Mediterranean diet and diabetic microvascular complications: a systematic review and meta-analysis

Abstract

Background

Diabetic microvascular complications, including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN), contribute significantly to morbidity and healthcare burdens among individuals with diabetes. The Mediterranean diet (MD) has been associated with improved metabolic health, but its role in mitigating microvascular complications remains unclear. This systematic review and meta-analysis aimed to assess the impact of MD adherence on the risk and progression of these complications.

Methods

A comprehensive search of PubMed, Web of Science, Embase, and Scopus was conducted through February 12, 2025 to identify studies evaluating MD adherence and diabetic microvascular complications. Meta-analysis was performed where possible, with effect sizes reported as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Fourteen studies, encompassing 138 to 71,392 participants, were included. Meta-analysis indicated a significant reduction in DR risk among individuals adhering to the MD (HR: 0.69, 95% CI: 0.49–0.97, p = 0.03; OR: 0.32, 95% CI: 0.12–0.82, p = 0.02). A lower likelihood of DN development was observed (HR: 0.85, 95% CI: 0.73–0.99, p = 0.04; OR: 0.49, 95% CI: 0.25–0.96, p = 0.04). However, results for diabetic neuropathy were inconclusive due to study heterogeneity. Sensitivity analyses revealed notable heterogeneity and publication bias was detected in some analyses.

Conclusion

Adherence to the Mediterranean diet is associated with a reduced risk of diabetic nephropathy and retinopathy, supporting its potential as a dietary intervention for diabetes management. However, the evidence for neuropathy remains inconclusive. Future well-controlled randomized trials are needed to strengthen causal inferences and refine clinical recommendations for MD-based interventions in diabetic microvascular complications.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40795-025-01038-w.

Introduction

Retinopathy, nephropathy, and neuropathy are major microvascular complications of diabetes mellitus (DM), contributing to significant morbidity and economic burden. Diabetic retinopathy (DR), the leading cause of blindness among working-age individuals in the western world, affects approximately 22% of patients with DM worldwide [1]. Diabetic kidney disease (DKD) occurs in 40% of individuals with DM and represents the most common cause of end-stage renal disease (ESRD), significantly increasing healthcare costs due to the need for dialysis and kidney transplantation [2]. Diabetic neuropathy (DN) leads to nerve damage, impairing movement, sensation, and organ function, with a reported prevalence ranging from 6 to 51% [3]. These complications impose substantial financial burdens and negatively impact quality of life [4]. Early detection and management are essential to prevent disease progression and reduce associated costs.

The Mediterranean diet (MD) is characterized by a high intake of vegetables, fruits, whole grains, nuts, legumes, and olive oil, along with moderate consumption of fish and low intake of dairy products and red meat. This dietary pattern has been associated with a reduced risk of cardiovascular disease [5]. The MD has been shown to improve glycemic control and reduce insulin resistance, making it a key component of DM management [6]. Adherence to the MD may lower the risk of DR by reducing oxidative stress and inflammation in retinal tissue [7]. Additionally, nephroprotective nutrients in the MD can slow the progression of diabetic nephropathy [8]. In DN, MD components including lycopene may enhance nerve function and reduce neuropathic pain by decreasing systemic inflammation [9]. Thus, the MD provides a range of benefits for managing and potentially mitigating microvascular complications associated with DM while promoting overall health.

Recent systematic reviews have examined the relationship between the MD and DR risk, with all reporting a protective effect [10–13]. However, the association between the MD and other diabetic microvascular complications, such as DKD and DN, remains less explored. Moreover, previous studies did not provide any analysis. This systematic review and meta-analysis aims to identify, summarize, and interpret the existing literature on the relationship between the MD and microvascular complications of DM.

Methods and materials

Registration

This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews and meta-analyses [14]. The protocol for this systematic review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42024506615.

Search strategy

A comprehensive literature search was conducted in PubMed, Web of Science, Embase and Scopus up to February 12, 2025, using keywords such as “Mediterranean diet,” “diabetic nephropathy,” “diabetic neuropathy,” and “diabetic retinopathy.” All identified studies were imported into EndNote 21.2 for screening. Additionally, relevant systematic reviews and meta-analyses were manually searched to identify any additional articles not captured in the electronic search. The search strategy of each database is available in Supplementary Materials.

Inclusion criteria

Studies were included if they met the following criteria:

1. Design: Randomized clinical trials or observational studies with prospective, case–control, or cross-sectional designs.

2. Intervention: Reporting MD adherence.

3. Outcome: Assessing diabetic microvascular complications, including DR, nephropathy, or DN.

Exclusion criteria

The following types of studies were excluded: letters, comments, short communications, reviews, ecological studies, and animal studies. Studies that lacked sufficient information to assess the impact of the MD on diabetic microvascular complications or did not report methods for measuring MD adherence were also excluded. We did not include non-English studies.

Data extraction

A standardized data extraction form was developed. Two independent investigators extracted the following information:

1. Author’s name.

2. Year of publication.

3. Sample size and study design.

4. Country of origin.

5. Patient data (mean age, follow-up duration, and diabetes duration).

6. MD assessment method and score.

7. Outcome and its assessment.

8. Hazard ratio (HR) and odds ratio (OR) with corresponding confidence intervals (CIs) assessing the risk of diabetic microvascular complications in patients with higher adherence to MD or its component compared to those with lower or no adherence.

The extracted data are summarized in Table 1.

Table 1.

Baseline characteristics of the studies

Author (Year)	Disease	Country	Design	Source	Sample Size	Male (%)	Age	Follow-up(years)	Outcome Assessment	Adherence to MD	Diabetes type	Duration of Diabetes	Adjustment/Matched
Aziz (2021) [15]	DKD	Iran	Case-control	Kowsar Diabetes Clinic	210	0	55.37	N/A	urinary ACR ≥ 30 mg/g in a random spot urine sample	food-frequency questionnaire (FFQ)	T2DM	7.58	age, BMI, energy intake, physical activity, diabetes duration, cardiovascular disease history, and type of drug
Ghaemi (2021) [16]	DR, DN, and DKD	Iran	Longitudinal	National Program for Prevention and Control of Diabetes	71392	30.2	T1DM: 50.7, T2DM: 59.9	1-22 months	ICD-10	MEDAS-14	T1DM and T2DM	T1DM: 11.34, T2DM: 10.05	age, sex, type of diabetes, use of statin, duration of diabetes, HbA1c, FPG, hypertension, obesity, smoking, HDL-c, LDL-c, total cholesterol, and TG
Hao-Wen Chen (2024) [17]	DR, DN, and DKD	UK	Cohort	UK Biobank cohort	11267	49	59.47	13.77	ICD-10 and ICD-9	The modified MEDLIFE index	T2DM	N/A	age, sex, education, race, deprivation index, smoking status, baseline cardiovascular diseases, baseline hypertension, medication use for cholesterol, blood pressure or diabetes, and total energy intake, MEDLIFE score or VAT
Jayedi (2019) [18]	DKD	Iran	Case-control	Kowsar Diabetes Clinic	210	0	55.37	N/A	urinary ACR ≥ 30 mg/g in a random spot urine sample	MedDiet Score and DASH Score	T2DM	7,58	BMI, HbA1c, and total energy intake
Moradi (2020) [19]	DKD	Iran	cross-sectional	Alzahra hospital	270	36.2	65.91	N/A	NA	Food Frequency Questionnaire (FFQ)	N/A	N/A	sex, age, physical activity, WC, smoking and drug use, and BMI
Noori (2022) [20]	DKD	Iran	Case-control	Kowsar Diabetes Clinic	210	0	55.37	N/A	urinary ACR ≥ 30 mg/g in a random spot urine sample	Food Frequency Questionnaire (FFQ)	T2DM	7,58	BMI, HbA1C, total energy intake, and diabetes duration.
Qu (2024) [21]	DR, DN, and DKD	UK	Cohort	UK Biobank cohort	33441	48.9	58.36	12.3	ICD-10	The alternate Mediterranean Diet (AMED) score	T2DM	N/A	Age, gender, ethnicity, index of multiple deprivations, WC, alcohol consumption, physical activity, hypertension, family history of diabetes, family history of hypertension, family history of heart disease,family history of stroke , HbA1c , HDL-C, LDL-, IGF, TG , CHOL, use of antihypertensive medication, use of cholesterol-lowering medication or use of diabetes medication
Sala-vila (2016) [22]	DR	Spain	Cohort	(PREDIMED) study	3482	48	67	6	any nonproliferative or proliferative DR, or laser photocoagulation treatment for DR,	Questionnaire validated for the PREDIMED study (13-point score)	T2DM	N/A	age, sex, BMI, intervention group, years after diagnosis of diabetes, use of insulin, use of oral hypoglycemic agents, smoking status, systolic blood pressure, history of hypertension, use of ACE inhibitors or ARB, physical activity, and adherence to the Mediterranean diet (13-point score)
Yang Ao (2024) [23]	DKD	UK	Cohort	UK Biobank	24497	NA	NA	11.3	NA	NA	NA	NA	NA
Ziyu Wang (2024) [24]	DR	China	Case-control	Wenzhou Medical University and Anhui Medical University	138	40	54.5	N/A	Clinical diagnostic and imaging guidelines	Measurement of monounsaturated fatty acid	T2DM	N/A	duration of diabetes and ever insulin therapy
Zúnica‑García (2024) [25, 26]	DN	Spain	Observational study	Endocrinology clinic of a hospital	174	61.5	69.56	N/A	Impaired both Semmes Weinsten 5.07–10 g monoflament test and sensitivity to vibration test	MEDAS-14	T2DM	15.35	NA
Tina Costacou (2018) [27]	DKD	USA	Cohort	The SEARCH cohort study	461	43	20	108 months	Microalbuminuria was defined as a UACR 30–300 mg/mg	a modified Mediterranean diet score for children and adolescents (mKIDMED) index	T1DM	108.1 months for microalbuminuria and 113.1 months for macroalbuminuria	kcal/day, protein intake, smoking status, demographic factors (age, sex, race, parental education), disease factors (disease duration, insulin regimen), systolic bloodpressure and HbA1c
Diaz-Lopez (2015) [28, 29]	DR and DKD	Spain	Cohort	(PREDIMED) study	3614	47.2	67	6	as reported in the medical records	Questionnaire validated for the PREDIMED study	T2DM	N/A	Age, sex, baseline BMI, WC, smoking, physical activity,educational level, hypertension, dyslipidemia, family history of premature coronary heart disease, andbaseline adherence to the MedDiet

Abbreviations: DR Diabetic Retinopathy, DN Diabetic Neuropathy, DKD Diabetic Kidney Disease, ACR Albumin-Creatinine Ratio, DASH Dietary Approaches to Stop Hypertension, AMED Alternate Mediterranean Diet, MEDAS Mediterranean Diet Adherence Screener, T1DM Type 1 Diabetes Mellitus, T2DM Type 2 Diabetes Mellitus, PREDIMED Prevención con Dieta Mediterránea, BMI Body Mass Index, WC Waist Circumference, TG Triglycerides, HDL-C High-Density Lipoprotein Cholesterol, LDL-C Low-Density Lipoprotein Cholesterol, CHOL Total Cholesterol, FPG Fasting Plasma Glucose, BUN Blood Urea Nitrogen, GFR Glomerular Filtration Rate, ACE Angiotensin-Converting Enzyme, ARB Angiotensin II Receptor Blocker

Study quality assessment

The quality of observational studies was assessed using the Newcastle–Ottawa Scale (NOS). This scale assigns a maximum of nine points per study: four points for participant selection, two points for comparability, and three points for outcome assessment. Only high-quality studies (score: 6–9) were included in the analysis.

Statistical analysis

We pooled the effect sizes assessing the risk of each microvascular complications in patients who were adherent to MD or its components compared to those with lower or no adherence. The natural logarithm (Ln) of effect sizes (HR and OR) and their 95% CIs was calculated. The standard error of the effect size was determined using the Ln of the lower and upper CIs. The pooled Ln of effect sizes and standard errors were then used to compute the overall effect size. The exponentiated HR and OR with their 95% CIs were reported as the final results. A random-effects model was applied to account for both between-study and within-study variability. An I² value greater than 50% and P-value < 0.05 calculated from Cochrane’s Q-test in our analysis indicated substantial heterogeneity. Sensitivity analysis was conducted by sequentially excluding each study from the analysis. Publication bias was assessed using Egger’s test. All statistical analyses were performed using STATA 17. A p-value < 0.05 was considered statistically significant.

Results

Search results

A total of 486 studies were identified from four databases. After removing 234 duplicates, 252 studies remained and were screened based on title and abstract. Of these, 216 studies were excluded for reasons such as the absence of information on diabetic microvascular complications or MD adherence. The remaining 36 studies underwent full-text screening, resulting in the exclusion of an additional 22 studies. Ultimately, 14 studies were included in this systematic review. Figure 1 presents the PRISMA Study Flow Diagram.

Fig. 1.

PRISMA study flow diagram

Study characteristics

The total number of participants in these studies ranged from 138 to 71,392, with the proportion of male participants ranging from 0% to 61.5%. The studies were published between 2016 and 2024 and were conducted in Iran (n = 5), Spain (n = 4), the United Kingdom (UK) (n = 3), China (n = 1), and the United States (USA) (n = 1). The review included six cohort studies, four case–control studies, and one cross-sectional study. Cohort studies followed participants for durations ranging from one month to 13.77 years. The average age of participants ranged from 20 to 69.5 years. Twelve studies assessed patients with T2DM, while three studies included individuals with T1DM. Table 1 presents the baseline characteristics of the included studies.

Assessing the method of MD adherence

In 14 included studies, MD adherence was assessed using several scoring systems. Four studies [15, 18–20] utilized a modified scale from Trichopoulou et al. [30]. The original Alternate Mediterranean Diet Score (AMED) and the Mediterranean Diet Adherence Screener (MEDAS) were used in one study [21] and three studies [16, 25, 26], respectively. Two studies applied the 14-item Prevención con Dieta Mediterránea (PREDIMED) study tool [22, 28]. One study used a 13-point scale [31]. The modified Mediterranean Diet Score for children and adolescents (mKIDMED index) was employed in one study [27]. Additionally, one study assessed monounsaturated fatty acid levels in plasma [24], and another used the modified MEDLIFE index [17].

Diagnosis of diabetic microvascular complication

The outcomes of diabetic complications outcomes were measured in different ways. Three studies were based on a medically confirmed diagnosis of DR by an ophthalmologist [22, 24, 28]. Four studies defined diabetic nephropathy as an albumin-creatinine ratio (ACR) ≥ 30 mg/g in a random urine sample [15, 20, 27, 29]. Two studies used a 5.07–10 g monofilament, a pinprick test, and a 128 Hz tuning fork to examine sensitivity to pressure, pain, and vibration test [25, 26] Three studies used the International Classification of Diseases, Tenth Revision (ICD-10) for diabetic complications [16, 17, 32].

MD and diabetic neuropathy

Four studies, including two observational studies and a longitudinal study, indicated that adherence to the MD may reduce the risk of various types of DN [16, 17, 25, 26]. However, a prospective cohort study found no significant reduction in DN risk associated with MD adherence [32]. Zúnica García et al. reported a significantly lower MEDAS score among patients experiencing a loss of pressure sensitivity (p = 0.047) and vibration (p = 0.021) [25]. Additionally, patients without diabetic peripheral neuropathy (DPN) had a significantly higher mean MEDAS score than those with DN (7.23 ± 1.79 vs. 6.68 ± 1.49; p = 0.047) [25]. Adherence to the MD was significantly associated with altered sensitivity to pressure (OR = 2.9; 95% CI: 1.02–8.22; p = 0.045) [25]. In another study, Zúnica García et al. found a significantly higher risk of diabetic foot ulcers in patients not adherent to the MD (p = 0.030) [26]. A higher MEDAS score was also observed in patients without diabetic foot ulcer risk (p = 0.011) [26]. Ghaemi et al. reported that adherence to the MD significantly reduced the risk of DN in patients with T1DM (OR = 0.32; 95% CI: 0.23–0.43; p < 0.001) and T2DM (OR = 0.68; 95% CI: 0.64–0.72; p < 0.001) [16]. In contrast, Qu et al. found no significant association between an increased risk of DN and high consumption of MD components [32].

MD and diabetic nephropathy

Ten studies have investigated the association between MD and diabetic nephropathy [15–20, 23, 27, 28, 32]. An analysis of cohort studies indicated that patients with higher adherence to MD or its components had a significantly lower risk of diabetic nephropathy compared to those with low adherence (HR: 0.85, 95% CI: 0.73–0.99, p = 0.04, I² = 81.80%, Fig. 2). However, sensitivity analysis demonstrated that the results were not robust (Supplementary Fig. 1). Egger’s test indicated no publication bias (p = 0.916). Additionally, the analysis of other studies yielded similar findings (OR: 0.49, 95% CI: 0.25–0.96, p = 0.04, I² = 93.26, Fig. 3). However, this analysis also revealed significant publication bias (p < 0.001) and unstable results in the sensitivity analysis (Supplementary Fig. 2).

Fig. 2.

Forrest plot assessing the risk of diabetic nephropathy in patients with higher adherence to the Mediterranean diet or its components compared to the reference group with the lowest or no adherence among cohort studies (HR: hazard ratio)

Fig. 3.

Forrest plot assessing the risk of diabetic nephropathy in patients with higher adherence to the Mediterranean diet or its components compared to the reference group with the lowest or no adherence among cross-sectional and case–control studies (OR: odds ratio)

Findings from a systematic review

Qu et al. identified a significant inverse linear relationship between adherence to MD and the risk of diabetic nephropathy [21]. They also reported that adherence to legumes reduced the risk of diabetic nephropathy by 8% and 11% in patients with hyperglycemia and T2DM, respectively. However, no significant associations were observed for other components of MD [21]. In an adjusted model, Noori et al. found that high consumption of grains, legumes, vegetables, fruits, and fish, as the main components of MD, was associated with a significant reduction in the risk of diabetic nephropathy by 64%, 84%, 73%, 82%, and 54%, respectively [20]. Conversely, high meat consumption, which is not recommended in MD, was associated with a significant increase in the risk of diabetic nephropathy [20].

In contrast, three studies reported no significant association between MD and diabetic nephropathy [27, 29, 33] . In a cohort study by Diaz-Lopez et al., no differences were observed in the incidence of diabetic nephropathy between the two MD intervention groups and the control group [29]. Similarly, another cohort study reported no meaningful association between high adherence to MD and a reduced risk of microalbuminuria in patients with T1DM [27]. Moreover, no significant differences in renal function markers, including creatinine, blood urea nitrogen (BUN), and glomerular filtration rate (GFR), were observed among patients with varying levels of adherence to MD [33].

MD and diabetic retinopathy

This review identified six studies that examined the association between MD and DR, including three cohort studies [16, 17, 22, 24, 28, 32]. The analysis of cohort studies demonstrated a significant reduction in DR risk among patients with high adherence to MD and its components compared to the control group (HR: 0.69, 95% CI: 0.49–0.97, p = 0.03, I² = 51.01; Fig. 4). Moreover, the analysis of other studies revealed similar findings (OR: 0.32, 95% CI: 0.12–0.82, p = 0.02, I² = 96.37%; Fig. 5). However, both analyses showed inconsistent sensitivity results (Supplementary Figs. 3 and 4) and significant publication bias (p = 0.044, p = 0.0002).

Fig. 4.

Forrest plot assessing the risk of diabetic retinopathy in patients with higher adherence to the Mediterranean diet or its components compared to the reference group with the lowest or no adherence among cohort studies (HR: hazard ratio)

Fig. 5.

Forrest plot assessing the risk of diabetic retinopathy in patients with higher adherence to the Mediterranean diet or its components compared to the reference group with the lowest or no adherence among cross-sectional and case–control studies (OR: odds ratio)

Findings from the systematic review

Wang et al. reported a significant inverse association between plasma levels of five monounsaturated fatty acid (MUFA)s and the risk of DR, identifying oleic acid (OA) as the strongest predictor of DR among patients with T2DM [24]. Additionally, they observed a nonlinear inverse relationship between plasma OA and DR risk [24]. Similarly, Qu et al. demonstrated a 29% reduction in DR risk with a higher MUFA: Saturated fatty acids (SFA) ratio in patients with hyperglycemia. However, no significant association was found between MD and its main components and DR risk [21].

Quality of the studies

Quality assessment of included studies has been provided in Supplementary Materials. All studies provided an overall NOS score ranging from 7 to 9. However, the study of Ao et al. has not been assessed due to unavailable full-text [23].

Discussion

This systematic review summarized 14 studies examining the association between adherence to the MD and the risk of diabetic microvascular complications. Evidence regarding the relationship between MD adherence and DN remained inconclusive. However, findings from systematic review and meta-analyses indicate that adherence to the MD and its components significantly reduces the risk of diabetic nephropathy and retinopathy. However, these results are affected by significant publication bias and a non-robust sensitivity analysis. Additionally, some included studies did not report significant findings for retinopathy and nephropathy.

Diabetic microvascular complications affect a wide range of patients with DM depending on the population and are responsible for morbidity and healthcare costs related to DM. The MD has been found to reduce the risk of several common diseases such as cardiovascular diseases, certain cancers, and neurodegenerative diseases [5, 34, 35]. High adherence to MD is associated with improved glycemic control, lower oxidative stress, and lower inflammation, which may help reduce the progression of DR, nephropathy, and DN through multiple biochemical pathways [6]. One key mechanism is its enhancement of endothelial function, largely mediated by increased nitric oxide (NO) bioavailability [36]. NO plays a crucial role in maintaining vascular homeostasis by promoting vasodilation and reducing oxidative stress [37]. MD components, such as polyphenols found in olive oil and flavonoids in fruits and vegetables, contribute to NO production, thereby improving endothelial integrity and reducing vascular damage [38, 39]. Epigenetic regulation also plays a significant role in MD’s protective effects. Bioactive compounds in MD, such as resveratrol and omega-3 fatty acids, influence gene expression through histone modifications and DNA methylation, which can down-regulate pro-inflammatory pathways linked to microvascular damage [40, 41]. Another emerging mechanism is MD’s role in gut microbiota modulation. Dysbiosis, or an imbalance in gut microbiota, is increasingly recognized as a contributor to diabetic complications [42]. High-fiber components of MD, including legumes foster a beneficial gut microbiome composition that enhances short-chain fatty acid production, reduces systemic inflammation, and improves insulin sensitivity [43]. These mechanisms explain how MD can be involved in the management of microvascular complications.

Studies on the effects of the MD on DN were inconclusive. This can be attributed to several factors. One major limitation is the variability in study designs, population characteristics, a limited number of included studies, and methods used to assess DN. These prevented us from performing a meta-analysis and reporting an overall finding. Some studies reported a protective effect of MD, particularly in improving sensitivity to pressure and reducing neuropathic pain [25, 26], while others failed to find significant associations [32]. The lack of standardized diagnostic criteria for DN across studies may have contributed to inconsistent results. Additionally, confounding factors such as physical activity levels, medication use, and comorbid conditions were not consistently controlled, potentially influencing outcomes.

Potential mechanisms underlying the protective effects of the MD in DN include improved glycemic control, reduced inflammation, and enhanced lipid profile regulation. DPN is associated with elevated inflammatory biomarkers [44]. Omega-3 fatty acid supplementation modulates cellular signaling and generates anti-inflammatory mediators, potentially mitigating nerve damage linked to DN [35]. Individuals with severe DN exhibit lipid profile alterations indicative of impaired energy metabolism [45]. These findings suggest that lipid profiles may serve as biomarkers for metabolic dysfunction contributing to DN [45]. Given the complex pathophysiology of DN, further high-quality longitudinal studies are required to elucidate the potential benefits of MD and its components in reducing DN risk.

Seven of the ten included studies and analyses demonstrated that high adherence to the MD significantly reduces the risk of diabetic nephropathy progression. MD and its components influence diabetic nephropathy through various mechanisms. MD reduces the accumulation of advanced glycation end products (AGEs), which exacerbate diabetic complications by inducing inflammation and oxidative stress [46, 47]. Additionally, MD lowers systolic and diastolic blood pressure and improves insulin sensitivity, both of which contribute to diabetic microvascular complications, particularly diabetic nephropathy [6, 48].

Previous systematic reviews have reported the protective effect of MD on DR [11–13, 49]. Consistent with these findings, our analysis showed that adherence to MD significantly reduces the risk of DR. Moreover, findings from the systematic review highlighted the role of MUFAs and long chain ω−3 polyunsaturated fatty acids on the risk of vision-threatening retinopathy [24, 31]. Dietary omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against abnormal vascular growth and retinopathy by converting to the metabolite 4-hydroxy-docosahexaenoic acid (4-HDHA), which inhibits pathological vessel proliferation [50]. Furthermore, alpha-linolenic acid (ALA), along with EPA and DHA, alleviates retinal oxidative stress and inflammation, potentially preventing DR [51].

However, some studies reported no significant association between MD and diabetic nephropathy and retinopathy [28, 32, 33]. Moreover, significant publication bias and unstable sensitivity analysis were observed. This should be taken into consider when interpreting the results of this study. Bias and heterogeneity in analyses of DR and nephropathy can arise from various confounding factors, including lifestyle behaviors, medication use, medical history, and socioeconomic status. Variations in medication regimens, such as antihypertensive or lipid-lowering drugs, may introduce inconsistencies in study outcomes. Medical history, including the presence of comorbid conditions like hypertension or cardiovascular disease, further complicates comparisons between study populations. These confounding variables may contribute to heterogeneity across studies, limiting the generalizability of findings and highlighting the need for rigorous adjustments and sensitivity analyses to ensure robust conclusions. Moreover, this study was not able to perform a meta-analysis on the association between MD and DN. Thus, future research should consider standardized methodologies, adjustment of cofounders and longer follow-up to improve the comparability and reliability of findings particularly on DN.

Conclusion

This review highlights the promising role of the MD as a beneficial strategy in diabetes management, particularly in mitigating microvascular complications. Strong evidence suggests that MD adherence is associated with a significant reduction in the risk of diabetic nephropathy and retinopathy. These findings reinforce the potential of MD as a non-pharmacological intervention that can complement standard diabetes treatments, offering patients a practical and sustainable dietary approach to improve long-term health outcomes. However, the translation of these benefits into clinical practice is limited by the predominance of observational studies and significant heterogeneity among studies. Furthermore, the evidence for DN remains inconclusive, necessitating long-term, controlled trials to establish causality. Future research should prioritize randomized clinical trials to determine the direct impact of MD on diabetes progression and microvascular complications, ensuring clearer clinical recommendations for patient management.

Abbreviations

DM

Diabetes Mellitus

MD

Mediterranean Diet

DR

Diabetic Retinopathy

DN

Diabetic Neuropathy

DKD

Diabetic Kidney Disease

ESRD

End-Stage Renal Disease

T1DM

Type 1 Diabetes Mellitus

T2DM

Type 2 Diabetes Mellitus

AGE

Advanced Glycation End Product

NO

Nitric Oxide

HbA1c

Hemoglobin A1c

EPA

Eicosapentaenoic Acid

DHA

Docosahexaenoic Acid

4-HDHA

4-Hydroxy Docosahexaenoic Acid

ALA

Alpha-Linolenic Acid

ICD-10

International Classification of Diseases, Tenth Revision

BMI

Body Mass Index

WC

Waist Circumference

TG

Triglycerides

HDL-C

High-Density Lipoprotein Cholesterol

LDL-C

Low-Density Lipoprotein Cholesterol

CHOL

Total Cholesterol

FPG

Fasting Plasma Glucose

BUN

Blood Urea Nitrogen

GFR

Glomerular Filtration Rate

ACE

Angiotensin-Converting Enzyme

ARB

Angiotensin II Receptor Blocker

ACR

Albumin-Creatinine Ratio

MEDAS

Mediterranean Diet Adherence Screener

PREDIMED

Prevención con Dieta Mediterránea

AMED

Alternate Mediterranean Diet

DASH

Dietary Approaches to Stop Hypertension

Authors’ contributions

DZ and PS contributed in the systematic search and data extraction. DZ, SK and PS contributed in the data interpretation. DZ, SK and PS contributes in manuscript drafting and data interpretation. All authors approved the final manuscript for submission.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study was conducted by the Declaration of Helsinki. Approval was obtained from the Iran University of Medical Sciences Ethics Committee (Approval No. IR.IUMS.REC.2024.123).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.