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Biomedical subjects

Thomas M S Wolever

Publications and source records attributed to Thomas M S Wolever.

At least 19 recordsLinked to original sources

Carbohydrate nutrition, glycaemic load, and plasma lipids: the Insulin Resistance Atherosclerosis Study.

AIMS: We evaluated the relationship of carbohydrate nutrition and selected food groups with lipids using data from the Insulin Resistance Atherosclerosis Study (IRAS Exam I, 1992-1994). METHODS AND RESULTS: A total of 1026 middle-aged adults with normal or impaired glucose tolerance had complete data on fasting lipids and usual dietary intake from an interviewer-administered, validated food frequency questionnaire. Published glycaemic index (GI) values were assigned to food items and average dietary GI and glycaemic load (GL) were calculated per participant. Intake of carbohydrates differed by gender, men consuming more absolute digestible carbohydrates with higher GI and GL than women. In multivariate models adjusting for energy intake, in men, GL and carbohydrates were associated positively with total and LDL cholesterol, and inversely with HDL. In women, associations were limited to triglycerides. We estimated that a 100 g higher intake in GL or carbohydrates was associated with a 7-8 mg/dL higher total or LDL cholesterol level in men, and a 13-17 mg/dL higher triglyceride level in women. In the combined sample, GL and carbohydrates were consistently associated with all lipid levels and GI was inversely associated with HDL cholesterol. CONCLUSION: Our findings underscore the importance of carbohydrate nutrition for plasma lipids.

Adult↗

Equivalent glycemic load (EGL): a method for quantifying the glycemic responses elicited by low carbohydrate foods.

BACKGROUND: Glycemic load (GL) is used to quantify the glycemic impact of high-carbohydrate (CHO) foods, but cannot be used for low-CHO foods. Therefore, we evaluated the accuracy of equivalent-glycemic-load (EGL), a measure of the glycemic impact of low-CHO foods defined as the amount of CHO from white-bread (WB) with the same glycemic impact as one serving of food. METHODS: Several randomized, cross-over trials were performed by a contract research organization using overnight-fasted healthy subjects drawn from a pool of 63 recruited from the general population by newspaper advertisement. Incremental blood-glucose response area-under-the-curve (AUC) elicited by 0, 5, 10, 20, 35 and 50 g CHO portions of WB (WB-CHO) and 3, 5, 10 and 20 g glucose were measured. EGL values of the different doses of glucose and WB and 4 low-CHO foods were determined as: EGL = (F-B)/M, where F is AUC after food and B is y-intercept and M slope of the regression of AUC on grams WB-CHO. The dose-response curves of WB and glucose were used to derive an equation to estimate GL from EGL, and the resulting values compared to GL calculated from the glucose dose-response curve. The accuracy of EGL was assessed by comparing the GL (estimated from EGL) values of the 4 doses of oral-glucose with the amounts actually consumed. RESULTS: Over 0-50 g WB-CHO (n = 10), the dose-response curve was non-linear, but over the range 0-20 g the curve was indistinguishable from linear, with AUC after 0, 5, 10 and 20 g WB-CHO, 10 +/- 1, 28 +/- 2, 58 +/- 5 and 100 +/- 6 mmol x min/L, differing significantly from each other (n = 48). The difference between GL values estimated from EGL and those calculated from the dose-response curve was 0 g (95% confidence-interval, +/- 0.5 g). The difference between the GL values of the 4 doses of glucose estimated from EGL, and the amounts of glucose actually consumed was 0.2 g (95% confidence-interval, +/- 1 g). CONCLUSION: EGL, a measure of the glycemic impact of low-carbohydrate foods, is valid across the range of 0-20 g CHO, accurate to within 1 g, and at least sensitive enough to detect a glycemic response equivalent to that produced by 3 g oral-glucose in 10 subjects.

Journal Article↗

Measuring glycaemic responses: duplicate fasting samples or duplicate measures of one fasting sample?

The precision with which glycaemic responses, expressed as incremental area under the curve (AUC), can be measured may be improved by using the average of several measures of fasting blood glucose (FBG). To see if taking two fasting blood samples would increase the precision of AUC, the glycaemic responses elicited by four test meals (50 g glucose; 50 g glucose plus 10 g fat and 10 g protein; 100 g white bread; 100 g white bread plus 10 g fat and 10 g protein) were determined in thirteen overnight-fasted healthy subjects. Two fasting blood samples were taken 5 min apart (-5 min and 0 min before starting to eat) with glucose measured three times in each sample. AUC was calculated using different estimates of FBG derived from the three measures of glucose in the two fasting blood samples and each set of AUC values subjected to ANOVA. Unexpectedly, the results were more precise when AUC was calculated from mean glucose in the 0 min blood sample (FBG0) than from mean glucose in the two different fasting blood samples. The 95 % CI of the AUC calculated using FBG0 in thirteen subjects was +/-29.8; to obtain the same CI using the mean of the two fasting blood samples would require fourteen subjects. These results suggest that taking two fasting blood samples does not necessarily improve, and may even reduce, the precision of AUC as a measure of glycaemic response. Further studies are needed before requiring that two fasting blood samples be taken for determining glycaemic index.

Adult↗

Food glycemic index, as given in glycemic index tables, is a significant determinant of glycemic responses elicited by composite breakfast meals.

BACKGROUND: Recent studies have concluded that the carbohydrate content and glycemic index (GI) of individual foods do not predict the glycemic and insulinemic effects of mixed meals. We hypothesized that these conclusions may be unwarranted because of methodologic considerations. OBJECTIVE: The aim was to ascertain whether the GI and carbohydrate content of individual foods influence glucose and insulin responses elicited by realistic mixed meals in normal subjects. DESIGN: With the use of a crossover design, we determined the glucose and insulin responses of 6 test meals in 16 subjects in Sydney and the glucose responses of 8 test meals in 10 subjects in Toronto and then the results were pooled. The 14 different test meals varied in energy (220-450 kcal), protein (0-18 g), fat (0-18 g), and available carbohydrate (16-79 g) content and in GI (35-100; values were rounded). RESULTS: The glucose and insulin responses of the Sydney test meals varied over a 3-fold range (P < 0.001), and the glucose responses of the Toronto test meals varied over a 2.4-fold range (P < 0.001). The glucose responses were not related to the fat or protein content of the test meal. Carbohydrate content (P = 0.002) and GI (P = 0.022) alone were related to glucose responses; together they accounted for 88% of the variation in the glycemic response (P < 0.0001). The insulin response was significantly related to the glucose response (r = 0.94, P = 0.005). CONCLUSIONS: When properly applied in realistic settings, GI is a significant determinant of the glycemic effect of mixed meals in normal subjects. For mixed meals within the broad range of nutrient composition that we tested, carbohydrate content and GI together explained approximately 90% of the variation in the mean glycemic response, with protein and fat having negligible effects.

Adult↗

The effects of fat and protein on glycemic responses in nondiabetic humans vary with waist circumference, fasting plasma insulin, and dietary fiber intake.

The effects of protein and fat on glycemic responses have not been studied systematically. Therefore, our aim was to determine the dose-response effects of protein and fat on the glycemic response elicited by 50 g glucose in humans and whether subjects' fasting plasma insulin (FPI) and diet influenced the results. Nondiabetic humans, 10 with FPI < [corrected] or =40 pmol/L and 10 with FPI >40 pmol/L, were studied on 18 occasions after 10 14-h overnight fasts. Subjects consumed 50 g glucose dissolved in 250 mL water plus 0, 5, 10, or 30 g fat and/or 0, 5, 10, or 30 g protein. Each level of fat was tested with each level of protein. Dietary intake was measured using a 3-d food record. Gram per gram, protein reduced glucose responses approximately 2 times more than fat (P < 0.001) with no significant fat x protein interaction (P = 0.051). The effect of protein on glycemic responses was related to waist circumference (WC) (r = -0.56, P = 0.011) and intake of dietary fiber (r = -0.60, P = 0.005) but was unrelated to FPI or other nutrient intakes. The effect of fat on glycemic responses was related to FPI (r = 0.49, P = 0.029) but was unrelated to WC or diet. We conclude that, across the range of 0-30 g, protein and fat reduced glycemic responses independently from each other in a linear, dose-dependent fashion, with protein having approximately 3-times the effect of fat. A large protein effect was associated with high WC and high dietary-fiber intake, whereas a large fat effect was associated with low FPI. These conclusions may not apply to solid meals. Further studies are needed to determine the mechanisms for these effects.

Adolescent↗

L-rhamnose and lactulose decrease serum triacylglycerols and their rates of synthesis, but do not affect serum cholesterol concentrations in men.

Colonic short-chain fatty acids (SCFA) may affect hepatic lipid metabolism. Lactulose increases colonic acetate production, whereas L-rhamnose increases propionate. To test the effects of oral L-rhamnose and lactulose for 28 d on fasting concentrations and hepatic synthesis of lipids in humans, 18 men were administered 25 g/d of L-rhamnose, lactulose, or d-glucose for 4 wk in a partially randomized crossover design, with blood collected from fasting subjects on the first and last day of each period. Cholesterol and triacylglycerol (TG) synthesis rates were determined using deuterated water uptake rate over the last 24 h of each period. Postprandial blood lipids, and glucose and insulin were assessed in 11 subjects on d 28. Fasting serum cholesterol was unchanged; however, when expressed as a percentage change, TG were decreased, relative to baseline (P < 0.04), by L-rhamnose (-10%) and lactulose (-10%), compared with D-glucose, which increased serum TG (+11%). Net TG-fatty acid (TGFA) synthesis on d 28 was lower with L-rhamnose (2.42 +/- 0.38 g/d) and lactulose (2.62 +/- 0.35 g/d) than with D-glucose (2.96 +/- 0.31 g/d, P < 0.01). We conclude that these results do not support a primary role for propionate in the cholesterol-lowering effect of soluble fiber. However, both lactulose and L-rhamnose lowered serum TG (expressed as a percentage change) and TGFA synthesis, compared with d-glucose, which increased them. Although these data are consistent with inhibition of TGFA synthesis by SCFA, other aspects of the metabolism of these sugars cannot be ruled out as putative agents of their TG-lowering effects.

Adult↗

Insulin resistance and adiponectin levels in drug-free patients with schizophrenia: A preliminary report.

OBJECTIVE: To compare the insulin sensitivity and adiponectin levels of medication-free patients suffering from schizophrenia or schizoaffective disorder with that of matched healthy volunteers. METHOD: We evaluated 9 nondiabetic patients aged 26.6 years (median 26 years, range 17 to 41 years) and matched volunteers, using the frequently sampled intravenous glucose tolerance test, minimal model analysis, and fasting adiponectin levels. RESULTS: The mean insulin sensitivity index of the patients was 42% lower than that of the healthy volunteers (P = 0.026), with inadequate compensation in insulin secretion. Patients with schizophrenia tended to have reduced adiponectin levels (P = 0.055). CONCLUSIONS: By direct measurement, this study provides evidence of insulin resistance and susceptibility to type 2 diabetes in patients with schizophrenia who are free of antipsychotic drugs.

Adiponectin↗

Evaluation of a glucose meter for determining the glycemic responses of foods.

BACKGROUND: Glucose meters are convenient for measuring postprandial glycemic responses. However, their performance for this purpose has not been evaluated. METHODS: Glucose responses of 7 potato meals were measured using the One Touch Ultra(R) (OTU) glucose meter and a reference method (Yellow Springs Instruments Glucose Analyzer, YSI) and the incremental areas under the curves (AUC) and glycemic index (GI) values compared. RESULTS: Mean AUC(OTU) was greater than AUC(YSI) (192+/-8 vs. 175+/-7 mmolxmin/l, p=0.001), but GI(OTU) tended to be less than GI(YSI) (69+/-3 vs. 74+/-3, p=0.052). Bland-Altman difference plots showed wide 95% limits of agreement for AUC (-84 to 119 mmolxmin/l) and GI (-21 to 26) values of individual subjects, and for the mean GI values of the 7 foods (-11 to 21). Total and error variance of AUC and GI values were greater for OTU than YSI, and food means differed significantly for YSI (p<0.01) but not OTU (p=0.11). CONCLUSION: AUC and GI values determined by OTU are more variable and do not agree well with those obtained by YSI. Thus, the OTU is not recommended for determining AUC or GI in normal subjects. This conclusion does not necessarily apply to other glucose meters whose performance should be evaluated.

Adolescent↗

Glycemic index of potatoes commonly consumed in North America.

OBJECTIVE: To determine the effect of variety and cooking method on glycemic response and glycemic index of common North American potatoes. DESIGN: Study 1: subjects consumed 200 g Russet or white potatoes that were either (a) precooked, refrigerated, and reheated (precooked) or (b) cooked and consumed immediately (day-cooked). Incremental area under the curve was determined. Study 2: subjects consumed 50 g carbohydrate portions of white bread or potatoes (six different varieties and two different cooking methods). Glycemic index values were calculated. In both studies meals were consumed after a 10- to 12-hour overnight fast and finger-prick capillary-blood glucose was measured before and at intervals for 2 hours after consumption. SUBJECTS: The study groups were as follows: Study 1 comprised four men and six women, aged 20 to 44 and Study 2 comprised 11 men and one woman, aged 18 to 50. STATISTICAL ANALYSES: Repeated measures analysis of variance with Newman-Kuels to protect for multiple comparisons (criterion of significance two-tailed P <.05). RESULTS: Study 1: Precooked Russet potatoes elicited lower area under the curve than day-cooked (P <.05), while precooking had no effect on boiled white potatoes. Study 2: The glycemic index values of potatoes varied significantly, depending on the variety and cooking method used (P =.003) ranging from intermediate (boiled red potatoes consumed cold: 56) to moderately high (roasted California white potatoes: 72; baked US Russet potatoes: 77) to high (instant mashed potatoes: 88; boiled red potatoes: 89). CONCLUSIONS: The glycemic index of potatoes is influenced by variety and method of cooking and US Russet potatoes have only a moderately high glycemic index. Individuals who wish to minimize dietary glycemic index can be advised to precook potatoes and consume them cold or reheated.

Adolescent↗

Effect of antibiotics as cholesterol-lowering agents.

Antibiotics were once proposed as hypercholesterolemic agents although the mechanism is unclear, despite broad implications, including providing an alternative approach to cholesterol reduction, with potential relevance for current trials of antibiotics to reduce cardiovascular disease, and possible confounding of routine diagnostic cholesterol measurements. The effect on serum lipids of antibiotics against aerobes and anaerobes, together with possible mechanisms, was therefore explored. Twenty-two men and women took antibiotics for 10 days (either ciprofloxacin for 13 subjects or metronidazole for 10 subjects), with 10 days control in random order separated by 2-week washout periods. Subjects maintained low-fat diets throughout the study. Blood samples and blood pressure were obtained on days 0 and 10 of each phase with 3-day fecal collections and 12-hour breath gas collections at the end of each phase. The results indicated that metronidazole markedly reduced low-density lipoprotein cholesterol (-14.0 +/- 4.0%, P = .006), oxidized low-density lipoprotein (-23.0 +/- 5.1%, P = .002), and the apolipoprotein B/A-I ratio (-18.0 +/- 2.8%, P < .001), whereas the reduction with ciprofloxacin was less pronounced (apolipoprotein B/A-I, -5.0 +/- 1.8%, P = .017). Neither antibiotic altered C-reactive protein or blood pressure. The low-density lipoprotein cholesterol reduction related to an increase in bifidobacteria (r = -0.46, P = .029), but not to markers of colonic fermentation. We conclude that antibiotics can reduce serum lipids acutely. These effects may confound diagnostic measurements but indicate possible links between colonic microflora and blood lipids and the need to study ways of altering colonic microflora by nonantibiotic means as a potential therapeutic option.

Aged↗

Dietary glycemic index and glycemic load, carbohydrate and fiber intake, and measures of insulin sensitivity, secretion, and adiposity in the Insulin Resistance Atherosclerosis Study.

OBJECTIVE: We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (S(I)), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference. RESEARCH DESIGN AND METHODS: Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992-1994) were analyzed. Usual dietary intake was assessed via a 114-item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. S(I) and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying S(I) with AIR. Multiple linear regression modeling was employed. RESULTS: No association was observed between glycemic index and S(I), fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with S(I), insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with S(I) and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR. CONCLUSION: Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects on insulin sensitivity and adiposity, but also on pancreatic functionality.

Adipose Tissue↗

Effect of carbohydrate source on post-prandial blood glucose in subjects with type 1 diabetes treated with insulin lispro.

Our purpose was to determine if the glycemic index (GI) and proportion of carbohydrate absorbed as glucose (Pg) affected glycemic responses and occurrence of post-prandial hypoglycemia in subjects with type 1 diabetes treated with insulin lispro. Subjects (n=8) were studied on five separate occasions after 10-12 h overnight fasts following a standard dinner. After their morning insulin dose, subjects ate 50 g carbohydrate from a starchy food (Pg=1; mashed potato GI=83, white bread GI=71, spaghetti GI=41, barley GI=25) or pineapple juice (Pg=0.5; GI=46). Blood glucose was measured fasting and at 30 min intervals for 4 h. Glucose responses after different foods differed significantly from 30 to 180 min, with mean incremental area under the curve being closely related to GI (r=0.98, P<0.01). By multiple regression analysis, occurrence of post-prandial hypoglycemia was influenced (P<0.05) by subject and Pg. Time to hypoglycemia was affected by subject, fasting glucose, and GI. Thus, in subjects with type 1 diabetes treated with insulin lispro, GI predicts glycemic responses of carbohydrate foods. Pg may affect the occurrence of post-prandial hypoglycemia, while GI may affect its timing. Further studies using mixed meals are required to confirm how carbohydrate source affects glycemic responses and occurrence of hypoglycemia in normal meal setting.

Adolescent↗

Effect of blood sampling schedule and method of calculating the area under the curve on validity and precision of glycaemic index values.

To evaluate the suitability for glycaemic index (GI) calculations of using blood sampling schedules and methods of calculating area under the curve (AUC) different from those recommended, the GI values of five foods were determined by recommended methods (capillary blood glucose measured seven times over 2.0 h) in forty-seven normal subjects and different calculations performed on the same data set. The AUC was calculated in four ways: incremental AUC (iAUC; recommended method), iAUC above the minimum blood glucose value (AUCmin), net AUC (netAUC) and iAUC including area only before the glycaemic response curve cuts the baseline (AUCcut). In addition, iAUC was calculated using four different sets of less than seven blood samples. GI values were derived using each AUC calculation. The mean GI values of the foods varied significantly according to the method of calculating GI. The standard deviation of GI values calculating using iAUC (20.4), was lower than six of the seven other methods, and significantly less (P<0.05) than that using netAUC (24.0). To be a valid index of food glycaemic response independent of subject characteristics, GI values in subjects should not be related to their AUC after oral glucose. However, calculating GI using AUCmin or less than seven blood samples resulted in significant (P<0.05) relationships between GI and mean AUC. It is concluded that, in subjects without diabetes, the recommended blood sampling schedule and method of AUC calculation yields more valid and/or more precise GI values than the seven other methods tested here. The only method whose results agreed reasonably well with the recommended method (ie. within +/-5 %) was AUCcut.

Adult↗

Glycaemic index of selected staples commonly eaten in the Caribbean and the effects of boiling v. crushing.

Integrating information about the glycaemic index (GI) of foods into the Caribbean diet is limited by the lack of data. Therefore, we determined the GI of eight staple foods eaten in the Caribbean and the effect on GI of crushing selected tubers. Groups of eight to ten healthy volunteers participated in three studies at two sites. GI was determined using a standard method with white bread and adjusted relative to glucose. The mean area under the glucose response curve elicited by white bread was similar for the different groups of subjects. In study 1, the GI of cassava (Manihot esculenta; 94 (sem 11)) was significantly higher than those of breadfruit (Artocarpus altilis; 60 (sem 9)), cooking 'green' banana (Musa spp.; 65 (sem 11)) and sadha roti (65 (sem 9)) (P=0.018). There was no significant difference in the GI of the foods in study 2: dasheen (Colocasia esculenta var. esculenta; 77 (sem 10)), eddoes (Colocasia esculenta var. antiquorum; 61 (sem 10)), Irish potato (Solanum tuberosum; 71 (sem 8)), tannia (Xanthosoma sagittifolium; 60 (sem 5)) and white yam (Dioscorea alata; 62 (sem 6)), and, in study 3, crushing did not significantly affect the GI of dasheen, tannia or Irish potato. However, when the results from studies 2 and 3 were pooled, the GI of dasheen (76 (sem 7)) was significantly greater than that of tannia (55 (sem 5); P=0.015) with potato being intermediate (69 (sem 6)). We conclude that dasheen and cassava are high-GI foods, whereas the other tubers studied and sadha roti are intermediate-GI foods. Given the regular usage of cassava and dasheen in Caribbean diets we speculate that these diets would tend to be high GI, although this could be reduced by foods such as sadha roti and white yam. The range of GI between the staples is sufficiently large that health benefits may be accrued by replacing high-GI staples with intermediate-GI staples in the Caribbean diet.

Adult↗

Postprandial lipemia in subjects with the threonine 54 variant of the fatty acid-binding protein 2 gene is dependent on the type of fat ingested.

BACKGROUND: The alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Obese and diabetic T54 carriers have greater postprandial lipemia than do A54 homozygotes. The T54 protein isoform is also associated with increased triacylglycerol secretion in vitro. OBJECTIVE: We investigated diet-gene interactions by measuring postprandial lipids, glucose, insulin, and C-peptide in healthy, nonobese A54 homozygotes and T54 carriers after ingestion of 3 different fats. DESIGN: Eleven A54 homozygotes and 11 T54 carriers were given 3 oral-fat-tolerance tests (butter, safflower oil, and olive oil). Cholesterol and triacylglycerol were measured in plasma and in chylomicron fractions. RESULTS: There was no main effect of FABP2 genotype for chylomicron triacylglycerol, glucose, or C-peptide. The area under the insulin curve and the ratio of insulin to C-peptide were lower in T54 carriers than in A54 homozygotes [312 +/- 29 ( +/- SEM) compared with 425 +/- 31 pmol. h/L (P = 0.05) and 0.23 +/- 0.03 compared with 0.40 +/- 0.05 (P = 0.04), respectively], which suggests greater hepatic insulin clearance in T54 carriers. An association between genotype and chylomicron cholesterol was seen only after olive oil: values were higher (P = 0.02) in T54 carriers (0.087 +/- 0.006 mmol. h/L) than in A54 homozygotes (0.058 +/- 0.004 mmol. h/L). The main effect of fat was significant for the areas under the chylomicron cholesterol and chylomicron triacylglycerol curves [higher values for safflower (0.635 +/- 0.053 and 2.48 +/- 0.30 mmol. h/L, respectively) and olive (0.592 +/- 0.052 and 2.48 +/- 0.32 mmol. h/L, respectively) oils than for butter (0.425 +/- 0.043 and 1.69 +/- 0.20 mmol. h/L, respectively); P < 0.05]. CONCLUSIONS: The A54T polymorphism results in a diet-gene interaction: the T54 group had increased chylomicron cholesterol after olive oil only. Nevertheless, the greater hepatic insulin clearance in T54 carriers suggests that the polymorphism may not be deleterious in nonobese subjects.

Adult↗