Effect of vitamin D supplementation on oral glucose tolerance in individuals with low vitamin D status and increased risk for developing type 2 diabetes (EVIDENCE): A double-blind, randomized, placebo-controlled clinical trial.

AIMS: Low serum 25-hydroxyvitamin-D (25(OH)D) concentrations are associated with insulin resistance, ß-cell dysfunction and type 2 diabetes. We conducted a 24-week double-blind, randomized, placebo-controlled trial to examine the effect of 28 000 IU of vitamin D3 once weekly on plasma glucose after a 2 hour-75 g oral glucose tolerance test (2hrPC glucose), insulin sensitivity and ß-cell function. STUDY DESIGN AND METHODS: A total of 71 participants with serum 25(OH)D ≤65 nmol/L, impaired fasting glucose and elevated glycated hemoglobin were randomly assigned to receive 28 000 IU of vitamin D3 (VitD; n = 35) or placebo (n = 36) in cheese once weekly for 24 weeks. The primary outcome was the change in 2hPC glucose. Secondary outcomes were fasting glucose, fasting and postprandial insulin, indices of insulin sensitivity and ß-cell function, glycated hemoglobin and lipid profile. Participants underwent an oral glucose tolerance test to determine 2hPC glucose. RESULTS: Mean baseline serum 25(OH)D was 48.1 and 47.6 nmol/L in the VitD and placebo groups, respectively. Serum 25(OH)D significantly increased to 98.7 nmol/L (51 nmol/L increase; P < .0001) in the VitD group. No significant differences in fasting ( P = .42) or 2hPC glucose ( P = .55) or other indices of glucose metabolism, including ß-cell function and insulin sensitivity, were observed between groups. A subgroup analysis of individuals with 25(OH)D < 50 nmol/L and prediabetes did not change these results. The VitD group exhibited a significant reduction in LDL cholesterol (-0.27 vs 0.01 mmol/L, P = .03). CONCLUSION: Weekly doses of vitamin D3 in individuals with suboptimal vitamin D levels who were at risk for type 2 diabetes did not improve oral glucose tolerance or markers of glycaemic status.

Bioactive oat ß-glucan reduces LDL cholesterol in Caucasians and non-Caucasians.

BACKGROUND: There is increasing global acceptance that viscous soluble fibers lower serum LDL cholesterol (LDL-C), but most evidence for this comes from studies in Caucasians. To see if oat ß-glucan lowers LDL-C in Caucasians and non-Caucasians we conducted a post-hoc analysis of the results of a randomized, controlled, double-blind, multi-center clinical trial whose primary aim was to determine if molecular-weight (MW) influenced the LDL-C-lowering effect of oat ß-glucan. RESULTS: Caucasian and non-Caucasian subjects with LDL-C-C ≥ 3.0 and ≤ 5.0 mmol/L (n = 786 screened, n = 400 ineligible, n = 19 refused, n = 367 randomized, n = 345 completed, n = 1 excluded for missing ethnicity) were randomly assigned to consume cereal containing wheat-fiber (Control, n = 74:13 Caucasian:non-Caucasian) or 3 g high-MW (3H, 2,250,000 g/mol, n = 67:19), 4 g medium-MW (4 M, 850,000 g/mol, n = 50:17), 3 g medium-MW (3M, 530,000 g/mol, n = 54:9) or 4 g low-MW (4 L, 210,000 g/mol, n = 51:12) oat ß-glucan daily for 4 weeks. LDL-C after 4 weeks was influenced by baseline LDL-C (p < 0.001) and treatment (p = 0.003), but not ethnicity (p = 0.74). In all subjects, compared to control, 3 H, 4 M and 3 M reduced LDL-C significantly by 4.8 to 6.5%, but 4 L had no effect. Compared to control, the bioactive oat ß-glucan treatments (3H, 4M and 3M) reduced LDL-C by a combined mean (95% CI) of 0.18 (0.06, 0.31) mmol/L (4.8%, n = 171, p = 0.004) in Caucasians, a value not significantly different from the 0.37 (0.09, 0.65) mmol/L (10.3%, n = 45, p = 0.008) reduction in non-Caucasians. CONCLUSION: We conclude that oat ß-glucan reduces LDL-C in both Caucasians and non-Caucasians; there was insufficient power to determine if the magnitude of LDL-C-lowering differed by ethnicity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981981.

Physicochemical properties of oat ß-glucan influence its ability to reduce serum LDL cholesterol in humans: a randomized clinical trial.

BACKGROUND: Consumption of 3 g oat ß-glucan/d is considered sufficient to lower serum LDL cholesterol, but some studies have shown no effect. LDL cholesterol lowering by oat ß-glucan may depend on viscosity, which is controlled by the molecular weight (MW) and amount of oat ß-glucan solubilized in the intestine (C). OBJECTIVES: Our 2 primary objectives were to determine whether consumption of 3 g high-MW oat ß-glucan/d would reduce LDL cholesterol and whether LDL cholesterol lowering was related to the log(MW × C) of oat ß-glucan. DESIGN: In a double-blind, parallel-design, multicenter clinical trial, subjects with LDL cholesterol ≥3.0 and ≤5.0 mmol/L (n = 786 screened, n = 400 ineligible, n = 19 refused, n = 367 enrolled, and n = 345 completed) were randomly assigned to receive cereal containing wheat fiber (n = 87) or 3 g high-MW (2,210,000 g/mol, n = 86), 4 g medium-MW (850,000 g/mol, n = 67), 3 g medium-MW (530,000 g/mol, n = 64), or 4 g low-MW (210,000 g/mol, n = 63) oat ß-glucan/d (divided doses, twice daily) for 4 wk. RESULTS: LDL cholesterol was significantly less with 3 g high-MW, 4 g medium-MW, and 3 g medium-MW oat ß-glucan cereals than with the wheat-fiber cereal by 0.21 (5.5%; 95% CI: -0.11, -0.30; P = 0.002), 0.26 (6.5%; 95% CI: -0.14, -0.37; P = 0.0007), and 0.19 (4.7%; 95% CI: -0.08, -0.30; P = 0.01) mmol/L, respectively. However, the effect of 4 g low-MW oat ß-glucan/d (0.10 mmol/L) was not significant (2.3%; 95% CI: 0.02, -0.20). By analysis of covariance, log(MW × C) was a significant determinant of LDL cholesterol (P = 0.003). Treatment effects were not significantly influenced by age, sex, study center, or baseline LDL cholesterol. CONCLUSIONS: The physicochemical properties of oat ß-glucan should be considered when assessing the cholesterol-lowering ability of oat-containing products; an extruded breakfast cereal containing 3 g oat ß-glucan/d with a high-MW (2,210,000 g/mol) or a medium-MW (530,000 g/mol) lowered LDL cholesterol similarly by ≈0.2 mmol/L (5%), but efficacy was reduced by 50% when MW was reduced to 210,000 g/mol. This trial was registered at www.clinicaltrials.gov as NCT00981981.

The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein.

BACKGROUND: The optimal source and amount of dietary carbohydrate for managing type 2 diabetes (T2DM) are unknown. OBJECTIVE: We aimed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin (HbA1c), plasma glucose, lipids, and C-reactive protein (CRP) in T2DM patients. DESIGN: Subjects with T2DM managed by diet alone (n=162) were randomly assigned to receive high-carbohydrate, high-glycemic-index (high-GI), high-carbohydrate, low-glycemic-index (low-GI), or low-carbohydrate, high-monounsaturated-fat (low-CHO) diets for 1 y. RESULTS: The high-GI, low-GI, and low-CHO diets contained, respectively, 47%, 52%, and 39% of energy as carbohydrate and 31%, 27%, and 40% of energy as fat; they had GIs of 63, 55, and 59, respectively. Body weight and HbA1c did not differ significantly between diets. Fasting glucose was higher (P=0.041), but 2-h postload glucose was lower (P=0.010) after 12 mo of the low-GI diet. With the low-GI diet, overall mean triacylglycerol was 12% higher and HDL cholesterol 4% lower than with the low-CHO diet (P<0.05), but the difference in the ratio of total to HDL cholesterol disappeared by 6 mo (time x diet interaction, P=0.044). Overall mean CRP with the low-GI diet, 1.95 mg/L, was 30% less than that with the high-GI diet, 2.75 mg/L (P=0.0078); the concentration with the low-CHO diet, 2.35 mg/L, was intermediate. CONCLUSIONS: In subjects with T2DM managed by diet alone with optimal glycemic control, long-term HbA1c was not affected by altering the GI or the amount of dietary carbohydrate. Differences in total:HDL cholesterol among diets had disappeared by 6 mo. However, because of sustained reductions in postprandial glucose and CRP, a low-GI diet may be preferred for the dietary management of T2DM.

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.

Fatigue and shift work.

Shift work is a ubiquitous phenomenon and its adverse effects on workers' physical and mental health have been documented. In the sleep literature, differentiating between the symptoms of fatigue and sleepiness, and developing appropriate objective and subjective measures, have become very important endeavors. From such research, fatigue and sleepiness have been shown to be distinct and independent phenomena. However, it is not known whether shift work differentially affects fatigue and sleepiness. In an attempt to answer this question, 489 workers from a major Ontario employer completed a series of subjective, self-report questionnaires, including the Fatigue Severity Scale (FSS) and the Epworth Sleepiness Scale. Workers were separated into four groups based on the frequency with which they are engaged in shift work (never, fewer than four times per month, 1-2 days per week, 3 days or more per week). The frequency of shift work was found to have a significant effect on subjective fatigue, but not on subjective sleepiness. Compared with the subjects who never had a shift schedule, those who worked in a shift for 3 days or more had significantly higher mean score of the FSS. In agreement with previous results, a low correlation was found between workers' subjective fatigue and sleepiness scores, providing further support for the concept of fatigue and sleepiness as distinct and independent phenomena. Future research should address the possibility of using the FSS as an indicator when the frequency of shift work has become high enough to adversely affect work performance or cause health problems.