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M ET ABOL I SM CL IN I CA L A N D EX PE RI ME N TA L 6 3 ( 2 0 14 ) 90 3–9 1 1

Available online at www.sciencedirect.com

Metabolism
www.metabolismjournal.com

The effect of Mediterranean diet on the development

of type 2 diabetes mellitus: A meta-analysis of 10
prospective studies and 136,846 participants

Efi Koloverou a , Katherine Esposito b , Dario Giugliano b , Demosthenes Panagiotakos a,⁎

a
School of Health Science and Education, Department of Nutrition and Dietetics, Harokopio University, Athens, Greece
b
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy

A R T I C LE I N FO AB S T R A C T

Article history: Objective. The purpose of this work was to meta-analyze prospective studies that have
Received 16 February 2014 evaluated the effect of a Mediterranean diet on the development of type 2 diabetes.
Accepted 16 April 2014 Materials/Methods. PubMed, Embase and the Cochrane Central Register of Controlled Trials
databases were searched up to 20 November 2013. English language publications were allocated;
Keywords: 17 original research studies (1 clinical trial, 9 prospective and 7 cross-sectional) were identified.
Chronic disease Primary analyses were limited to prospective studies and clinical trials, yielding to a sample of
Diabetes 136,846 participants. A systematic review and a random effects meta-analysis were conducted.
Incidence Results. Higher adherence to the Mediterranean diet was associated with 23% reduced
Dietary pattern risk of developing type 2 diabetes (combined relative risk for upper versus lowest available
Mediterranean centile: 0.77; 95% CI: 0.66, 0.89). Subgroup analyses based on region, health status of
Review participants and number of confounders controlling for, showed similar results. Limitations
Meta-analysis include variations in Mediterranean diet adherence assessment tools, confounders’
adjustment, duration of follow up and number of events with diabetes.
Conclusions. The presented results are of major public health importance, since no
consensus exists concerning the best anti-diabetic diet. Mediterranean diet could, if
appropriately adjusted to reflect local food availability and individual’s needs, constitute a
beneficial nutritional choice for the primary prevention of diabetes.
© 2014 Elsevier Inc. All rights reserved.

1. Introduction
The prevalence of diabetes mellitus has reached an epidemic
level of 340 million people worldwide [1], with type 2 diabetes
dominating and growing incessantly in parallel with obesity [2].
Not without reason, “diabesity” has become a major health
concern, with serious quality of life and economic impact,
stressing the need for immediate actions with effective inter-
ventions. Medical nutrition therapy, physical activity and
education have an important contribution to the general
management of a patient with diabetes [3]. Weight loss is part
of the initial treatment as most patients are overweight [4]. In
addition, specific foods and nutrients have been identified to
exert a protective [5] or aggravating [6] effect on type 2 diabetes

Abbreviations: DM, Diabetes mellitus; BMI, Body Mass Index; WC, Waist Circumference; WHR, Waist to Hip Ratio; MetS, Metabolic
syndrome; CVD, Cardiovascular disease; MI, Myocardial infarction; TC, Total cholesterol; CHD, Coronary heart disease; SBP, Systolic blood
pressure; DBP, Diastolic blood pressure; MET, Maximum exercise tolerance; FSG, Fasting serum glucose; MDS, Mediterranean diet score;
MD, Mediterranean Diet; PA, Physical activity; TEI, Total energy intake.
⁎ Corresponding author at: 46 Paleon Polemiston St., Glyfada, Attica, 166 74, Greece. Tel.: +30 210 9603116; fax: + 30 210 9600719.
E-mail address: d.b.panagiotakos@usa.net (D. Panagiotakos).

http://dx.doi.org/10.1016/j.metabol.2014.04.010
0026-0495/© 2014 Elsevier Inc. All rights reserved.
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904 M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 3 ( 2 0 14 ) 90 3–9 11
mellitus. The past years, scientific research in nutrition and
health has focused on the holistic dietary patterns approach,
instead of the evaluation of single foods or nutrients. This was,
mainly, because it was understood that foods might have
synergistic or antagonistic (competing) properties that may
alter the true food–health relationship. Moreover, in the real
world individuals consume a variety of foods, in different
combinations, and therefore the approach of single food or
nutrient does not reflect the reality [7]. Based on this holistic
approach, many dietary patterns have been suggested and some
of them seem to play a role in the prevention and/or
management of various chronic diseases [8,9]. One of the most
studied patterns is the Mediterranean diet, initially introduced
by Ancel Keys of the Seven Countries Study, in the late 1970’s
[10]. However, defining and measuring the Mediterranean diet
can be challenging, since various Mediterranean-style tools
have been proposed, which revolve similar dietary components
[11]. Overall, Mediterranean-type diets share some common
characteristics, i.e., basically, high consumption of olive oil,
legumes, whole grain cereals, fruits and vegetables and
moderate wine drinking, and, secondarily, moderate consump-
tion of fish, dairy products and low consumption of poultry,
meat and its products, highly processed foods, refined grains
and sugars [12]. Recently, in 2010, Mediterranean diet was
recognized by UNESCO as a cultural heritage of Humanity,
incorporating other aspects, such as conviviality, socialization,
biodiversity and seasonability, in its definition [13]. Therefore,
beyond food per se, other components of the dietary pattern
Articles identified through
literature research, n=410
Articles retrieved for
more detailed
evaluation, n=28
Articles eligible for inclusion in the metanalysis, n=17
Articles included in the analysis, n=16 (10 prospective studies
extracted)
Articles that did not provide the data in the form required for the
analysis, n=1
Fig. 1 – Process of studies’ selection for the meta-analysis.
may be important. Mediterranean diet has been related to
various health outcomes, for example coronary heart disease
[14], hypertension, dyslipidemia, obesity [15], cognitive impaire-
ment [16],metabolic syndrome and its components [17,18],
i.e., waist circumference > 102 cm for men or >88 cm for
women; triglyceride level > 150 mg/dL; HDL cholesterol
level <40 mg/dL for men or <50 mg/dL for women; blood
pressure >130/85 mm Hg; or fasting plasma glucose >110 mg/dL
[19]). It has also been suggested to have a beneficial effect in the
primary prevention of diabetes [20–22], but results have not been
consistent [23,24]. To the best of our knowledge no previous
systematic work exists regarding the relationship of the Mediter-
ranean dietary pattern to the onset of type 2 diabetes.
Thus, the aim of this work was to perform a systematic
review and a meta-analysis of the findings of published
original research studies that have evaluated the effect of a
Mediterranean type diet on the development of type 2
diabetes among healthy adults and identify potential inter-
actions, depending on studies’ methodological differences.
2. Methods
2.1. Data sources and searches
Internet searches in PubMed, Embase and the Cochrane Central
Register of Controlled Trials databases up to 20 November 2013,
using a search strategy that included the following keywords:
Articles excluded (n=382)
Title/abstract (n=296)
Reviews and metanalyses (n=73)
In language other than English (n=13)
Articles excluded (n=11)
Reasons for exclusion
Other outcome (n=4)
Mixed outcome (n=1)
Single food or nutrient (n=4)
Not obtainable data (n=1)
Commentaries (n=1)
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Weight Country
Author RR (95% CI) Events
(%) of origin

Martinez – Gonzalez et al. [21] 0.17 (0.04, 0.72) 0.31 33 Spain

Salas- Salvado et al. [20] 0.48 (0.27, 0.86) 8.02 54 Spain
Mozaffarian et al. [22] 0.65 (0.49, 0.85) 12.11 998 Italy
de Koning et al. [30] 0.75 (0.66, 0.86) 15.30 2795 USA
Tobias et al. [29] 0.76 (0.55, 1.05) 9.46 491 USA
Rossi et al. [28] 0.88 (0.78, 0.99) 15.12 2330 Greece
Romaguera et al. [31] 0.88 (0.79, 0.97) 15.65 11994 Europe
Brunner et al. [25] 1.04 (0.75, 1.43) 6.82 410 UK
Abiemo et al. [23] 1.09 (0.80, 1.49) 6.70 412 USA
Cabrera de Leon et al. [24] 1.10 (0.70, 1.70) 4.00 146 Spain
Combined 0.77 (0.66, 0.89) 100.00

Relative Risk 1

Fig. 2 – Forest plot of prospective studies that evaluated the effect of Mediterranean diet on the development of type 2 diabetes
mellitus [squares represent individual study’s effect size, i.e., RR and diamond represent the combined effect size; extended
lines show 95% confidence intervals (CI) of RR].

“diabetes”, “Mediterranean diet”, “incidence”, “development”
and other relevant keywords to identify original research
studies related to the aim of the paper, were performed.
References from the extracted articles and reviews were also
used, to complete the data bank. The relevance of studies was
performed using a hierarchical approach based on title,
abstract, and the full manuscript. In case the full article was
not accessible, it was requested from the corresponding author.
2.2. Study selection
Studies that evaluated the association of adhering to a Mediter-
ranean type of diet [12] and development of type 2 diabetes were
selected. Exclusion criteria included absence of control group
and lack of randomization for the clinical trials, single food or
nutrients’ effect assessment, results not obtainable from the
authors that were necessary for the meta-analysis, studies that
identified a-posteriori dietary patterns and claimed to be similar
to the Mediterranean diet, but with no inclusion of the
components of the traditional diet, and especially olive oil
(only the study by Brunner et al., [25] which a-posteriori
identified a pattern which was very similar to the traditional
Mediterranean diet, was included in the meta-analysis), and
finally papers not published in English language. Two indepen-
dent authors (EK, DP) collected the relevant papers, whereas two
other authors independently reviewed the literature (DG, KE);
disagreements were solved by consensus and by the opinion of a
fifth evaluator (CK), when necessary.
2.3. Data extraction and quality assessment
The outcome of interest was the development of type 2 diabetes
[26]. The following characteristics were extracted from the
original papers, in duplicate, using a standardized data
extraction form: design of the study (clinical-trial, cross-
sectional, case-control or prospective cohort), lead author
(for citation purposes), year of publication, country of origin,
sample size, data to estimate uncertainty (i.e., number of events
with diabetes), follow-up duration, effect size measurements
(i.e., relative risks, odds ratios, b-coefficients and their
corresponding 95% confidence intervals) and variables that
entered into the model as potential confounding factors. The
quality of the studies was evaluated according to the
adjustment for potential mediators (e.g., demographic,
anthropometric and traditional risk factors).
2.4. Data synthesis and analysis
Taking into consideration that cross-sectional studies are
mainly for hypothesis generation, but have little validity for
making causal inference, particularly for a risk factor as
changeable as diet and a disease as behaviour-altering as
diabetes, studies were handled separately based on their design.
Therefore, the primary analysis included only prospective
studies and clinical trials, whereas, secondary analysis, based
on the results of cross-sectional studies was also performed.
The statistical measure of interest for the prospective studies
was the hazard ratio (HR) or relative risk (RR) (according to what
each study has estimated) of development of type 2 diabetes
mellitus with their corresponding 95% CI. Estimates of the
aforementioned effect size measures of each study were
weighted by the inverse of their variances to obtain the
combined (pooled) estimate (Fig. 1). Uncertainty was accounted
for, through the number of diabetes events. In order to detect
possible heterogeneity in results across studies, Cochran’s Q test
and the inconsistency index I2 were calculated [27]. Since
heterogeneity existed among prospective studies (Cochran’s
Q = 21.53, df = 10, pQ = 0.01 and I2 = 58%), the random-effects
model was used to construct the combined confidence interval,
which considers both within and between studies variations. In
order to explore the source of heterogeneity across study's
characteristics, subgroup analyses were performed based on:
region of origin of the study’s reference population (i.e., European
or not), health status of the participants (at high CVD/diabetes
risk or not) and level of adjustment made. Specifically, based on
the number and importance of covariates, minimally adjusted
models were subjectively considered those accounted only for
age and sex [24], more adjusted models those additionally
accounted for energy or body mass index (BMI), physical activity
and family history of diabetes [20,22,28–30], whereas fully-
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adjusted models were those which included also smoking and
socioeconomic status (education or income) [21,23,25,31]. To
further explore the heterogeneity according to the aforemen-
tioned subgroups (i.e., region of origin, health status of the
participants and level of adjustment made) random-effects
meta-regression was applied including also as covariate the
sample size of each study. The validity of the random-effects
model was tested by sensitivity analysis, using the influence of
each study on the estimated regression coefficients, by
removing one study at a time as well as the calculation of
Cook’s distance to detect possible outliers (Cook’s d > 0.22 was
used to identify studies responsible for non normality of the
residuals). Publication bias was evaluated by plotting a funnel
plot of the effect size on the horizontal axis and standard error
on the vertical axis (Fig. 4). The present meta-analysis was
performed according to the most current standards of quality
for meta-analysis using the MOOSE guidelines, while for the one
clinical trial included the PRISMA guidelines were also taken
into consideration [32,33]. For the meta-analysis of cross-
sectional studies the combined effect was pooled using the
reported Odds Ratios (OR) and their corresponding 95% CI, using
fixed-effects model, since no heterogeneity was evident
(i.e., pQ = 0.27 and I2 = 22%) (see Appendix).
2.5. Statistical software
All statistical calculations were performed using a trial version
of STATA software version 12.0 (College Station, TX, USA);

Fig. 3 – Forest plots of studies that evaluated the effect of Mediterranean diet on the development of type 2 diabetes mellitus, by
participant’s health profile, level of adjustment for confounders and region of origin [squares represent individual study’s effect
size, i.e., Relative Risk and diamond represent the combined effect size; extended lines show 95% confidence intervals (CI) of RR].
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meta-analysis was performed using the metan command, meta-
regression using the metareg command with the eform option
and the funnel plot was derived using the funnel command.
3. Results
3.1. Studies' characteristics
The primary internet search resulted in 410 papers that were
scanned to ensure they were consistent to the search criteria.
Of them, 296 were excluded on the basis of the title or abstract
(i.e., irrelevant research hypothesis studied), 73 were reviews
or meta-analyses of other studies and 13 were in language
other than English. Of the remaining 28 articles, four were
excluded because their outcome was not the development of
type 2 diabetes (e.g., development of impaired fasting glucose,
mortality and improvement in metabolic syndrome compo-
nents), one because it had mixed outcome (e.g., diabetes with
cardiovascular events and death and no specific data on
diabetes were available), four focused on single food or
nutrients, one was not accessible and one was a commentary
on another paper. Thus, and after excluding one additional
paper that did not provide data, 16 papers (with 17 studies) were
extracted. From those studies, one was clinical trial [20] and 16
were observational (9 were prospective [21–25,28–31] and 7 were
cross sectional [15,34–38]). In brief, of the 17 studies, 3 were
carried out in the United States, 8 in Spain, 2 in Greece, 1 in Italy,
1 in UK, 1 in Cyprus and 1 was a pan-European project that
included 8 countries as part of the EPIC study. Sample sizes
varied between n = 120 and n = 27,792 participants yielding a
total sample of n = 136,846 individuals for the prospective
studies and the one clinical trial and n = 22,341 for the cross-
sectional studies. Mediterranean diet was evaluated differently
across studies. A diet index driven method was used in most
Fig. 3 (continued).
907
cases, except for the study of Brunner et al. [25], where a-
posteriori analysis was conducted and the trial of Salas Salvado
et al. [20], where a 14-item MedDiet score was used only for
baseline assessment of the adherence to a Mediterranean diet
and the primary results (used in this meta-analysis) were
based on the comparison among the three groups. The rest of
the studies used 5 different diet scores, i.e., MDS [21,24,28],
rMED [31], aMED [29,30], MeDiet [23] and a 15-item question-
naire [22]. Fruits, vegetables, olive oil and fish intake, were
components in all scores. Grains, nuts and legumes were
included in almost all scores, by the exception of one study
[22]. Fat quality was differently evaluated: through meat,
dairy products and olive oil intake, or counted in the
monounsaturated/saturated fat ratio. Frequency (servings/
day or week) or quantity (g) was used to quantify consump-
tion. The characteristics of all studies are shown in Supple-
mentary Table 1, available in an online appendix.
For prospective studies the length of the follow up ranged
from 3.5 to 14 years. Adjustments differed across studies, but in
most of them all known potential confounders, such as age, sex,
BMI, physical activity, smoking, socioeconomic status, were
taken into consideration in multi-adjusted models. Individual
effect estimates for the highest versus the lowest centile of the
diet score used (i.e., reflecting better versus worst compliance
with Mediterranean diet) (Supplementary Table 1).
3.2. Mediterranean diet and type 2 diabetes mellitus
In the present meta-analysis 10 entries representing the 10
prospective studies (9 prospective and 1 clinical trial), were
considered for the primary analysis. The combined effect
suggests a significant 23% reduction in the risk of developing
type 2 diabetes mellitus for the highest versus the lowest centile
of the score used to evaluate adherence to the Mediterranean
diet (combined effect, RR = 0.77; 95% CI: 0.66, 0.89) (Fig. 2).
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3.3. Subgroup analyses
However, as reported, heterogeneity was observed when ana-
lyzing the data. Thus, subgroup analyses were performed to
explore the source of heterogeneity across: (a) region of origin of
the studied sample, (b) participants’ health profile and (c) number
of confounders included in the analysis. After stratification by
region of origin, the effect of Mediterranean diet was similar for
the studies that included only European populations (RR = 0.74;
95% CI: 0.58, 0.91; pQ < 0.001, I2 =78.8%), as well as for studies that
included non-European populations (RR = 0.81; 95% CI: 0.65, 0.97,
pQ = 0.178 and I2 = 42.1%). Further analysis was performed
according to participants' health status. Studies that en-
rolled participants with prior gestational diabetes, or partic-
ipants at high risk for cardiovascular disease and/or
diabetes, reported that adherence to a Mediterranean
diet was inversely associated with diabetes development
(RR = 0.65; 95% CI: 0.51, 0.78; pQ = 0.365 and I 2 = 0.80%);
similarly, studies that included apparently healthy partici-
pants confirmed this inverse association (RR = 0.83; 95% CI:
0.70, 0.96; pQ = 0.001 and I 2 = 74.7%). Finally, the analysis was
stratified by studies’ level of adjustment for potential con-
founders. Only one study was considered “minimally adjust-
ed” [20], which reported a positive association between
Mediterranean diet and diabetes (RR = 1.10, 95% CI 0.70, 1.70).
However, both “more-adjusted” [24,25,28–30] and “fully-adjusted”
studies [20,21,23,31] reported a protective effect (RR = 0.79; 95% CI:
0.69, 0.90; pQ = 0.10 and I2 = 49%, and RR = 0.73; 95% CI: 0.43, 1.04;
pQ = 0.01 and I2 = 74%, respectively) (Fig. 3).
3.4. Meta-regression
There were no significant differences in the subgroup analyses
according to the region of origin (p = 0.88) and the level of
adjustment made (p = 0.71), although there was evidence for a
difference between the effect size measure derived from cohorts
that included individuals at-high-risk and apparently healthy
participants (p = 0.014), a fact that supports the finding from the
sub-group analysis. The sample size of the included cohorts did
not significantly affect the regression estimates (p > 0.90).
3.5. Sensitivity analysis
The results of the sensitivity analysis confirmed the stability
of the previous findings. In particular, the combined effect
ranged from RR = 0.77; 95% CI 0.59, 0.96 (after excluding the
study by Mozaffarian et al. [22]) to RR = 0.76; 95% CI 0.57, 0.96
(after excluding the study by de Koning et al. [30] or the study
by Brunner et al [25]). Moreover, none of the above sensitivity
analyses shifted the meta-analysis towards homogeneity
(p for heterogeneity was still < 0.05 in all models). Finally, the
funnel plot was substantially asymmetric and therefore,
publication bias may exist (Fig. 4).
As far as the cross-sectional studies are concerned, the 6
entries representing the 7 cross-sectional studies (the two
studies of Ortega et al., were firstly pooled together, then the
single estimate was re-introduced in the program and meta-
analyzed with the rest 5 studies) which examined the
association between Mediterranean dietary pattern and
history of type 2 diabetes, were analyzed. The combined
effect indicates a significant 8% reduction in the likelihood of
having diabetes mellitus for the highest versus the lowest
centile of the score (combined effect, OR = 0.91; 95% CI: 0.88,
0.95) (see Appendix). As mentioned above, no heterogeneity
was observed among cross-sectional studies.
4. Discussion
In the present meta-analysis a total sample of 136,846
individuals, from various regions of the world, which partici-
pated in 9 prospective studies and 1 randomized clinical trial,
was studied. A beneficial effect of greater adherence to the
Mediterranean diet on the development of type 2 diabetes was
evident, irrespective of region of origin and the level of
adjustment; but seemed to be more prominent among partic-
ipants with prior gestational diabetes, or participants at high
risk for cardiovascular disease and/or diabetes, according to the
following meta-regression analysis followed on. This work adds
to the current scientific knowledge a new direction towards
diabetes prevention even though evidence exists on assess-
ment of a variety of dietary patterns on the incidence of type 2
diabetes [9]. With regards to Mediterranean diet per se, it has
been well-studied for other chronic diseases, like CVD, the
metabolic syndrome [18], cognitive impairment [16], but results
regarding its effect against diabetes have not been consistently
supportive [20,23,25,29]. The aforementioned findings, and
under the power of a meta-analysis, could reinforce current
scientific knowledge and supplement existing guidelines for the
prevention of diabetes at the population level, if taken into
account by public health authorities.
The finding that Mediterranean diet was beneficial against
the development of diabetes may have a biological explana-
tion. At first, the antioxidant profile of the diet may suspend
oxidative stress accumulation, which has been reported to
mediate the development of insulin resistance and b-cell
dysfunction [39]. In addition, magnesium-rich foods, such as
vegetables, nuts and legumes can prevent a magnesium
deficiency. It was found that decreased intracellular enzy-
matic activity, attributed to magnesium deficiency, might
favor insulin resistance [40], while extracellular magnesium is
also needed to prevent a rise in intracellular calcium
concentration, which impairs insulin signaling as well [41].
Another mechanism implicates dietary fiber, particularly those
found in cereal [42,43]. Their beneficial properties could derive
from high magnesium concentrations (bran) or delayed gastric
emptying rate, which slows down digestion and glucose
absorption and reduces plasma insulin levels [44]. Moreover,
moderate alcohol consumption has been associated with
enhanced insulin sensitivity, possibly through adiponectin or
HDL cholesterol [45], whereas resveratrol, a phytophenol
primarily found in wine, has also been implicated in insulin
signaling amelioration [46]. Last but not least, it has been
suggested that Mediterranean diet may protect, contributing to
weight control [47], which is crucial since abdominal fat is a
significant risk factor for type 2 diabetes [48]. Being obese leads
to increased release of non-esterified fatty acids from visceral
fat, inhibiting insulin-stimulated glucose metabolism in
skeletal muscle and stimulating gluconeogenesis in the liver,
which may aggravate hepatic metabolism. Furthermore, weight
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0.00
0.05
1/SE (RR)
0.10
0.15
0.20
0.20 0.40 0.60 0.80 1.00
Effect Size
Fig. 4 – Funnel plot for the evaluation of publication bias
among prospective studies (the effect measure is on the
horizontal axis and the precision (i.e., 1/standard error (SE) is
on the vertical axis).
loss is associated with a decrease in adipokine level [49], which
adversely affects the insulin-signaling pathway [47]. When
complying to Mediterranean diet, weight control is also to some
extent achieved through food intake regulation, resulting from
higher satiety and satiation, due to dietary fiber [50] and better
fat oxidation due to the high unsaturated/saturated ratio
(i.e., fish, olive oil vs. meat, dairy) [51]. Apart from the last
mechanism, i.e., weight control, which can be achieved by
various dietary patterns, the rest of the mechanisms, which
implicate the antioxidant profile, e.g., fiber, resveratrol, high
unsaturated/saturated fat ratio, can be hardly found, particu-
larly in combination, in other dietary patterns. For example, a
low-fat diet could be very low in fish, nuts and olive oil, whereas
a low-carb diet could be low in fruits, dairy and legumes.
Despite the strengths of the present meta-analysis, het-
erogeneity was not negligible and could be attributed to
various sources, like differences in methodology, duration of
studies or clinical characteristics of patients. Another poten-
tial source of heterogeneity is the variation in assessment of
the Mediterranean diet across studies.
Subgroup analysis revealed that the beneficial effect of
Mediterranean diet was irrelevant of the region of origin of the
study, the number of confounders adjusted for, and was evident
both among healthy and at high cardiovascular or diabetes risk
individuals. With regards to adherence, Mediterranean diet
represents an eating pattern, easy to adopt, tasteful and with
various health benefits, but also with variations across coun-
tries around the Mediterranean basin. Taking into consideration
the aforementioned health benefits, it could be suggested that
health related organizations and institutions may inform
people regarding this pattern and provide choices of available
local foods and products that are close to the Mediterranean
pattern. Replacement of olive oil with another “healthy”
vegetable oil and consumption of available salads and fruits
over red meat and meat products are examples of easy
adjustments, which increase unsaturated/saturated fat ratio,
fiber and antioxidants intake. Chile and Canada have already
909
embraced easy to adopt modifications, which prove that
Mediterranean diet can be a dietary model, adopted from
non-European populations as well [52,53]. Still, it should be
noted that this is a simplified recommendation, since health
benefits may be ascribed to micronutrients, and differences
may exist even within the food per se; for example PREMIDED
trial used and studied extra virgin olive oil against type 2
diabetes [20], but it warrants consideration whether this
finding can be extended to regular olive oil as well.
4.1. Limitations and strengths
1.20 A limitation of the present meta-analysis is that adherence to
the Mediterranean diet was not assessed with a systematic
way across studies, i.e., the same diet index. As mentioned
above, although most of them incorporated all core food
groups of the model, in one study [22] consumption of nuts,
legumes and grains was not accounted for. Furthermore, in
prospective studies follow up varied from 3.5 years to
14 years. Since categories of diet scores varied dramatically
between studies, further standardization was very difficult to
interpret; thus, it was preferred to combine the extreme
categories based on the rational best-to-worst adherence to
the Mediterranean diet. Another issue in these studies is that
adherence to Mediterranean diet may have changed during the
long period of follow up without timely information updates.
Moreover, even if most studies were adjusted for major
confounders (e.g., age, BMI, physical activity, family history of
diabetes), another possible risk factor for type 2 diabetes,
smoking, [54] was not present in all models. Furthermore,
statistical heterogeneity was substantial and generalization
of our results warrants consideration. To the best of our
knowledge so far only one randomized clinical trial has assessed
the role of Mediterranean diet in the development of type 2
diabetes. Since this type of studies is the most robust from a
methodological point of view, it could be suggested that further
research shifted towards this direction should be made in order
to better understand efficacy of Mediterranean diet in detaining
type 2 diabetes onset, as well as evaluate the feasibility and
sustainability of adopting this pattern from other countries.
Finally, publication bias seemed to be evident and therefore the
results of this meta-analysis should be interpreted with some
conscious. However, the present meta-analysis has several
strengths. It was based on a systematic review in the acquisition
of studies, following international standards (i.e., the MOOSE
protocol for observational studies and PRISMA protocol for the
clinical trial) and the data analysis was performed using all up to
date statistical methods. Regarding the observed heterogeneity,
subgroup analyses were performed to further investigate the
source of variation across studies. A sensitivity analysis was also
conducted to eliminate the possibility that one single study was
responsible for results found.
5. Conclusion
Mediterranean dietary pattern seems to have additional benefits
on health, including type 2 diabetes mellitus development. This
result is of considerable public health importance, because this
pattern may be adopted, if appropriately adjusted to reflect local
 Author's personal copy
910 M ET ABOL I SM CL IN I CA L A N D E XP E RI ME N TAL 6 3 ( 2 0 14 ) 90 3–9 11
food availability as well as individual’s preferences, by not only
Mediterranean populations [55]. It is not suggested that
Mediterranean diet is a panacea, but since no consensus exists
on which is the best anti-diabetic diet, Mediterranean dietary
pattern could constitute a beneficial nutritional choice for the
primary prevention of type 2 diabetes.
Authors Contribution
EK: performed literature search, the meta-analysis and wrote
the paper; KE, DG, CK (Dr Christina-Maria Kastorini): critically
reviewed the paper, DBP: guarantor of the work, designed the
meta-analysis, supervised the data-analysis and critically
reviewed the paper.
Funding
No funding was provided.
Conflict of Interest
The authors have no relevant conflict of interest to disclose.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
http://dx.doi.org/10.1016/j.metabol.2014.04.010.
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