Meta-analyses of Impotrant Food Sources of Sugars and Incident Cardiometabolic Diseases

NCT ID: NCT02702375

Last Updated: 2016-08-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

1 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-09-30

Study Completion Date

2018-09-30

Brief Summary

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There is an urgent need for stronger evidence to support recommendations for the role of sugars in diabetes and related cardiometabolic diseases. Although large prospective cohort studies have shown a significant positive association of fructose-containing sugars-sweetened beverages with incident obesity, diabetes, heart disease, and stroke, these associations do not appear to hold true for total fructose-containing sugars and other important sources of free fructose-containing sugars such as pure fruit juice, yogurt, or even cakes and sweets. As dietary guidelines have moved away from macronutrient centric recommendations towards more food and dietary-pattern based recommendations, this inconsistency in the data has not been appreciated. There remains a focus on free sugars, in the absence of sufficient information on the role of different food sources of fructose-containing sugars in diabetes and related cardiometabolic diseases. A systematic review and meta-analysis of prospective cohort studies is considered to be the "Gold Standard" of evidence. To provide evidence-based guidance to support the development of public health policy in relation sugars and the primary prevention of diabetes, we will conduct a series of systematic reviews and meta-analyses of the relation of food sources of fructose-containing sugars with incident type 2 diabetes and related cardiometabolic diseases in prospective cohort studies.

Detailed Description

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Background: Sugars have emerged as one of the most important public health targets. Attention has focused on the special role of fructose based on its unique biochemical, metabolic, and endocrine responses. These mechanisms, however, have failed to translate into clinically meaningful effects in calorie-matched comparisons with other sources of carbohydrate. Sugars-sweetened beverage (SSBs) appear to be the special case. Whereas large prospective cohort studies have shown a consistent relation of SSBs with incident obesity, diabetes, metabolic syndrome (MetS), hypertension, coronary heart disease (CHD), stroke, and gout, associations have not been shown when modeling total sugars (with the exception of gout) or other food sources of added/free sugars such as pure fruit juices, yogurt, or even sweets. In the absence of a clear signal for sugars alone, it is unclear whether the associations seen for SSBs hold for other important food sources of sugars.

Need for a review: As dietary guidelines and public health policy have shifted toward food and dietary-pattern based recommendations, the lack of high quality syntheses and translation of the role of different food sources of sugars in cardiometabolic diseases represents an urgent call for stronger evidence to support guidelines development.

Objectives: To build on our previous work, we will conduct a series of systematic reviews and meta-analyses to compare important food sources of added/free sugars (SSBs, pure fruit juice, yogurt, sweets, cereals, etc). in their relation with incident cardiometabolic diseases.

Design: Our proposed series of systematic reviews and meta-analyses will follow the same successful protocol we used for our previous CIHR-funded knowledge synthesis of fructose and cardiometabolic risk (clinicaltrials.gov, NCT01363791). The knowledge syntheses will be conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Data sources: MEDLINE, EMBASE, and The Cochrane library will be searched.

Study selection: We will include cohorts assessing the relation of different food sources of fructose-containing sugars (SSBs, pure fruit juice, yogurt, sweets, cereals, etc) with incident type 2 diabetes, MetS, hypertension, CHD, stroke, and gout.

Data extraction: Two investigators will independently extract relevant data and assess risk of bias.

Outcomes: We will assess 6 outcomes: type 2 diabetes, MetS, hypertension, CHD, stroke, and gout.

Data synthesis: Risk ratios will be pooled using the generic inverse variance method for each food source of fructose-containing sugars. Random-effects models will be used even in the absence of statistically significant between-study heterogeneity, as they yield more conservative summary effect estimates in the presence of residual heterogeneity. Fixed-effects models will only be used where there is \<5 included studies. Paired analyses will be applied for crossover trials. Heterogeneity will be assessed by the Cochran Q statistic and quantified by the I2 statistic. To explore sources of heterogeneity, the investigators will conduct sensitivity analyses, in which each study is systematically removed. If there are \>=10 studies, then the investigators will also explore sources of heterogeneity by a priori subgroup analyses (follow-up, adjustments, exposure assessment, dose, outcome ascertainment, risk of bias). Meta-regression analyses will assess the significance of categorical and continuous subgroups analyses. When \>=10 studies are available, publication bias will be investigated by inspection of funnel plots and formal testing using the Egger and Begg tests. If publication bias is suspected, then the investigators will attempt to adjust for funnel plot asymmetry by imputing the missing study data using the Duval and Tweedie trim and fill method.

Evidence Assessment: The strength of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Knowledge translation plan: We will follow the Ottawa model. Results will be disseminated through presentations at scientific meetings and publication in high impact journals. Webcasts and social media posts on YouTube videos, Facebook, twitter and LinkedIn will also be used. Target adopters will include clinicians, allied health professionals, policy makers, industry, researchers, and patient groups.

Significance: The proposed project will aid in knowledge translation related to the health effects of food sources of sugars, informing evidence-based guidelines and improving health outcomes by educating healthcare providers and patients, stimulating industry innovation, and guiding future research design.

Conditions

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Diabetes Mellitus, Type 2 Metabolic Syndrome X Hypertension Cardiovascular Diseases Stroke Gout

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Fructose-containing Sugars

Intervention Type OTHER

Other Intervention Names

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fructose, sucrose, high-fructose corn syrup (HFCS)

Eligibility Criteria

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Inclusion Criteria

* Prospective cohort studies or case-cohort studies
* Duration \>= 1 year
* Assessment of the exposure of fructose-containing sugars or important food sources
* Ascertainment of viable data by level of exposure

Exclusion Criteria

* Ecological, cross-sectional, and retrospective observational studies, clinical trials, and non-human studies
* Duration \< 1 year
* No assessment of exposures of fructose-containing sugars or important food sources
* No ascertainment viable clinical outcome data by level of exposure
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role collaborator

Canadian Diabetes Association

OTHER

Sponsor Role collaborator

University of Toronto

OTHER

Sponsor Role lead

Responsible Party

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John Sievenpiper

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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JOHN L SIEVENPIPER, MD, PHD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Locations

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The Toronto 3D (Diet, Digestive tract and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Micheal's Hospital

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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Sievenpiper JL, de Souza RJ, Cozma AI, Chiavaroli L, Ha V, Mirrahimi A. Fructose vs. glucose and metabolism: do the metabolic differences matter? Curr Opin Lipidol. 2014 Feb;25(1):8-19. doi: 10.1097/MOL.0000000000000042.

Reference Type BACKGROUND
PMID: 24370846 (View on PubMed)

Sievenpiper JL, Chiavaroli L, de Souza RJ, Mirrahimi A, Cozma AI, Ha V, Wang DD, Yu ME, Carleton AJ, Beyene J, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. 'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials. Br J Nutr. 2012 Aug;108(3):418-23. doi: 10.1017/S000711451200013X. Epub 2012 Feb 21.

Reference Type BACKGROUND
PMID: 22354959 (View on PubMed)

Jayalath VH, Sievenpiper JL, de Souza RJ, Ha V, Mirrahimi A, Santaren ID, Blanco Mejia S, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ. Total fructose intake and risk of hypertension: a systematic review and meta-analysis of prospective cohorts. J Am Coll Nutr. 2014;33(4):328-39. doi: 10.1080/07315724.2014.916237. Epub 2014 Aug 21.

Reference Type BACKGROUND
PMID: 25144126 (View on PubMed)

Mirrahimi A, de Souza RJ, Chiavaroli L, Sievenpiper JL, Beyene J, Hanley AJ, Augustin LS, Kendall CW, Jenkins DJ. Associations of glycemic index and load with coronary heart disease events: a systematic review and meta-analysis of prospective cohorts. J Am Heart Assoc. 2012 Oct;1(5):e000752. doi: 10.1161/JAHA.112.000752. Epub 2012 Oct 25.

Reference Type BACKGROUND
PMID: 23316283 (View on PubMed)

Liu Q, Ayoub-Charette S, Khan TA, Au-Yeung F, Blanco Mejia S, de Souza RJ, Wolever TMS, Leiter LA, Kendall CWC, Sievenpiper JL. Important Food Sources of Fructose-Containing Sugars and Incident Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. J Am Heart Assoc. 2019 Dec 17;8(24):e010977. doi: 10.1161/JAHA.118.010977. Epub 2019 Dec 12.

Reference Type DERIVED
PMID: 31826724 (View on PubMed)

Ayoub-Charette S, Liu Q, Khan TA, Au-Yeung F, Blanco Mejia S, de Souza RJ, Wolever TM, Leiter LA, Kendall C, Sievenpiper JL. Important food sources of fructose-containing sugars and incident gout: a systematic review and meta-analysis of prospective cohort studies. BMJ Open. 2019 May 5;9(5):e024171. doi: 10.1136/bmjopen-2018-024171.

Reference Type DERIVED
PMID: 31061018 (View on PubMed)

Other Identifiers

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CIHR-Sugars 2015

Identifier Type: -

Identifier Source: org_study_id

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