Nutrition and Diet Therapy in Diabetes Mellitus: A Roadmap based on available evidence

Abstract

Background

Nutrition is considered as a primary approach for diabetes management. It needs a comprehensive assessment of evidence to identify nutritional dimensions that should be explored in the future. We aimed to provide a roadmap on diabetes and nutrition and clarify research gaps in this field.

Methods

In the present review, we searched Scopus and PubMed electronic databases to collect eligible publications with English and Farsi languages from 2015 to December 2019 in the field of nutrition and diabetes. Relevant papers were classified into six subgroups including biochemistry/ animal studies, clinical nutrition, food industry, genetic, public health, and dietary supplements. Based on evidence-based pyramid, publications were categorized as well. Publications trend from 2015 to 2019 and frequency of publications in each category were provided.

Results

Finally, we reached 438 eligible papers. Most studies (40.86%) were clinical trials and in most human studies (n = 224) patients with type 2 diabetes were considered. Probiotic/prebiotic/ symbiotic, vitamin D, and omega-3/fish oil were the most frequent studied dietary supplements. Low portions of studies were dedicated to diabetic children (n = 3), type 1 diabetes (n = 6), diabetes complications (n = 23) and GDM (n = 25).

Conclusion

An increasing trend in nutrition publications in the field of diabetes was observed. Publications were mostly dedicated to clinical trials with a focus on dietary supplements. Low portion of studies have been dedicated to children with diabetes, diabetes complications, and GDM. More attention to high quality basic research, product-based projects, and interdisciplinary studies in the field of nutrition and diabetes are needed.

Introduction

Due to the rising burden of diabetes mellitus (DM), controlling and preventing DM is one of public health priority across the world [1]. Based on the recent report, approximately 425 million people suffered from DM in 2017; and it is predicted to rise to 629 million by 2045 [2]. The risk of developing dyslipidemia, hypertension, atherosclerosis, and other cardiovascular diseases in patients with DM is greater than other individuals [3]. Following uncontrolled glucose level, retinopathy, neuropathy, nephropathy, and other complications related to DM can be occurred [4]. Not only do DM and its complications result in a considerable financial burden on patients [5], their families, and government, but also they can cause negative effects on the quality of life and mental health [6, 7].

DM can be affected by both genetic and environmental factors [8]. Lifestyle modifications including changing the direction of dietary habits and dietary patterns toward healthy dietary recommendations are the examples of approaches to blunt the growth of DM [9].

Nutrition and diet therapy are considered as primary approach for diabetes management [10]. They can help clinicians and patients to control diabetes and prevent the development of diabetes complications [11]. Based on evidence, it is more effective to focus on a whole diet instead of a specific nutrient or food [12, 13]. There is accumulating evidence on the various types of dietary patterns [14–17], and dietary supplements [18–20]. However, it seems studies on each type of DM are conducted without any particular nutritional roadmap in Iran. Although a roadmap has been published based on Iranian publications up to 2015 [21], it seems an update is helpful to shed light on the future research projects based on recent publications. Ebrahimi et al., reported that the most percentage of publications in the field of nutrition and DM was dedicated on clinical research (78%) and the least studies were on health service studies (0.08%). They also revealed that the most studies were on type 2 diabetes mellitus (T2DM) and its complications, while the least publications were on Gestational Diabetes Mellitus (GDM) [21]. Due to an increase in the incidence of GDM in recent years, more focus in this issue seems to be helpful for prevention. However, it needs a comprehensive assessment of evidence to identify the exact nutritional dimensions that should be considered. In the present scoping review, we aimed to response to three main research questions in the field of nutrition and diabetes based on available evidence as follows: (i) What are the types and the levels of evidence?, (ii) What are the key characteristics of available evidence?, and (iii) What are research gapes?

Methods

In the present review, we searched Scopus and PubMed electronic databases to collect publications of Iranian researchers with English and Farsi languages from 2015 to December 2019 in order to update a prior diabetes roadmap in Iran [21]. Original and review papers in the field of diabetes mellitus were included. Grey literatures including theses, interviews, editorials, protocols, books, commentaries, and conference papers as well as studies by non-Iranian researchers were excluded.

The present study is a part of a large project on diabetes roadmap in Iran. To identify related studies for main project, we used the following key terms: (diabetes OR diabetic) AND Iran; and reached 10,540 articles. All the retrieved publications were imported into EndNote software to do screening processes. First, the eligibility of papers was checked based on their titles and abstracts by two independent reviewers (N.N, SH.E). After removing duplicates and irrelevant articles, 4,144 possible eligible publications remained. In the second step, they were categorized into specific groups as follows: (i) Basic sciences, (ii) epidemiology, (iii) education, (iv) treatment, (v) prevention, (vi) complications, (vii) comorbidity, (viii) psychology, (ix) physical activity, (x) traditional medicine, and (xi) nutrition.

The rest of processes were performed on nutrition group only. After checking the titles and abstracts of papers collected in nutrition category and removing irrelevant papers, the eligible papers were categorized into any of six subgroups as follows: (i) biochemistry/ animal studies, (ii) clinical nutrition, (iii) food industry, (iv) genetic, (v) public health, and (vi) dietary supplements. Categories were checked by principal investigator (E.N) and after discussion on discrepancies and reaching consensuses, final categories were provided.

Data extractions

In the next step, the full-texts of eligible papers were identified to extract key characteristics. Based on research questions, variables were selected to be extracted from the papers. Type of study ((human, animal, In vitro)/ original, review)), study design (clinical trial, cohort, case–control, cross-section, case series, etc.), main topic (clinical nutrition, public health, intervention, nutrigenomics/ nutrigenetics, etc.), type of diabetes (type 1, type 2, GDM), participants in human studies (adults, children/adolescents), and non-diabetic target group (pre-diabetes, others). For clinical trials, either the names of dietary supplement or type of diet were extracted as well. Observational studies in which dietary patterns or indexes were examined were put into a specific category.

Due to the high numbers of included papers, we provided data extracted by only pie and bar charts to clarify main characteristics of available evidence in the field of nutrition and diabetes mellitus in Iran (Figs. 1 and 2).

Fig. 1.

Main categories of the included studies in the field of nutrition and diabetes

Fig. 2.

The numbers of included studies based on an evidence-based pyramid

Result

Study characteristics

In total, 452 publications in the field of nutrition were found after electronic search. Checking titles and abstracts of papers identified that 14 publications were relevant neither to nutrition nor diabetes and were excluded. Finally, 438 relevant papers to nutrition in diabetes mellitus were obtained.

In the next step, relevant papers were categorized into two main groups including human studies (n = 344) and animal/ In vitro studies (n = 94). Notably, only 4 studies were in the field of food industry that was transferred to a separate group. Another classification was based on topic as follows: biochemistry (n = 17), clinical nutrition (review, original) except dietary/herbal supplements (n = 66), food industry (n = 4), nutrigenetic/nutrigenomics (n = 2), public health (n = 95), and dietary supplements (n = 254) (Fig. 1). Notably, papers on medicinal herbs, extracts, and spices were not considered in nutrition category and they were all moved to traditional medicine group. However, wherever spices or medicinal herbs added to foodstuffs including bread and biscuits were considered in nutrition category.

Furthermore, the level of evidence for all included papers was determined. Among 438 papers, 10 had the highest level of evidence (systematic review and meta-analysis). The level of evidence for included studies is shown in Fig. 2. Based on study design, papers had cross-section (n = 72), cohort (n = 11), case–control design (n = 7), and randomized clinical trial (n = 179).

The annual trend of publications in the field of nutrition and diabetes are presented in Fig. 3. Based on Fig. 3, the number of related papers faced an increasing trend except 2017 through 2015 to 2019.

Fig. 3.

The trend of publications in the field of nutrition and diabetes during 2015–2019

Study characteristics

Most studies (40.86%) were clinical trials and in most human studies (n = 224) patients with type 2 diabetes were considered (Observational studies = 119, RCTs = 105). Notably, this frequency covered studies in which both types of diabetes (type 1 and type 2 diabetes mellitus) have been examined. Three dietary supplements that their effects were examined in patients with diabetes were probiotic/prebiotic/ symbiotic (n = 42), vitamin D (n = 37), and omega-3/fish oil (n = 16).

The total number of studies on type 1 diabetes and GDM were 6 and 25, respectively. In twenty-one clinical trials (of 170 clinical trials), women with GDM were included. From the view point of age group, all human studies except 3 were performed in adult populations. Few numbers of eligible papers were dedicated to diabetes complications (n = 23). Among the studies on complications, most (n = 12; 52.1%) were on kidney disorders related to diabetes. The remaining was on coronary disorders (n = 5), diabetic ulcer (n = 4), hypertension (n = 1), and retinopathy (n = 1).

As papers including metabolic parameters related to diabetes were also included, a part of eligible human studies (n = 41) were dedicated to such publications. Based on classifications on type of diet, 29 and 5 articles in public health/ clinical nutrition studies examined different dietary patterns and dietary indices, respectively.

Proposed types of studies and main topics in the field of nutrition and diabetes for the future research based on this roadmap are presented in Boxes 1 & 2.

Box 1 Proposed studies for the future research in the field of nutrition and diabetes

Bacis studies (studies on genetic, microbiota, animal studies and in vitro studies to clarify mechanisims involving in diabetes and complications

High- quality, product-based clinical trials

Cohort studies at national and sub-national levels to follow nutrition status and its association with each type of diabetes and complications

High quality secondary studies (eg., systematic reviews and meta-analyses, umberella reviews)

Box 2 Proposed main topics for the future research in the field of nutrition and diabetes

Personalized nutrition

Studies on children with diabetes

Diabetes complications

GDM

Interations between diet, genetic, gut microbiota

Cost and effect of dietary supplements

Discussion

In general, an increasing trend in nutrition publications in the field of diabetes was observed throughout the recent 5 years. Most publications were on T2DM that was followed by GDM. Papers on diabetes complications and T1DM were on the next ranks. Publications were mostly dedicated to public health studies and clinical trials; and focus on dietary supplements was greater than topics considering whole diet and dietary patterns. In the evidence-based pyramid, most studies were categorized into the level of evidence II.

The present study is an update for the previous roadmap on diabetes in Iran that was conducted in 2015. Due to differences in methodology and search sources, we cannot compare the trend in each type of study. In general, in line with the previous study RCT was the most type of study and a low portion of publications were dedicated to GDM. Although it is expected that roadmap studies are taken into account for the determination of research priorities, in most cases regardless to such studies research projects are designed. There was a fluctuation in the numbers of publications through up to 2015. However, between 2015 and 2019 except a reduction in 2017 an increase trend was observed during last five years. An increasing trend in publications in this field may be due to more attention to the roles of nutrition for prevention and management of diabetes.

One of research gap in the field of nutrition and diabetes is low portion of basic studies. These types of studies can clarify mechanisms, novel facts, and the safety of nutritional interventions. Collaborations of researchers with various fields can expand these types of studies and open windows to new and effective approaches such as developing novel dietary supplements and food products to prevent or manage diabetes. Another research gap is related to the roles of genetic in nutritional topics. Personalized nutrition (PM) is a hot topic to improve health and manage diseases including diabetes. PN is derived from this concept that one size cannot fit all. It has been reported that conflicting results in the association between dietary intake and the risk of T2DM risk and glycemic status can be partly justified by differences in genetic and gut microbiota. Exploring and finding interactions among diet, genetic factors, and microbiota may be helpful to use effective approach for each individual [22]. However, due to relatively high expenditure to do such studies, insufficient equipments in some research centers, and low interdisciplinary collaborations, less attention are taken on this topic in Iran.

In addition, we reached a limited number of studies related to food industry. It might show that product-based projects in the field of nutrition and diabetes are at low level. This issue must be considered in research priorities. Maybe joint projects with food industry can be helpful to increase product-based and practical research.

Based on findings, most clinical trials are focused on dietary supplements instead of diet. Assessments of nutrition status, dietary patterns, and dietary habits rather than considering only a single nutrient such as vitamin or mineral can be more helpful to manage diabetes and prevent diabetes complications. Therefore, paying more attention to dietary habits and dietary patterns and suggesting solutions to improve the status of nutrition in a society can be cheaper and more effective than focusing on dietary supplementation. By another words, paying attention to prevention is more valuable than treatment. However, based on papers more publications are focused on patients instead of controlling glycemic status and other cardiometabolic risk factors.

Probiotics, Vitamin D, and omega-3 are the most frequent supplements examined in clinical trials in recent years. As there are systematic review and meta-analysis [23–28] on some parameters related to diabetes, it seems doing further clinical trials on these topics are not needed. Overall, if there is a high quality systematic review and meta-analysis with reliable findings that clarified the effects of a specific diet or a dietary supplement, no more clinical trial on that topic must be conducted and other topics with low evidence should be considered as a priority. Only providing reasonable documents on the novelty of topics regarding the aforementioned dietary supplements can permit additional clinical trials in these fields.

According to findings, low percentage of publication was attributed to diabetes complications. It seems to determine priorities on this topic three main points should be keep in mind. First, the prevalence of each disease/complication at national and sub-national levels. Second, the roles and the power of nutrition science to control each disease/complications. Third, available evidence and requirement for further research. Considering these three points can help us to make a decision on research priority. For instance, based on a systematic review and meta-analysis on diabetes complications, the prevalence of cardiovascular diseases (CVD), diabetic foot ulcer, retinopathy, neuropathy and nephropathy in Iranian patients with T2DM were 33, 3, 36, 38, and 43%, respectively. Due to high prevalence of microvascular complications, it seems most research projects are better focus on this topic [29]. Prospective analysis from nationwide diabetes report in Iran also reported that the proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot, and ischemic heart disease were 21.9, 17.6, 28.0, 6.2, and 23.9%, respectively [30]. However, evidence showed that the roles of nutrition on controlling CVD is more considerable that neuropathy. Therefore, it is not sufficient to pay attention on only the prevalence of a disorder, and in the next step, available evidence and requirements for further studies in the field of nutrition and CVD or other topic should be explored. Considering all this data, experts in nutrition can make a decision on research priorities. Notably, the requirements and priorities can be changed based on disease conditions in each society. Therefore, an update is necessary in reasonable intervals.

Based on our findings, systematic reviews and meta-analyses that are at the top of the evidence-based pyramid attributed to few publications. Although in world accumulating studies are dedicated to summarize findings of previous studies to help clinicians and policy makers to choose effective approaches. Nevertheless the most studies in Iran are clinical trials, low quality in most cases result in bias for making a decision. In the present study, the quality of eligible clinical trials has not been examined. However, based on previous studies most ones did not obtain a minimum score to be categorized as high quality clinical trials. Therefore, conducting high-quality clinical trials are recommended for the future research.

The present study has some limitations that should be addressed. First, as the present study is a part of a larger project, a specific search strategy was not used. Second, Persian databases were not considered. Third, the quality of methodology for available evidence was not examined. Strength points of the present study are as follows: (i) providing a roadmap to manage time and expenditure in research, (ii) clarifying research gaps in the field of nutrition and diabetes, (iii) classifications of publications based on the level of evidence, and (iv) providing a ground for shedding light on the correct pathway ahead.

Conclusion

In general, an increasing trend in nutrition publications in the field of diabetes was observed in the recent 5 years. Publications were mostly dedicated to clinical trials with a focus on dietary supplements. Low portion of studies have been dedicated to children with diabetes, diabetes complications, and GDM. It is suggested to pay more attention to high quality basic research, product-based projects, and interdisciplinary studies in the field of nutrition and diabetes in the future research.

Declarations

Conflict of interest

All authors declared no conflict of interest.