Article Text
PDF
Abstract
Introduction Almonds have prebiotic potential to maintain gut health and regulate glycaemia. Western studies have shown their positive effects on preventing non-communicable diseases like diabetes and cardiovascular diseases. However, there is a lack of research involving Asian Indians, who have a higher predisposition to diabetes due to their unique ‘Asian phenotype’. Therefore, this study aims to evaluate the impact of almond supplementation on glycaemic control and gut health in adults with pre-diabetes in rural India through a randomised clinical trial.
Methods and analysis A parallel cluster randomised controlled trial with 178 participants with pre-diabetes (assigned 1:1) aged 20–50 years, of both genders, with a body mass index of 18.9–25 kg/m2, will be conducted in rural areas of Chikkaballapur, Kolar and Rural Bangalore districts in India. The intervention group will receive 56 g of almonds as mid-morning snacks for 16 weeks, while the control group will receive cereal/pulse-based traditional isocaloric snacks under the closed supervision of the study investigators. The primary outcome of the study is HbA1c measured at the 16th week. The secondary outcomes—anthropometry, clinical and other biochemical parameters—will be measured at 0th, 8th and 16th weeks, and a subgroup of 120 participants will undergo gut health analysis. Glucagon-like peptide 1 analysis will be conducted on 30 participants at 0th and 16th weeks. Statistical analysis will be performed using SPSS for Windows V.27.0, and both intention-to-treat and per-protocol analyses will be conducted.
Ethics and dissemination Ethics approval was obtained from the Institutional Ethics Committee at Ramaiah Medical College, Bangalore, Karnataka, India (DRPEFP7672021). We will obtain the informed written consent of the participants prior to screening and enrolling them in the study. Results from this trial will be disseminated through publication in peer-reviewed journals and scientific gatherings.
Trial registration number Clinical Trial Registry of India (CTRI/2023/03/050421).
- clinical trial
- diabetes & endocrinology
- microbiology
- nutrition
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
STRENGTHS AND LIMITATIONS OF THIS STUDY
This study has the potential to expand current understanding of how regular consumption of almonds may help improve the pre-diabetic condition and improve gut health.
In this community-based trial, stakeholders, including site residents, actively participate in designing the study implementation through surveys and focus group discussions to assess the acceptability and feasibility of the study food and intervention methods within the community before its implementation.
The planned metagenomic and the gut metabolite analyses will advance our understanding of the impact of almonds on gut health among adults with pre-diabetes.
Blinding of study participants and staff members will not be possible.
Introduction
India is at the forefront of the global diabetes epidemic, with 33 million individuals identified as pre-diabetic and 77 million living with diabetes.1 The ‘South Asian’ or ‘Asian Indian’ phenotype predisposes them to type 2 diabetes and premature coronary artery disease.2 This phenotype is characterised by elevated levels of central adiposity, diabetes, insulin resistance and dyslipidaemia (high serum triglycerides and low high-density lipoprotein cholesterol).3 While genetic factors may play a minor role, lifestyle choices, particularly unhealthy diet and lack of physical activity, are the primary drivers of the current diabetes epidemic.4
Recent studies suggest a link between human metabolic health and gut bacteria composition, with diet being the primary determinant. Lifestyle and dietary factors can significantly influence the composition of colon bacteria, which in turn can impact the risk of obesity, lifestyle-related non-communicable diseases (such as diabetes, cardiovascular disease and metabolic syndrome) and infectious diseases. Diabetes, a metabolic disorder, alters the gut microbiome.5 Therefore, it is crucial to explore ways to modify gut microbiota to regulate hyperglycaemia and lipemic processes.
Microbial byproducts, including short-chain fatty acids (SCFAs), have the potential to impact metabolism through their involvement in lipogenesis, gluconeogenesis, inflammation regulation and the synthesis of glucagon-like peptide 1 (GLP-1), which regulates glucose metabolism. In contrast, intestinal dysbiosis has the potential to disrupt the operations of the gut barrier and gut-associated lymphoid tissues, thereby stimulating inflammatory pathways and potentially playing a role in the pathogenesis of insulin resistance, hyperglycaemia and cardiometabolic complications.6
Almonds, commonly consumed raw or roasted throughout India, have shown potential in promoting healthy microbiota.7–11 They contain considerable amounts of potential prebiotic components such as pectic substances that encase the cellulose microfibrils as well as small hemicellulose such as xyloglucan and α-glucan. A study of healthy Chinese adults found that almond supplementation altered intestinal bacterial activities (faecal β-galactosidase activity significantly increased, while faecal β-glucuronidase, nitroreductase and azoreductase activities decreased).7 The profile of intestinal microbiota including Bifidobacterium spp and Lactobacillus spp was also significantly enhanced. In addition to the prebiotic properties, almonds are rich in healthy unsaturated fats, fibre, proteins, vitamins E and B complex, calcium, magnesium, copper, phytosterols and polyphenols, in addition to their prebiotic properties. Their low available carbohydrate content can support various biomarkers associated with the prevention and management of chronic diseases.11
In Karnataka, pre-diabetes prevalence among adults aged 20 years and older is 11.7%, with 10.6% in rural areas and 14.2% in urban areas.12 The spread of pre-diabetes and diabetes to socioeconomically disadvantaged segments of the population is a significant concern in India, where patients bear the majority of the financial burden associated with diabetes treatment.
With 65% of India’s population living in rural areas, even a small rise in the occurrence of diabetes in these regions may result in a significant number of individuals needing long-term medical attention. Given the limited knowledge and inadequate healthcare resources in rural areas, it is necessary to develop strategies to prevent the rise of diabetes and its associated complications. Therefore, there is an urgent need to advance dietary approaches based on rigorously conducted randomised clinical trials to mitigate the health and financial impacts of diabetes. This article outlines the study design and methodology used in a randomised trial to evaluate the effects of a 16-week, 56 g almond supplementation on rural Indian individuals with pre-diabetes.
Study objectives
Primary objective
The primary objective of the study is to evaluate the effect of almond consumption for 16 weeks on glycaemic control (HbA1c levels) among rural Indian adults with pre-diabetes compared with that of consumption of traditional cereal/pulse-based snacks.
Our hypothesis posits that the daily intake of 56 g of almonds over 16 weeks could foster the growth of beneficial bacteria and stimulate the production of SCFAs. This process is believed to play a crucial role in regulating blood glucose levels in adults with pre-diabetes, as compared with the consumption of the typical cereal/pulse-based snack.
Secondary objectives
The secondary aim is to determine the influence of almond consumption on the colonisation of beneficial gut microflora and faecal SCFAs. Our objective is to investigate the correlation between gut bacterial activity and blood glucose levels in rural Indian adults with pre-diabetes.
Tertiary objectives
The tertiary objective is to evaluate whether almond consumption over 16 weeks compared with traditional mid-morning snacks results in any beneficial changes in anthropometric measurements, in particular, waist circumference and body weight, and whether it improves liver enzyme profiles, inflammatory biomarkers, lipid profile, fasting insulin, Homeostatic Model Assessment for Insulin Resistance (HOMAIR), serum creatinine and gut hormones like GLP-1. Additionally, the study also aims to observe any beneficial association in their physical activity pattern and nutrient intake upon consumption of almonds over traditional cereal/pulse-based snacks for a period of 16 weeks.
Methods and analysis
Study design
The study is designed as a 16-week cluster randomised parallel-arm controlled dietary intervention in the rural settings of India. It employs a robust trial framework with an equal allocation ratio of the participants in both arms. The trial will be conducted in the research facilities of the Ramaiah International Centre for Public Health Innovations (RICPHI), Bangalore, Karnataka, India. The Standard Protocol Items: Recommendations for Interventional Trials guidelines were used in the development of this protocol.13
Study settings
This community-based trial will be implemented among a free-living population in rural settings of Karnataka (South India). Considering the lack of awareness and inadequate healthcare facilities in rural areas, where nearly 65% of the Indian population resides, the purpose of this research is to provide rural adults with a culturally sensitive and easily accessible dietary approach to prevent diabetes. RICPHI manages a multidistrict community outreach programme, with subdistricts as clusters for intervention on chronic diseases. Therefore, the study population will be recruited from the villages of Chikkaballapur, Kolar and Rural Bangalore districts of Karnataka, which are within the geographical scope of the community outreach programme implemented by RICPHI.
Participant eligibility
This study encompasses individuals aged 20–50 years, whose body mass index (BMI) falls within the range of 18.9–25 kg/m². Considering that the selected cohort predominantly exhibits the Asian Indian phenotype, the incidence of diabetes is significantly high among adults over the age of 20 years, irrespective of their body weight status.3 This age bracket ensures the attainment of physical maturity. Additionally, within this age range, the prevalence of chronic health conditions that align with our exclusion criteria for volunteer inclusion in the study is relatively low.
Consequently, prospective participants in the study are expected to express a willingness to partake, with the absence of any allergies to nuts. Their fasting plasma glucose levels should fall within the range of 100–125 mg/dL, or their random blood glucose levels should range between 140 and 199 mg/dL. Participants’ HbA1c levels should register between 5.7% and 6.4% and should have normal bowel movements. Importantly, they should not present with comorbidities, such as thyroid disorders, diabetes, chronic kidney disease, alcoholic liver disease or any known instances of cardiovascular conditions or other chronic illnesses. Moreover, eligible participants should not be on any medications that are known to impact metabolism and appetite, such as steroids, β-blockers or antibiotics, and should not exhibit chronic dependence on alcohol. The participants should not be on any prebiotic, probiotic or symbiotic supplements. All participants meeting these criteria will undergo a comprehensive screening process and will be enrolled into the study only after providing informed consent.
Recruitment and screening process
The selection of villages for the study will be determined based on their population size and proximity to the central office. Subsequently, the research team will engage with district health officers, medical officers and primary healthcare workers within the chosen areas to discuss the programme’s objectives and secure their formal consent.
In order to facilitate active participation and foster a sense of community trust, preliminary activities will encompass sensitisation and rapport-building exercises. The study will extend invitations exclusively to adults ranging in age from 20 to 50 years who have been residents of the selected village for a minimum duration of 6 months. These individuals will be subjected to level 1 screening to evaluate their susceptibility to pre-diabetes. To assess the pre-diabetes risk within this cohort, the research will deploy the Indian Diabetes Risk Score14 and the pre-diabetes risk score (Prediabetes Risk Evaluation Scoring System).15
Individuals identified as falling into the high or moderate-risk categories will advance to level 2 screening, which involves HbA1c analysis for pre-diabetes diagnosis. Furthermore, adults with confirmed pre-diabetes will be subjected to comprehensive investigations to ascertain the presence of any additional comorbidities, including but not limited to liver disorders, kidney disorders, thyroid abnormalities, cardiac health, inflammatory markers and other relevant comorbid conditions. Upon obtaining informed consent, individuals who meet all the established inclusion criteria will be formally enrolled in the study. The enrolment of the study participants was initiated in April 2023 and the study will be completed by August 2024.
Sample size calculation
We determined that for a minimum clinically significant difference in mean HbA1c levels of 0.65, with an SD of 1, for 80% power and 5% level of significance, the minimum number of participants required for the study after considering a 20% dropout rate is 148. The difference in HbA1c of 0.65 aligns with previous studies investigating the effects of dietary interventions, including almond consumption, on HbA1c levels.16 Considering a design effect of 1.2, the minimum number of total participants required is 178. The study will identify 20 clusters, with 10 each for the control and intervention groups. Each cluster will define one Anganwadi worker’s (AWW) area as a unit. An AWW in an Indian rural setting covers 1000 population. The cluster size will be limited to 10–12 participants.
Randomisation, allocation concealment and sequence generation
Randomisation will be executed by an independent biostatistician using a computer-generated random number sequence that will be sealed in numbered opaque envelopes.17 Subsequently, a team member who is unaffiliated with both the evaluation of study outcomes and the subsequent statistical analysis will carry out the allocation of treatments. The sealed envelopes will be securely stored in a designated location, accessible only to authorised personnel. It is pertinent to note that due to the nature of the study, where participants will be consuming easily recognisable whole foods, the implementation of blinding measures for both the participants and the staff engaged in the intervention will not be feasible.
Pre-intervention phase
Analysis of snack consumption patterns
In order to gain insights into the snack consumption behaviours within the community residing in the study areas, a preliminary investigation was conducted. This investigation encompassed both focus group discussions and individual interviews. The findings revealed that a predominant portion of the participants habitually consumed snacks during the mid-morning and evening intervals. Notably, their snack choices predominantly revolved around tea or coffee, typically imbibed three to four times daily, complemented by cereal/pulse-based snacks, which were either homemade or procured from local stores and bakeries.
Assessment of almond acceptability
To evaluate the acceptability of almonds as a snack option, 10 adults were administered a quantity of 56 g of almonds consecutively over the course of 3 days. Subsequently, an evaluation was conducted to ascertain their inclination towards almond consumption. The results revealed a unanimous appreciation for the taste of almonds, with a preference for integrating them into their mid-morning snack regimen. During a subsequent focus group discussion, participants recommended a communal gathering for the consumption of almonds, as opposed to taking individual packets home.
Selection of isocaloric control foods
An additional facet of the pre-intervention phase involved an exploration of the snack options available in the local grocery establishments situated within the study areas. The investigation focused on the most popular snack varieties, with a detailed analysis of their macronutrient composition and ingredients. The control foods are the processed food items commonly consumed by the study participants. They are predominantly made up of cereal and pulse-based combinations and are devoid of nuts. Furthermore, the selected snacks underwent meticulous macronutrient analysis. Subsequently, three widely consumed ready-to-eat snack items were chosen as control foods. A comparative breakdown of their nutritional compositions can be found in table 1.
Nutrient content of intervention and control food selections
Intervention
The study intervention plan is summarised in table 2. Following the acquisition of informed consent, eligible participants will be enrolled in the study. Prior to commencing the intervention phase, a 2-week run-in period will be initiated. The intervention arm participants will receive California almonds as mid-morning snacks. In contrast, the control group will receive cereal/pulse-based traditional snacks with calories equivalent to the almonds consumed by the intervention group daily for 16 weeks. The almonds to be supplemented will be California almonds with unblanched kernels and brown skin intact, and the participants should consume 56 g of almonds daily for 16 weeks as a replacement for their traditional cereal/pulse-based mid-morning snack. The consumption of almonds will be closely supervised by field workers. The participants will replace approximately 326 calories of their regular diet with 56 g of California almonds. During the study, participants from both groups will be instructed to maintain their usual dietary and physical activity routines. We will closely monitor their adherence to these practices on a weekly basis using a mobile application-based monitoring system.
Intervention and assessment plan
Protocol amendments
The current protocol manuscript was initially submitted on 21 June 2023. Following the reviewers’ and editors’ feedback, we proposed modifications to the primary and secondary outcomes in consultation with the Study Advisory Board and the Data and Safety Monitoring Board (DSMB). The gut health parameters were changed to secondary outcomes as gut health parameters were to be performed only in subsamples. These changes were subsequently approved by the Ethics Committee and later resubmitted and accepted by the Clinical Trials Registry of India (CTRI). Table 3 provides detailed information on the amendments made to the protocol, including the original and revised statuses of the outcomes.
Protocol amendments
These amendments were implemented during the baseline data collection phase. However, it did not affect the data collection process and we ensure the clarity and focus of our study’s primary outcome while maintaining the integrity of the data collection process. The overall parameters remained consistent, and detailed descriptions of the outcomes are provided in the Study outcomes section below.
Study outcomes
Primary outcome
The main focus of this study centres on assessing the impact of almond consumption versus traditional cereal/pulse-based snacks on glycaemic control among rural Indian adults with pre-diabetes. The primary outcome of interest is the HbA1c level at the 16th week of the intervention.
Secondary outcomes
Glycaemic response: blood will be drawn at 0, 8 and 16 weeks to measure fasting blood glucose levels, HbA1c and insulin levels to analyse the glycaemic response.
Gut health: we will collect the faecal samples in a subgroup of 120 participants at baseline (0), midline (8 weeks) and endline (16 weeks) to measure the SCFA levels and beneficial gut microbiota counts. Faecal samples will be assessed for SCFA composition (gas chromatography-mass spectrometry method)18 and gut microbiota sequencing (PCR)19 at baseline, midline and at the end of the study period. The blood and faecal samples will be collected and stored in sterilised temperature-controlled storage boxes and transported to the laboratories for testing within 6–8 hours.
Other tests: the metabolic markers such as lipid profile, liver function tests (serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase, gamma-glutamyl transferase, serum bilirubin and serum protein albumin), serum creatinine and serum urea, thyroid-stimulating hormone and thyroxine hormone levels and inflammatory markers (high-sensitivity C reactive protein and interleukin 6) will be measured at baseline (0 week) and endline (16 weeks).
In a subgroup of 60 participants, active plasma GLP-1 levels20 will be estimated immediately after the consumption of mid-morning snacks at baseline and endline of the study. For this, blood samples will be drawn at the following periods after almond consumption: 0 (immediately after consumption) and at 10 and 30 min.
Anthropometry: anthropometric measurements (body weight, body height, BMI, waist circumference, neck circumference and hip circumference) and systolic and diastolic blood pressure will be measured at baseline (0 week), midline (8 weeks) and the end of the study (16 weeks).
Dietary and physical assessments: the dietary intake and physical activity pattern will be monitored periodically using validated tools, 24-hour dietary recall and the Global Physical Activity Questionnaire. A mobile phone-based electronic data capture tool will be specially developed based on the tools.
Adverse events
Adverse events will be recorded in the case report form and will be reported to the Institutional Ethics Committee. Side effects will be unlikely, but if any severe side effects due to the intervention are detected, participants will be withdrawn from the study. Adverse events that lead to withdrawals will be reported in future publications. We do not intend to analyse adverse events formally.
In order to ensure a high degree of compliance, incentives and personal health and fitness services will be provided to the study participants in both groups at the end of the study for a month by a team of certified fitness trainers, nutritionists and physicians via an official agreement with the community heads of those rural settings. The compliance will also be assessed using α-tocopherol level estimation of the participants at baseline, midline and endline assessments.
Data management
An electronic Management Information System application has been developed to monitor the field activities, enable real-time data collection and support the trial implementation team with dashboards to assist real-time decisions. The data will be collected in the field in a physical form and electronic form into a central database. The platform has an inherent capability to create a unique ID for each participant’s data being submitted, which will be used to identify their electronic and paper-based data and biological samples. A password-protected computer database, accessible to the researchers only, will store participant identifiers (eg, name, email address, phone number) and their associated code. Paper-based data will be stored securely at the Ramaiah Institute of Public Health Innovations for 5 years, after which it may be destroyed. Biological samples will be stored at −80°C freezer, and will be stored for up to 3 years from the collection date and disposed of accordingly after that time.
Statistical analysis plan
Statistical analysis will be performed using SPSS for Windows V.27.0. Intention-to-treat (ITT) and per-protocol analyses (for those who achieve a minimum of 80% compliance with test food consumption) will be performed. Bonferroni post hoc tests will be performed where main effects are identified to identify significant differences between means (p<0.05). While the ITT analysis will be the primary analysis, the per-protocol analysis will allow us to decipher whether the effects are due to participants being compliant with consuming test foods. We will also run subanalyses. Descriptive statistics (means and SDs, quartiles for continuous variables and frequencies and percentages for categorical variables) will be reported. Bivariate comparisons, using Χ2 tests for categorical, one-way analysis of variance (ANOVA)/Kruskal-Wallis test, independent Student’s t-test/Mann-Whitney U test for continuous variables based on the normality of the data, will be conducted. The impact of the intervention will be assessed using repeated-measures ANOVA. ANOVA with Tukey’s post hoc test will be used for intragroup and intergroup comparisons. A two-tailed p value of <0.05 will be considered statistically significant. The protocol non-adherence data or the missed data will not be considered for analysis.
The quality assurance team independent from the funders will perform frequent auditing of the intervention protocol and data collection throughout the trial. A DSMB is formed to monitor participant safety, data quality and progress of the ABC Trial Programme. In addition, the DSMB will review study data periodically to evaluate the study’s safety, conduct, scientific validity and data integrity. The members of the DSMB are selected by the advisory panel of the project.
Patient and public involvement
The present study represents a community-based randomised controlled trial (RCT), characterised by active community engagement in both the formulation of the study intervention and the development of the implementation plan. This inclusive approach involved surveys and focus group discussions to assess the acceptability and feasibility of the study’s dietary and intervention protocols within the community, prior to the study’s commencement. This initiative can be best described as a collaborative undertaking, as it involves community members in the process of designing the study to ensure that it aligns closely with the needs and preferences of the local community. In this regard, comprehensive explanations regarding the study’s objectives and procedures were provided to the participants, and informed consent was diligently obtained. Community volunteers will play a crucial role in the recruitment process and community mobilisation efforts. Participants who meet the inclusion criteria will be provided with comprehensive information about the study and its expected duration before obtaining their informed consent. Furthermore, individual clinical and biochemical reports will be provided to the participants, complemented by one-on-one lifestyle counselling sessions post-intervention. The study’s outcomes will be disseminated to the participants and the broader village community through presentations during village meetings and community gatherings.
Ethics and dissemination
Ethics approval was obtained from the Institutional Ethics Committee at Ramaiah Medical College, Bangalore, Karnataka, India (DRPEFP7672021). Written informed consent will be obtained from the participants before their enrolment by the field investigators. The consent form will be in English and vernacular language, and it will have all the details regarding the intervention trial. The personal information about potential and enrolled participants will be kept confidential in order to protect confidentiality before, during and after the trial. Participants will receive a copy of their results (with the exception of their faecal sample testing as well as a summary of the study findings). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations. The trial is registered in the CTRI (CTRI/2023/03/050421).
Discussion
RCTs have demonstrated the effectiveness and cost-efficiency of medical nutrition therapy in improving the metabolic outcomes of patients, as evidenced by numerous studies.21 It is increasingly acknowledged that nutrition science would benefit from more robust and well-conducted RCTs to evaluate the impact of nutrients and foods on clinical outcomes, which can complement findings from prospective cohorts and metabolic studies. Each of these investigative approaches bears its own set of advantages and constraints, and congruous findings can play a pivotal role in shaping dietary guidelines and facilitating their effective implementation.
In India, a nation grappling with escalating burdens of cardiovascular disease and diabetes, which significantly augment disability-adjusted life years,22 the establishment of nutrition interventions that can aid in averting these diseases is of paramount importance, particularly considering their potential to modulate risk factors such as hyperglycaemia. The consumption of nuts is well aligned with this pressing need.
Almonds have beneficial effects on various health markers, including the lipid profile, atherogenic indices, endothelial function, inflammatory markers, glycaemic control, HbA1c and blood pressure, as supported by research.23 24 Nevertheless, a noteworthy research gap exists regarding the effects of almond consumption on glucose responses and gut health in the Indian context. A short-term intervention trial lasting up to 4 weeks has shown the beneficial effect of almond consumption on glycaemic response and cardiometabolic risks in healthy and at-risk adolescents and young adults in India.25
To bridge this knowledge gap, a long-term pre/post-clinical trial was undertaken, involving 50 North Indian subjects diagnosed with type 2 diabetes in New Delhi, India. Middle-aged adults (mean age 46 years, mean BMI 29) were recruited for a 3-week run-in diet, succeeded by a post-run-in diet regimen incorporating 20% of daily energy intake from raw almonds (approximately 60 g/day) over a period of 24 weeks. Compared with the initial run-in diet, the almond-enriched diet exhibited statistically significant improvements in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglyceride levels, HbA1c levels, high-sensitivity C reactive protein levels and pulse wave velocity.16 26 However, the study has yet to explore the mechanisms and prebiotic potential of almonds, as well as their role in the regulation of glycaemic and lipemic profiles. Furthermore, there is a dearth of studies investigating almond consumption in individuals with pre-diabetes in the Indian context.
This study, based in a rural setting, holds the potential to broaden our current understanding of how regular consumption of almonds may help improve or reverse the pre-diabetes condition and improve gut health. The study is community based, with active involvement from stakeholders, including the community, in planning and designing the intervention trial. This participation includes surveys and focus group discussions to evaluate the acceptability and feasibility of the study’s food and intervention method within the community before commencement. It is essentially a collaborative endeavour, with community members contributing to the study’s design to ensure alignment with community needs and preferences. Compliance management is crucially designed by performing an intervention on one-to-one closed supervision, assessment of serum tocopherol levels and daily follow-up of any adverse events throughout the intervention. In India, where diabetes is known to increase disability-adjusted life years, it is crucial to establish nutrition interventions that can help prevent the disease, mainly through their impact on modifiable risk factors like hyperglycaemia. The consumption of nuts aligns with this urgent need. Moreover, the upcoming metagenomic analysis and the gut metabolites like SCFAs and GLP-1 will significantly advance our understanding of the impact of almonds on gut health.
However, a potential limitation of the study is that it will not be feasible to follow up with the participants after the intervention. Blinding study participants and staff members is not feasible due to the identifiable nature of the supplements. However, the study’s cluster design, with clusters situated at a considerable distance from each other, may help mitigate concerns regarding contamination and the study food. The present RCT could provide valuable insights into evidence-based approaches for preventing non-communicable diseases, such as diabetes, by incorporating simple lifestyle changes such as adding almonds to a diet as a powerful dietary supplement. Positive results from the study could lead to recommendations to replace commonly consumed cereal and pulse-based snacks with nuts, resulting in improved regulation of blood glucose levels and enhanced gut health.
Ethics statements
Patient consent for publication
Acknowledgments
The gut microbiome and GLP-1 analysis will be performed by the Medgenome Laboratories, Bengaluru, India. The short-chain fatty acid (SCFA) analysis will be performed in the Sophisticated Instrumentation Centre for Applied and Research Training (SICART) Laboratories and GSFC Research and Development Laboratories, Gujarat, India.
References
Footnotes
Contributors VR, CN and PK were the co-applicants for the grant application and were primarily involved in study design. VR was the lead applicant and principal investigator of the study. CN, PK, NSN and BP contributed to the method development and writing and development of the study protocol. All authors contributed to the editing of the manuscript. All authors read and approved the final manuscript.
Funding This work is funded by Almond Board of California, California, USA.
Disclaimer The funding source had no role in the design of the study and will have no role in analysis and interpretation of the data.
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.