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Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study.
Ayoub-Charette, S, McGlynn, ND, Lee, D, Khan, TA, Blanco Mejia, S, Chiavaroli, L, Kavanagh, ME, Seider, M, Taibi, A, Chen, CT, et al
Nutrients. 2023;15(5)
Abstract
BACKGROUND Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the "intended substitution") versus water (the "standard of care substitution") for SSBs on glucose tolerance and microbiota diversity. DESIGN AND METHODS The STOP Sugars NOW trial (NCT03543644) is a pragmatic, "head-to-head", open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle. BASELINE RESULTS Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%). CONCLUSIONS Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT03543644.
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Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial.
Jenkins, DJA, Chiavaroli, L, Mirrahimi, A, Mitchell, S, Faulkner, D, Sahye-Pudaruth, S, Paquette, M, Coveney, J, Olowoyeye, O, Patel, D, et al
Diabetes care. 2022;(12):2862-2870
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OBJECTIVE High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.
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A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial.
Braunstein, CR, Noronha, JC, Glenn, AJ, Viguiliouk, E, Noseworthy, R, Khan, TA, Au-Yeung, F, Blanco Mejia, S, Wolever, TMS, Josse, RG, et al
Nutrients. 2018;(6)
Abstract
UNLABELLED Recent literature suggests that catalytic doses (≤10 g/meal or 36 g/day) of D-fructose and D-allulose may reduce postprandial blood glucose responses to carbohydrate loads in people with and without type 2 diabetes by inducing glycogen synthesis. To assess the effect of small single doses of fructose and allulose on postprandial blood glucose regulation in response to a 75 g-oral glucose tolerance test (75 g-OGTT) in healthy individuals, we conducted an acute randomized, crossover, equivalence trial in healthy adults. Each participant randomly received six treatments, separated by a minimum one-week washout. Treatments consisted of a 75 g-OGTT with the addition of fructose or allulose at 0 g (control), 5 g or 10 g. A standard 75 g-OGTT protocol was followed with blood samples at −30, 0, 30, 60, 90, 120 min. The primary outcome was the difference in plasma glucose incremental area under the curve (iAUC). A total of 27 participants underwent randomization with data available from 25 participants. Small doses of fructose or allulose did not show a significant effect on plasma glucose iAUC or other secondary markers of postprandial blood glucose regulation in response to a 75 g-OGTT in healthy individuals. These results were limited by the low power to detect a significant difference, owing to greater than expected intra-individual coefficient of variation (CV) in plasma glucose iAUC. Overall, we failed to confirm the catalytic effects of small doses of fructose and allulose in healthy individuals. Future trials may consider recruiting larger sample sizes of healthy individuals. TRIAL REGISTRATION clinicaltrials.gov identifier, NCT02459834.
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The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double-blind, randomized, controlled, acute feeding, equivalence trial.
Noronha, JC, Braunstein, CR, Glenn, AJ, Khan, TA, Viguiliouk, E, Noseworthy, R, Blanco Mejia, S, Kendall, CWC, Wolever, TMS, Leiter, LA, et al
Diabetes, obesity & metabolism. 2018;(10):2361-2370
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AIM: To assess and compare the effect of small doses of fructose and allulose on postprandial blood glucose regulation in type 2 diabetes. METHODS A double-blind, multiple-crossover, randomized, controlled, acute feeding, equivalence trial in 24 participants with type 2 diabetes was conducted. Each participant was randomly assigned six treatments separated by >1-week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75-g glucose solution. A standard 75-g oral glucose tolerance test protocol was followed with blood samples at -30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC). RESULTS Allulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 ± 38.3 vs. 777.5 ± 39.9 mmol × min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [Cmax ], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre-specified equivalence margins of ±20%. CONCLUSION Allulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long-term randomized trials to confirm the sustainability of these improvements.
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Effect of dried fruit on postprandial glycemia: a randomized acute-feeding trial.
Viguiliouk, E, Jenkins, AL, Blanco Mejia, S, Sievenpiper, JL, Kendall, CWC
Nutrition & diabetes. 2018;8(1):59
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Plain language summary
Dried fruits show promising potential for blood glucose management. However, the effect of combining dried fruits with high glycaemic index (GI) foods has not been adequately addressed. The main objectives of this study were to: a) quantify the GI of 4 different types of dried fruit (dates, apricots, raisins, sultanas); and b) assess the ability of these 4 dried fruits to decrease the postprandial glycaemic response to white bread by partially displacing available carbohydrate and by providing a ‘catalytic’ dose of fructose. This study is a randomised multiple - crossover acute feeding trial which enrolled 10 participants of which 7 were males. Each participant underwent a total of 15 separate study meals consisting of 3 white bread control meals and 12 dried fruit test meals. Results demonstrate that dried fruit have a lower GI than white bread and can lower the glycaemic response of white bread through displacement of half of the available carbohydrate. None of the dried fruits showed a beneficial ‘catalytic’ fructose effect. Authors conclude that their findings may help to stimulate important industry innovation and improve the design of future clinical investigations that will potentially lead to the use of dried fruits as an effective tool to modify the glycaemic response of high carbohydrate foods.
Abstract
BACKGROUND/OBJECTIVES To investigate the effect of dried fruit in modifying postprandial glycemia, we assessed the ability of 4 dried fruits (dates, apricots, raisins, sultanas) to decrease postprandial glycemia through three mechanisms: a glycemic index (GI) effect, displacement effect, or 'catalytic' fructose effect. SUBJECTS/METHODS We conducted an acute randomized, multiple-crossover trial in an outpatient setting in 10 healthy adults. Participants received 3 white bread control meals and 12 dried fruit test meals in random order. The test meals included each of 4 dried fruits (dates, apricots, raisins, sultanas) alone (GI effect), 4 of the dried fruits displacing half the available carbohydrate in white bread (displacement effect), or 4 of the dried fruits providing a small 'catalytic' dose (7.5 g) of fructose added to white bread ('catalytic' fructose effect). The protocol followed the ISO method for the determination of GI (ISO 26642:2010). The primary outcome was mean ± SEM GI (glucose scale) for ease of comparison across the three mechanisms. RESULTS Ten healthy participants (7 men, 3 women; mean ± SD age and BMI: 39 ± 12 years and 25 ± 2 kg/m2) were recruited and completed the trial. All dried fruit had a GI below that of white bread (GI = 71); however, only dried apricots (GI = 42 ± 5), raisins (GI = 55 ± 5), and sultanas (51 ± 4) showed a significant GI effect (P < 0.05). When displacing half the available carbohydrate in white bread, all dried fruit lowered the GI; however, only dried apricots (GI = 57 ± 5) showed a significant displacement effect (P = 0.025). None of the dried fruits showed a beneficial 'catalytic' fructose effect. CONCLUSIONS In conclusion, dried fruits have a lower GI and reduce the glycemic response of white bread through displacement of half of the available carbohydrate. Longer-term randomized trials are needed to confirm whether dried fruit can contribute to sustainable improvements in glycemic control. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT02960373.
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Cross-sectional associations between dietary intake and carotid intima media thickness in type 2 diabetes: baseline data from a randomised trial.
Chiavaroli, L, Mirrahimi, A, Ireland, C, Mitchell, S, Sahye-Pudaruth, S, Coveney, J, Olowoyeye, O, Patel, D, de Souza, RJ, Augustin, LS, et al
BMJ open. 2017;(3):e015026
Abstract
OBJECTIVE To assess associations between dietary intake and carotid intima media thickness (CIMT) by carotid ultrasound (CUS), a surrogate marker of cardiovascular disease (CVD) risk, in those with type 2 diabetes. DESIGN Cross-sectional analysis of baseline data from 325 participants from three randomised controlled trials collected in the same way. SETTING Risk Factor Modification Centre, St. Michael's Hospital, Toronto, Canada. PARTICIPANTS 325 participants with type 2 diabetes, taking oral antidiabetic agents, with an HbA1c between 6.5% and 8.0% at screening, without a recent cardiovascular event. MAIN OUTCOME MEASURES CIMT by CUS and associations with dietary intake from 7-day food records, as well as anthropometric measures and fasting serum samples. RESULTS CIMT was significantly inversely associated with dietary pulse intake (β=-0.019, p=0.009), available carbohydrate (β=-0.004, p=0.008), glycaemic load (β=-0.001, p=0.007) and starch (β=-0.126, p=0.010), and directly associated with total (β=0.004, p=0.028) and saturated (β=0.012, p=0.006) fat intake in multivariate regression models adjusted for age, smoking, previous CVD event, blood pressure medication, antidiabetic medication and ultrasonographer. CONCLUSIONS Lower CIMT was significantly associated with greater consumption of dietary pulses and carbohydrates and lower total and saturated fat intake, suggesting a potential role for diet in CVD risk management in type 2 diabetes. Randomised controlled trials are anticipated to explore these associations further. TRIAL REGISTRATION NUMBER NCT01063374.
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Low-glycaemic index diet to improve glycaemic control and cardiovascular disease in type 2 diabetes: design and methods for a randomised, controlled, clinical trial.
Chiavaroli, L, Mirrahimi, A, Ireland, C, Mitchell, S, Sahye-Pudaruth, S, Coveney, J, Olowoyeye, O, Maraj, T, Patel, D, de Souza, RJ, et al
BMJ open. 2016;(7):e012220
Abstract
INTRODUCTION Type 2 diabetes (T2DM) produces macrovascular and microvascular damage, significantly increasing the risk of cardiovascular disease (CVD), renal failure and blindness. As rates of T2DM rise, the need for effective dietary and other lifestyle changes to improve diabetes management become more urgent. Low-glycaemic index (GI) diets may improve glycaemic control in diabetes in the short term; however, there is a lack of evidence on the long-term adherence to low-GI diets, as well as on the association with surrogate markers of CVD beyond traditional risk factors. Recently, advances have been made in measures of subclinical arterial disease through the use of MRI, which, along with standard measures from carotid ultrasound (CUS) scanning, have been associated with CVD events. We therefore designed a randomised, controlled, clinical trial to assess whether low-GI dietary advice can significantly improve surrogate markers of CVD and long-term glycaemic control in T2DM. METHODS AND ANALYSIS 169 otherwise healthy individuals with T2DM were recruited to receive intensive counselling on a low-GI or high-cereal fibre diet for 3 years. To assess macrovascular disease, MRI and CUS are used, and to assess microvascular disease, retinal photography and 24-hour urinary collections are taken at baseline and years 1 and 3. Risk factors for CVD are assessed every 3 months. ETHICS AND DISSEMINATION The study protocol and consent form have been approved by the research ethics board of St. Michael's Hospital. If the study shows a benefit, these data will support the use of low-GI and/or high-fibre foods in the management of T2DM and its complications. TRIAL REGISTRATION NUMBER NCT01063374; Pre-results.
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Effect of lowering the glycemic load with canola oil on glycemic control and cardiovascular risk factors: a randomized controlled trial.
Jenkins, DJ, Kendall, CW, Vuksan, V, Faulkner, D, Augustin, LS, Mitchell, S, Ireland, C, Srichaikul, K, Mirrahimi, A, Chiavaroli, L, et al
Diabetes care. 2014;(7):1806-14
Abstract
OBJECTIVE Despite their independent cardiovascular disease (CVD) advantages, effects of α-linolenic acid (ALA), monounsaturated fatty acid (MUFA), and low-glycemic-load (GL) diets have not been assessed in combination. We therefore determined the combined effect of ALA, MUFA, and low GL on glycemic control and CVD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS The study was a parallel design, randomized trial wherein each 3-month treatment was conducted in a Canadian academic center between March 2011 and September 2012 and involved 141 participants with type 2 diabetes (HbA1c 6.5%-8.5% [48-69 mmol/mol]) treated with oral antihyperglycemic agents. Participants were provided with dietary advice on either a low-GL diet with ALA and MUFA given as a canola oil-enriched bread supplement (31 g canola oil per 2,000 kcal) (test) or a whole-grain diet with a whole-wheat bread supplement (control). The primary outcome was HbA1c change. Secondary outcomes included calculated Framingham CVD risk score and reactive hyperemia index (RHI) ratio. RESULTS Seventy-nine percent of the test group and 90% of the control group completed the trial. The test diet reduction in HbA1c units of -0.47% (-5.15 mmol/mol) (95% CI -0.54% to -0.40% [-5.92 to -4.38 mmol/mol]) was greater than that for the control diet (-0.31% [-3.44 mmol/mol] [95% CI -0.38% to -0.25% (-4.17 to -2.71 mmol/mol)], P = 0.002), with the greatest benefit observed in those with higher systolic blood pressure (SBP). Greater reductions were seen in CVD risk score for the test diet, whereas the RHI ratio increased for the control diet. CONCLUSIONS A canola oil-enriched low-GL diet improved glycemic control in type 2 diabetes, particularly in participants with raised SBP, whereas whole grains improved vascular reactivity.
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Nut consumption, serum fatty acid profile and estimated coronary heart disease risk in type 2 diabetes.
Nishi, SK, Kendall, CW, Bazinet, RP, Bashyam, B, Ireland, CA, Augustin, LS, Blanco Mejia, S, Sievenpiper, JL, Jenkins, DJ
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2014;(8):845-52
Abstract
BACKGROUND AND AIMS Nut consumption has been associated with decreased risk of coronary heart disease (CHD) and type 2 diabetes which has been largely attributed to their healthy fatty acid profile, yet this has not been ascertained. Therefore, we investigated the effect of nut consumption on serum fatty acid concentrations and how these relate to changes in markers of glycemic control and calculated CHD risk score in type 2 diabetes. METHODS AND RESULTS 117 subjects with type 2 diabetes consumed one of three iso-energetic (mean 475 kcal/d) supplements for 12 weeks: 1. full-dose nuts (50-100 g/d); 2. half-dose nuts with half-dose muffins; and 3. full-dose muffins. In this secondary analysis, fatty acid concentrations in the phospholipid, triacylglycerol, free fatty acid, and cholesteryl ester fractions from fasting blood samples obtained at baseline and week 12 were analyzed using thin layer and gas chromatography. Full-dose nut supplementation significantly increased serum oleic acid (OA) and MUFAs compared to the control in the phospholipid fraction (OA: P = 0.036; MUFAs: P = 0.024). Inverse associations were found with changes in CHD risk versus changes in OA and MUFAs in the triacylglycerol (r = -0.256, P = 0.011; r = -0.228, P = 0.024, respectively) and phospholipid (r = -0.278, P = 0.006; r = -0.260, P = 0.010, respectively) fractions. In the cholesteryl ester fraction, change in MUFAs was inversely associated with markers of glycemic control (HbA1c: r = -0.250, P = 0.013; fasting blood glucose: r = -0.395, P < 0.0001). CONCLUSION Nut consumption increased OA and MUFA content of the serum phospholipid fraction, which was inversely associated with CHD risk factors and 10-year CHD risk. CLINICAL TRIAL REG NO NCT00410722, clinicaltrials.gov.
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Effect of legumes as part of a low glycemic index diet on glycemic control and cardiovascular risk factors in type 2 diabetes mellitus: a randomized controlled trial.
Jenkins, DJ, Kendall, CW, Augustin, LS, Mitchell, S, Sahye-Pudaruth, S, Blanco Mejia, S, Chiavaroli, L, Mirrahimi, A, Ireland, C, Bashyam, B, et al
Archives of internal medicine. 2012;(21):1653-60
Abstract
BACKGROUND Legumes, including beans, chickpeas, and lentils, are among the lowest glycemic index (GI) foods and have been recommended in national diabetes mellitus (DM) guidelines. Yet, to our knowledge, they have never been used specifically to lower the GI of the diet. We have therefore undertaken a study of low-GI foods in type 2 DM with a focus on legumes in the intervention. METHODS A total of 121 participants with type 2 DM were randomized to either a low-GI legume diet that encouraged participants to increase legume intake by at least 1 cup per day, or to increase insoluble fiber by consumption of whole wheat products, for 3 months. The primary outcome was change in hemoglobin A1c (HbA1c) values with calculated coronary heart disease (CHD) risk score as a secondary outcome. RESULTS The low-GI legume diet reduced HbA1c values by -0.5% (95% CI, -0.6% to -0.4%) and the high wheat fiber diet reduced HbA1c values by -0.3% (95% CI, -0.4% to -0.2%). The relative reduction in HbA1c values after the low-GI legume diet was greater than after the high wheat fiber diet by -0.2% (95% CI, -0.3% to -0.1%; P < .001). The respective CHD risk reduction on the low-GI legume diet was -0.8% (95% CI, -1.4% to -0.3%; P = .003), largely owing to a greater relative reduction in systolic blood pressure on the low-GI legume diet compared with the high wheat fiber diet (-4.5 mm Hg; 95% CI, -7.0 to -2.1 mm Hg; P < .001). CONCLUSION Incorporation of legumes as part of a low-GI diet improved both glycemic control and reduced calculated CHD risk score in type 2 DM.