and 2 mM partially and significantly reversed the inhibitory effect of lower concentrations of phosphate (0.01 mM and 0.1 mM). These data demonstrate the complexity of the phosphate-lead interaction, in addition to directly showing an effect of dietary phosphate on intestinal lead absorption.

Brush border membrane vesicles were isolated from mucosal homogenates of duodena from normal, rachitic and vitamin D-treated rachitic chicks using a discontinuous sucrose gradient, and further purified by glycerol gradient centrifugation. In vitro uptake of 75Se-selenite by purified brush border membrane vesicles was studied using a rapid filtration technique. The time course of 75Se uptake was non-linear; rapid initial binding was followed by a gradual decrease in the rate of uptake until an equilibrium value was reached at 60–120 min. The initial binding at 36 s was not affected by selenite concentration in the incubation buffer, while the fractional rate of uptake between the 36 s and 2 min time periods was clearly lower with 1 mM Se than with 4–100 µM Se. 75Se uptake did not show any dependency on the external Na-gradient, nor could it be inhibited by other anions (arsenate, phosphate). Treatment of rachitic chicks either with cholecalciferol (500 IU, 72 h) or with 1,25(OH)2-cholecalciferol (0.5 µg given 16 h prior to isolation of the vesicles) significantly enhanced 75Se uptake. A threefold excess of mannitol in the outside buffer reduced 75Se uptake by vesicles from vitamin D-deficient and D-treated chicks 60% and 35% respectively, but had no effect on vesicles from vitamin D-treated chicks preloaded with 75Se. Neither saponin treatment nor excess cold selenite could release the label from the vesicles preloaded with 75Se. These data are compatible with the hypothesis that selenite easily crosses the brush border membrane into the intravesicular space and, once inside, is tightly bound by the membrane. Vitamin D affects this process possibly by increasing the number or the availability of sites binding selenite in the vesicles.