Umbrella Review and Updated Systematic Review and Meta-analysis of Pulses/Legumes and Incident Cardiometabolic Diseases
Umbrella Review and Updated Systematic Review and Meta-analysis of Pulses/Legumes and Incident Cardiometabolic Diseases
The European Association for the Study of Diabetes (EASD) guidelines have not made any
 specific recommendations regarding dietary pulses. To update the recommendations, the
 Diabetes and Nutrition Study Group (DNSG) of the EASD commissioned an umbrella review and
 updated systematic review and meta-analysis using the Grading of Recommendations Assessment,
 Development, and Evaluation (GRADE) approach to summarize the available evidence from
 prospective cohort studies of the association between dietary pulses/legumes and
 cardiometabolic disease outcomes (incident cardiovascular diseases, diabetes, hypertension
 and overweight/obesity).
Background: Dietary pulses, the edible dried seeds of legumes, are high in fiber, plant
 protein, and various micronutrients and low in fat and glycemic index (GI), have shown a wide
 range of health benefits for the prevention and management of type 2 diabetes and
 cardiovascular disease. However, dietary pulses are not well recognized for these advantages.
 Recommendations for dietary pulse intake vary across chronic disease guidelines. In specific,
 the European Association for the Study of Diabetes (EASD) guidelines for nutrition therapy
 have not made any specific recommendations regarding dietary pulses. The present umbrella
 review and updated systematic review and meta-analysis using the Grading of Recommendations
 Assessment, Development, and Evaluation (GRADE) approach was thus commissioned by the
 Diabetes and Nutrition Study Group (DNSG) of the EASD to summarize the available evidence
 from prospective cohort studies of the association between dietary pulses/legumes and
 cardiometabolic disease outcomes (incident cardiovascular diseases, diabetes, hypertension
 and overweight/obesity).

 Need for proposed research: High quality systematic reviews and meta-analyses represent the
 highest level of evidence to support dietary guidelines and public health policy development.
 As dietary guidelines and public health policy have shifted toward food and dietary-pattern
 based recommendations, there is a need for a systematic review and meta-analysis assessing
 the pooled association between dietary pulses/legumes and cardiometabolic disease outcomes.

 Objective: The investigators will conduct an umbrella review and updated systematic review
 and meta-analysis to summarize the association between dietary pulses/legumes and
 cardiometabolic disease outcomes in prospective cohort studies.

 Design: The umbrella review will consist of a literature search of the most recent and/or
 comprehensive systematic reviews and meta-analyses published in this area. The included
 systematic reviews and meta-analyses will be updated conducting a systematic search for
 prospective cohort studies published after the census dates of the included systematic
 reviews and meta-analyses. The planning and conduct of the updated systematic review and
 meta-analysis will follow the Cochrane handbook for systematic reviews of interventions. The
 reporting will follow the Meta-analysis Of Observational Studies in Epidemiology (MOOSE)
 guidelines.

 Data sources:

 The umbrella review will consist of searching PubMed databases using appropriate search terms
 to identify the most recent and/or comprehensive systematic reviews and meta-analyses
 published in this area. The updated systematic review and meta-analysis will consist of
 searching MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials after the
 census dates of the included systematic reviews and meta-analyses from the umbrella review
 using appropriate search terms supplemented by manual searches of references of included
 studies. Authors will be contacted for applicable missing data.

 Study selection:

 The umbrella review will include the most recent and/or comprehensive systematic reviews and
 meta-analyses of prospective cohort studies assessing the association between pulse/legume
 intake and cardiometabolic diseases outcomes (cardiovascular diseases, diabetes,
 hypertension, overweight/obesity). The updated systematic review and meta-analysis will
 include prospective cohort studies ≥1 year assessing the association between pulse/legume
 intake and cardiometabolic diseases outcomes (cardiovascular diseases, diabetes,
 hypertension, overweight/obesity) published since the last census dates of the included
 systematic reviews and meta-analyses from the umbrella review.

 Data extraction: Data from prospective cohort studies in the most recent and/or comprehensive
 systematic reviews and meta-analyses will be included in the updated systematic review and
 meta-analysis. For newly identified prospective cohort studies, two or more investigators
 will independently extract relevant data and assess risk of bias using the Newcastle-Ottawa
 Scale (NOS) for observational studies. Risk ratios, odds ratios and hazard ratios for
 clinical outcomes will be extracted or derived from clinical event data across quantiles of
 exposure. All disagreements will be resolved by consensus.

 Outcomes: The primary outcome of the systematic review and meta-analysis will be incident
 cardiovascular disease. Secondary outcomes will include incident coronary heart disease,
 stroke, diabetes, hypertension and overweight/obesity.

 Data synthesis: The natural log-transformed relative risks of outcomes comparing the exposure
 to the reference group from each cohort will be pooled using the generic inverse variance
 method with random effects models and expressed as risk ratios (RR) with 95% confidence
 intervals (CIs). Heterogeneity will be assessed by Cochran Q statistic and quantified by I2.
 The significance level will be set at p<0.10 and an I2≥ 50% will be considered evidence of
 substantial heterogeneity. To explore sources of heterogeneity, the investigators will
 conduct sensitivity analyses, in which each study is systematically removed with
 recalculation of the summary estimates. If there are ≥10 studies, then the investigators will
 also explore sources of heterogeneity by a priori subgroup analyses (cohorts, sex, health
 status, follow-up [<10-years, ≥10-years], dose, level of adjustment of models, quality of the
 studies (NOS), and validation of the dietary assessment instruments). Meta-regression
 analyses will be used to assess the significance of categorical and continuous subgroups
 analyses. If there are ≥10 studies available, publication bias will be assessed by the visual
 inspection of funnel plots and formal testing using Begg's and Egger's 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 certainty of the evidence for each outcome will be assessed using
 the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

 Knowledge translation plan: The results will be disseminated through interactive
 presentations at local, national, and international scientific meetings and publication in
 high impact factor journals. Target audiences will include the public health and scientific
 communities with interest in nutrition, diabetes, obesity, and cardiovascular disease.
 Feedback will be incorporated and used to improve the public health message and key areas for
 future research will be defined. Applicant/Co-applicant Decision Makers will network among
 opinion leaders to increase awareness and participate directly as committee members in the
 development of future guidelines.

 Significance: The proposed project will aid in knowledge translation related to the role of
 dietary pulses in cardiometabolic disease risk, strengthening the evidence-base for
 guidelines and improving health outcomes by educating healthcare providers and patients,
 stimulating industry innovation, and guiding future research design.
Inclusion Criteria:

 Umbrella review:

 Systematic reviews and meta-analyses of prospective cohort studies assessing the
 relationship of dietary pulses or legumes with incident cardiometabolic diseases
 (cardiovascular diseases, diabetes, and hypertension).

 Updated systematic review and meta-analysis:

 -  Prospective cohorts studies

 -  Follow-up duration >=1 year

 -  Assessment of the exposure of pulses or legumes

 -  Ascertainment of viable data by level of exposure (cardiovascular diseases, diabetes,
 and hypertension).

 Exclusion Criteria:

 Umbrella review:

 Not a systematic review and meta-analysis of prospective cohort studies that assess' the
 relationship of dietary pulses or legumes with incident cardiometabolic diseases

 Updated systematic review and meta-analysis:

 -  Ecological, cross-sectional, retrospective observational studies, clinical trials and
 non-human studies

 -  Duration <1 year

 -  No assessment of the exposure of pulses or legumes

 -  No ascertainment of viable data by level of exposure