Effect of diet on the management of hypertension and type 2 diabetes mellitus in adults from low-income and middle-income countries: protocol for a systematic review of randomised controlled trials

Abstract

Introduction

Hypertension and type 2 diabetes mellitus (T2DM) are two highly prevalent non-communicable diseases worldwide, both leading to disability and premature mortality in low-and-middle-income countries (LMICs). Nutritional interventions towards a healthier dietary pattern or food and nutrients intake have an important role on the management of this disease. This systematic review aims to evaluate the effect of nutritional interventions on the management of blood pressure and glycaemia in adults with hypertension and T2DM from LMICs.

Methods and analysis

We will conduct a systematic review of randomised controlled trials (RCTs) on the effect of nutritional interventions on blood pressure and glycaemia in adult patients with hypertension and T2DM. Literature search will be conducted in MEDLINE, EMBASE, Scopus, Cochrane and Web of Science databases from anytime until April 2024. Nutritional interventions would have been applied in addition to regular or standard treatment, which is prescribed and/or provided by the healthcare system. Studies in English and Spanish will be selected and reviewed by two independent reviewers. Risk of bias will be assessed using the Cochrane tool for RCTs. Heterogeneity and publication bias will be estimated using the I² and Egger’s test, respectively.

Ethics and dissemination

Ethics approval was not required for this systematic review, considering there was no direct data collection or participation of patients. The investigators will write a manuscript of the final detailed report with the study development and main findings to be published in a peer- reviewed journal. The main findings may be shared with academia partners and groups working on similar topics in LMICs, in addition to policymakers and authorities in these countries.

PROSPERO registration number

CRD42023483847.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Literature search will be conducted in five important databases and study selection will be conducted by two independent reviewers.

• This review will synthesise the information available about the effectiveness of randomised controlled trials conducted in low-and-middle-income countries, summarising the main type of interventions conducted and the strategies in place to improve the management of hypertension and type 2 diabetes mellitus.

• Interventions and outcomes will be analysed independently for each of the chronic disease.

• A limited number of homogeneous randomised controlled trials may be available to conduct a meta-analysis.

Introduction

Hypertension and type 2 diabetes mellitus (T2DM) are two highly prevalent non-communicable diseases worldwide,^{1 2} both leading to disability and premature mortality in low-and-middle-income countries (LMICs).^{3 4} The adverse complications associated with the lack of control of hypertension and T2DM can be prevented or delayed, with effective pharmacological interventions to achieve an optimal blood pressure and glycaemic control in addition to non-pharmacological interventions such as healthy lifestyle recommendations.⁵,⁷ Importantly, changes towards a healthier diet may have effects similar to pharmacological treatment on controlling blood pressure and glycaemia at early disease stages and decreasing the medication dosage at advanced disease stages.⁸,¹¹ The biological mechanism lies primarily on the blood pressure regulation influenced by dietary factors that modulate vasoactive molecules, like inhibition of angiotensin¹² and may also diminish the effect of age on blood pressure in the general population,^{8 13} while glycaemia levels may be regulated by the long-term changes in insulin response due to optimal diet quality and gut microbiome modulation.¹⁴

Findings from previous systematic reviews have shown that dietary factors associated with the management of hypertension and T2DM range from individual nutrients or foods, to dietary patterns.¹⁵,¹⁸ The Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets have an important effect on the management of blood pressure in adults with and without hypertension,^{19 20} while the Mediterranean diet has also important benefits on glycaemic control in patients with diabetes.²¹

However, the majority of high-quality evidence synthesised in previous systematic reviews report information from high-income countries.¹¹²²,²⁴ Nutritional intervention approaches and recommendations may need further adaptation for LMICs considering local available foods, cultural norms and lifestyle habits. For example, certain dietary patterns like the Mediterranean or DASH diets may not be culturally accepted or context available in LMIC settings due to the lack of availability of certain foods in addition to other sociodemographic characteristics that influence the local-specific food choices. Therefore, alternative evidence-based strategies specific to LMICs could be in place to translate standardised recommendations. However, recent evidence from the development and implementation of randomised controlled trails investigating the effect of dietary nutritional interventions, provided alone or as part of other multi-component interventions, has not been systematised yet.

A recent systematic review synthesised the evidence about short-effectiveness of nutrition therapy on glycaemic control in LMICs, included those randomised controlled trials that had a follow-up of at least 12 weeks since the end of intervention finding promising results, but it was limited to a small number of eligible studies.²⁵

This systematic review aims to estimate the effect of nutritional interventions on the management of blood pressure and glycaemia in adults with hypertension and T2DM from LMICs.

Methods and analysis

This is a protocol for systematic review and meta-analysis, which was developed following the Preferred reporting items for systematic reviews and meta-analysis protocols guidelines²⁶ (online supplemental file 1). The systematic review started on December 2023 and will be finished by December 2024.

Eligibility criteria

Study designs

Randomised controlled trials (cluster randomised trials, crossover trials, community trials) will be included. Studies testing the feasibility of an intervention when the primary outcomes were assessed, or studies comparing different interventions without control/placebo groups will be excluded.

Participants

Adults, 18+ years old, with any type of hypertension and/or T2DM with any diagnosis length, and any body mass index (BMI) status from LMICs, as defined by the World Bank,²⁷ will be included. Studies that included participants <18 years of age partially or completely, participants who do not have previously diagnosed hypertension or T2DM, pregnant women or participants with reported eating disorders will be excluded.

Types of interventions

The interventions included will be any nutritional intervention alone or in combination (multicomponent) with any other lifestyle intervention, like physical activity, adoption or adherence to healthier lifestyles. A nutritional intervention is defined as any applied to individual, groups, populations or institutional areas with the main aim to improve management of hypertension or T2DM. These include changes of eating patterns, nutritional education sessions, behavioural messages to promote lifestyle changes, specific nutrient intake, supplementation, multifaceted interventions in primary care centres or communities, driven by community health workers.

The nutritional interventions would have been applied in addition to regular or standard treatment, which is prescribed and/or provided by the healthcare system. If any drug or medication is used as regular or standard care, the study will be included.

The intervention would have been applied directly by the research team, community leaders or staff working in the investigation, during a prior established frequency.

Interventions that use drugs for weight-loss alone or in combination with other interventions or observational studies will be excluded.

Comparators

The control will be the standard treatment by the local healthcare system (eg, counselling for self-management, standard medication) or placebo.

Outcomes

The primary outcomes are (1) blood pressure measured by systolic and diastolic blood pressure (SBP and DBP) and (2) glycaemia assessed by glycosylated haemoglobin (HbA1C),²⁸ or fasting blood sugar values, considering the complexity of assessing HbA1C in low-resource settings. The measures of effect will be the mean change of these primary outcomes before and after the intervention between study groups.

Secondary outcomes include controlled blood pressure (SBP/DBP <140/90 mm Hg), for those with hypertension; and controlled glycaemia (HbA1C <7%). In addition to this, changes in medication doses will be assessed.

Information sources

A search strategy will be developed using target terms adapted to the following bibliographic databases: MEDLINE/PubMed, EMBASE, Scopus, and Cochrane. The search dates will range from any until April 2024. Publications in English and Spanish will be included

Search strategy

The search strategy included terminologies and keywords in previous similar systematic reviews on hypertension and T2DM. Further combinations between the PICO terms will be considered in addition to the updated list of LMICs. Specific search strategies will be tailored to meet each of the database requirements. Search strategies will be adjusted to meet each of the information source requirements and will be piloted to compare the results obtained and modified, if needed. An example of the MEDLINE search strategy is found in online supplemental file 2.

Study records

Selection process

Results obtained from the different databases will be merged in a reference software and duplicates will be removed. Two reviewers will independently screen the titles and abstracts to decide whether to include the studies in the systematic review analysis. Possible disagreement will be resolved through discussion within the project team.

Data extraction and management

The reviewers will then read the full text of those selected studies. We will use a standardised form to extract data from the included studies. Regular meetings will be held to examine data extraction and the results will be summarised in a matrix form that will be made available to all reviewers on a web-based shared document. Any discrepancies of eligibility will be discussed within the team and documented in the data entry sheets.

The information about characteristics of original studies, study design, population, participants sociodemographic characteristics, sample size, interventions, outcomes, duration, blood pressure and glycaemia outcomes, will be collected and described in a Summary of Findings Table, following the PRISMA guidelines.²⁹

Risk of bias assessment

Risk of bias of the randomised controlled trials will be assessed using the Cochrane risk-of-bias tools for individually randomised, parallel-group, cluster-randomised and crossover trials.³⁰ Overall, the quality domains to assess the risk of bias will be (1) from the randomisation process, (2) due to deviations from the intended interventions, (3) missing outcome data, measurement of the outcome and (4) selection of the reported result, identified to potentially influence the research at different stages and might introduce bias into the results.³⁰ The degree of risk of bias in each domain and overall, across domains, for each selected study, will be classified into ‘low’, ‘some concerns’ and ‘high’ and summarised in a table, accordingly.

Data synthesis

We anticipate that different types of interventions will be eligible in this systematic review and further classification will be conducted. Specifically, those multicomponent interventions as well as different dietary patterns or plans will be classified according to their main characteristics and delivery method, such as vitamin supplementation, nutrition education or dietary meal plans. Weighted mean differences of blood pressure and glycaemia, and their corresponding 95% CI, will be measured within each subgroup of interventions, as effect sizes. Results will be reported in tables and figures for key characteristics such as world region, type of intervention, among others.

For comparable studies, meta-analyses will be carried out using random-effect models for the change of blood pressure and glycaemia for 10 or more studies. Statistical heterogeneity between studies will be quantified using I². Egger’s test will be assessed for publication bias using funnel plots.

Pooled estimates will also be presented by age group (ie, adults vs elderly) and sex (women and men).

Quality of synthesised evidence

The quality of evidence synthesised for analyses will be graded considering their heterogeneity, risk of bias, publication bias and rated as high, medium, low or very low.

Patient and public involvement

None.

Ethics and dissemination

Ethics approval was not required for this systematic review, considering there was not direct data collection or participation of patients. The investigators will write a manuscript of the final detailed report with the study development and main findings to be published in a peer- reviewed journal. The main findings may be also shared with academia partners and groups working on similar topics in LMICs as well as policymakers in these countries.