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Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials.

ABSTRACT: OBJECTIVE:The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on glycemic control in individuals with diabetes. RESEARCH DESIGN AND METHODS:We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ?7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expressed as mean difference (MD) for fasting glucose and insulin and standardized MD (SMD) with 95% CI for glycated hemoglobin (HbA(1c)) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I(2) statistic. Trial quality was assessed by the Heyland methodological quality score (MQS). RESULTS:Eighteen trials (n = 209) met the eligibility criteria. Isocaloric exchange of fructose for carbohydrate reduced glycated blood proteins (SMD -0.25 [95% CI -0.46 to -0.04]; P = 0.02) with significant intertrial heterogeneity (I(2) = 63%; P = 0.001). This reduction is equivalent to a ~0.53% reduction in HbA(1c). Fructose consumption did not significantly affect fasting glucose or insulin. A priori subgroup analyses showed no evidence of effect modification on any end point. CONCLUSIONS:Isocaloric exchange of fructose for other carbohydrate improves long-term glycemic control, as assessed by glycated blood proteins, without affecting insulin in people with diabetes. Generalizability may be limited because most of the trials were <12 weeks and had relatively low MQS (<8). To confirm these findings, larger and longer fructose feeding trials assessing both possible glycemic benefit and adverse metabolic effects are required.

SUBMITTER: Cozma AI

PROVIDER: S-EPMC3379616 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials.

Cozma Adrian I AI Sievenpiper John L JL de Souza Russell J RJ Chiavaroli Laura L Ha Vanessa V Wang D David DD Mirrahimi Arash A Yu Matt E ME Carleton Amanda J AJ Di Buono Marco M Jenkins Alexandra L AL Leiter Lawrence A LA Wolever Thomas M S TM Beyene Joseph J Kendall Cyril W C CW Jenkins David J A DJ

Diabetes care 20120701 7

<h4>Objective</h4>The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on glycemic control in individuals with diabetes.<h4>Research design and methods</h4>We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ≥7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expre ...[more]

PMID: 22723585

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Project description:Objective: Contrary to the concerns that fructose may have adverse metabolic effects, an emerging literature has shown that small doses (?10 g/meal) of fructose and its low-caloric epimers (allulose, tagatose, and sorbose) decrease the glycemic response to high glycemic index meals. Whether these acute reductions manifest as sustainable improvements in glycemic control is unclear. Our objective was to synthesize the evidence from controlled feeding trials that assessed the effect of small doses of fructose and its low-caloric epimers on glycemic control. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library through April 18, 2018. We included controlled feeding trials of ?1 week that investigated the effect of small doses (?50 g/day or ?10% of total energy intake/day) of fructose and its low-caloric epimers on HbA1c, fasting glucose, and fasting insulin. Two independent reviewers extracted data and assessed risk of bias. Data were pooled using the generic inverse variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Cochran Q statistic and quantified using the I² statistic. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessed the certainty of the evidence. Results: We identified 14 trial comparisons (N = 337) of the effect of fructose in individuals with and without diabetes, 3 trial comparisons (N = 138) of the effect of allulose in individuals without diabetes, 3 trial comparisons (N = 376) of the effect of tagatose mainly in individuals with type 2 diabetes, and 0 trial comparisons of the effect of sorbose. Small doses of fructose and tagatose significantly reduced HbA1c (MD = -0.38% (95% CI: -0.64%, -0.13%); MD = -0.20% (95% CI: -0.34%, -0.06%)) and fasting glucose (MD = -0.13 mmol/L (95% CI: -0.24 mmol/L, -0.03 mmol/L)); MD = -0.30 mmol/L (95% CI: -0.57 mmol/L, -0.04 mmol/L)) without affecting fasting insulin (p > 0.05). Small doses of allulose did not have a significant effect on HbA1c and fasting insulin (p > 0.05), while the reduction in fasting glucose was of borderline significance (p = 0.05). The certainty of the evidence of the effect of small doses of fructose and allulose on HbA1c, fasting glucose, and fasting insulin was graded as low. The certainty of the evidence of the effect of tagatose on HbA1c, fasting glucose, and fasting insulin was graded as moderate. Conclusions: Our results indicate that small doses of fructose and tagatose may improve glycemic control over the long term. There is a need for long-term randomized controlled trials for all four sugars to improve our certainty in the estimates.

Project description:BackgroundDebate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials.Methods and resultsMEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up ≥7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95% CI. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials.ConclusionsPooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required.Clinical trials registrationURL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791.

Project description:Abstract Objectives Current approved health claims in Canada, US and Europe recognize the ability of oat ß-glucan to lower blood cholesterol; however, its ability to improve glycemic control is less certain. We undertook a systematic review and meta-analysis of randomized controlled trials to update the evidence of the effect of oats and oat-fiber on markers of glycemic control in people with and without diabetes. Here we present data for the subgroup with diabetes. Methods MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through September 23rd, 2020. We included randomized controlled trials of ≥ 2-weeks of sources of oat ß-glucan and measures of glycemic control in diabetes. Two independent reviewers extracted relevant data and assessed the risk of bias (Cochrane Risk of Bias 2.0 Tool). The outcomes were fasting plasma glucose (FPG), 2h-plasma glucose (2h-PG) from a 75 g-oral glucose tolerance test, HbA1c and fasting plasma insulin (FPI). Data were pooled using the generic inverse variance method. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Pooled estimates were expressed as mean differences with 95% confidence intervals (CI). GRADE assessed the certainty of the evidence. Results Eligibility criteria were met by 5 trial comparisons (N = 359) in type 2 diabetes. No trials were identified in type 1 diabetes. Consumption of oat ß-glucan sources reduced FPG (MD = −0.37 mmol/L [95% CI: −0.70, −0.05 mmol/L], P = 0.03, I2 = 0.00%, PQ = 0.76) and 2h-PG (MD = −1.24 mmol/L [95% CI: −1.97, −0.51 mmol/L], P = 0.00, I2 = 0.00%, PQ = 0.56). There were non-significant reductions in HbA1c (MD = −0.12%, [95% CI: −0.26, 0.01%], P = 0.07, I2 = 0.00%, PQ = 1.00) and FPI (MD = −4.59 pmol/L, [95% CI: −14.71, 5.52 pmol/L], P = 0.37, I2 = 40.84%, PQ = 0.19). The certainty of evidence was high for 2h-PG and moderate for FPG, HbA1c and FPI (single downgrades for imprecision in each case). Conclusions Current evidence provides a good indication that consumption of oat ß-glucan results in small improvements of glycemic control in type 2 diabetes. More high quality randomized trials are required to improve the precision of the pooled estimates. (ClinicalTrials.gov identifier, NCT04631913) Funding Sources Quaker Oats Center of Excellence, Diabetes Canada, Banting & Best Diabetes Centre, Toronto 3D foundation

Project description:Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.

Project description:BackgroundFructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different levels of energy is unknown. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials on the effect of different food sources of fructose-containing sugars on inflammatory markers at different levels of energy control.MethodsMEDLINE, Embase, and the Cochrane Library were searched through March 2022 for controlled feeding trials ≥ 7 days. Four trial designs were prespecified by energy control: substitution (energy matched replacement of sugars); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Independent reviewers extracted data and assessed risk of bias. GRADE assessed certainty of evidence.ResultsWe identified 64 controlled trials (91 trial comparisons, n = 4094) assessing 12 food sources (SSB; sweetened dairy; sweetened dairy alternative [soy]; 100% fruit juice; fruit; dried fruit; mixed fruit forms; sweetened cereal grains and bars; sweets and desserts; added nutritive [caloric] sweetener; mixed sources [with SSBs]; and mixed sources [without SSBs]) at 4 levels of energy control over a median 6-weeks in predominantly healthy mixed weight or overweight/obese adults. Total fructose-containing sugars decreased CRP in addition trials and had no effect in substitution, subtraction or ad libitum trials. No effect was observed on other outcomes at any level of energy control. There was evidence of interaction/influence by food source: substitution trials (sweetened dairy alternative (soy) and 100% fruit juice decreased, and mixed sources (with SSBs) increased CRP); and addition trials (fruit decreased CRP and TNF-α; sweets and desserts (dark chocolate) decreased IL-6). The certainty of evidence was moderate-to-low for the majority of analyses.ConclusionsFood source appears to mediate the effect of fructose-containing sugars on inflammatory markers over the short-to-medium term. The evidence provides good indication that mixed sources that contain SSBs increase CRP, while most other food sources have no effect with some sources (fruit, 100% fruit juice, sweetened soy beverage or dark chocolate) showing decreases, which may be dependent on energy control.Clinicaltrialsgov: (NCT02716870).

Dataset Information

Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials.

Publications

Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials.

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