DIABETES/METABOLISM RESEARCH AND REVIEWS
Diabetes Metab Res Rev 2014; 30(Suppl. 1): 34–40
Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/dmrr.2516
Mediterranean diet and type 2 diabetes
Katherine Esposito1*
Dario Giugliano2
1
Department of Clinical and
Experimental Medicine, Second
University of Naples, Naples, Italy
2
Department of Medical, Surgical,
Neurological, Metabolic Sciences, and
Geriatrics, Second University of
Naples, Naples, Italy
*Correspondence to:
Katherine Esposito, Department of
Clinical and Experimental Medicine,
Second University of Naples, Naples,
Italy.
E-mail: katherine.esposito@unina2.it
Received: 23 October 2013
Accepted: 19 December 2013
Copyright © 2013 John Wiley & Sons, Ltd.
REVIEW ARTICLE
Abstract
Consumption of selected dietary components is favourably associated with
prevention of type 2 diabetes, but discordant results for some foods or single
nutrients continue to appear. The study of complete dietary patterns represents
the most adequate approach to assess the role of diet on the risk of diabetes. The
term ‘Mediterranean diet’ essentially refers to a primarily plant-based dietary
pattern whose greater consumption has been associated with higher survival
for lower all-cause mortality. At least five large prospective studies report a sub-
stantially lower risk of type 2 diabetes in healthy people or at risk patients with
the highest adherence to a Mediterranean diet. Five randomized controlled trials
have evaluated the effects of a Mediterranean diet, as compared with other com-
monly used diets, on glycaemic control in subjects with type 2 diabetes. Improve-
ment of HbA1c levels was greater with a Mediterranean diet and ranged from
0.1% to 0.6% for HbA1c. No trial reported worsening of glycaemic control with
a Mediterranean diet. Although no controlled trial specifically assessed the role
of a Mediterranean diet in reducing cardiovascular events in type 2 diabetes,
there is evidence that post-infarct or high-risk patients, including diabetic
patients, may have cardiovascular benefits from a Mediterranean diet. The
evidence so far accumulated suggests that adopting a Mediterranean diet may
help prevent type 2 diabetes; moreover, a lower carbohydrate, Mediterranean-
style diet seems good for HbA1c reduction in persons with established diabetes.
Copyright © 2013 John Wiley & Sons, Ltd.
Keywords Mediterranean diet; type 2 diabetes; dietary patterns; diabetes pre-
vention; glycaemic control; HbA1c
Introduction
The pandemic of type 2 diabetes is an enormous public health problem, with
552 million cases projected by 2030 worldwide [1]. There is an increasing
awareness for new therapeutic approaches that delay progression to type 2
diabetes in people at increased risk for the disease, including those with im-
paired glucose tolerance or impaired fasting glucose. Lifestyle intervention
studies have demonstrated a reduction of new diabetes ranging from 30% to
67%, which remains after the individual lifestyle counselling was stopped
[2–4]. However, little is known whether lifestyle intervention can also reduce
cardiovascular disease morbidity or mortality. The 20-year follow-up results
from the Chinese Da Qing Study and results of more than 10 years of follow-
up from the Finnish Diabetes Prevention Study showed no statistically signifi-
cant differences in cardiovascular outcomes between the intervention and
Mediterranean Diet, Type 2 Diabetes
control groups [4,5]. Although lifestyle interventions can
prevent type 2 diabetes, current nutritional recommenda-
tions for the primary prevention of type 2 diabetes are
limited, with little that is truly evidence based [6]. Little
emphasis has also been put on lifestyle change, including
diet, in current diabetic algorithms for management of
hyperglycaemia in type 2 diabetes [7].
Diet and prevention of type 2 diabetes
Consumption of selected dietary components, such as
foods or single nutrients, is favourably associated with
prevention of type 2 diabetes. Whole grains, coffee or
tea, low-fat milk and dairy products, moderate alcohol
consumption, fruits and vegetables, pulses, and nuts (in
women only) are associated with a decreased risk of type
2 diabetes [8]. As far as single nutrients are concerned,
moderate evidence from several prospective observational
studies or meta-analysis indicate a protective role for
cereal fibre and unsaturated fatty acids [8]. Although
selected micronutrients may affect glucose and insulin
metabolism, to date there, is no convincing evidence that
documents their role in the development of diabetes [9].
Moreover, discordant results continue to appear for whole
grains [10], fruit and vegetables [11] and fish [12]. In the
case of fruit and vegetable, for example, this may, in part,
be due to the effect of measurement error in the
assessment of their consumption on the association with
diabetes, as food frequency questionnaires are known to
overestimate fruit and vegetable consumption [13]. A
recent systematic review and meta-analysis [14] demon-
strated a small, protective effect of fruit and vegetable
consumption on incidence of type 2 diabetes; however,
the evidence was limited to only leafy vegetables, mostly
in women, and in four trials only, with 7422 cases out of
169 807 non-cases. By contrast, fruit was better than
vegetable in reducing diabetes risk in the European
Prospective Investigation of Cancer study during 12 years
of follow-up [15].
Dietary patterns
Dietary-patterning analysis has been increasingly used as
an alternative method to traditional single nutrient analy-
sis because it can assess cumulative effects of the overall
diet. The use of dietary patterns avoids focusing on single
foods or nutrients that can be correlated with, or interact
with, each other and assesses combinations of food which
alone may have effects too small to be identified. Thus,
the assessment of whole dietary patterns has become
instrumental in nutritional epidemiology, even because
Copyright © 2013 John Wiley & Sons, Ltd.
35
synergistic or antagonistic effects may exist between the
different components of a food pattern [16].
Three main approaches have been used to define
dietary patterns: factor analysis, cluster analysis and die-
tary indices [17]. The predominant a posteriori methods
are factor and cluster analyses which identify the major
dietary patterns independently of their relevance to
disease. The a priori approach is used to describe the ideal
diet for disease prevention based on available evidence of
the disease. Therefore, a diet score is obtained by
summing up foods considered to be important for a spe-
cific disease. Scores take into account both the quantity
and quality of food, whereas assessment of nutrient intake
cancels most dietary confounding by incorporating
possible nutritional confounders in the score, and capture
possible effect modification among nutritional variables
through the same process. More important than isolated
foods or nutrients, the study of complete dietary patterns
represents the most adequate approach to assess the role
of diet on the risk of diabetes.
Mediterranean diet
The term ‘Mediterranean diet’ essentially refers to a
primarily plant-based diet whose greater consumption
has been associated with higher survival for lower all-
cause mortality [18,19]. The Mediterranean diet was
first described in the 1960s by Ancel Keys, based on his
observation of food habits of some populations in the
Mediterranean region [20]: the traditional dietary
patterns typical of Crete, much of the rest of Greece,
and southern Italy in the early 1960s were considered
to be largely responsible for the good health observed
in these regions. There is no single Mediterranean diet,
as more than 20 countries have a coastline in the
Mediterranean basin; moreover, social, political, religious
and economic differences introduce variations to the
Mediterranean diet both between and within these coun-
tries. Despite this, a high consumption of foods of vegetable
origin, such as cereals and whole grains, fruits, vegetables,
legumes, nuts; olive oil as the principal source of fat; fish
and poultry consumed in low-to-moderate amounts; rela-
tively low consumption of red meat; and moderate consump-
tion of wine, normally with meals, could be considered
important characteristics of this dietary pattern [21].
Mediterranean diet and prevention of
type 2 diabetes
A recent systematic review and meta-analysis of pros-
pective studies assessed the effect of dietary patterns,
Diabetes Metab Res Rev 2014; 30(Suppl 1): 34–40.
DOI: 10.1002/dmrr
36
including Mediterranean-style dietary patterns, on pre-
vention of type 2 diabetes [22]. Ten large prospective
studies were identified that used either the a posteriori
or a priori approaches to explore the link between dietary
factors and the risk of type 2 diabetes. The analysis com-
prised 190 301 subjects free of type 2 diabetes at baseline,
followed for a time ranging from 2 to 23 years, and 8932
cases of incident diabetes. Overall, adherence to healthy
dietary pattern was associated with reduced risk of devel-
oping type 2 diabetes: combined mean difference =
0.39, 95% confidence interval (CI) 0.54 to 0.24. A
common characteristic of these ‘preventive’ dietary pat-
terns is their abundant plant food content. Two studies
specifically evaluated the role of Mediterranean diet in
diabetes prevention. In 13 380 Spanish university gradu-
ates without diabetes at baseline followed up for a median
of 4.4 years, participants who adhered closely to a
Mediterranean diet had a 83% lower risk of diabetes com-
pared with those with the lowest adherence score [23].
The Mediterranean score included legumes, grains, fruits
and nuts, vegetables, fish, meat and meat products,
alcohol, milk and dairy products, and ratio of monoun-
saturated to saturated fat. In the large post-infarct
GISSI-Prevenzione trial including 8291 Italian patients
with a recent myocardial infarction followed up for
3.5 years [24], a Mediterranean diet protected against
new diabetes (35% lower risk). The Mediterranean score
was based on consumption of cooked and raw vegetables,
fruit, fish and olive oil.
Not unexpectedly, the characteristics of dietary pat-
terns associated with prevention of type 2 diabetes are
reminiscent of the ‘prudent diet’ containing high amounts
of vegetables, legumes, whole grains, fruit, fish, poultry
and low-fat dairy products [25]. At the opposite, ‘the
Western diet’ characterized by a high consumption of
red meat, processed meat, eggs, refined grains, sweets
and dessert, French fries and high-fat dairy products was
associated with higher risk of developing type 2 diabetes
[22]. Interestingly, the potential protection from diabetes
by a Mediterranean-style diet reported in some cohorts
[23,24] may be considered as anti-inflammatory and
anti-oxidative, principally because of the increased intake
of protective nutrients such as dietary fibre, vitamins and
minerals, as well as antioxidants and polyphenols,
whereas they are also characterized by lower intake of
pro-inflammatory aliments and nutrients, such as satu-
rated and trans fatty acids, refined sugars and starches
and generally, foods that account for excess energy intake
[26]. Supporting this line of thought, a recent meta-
analysis of prospective studies identified two inflamma-
tory markers, that is, interleukin-6 and C-reactive protein,
significantly associated with diabetes, with an increased
risk of 26% for elevated C-reactive protein levels and of
31% for elevated interleukin-6 levels [27].
Copyright © 2013 John Wiley & Sons, Ltd.
K. Esposito and D. Giugliano
Since the publication of our meta-analysis [22], other
studies have addressed the topic of prevention of type 2
diabetes by dietary patterns. In the large prospective
European Prospective Investigation into Cancer and Nutri-
tion study [28], adherence to the Mediterranean dietary
pattern was associated with a small reduction in the risk
of developing type 2 diabetes: in particular, there was a
12% decreased risk among individuals with high adher-
ence to the Mediterranean dietary pattern (score 11–18
points) as compared with individuals with low adherence
(0–6 points). Participants from the Nurses’ Health Study II
with prior gestational diabetes mellitus were followed up
for 15 years: adherence to a Mediterranean diet pattern
was associated with 40% lower risk of type 2 diabetes,
partly attenuated by adjustment for body mass index
[29]. Similarly, men from the Health Professional Fol-
low-Up Study were followed up to 20 years for incidence
of type 2 diabetes: greater adherence to a Mediterranean
diet score was associated with 25% lower incidence of
future diabetes (quintile 5, score 7–9, versus quintile 1,
score 0–2) [30]. On the other hand, several diet-quality
scores, including Dietary Approach to Stop Hypertension
(DASH) and alternate Healthy Eating Index (aHEI) die-
tary patterns, were also associated with a lower risk of
type 2 diabetes [29,30], indicating that healthful dietary
patterns may reflect a common pattern characterized by
high intakes of plant-based foods, such as whole grains,
moderate alcohol, associated with low intakes of red and
processed meat, sodium, sugar-sweetened beverages and
trans fat. Equally important, these dietary patterns,
including Mediterranean diet, may yield the greatest risk
reduction in people with a high body mass index.
Mediterranean diet and glycaemic
control
An inverse association has been found between adherence
to Mediterranean diet and indices of glucose homeostasis
in the general population, including elderly people, and
high-risk patients [31]. Only few studies have specifically
evaluated the association between Mediterranean diet
and glycaemic control in type 2 diabetes. According to a
recent Italian study in 901 outpatients with type 2
diabetes [32], greater adherence to the traditional
Mediterranean diet was associated with lower HbA1c
levels and 2-h post-meal glucose levels independently of
variations in age, adiposity, energy intake, physical
activity and other potential confounders. The differences
between diabetic patients with high adherence to a
Mediterranean-type diet as compared with those with
low adherence were 0.9% for HbA1c (p < 0.001) and
39 mg/dL (p < 0.001) for 2-h glucose. These data were
Diabetes Metab Res Rev 2014; 30(Suppl 1): 34–40.
DOI: 10.1002/dmrr
Mediterranean Diet, Type 2 Diabetes
in part confirmed by a smaller cross-sectional study of 262
individuals with type 2 diabetes participating in a Spanish
trial at single centre [33]: after adjustment for age, sex,
physical activity, smoking, time of evolution of the type
2 diabetes, body mass index and insulin treatment, the
odds ratio for having HbA1c ≥7% was 0.69 (95% CI:
0.17–2.83) for those participants with the highest
adherence to the Mediterranean diet. Although there
was a potential inverse non-significant association
between adherence to Mediterranean diet and HbA1c
levels, it was not statistically significant.
Five randomized controlled trials [34–38] evaluated
the effects of Mediterranean diet, as compared with other
commonly used diets, on glycaemic control in type 2 dia-
betes. In postmenopausal women with type 2 diabetes
(n = 279) randomized to either usual care or compre-
hensive lifestyle self-management program including a
Mediterranean low-saturated fat diet, HbA1c decreased
by about 0.4% (p = 0.001) at 6 months, with no change
in control women [34]. In 772 high-risk persons, includ-
ing 421 (54.5%) diabetic patients, Estruch et al. [35]
evaluated the short-term effects of two Mediterranean
diets (supplemented with either 1 L/week of virgin olive
oil or 30 g/day of tree nuts), compared with a low-fat diet,
and found lower fasting glucose (7 mg/dL) in the
Mediterranean diet groups. In a 2-year trial, Shai et al.
[36] compared three weight-loss diets in 322 moderately
obese subjects; among the 46 participants with diabetes,
there was no difference in HbA1c decrease between the
groups assigned to the Mediterranean diet as compared
with the low-fat diet (mean difference: 0.1%,
p = 0.45), although a significant decrease in fasting
glucose concentration ( 32.8 mg/dL) was found in the
Mediterranean diet group. In a 4-year randomized inter-
ventional trial, the longest study performed up to now,
Esposito et al. [37] assigned a total of 215 patients with
newly diagnosed type 2 diabetes to follow-up, with 108
in the Mediterranean diet group and 107 on the low-fat
diet. The Mediterranean diet has a carbohydrate content
of less than 50% of daily energy and 30% of calories from
fat. Ten patients in each group were lost to follow-up. At
year 1, HbA1c levels were lower in the Mediterranean diet
group than the low-fat diet group (difference: 0.6%, 95%
CI 0.9–0.3%). Lastly, in a 12-month trial, comparative
study of low-carbohydrate Mediterranean diet versus the
American Diabetes Association (ADA) diet in 259 over-
weight diabetic patients type 2 diabetic patients on stable
anti-hyperglycaemic drug therapy, Elhayany et al. [38]
found a significantly greater reduction in HbA1c level
(0.4%, p = 0.02) in those allocated to the Mediterranean
diet with a lower carbohydrate content.
A recent systematic review evaluating the literature
published since 2001 until 2010 [39] found no advantage
in using the Mediterranean-style eating pattern compared
Copyright © 2013 John Wiley & Sons, Ltd.
37
with other eating patterns for glycaemic control. This
summary statement, however, was based on imperfect
reporting of published data and was also missing
reporting of published studies [40]. The evidence so far
accumulated from the long-term (from 12 to 48 months)
randomized controlled trials suggests that adopting a
Mediterranean diet may improve glycaemic control and
cardiovascular risk in individuals with established diabe-
tes [41]. Another systematic review with meta-analysis
included 21 randomized controlled trials with inter-
ventions lasting 6 or more months and compared low
carbohydrate, vegetarian, vegan, low glycaemic index,
high fibre, Mediterranean and high protein diets with con-
trol diets in type 2 diabetes [42]. The low carbohydrate,
low glycaemic index, Mediterranean and high protein
diets all led to a greater improvement in glycaemic control
compared with their respective control diets, with the
largest effect size seen in Mediterranean diet (mean
difference in HbA1c = 0.41% HbA1c, p < 0.001). The
heterogeneity between the three studies [34,37,38]
included in the meta-analysis was high (I2 = 82%,
p = 0.004), probably owing to the choice of including
the comparison between traditional Mediterranean diet
and the ADA diet which yielded an advantage of 0.2%
HbA1c for the ADA diet [38]. On the contrary, the reduc-
tion in HbA1c level was significantly greater (0.4% differ-
ence) in the low-carbohydrate Mediterranean diet than
in the ADA diet. Interestingly enough, the best results in
terms of HbA1c reduction in type 2 diabetic patients are
obtained with a Mediterranean-style diet with a carbohy-
drate content of less that 50% of daily energy [37,38].
Mediterranean diet and vascular
disease in type 2 diabetes
Coronary heart disease risk is increased in the presence of
type 2 diabetes [43]. Two controlled trials [36,37] evalu-
ated the effects of Mediterranean diet on cardiovascular
risk factors in type 2 diabetic patients and found more
marked improvement of traditional cardiovascular risk
factors, including systolic blood pressure, triglycerides,
ratio of total to high-density lipoprotein (HDL) cholesterol
and HDL cholesterol in those allocated to a Mediterranean
diet, as compared with diabetic subjects receiving a control
diet. There are no controlled clinical trials that specifically
assessed the role of a Mediterranean diet in reducing
cardiovascular events and mortality in type 2 diabetes.
However, two large interventional studies included a repre-
sentative diabetic population. In the GISSI-Prevenzione
clinical trial [44], a total of 11 323 men and women,
including 1700 diabetic subjects, with myocardial infarc-
tion from 172 centres in Italy, received advice to increase
Diabetes Metab Res Rev 2014; 30(Suppl 1): 34–40.
DOI: 10.1002/dmrr
38 K. Esposito and D. Giugliano

their consumption of Mediterranean foods, including fish,
fruit, raw and cooked vegetables and olive oil. Compared
with people in the worst dietary score quarter, the odds ra-
tio of mortality for those in the best score quarter was 0.51
(95% CI 0.44–0.59).
In the PREDIMED study [45], a multicentre trial in
Spain, 7447participants (age range, 55–80 years) at high-
cardiovascular risk, but with no cardiovascular disease at
enrolment, were randomly allocated to one of three diets:
a Mediterranean diet supplemented with extra-virgin olive
oil, a Mediterranean diet supplemented with mixed nuts or
a control diet (advice to reduce dietary fat). The primary
end point was the rate of major cardiovascular events
(myocardial infarction, stroke or death from cardiovascular
causes). The multivariable-adjusted hazard ratios were
0.70 (95% CI, 0.54–0.92) and 0.72 (95% CI, 0.54–0.96)
for the group assigned to a Mediterranean diet with
extra-virgin olive oil (96 events) and the group assigned
to a Mediterranean diet with nuts (83 events), respectively,
versus the control group (109 events). On the basis of these
positive results, the trial was stopped after a median
follow-up of 4.8 years. About one half of participants had
diabetes at baseline: in this population, the risk of the com-
posite primary endpoint was reduced by 29% (HR: 0.71,
0.53–0.96) and was not different from the reduction ob-
served in the non-diabetic people.
The Melbourne Collaborative Cohort Study [46] in-
cluded 16 610 males and 23 860 females and aimed to
determine whether a Mediterranean-style diet could re-
duce mortality in 2150 subjects who had previously been
diagnosed with diabetes or had elevated blood glucose
at baseline (1990–1994). There were 4082 deaths, includ-
ing 874 cardiovascular deaths, over an average follow-up
of 12.3 years. A personal Mediterranean Diet Score was
calculated using data from a validated 121-item food fre-
quency questionnaire. A trend for lower cardiovascular
mortality in those adhering more closely to the Mediterra-
nean diet was consistently seen across all glucose toler-
ance categories except impaired glucose tolerance in
men but only in the women with normal glucose tolerance
or newly identified diabetes. However, 95% CIs associated
with these mortality rates were wide and overlapping.
Although there is some evidence that adopting or
adhering closely to a Mediterranean dietary patterns
may help protect the cardiovascular system from diabetic
injuries, the lack of specific interventional trials represents
a major limitation for a widespread adoption of this diet
in every type 2 diabetic patient. On the other hand, there
is a robust epidemiological evidence in the general popula-
tion indicating that greater adherence to Mediterranean
diet is significantly associated with a reduced risk of both
overall and cardiovascular mortality [47].
Conclusions
At the question ‘which diet is best for diabetes?’, Sawyer
and Gale [48] gave their perspective about the ideal diet
that should be spare, sensible and taken with exercise, a
diet for which pharmacotherapy is an adjunct, rather
than a substitute, a diet that the patient believes in. An
ideal diet should include the many components thought
to be beneficial for cardio-metabolic risk. Although a de-
scription of such an all-inclusive diet is still lacking, it
seems that a low-carbohydrate (<50% of daily energy)
Mediterranean diet has most of the desired attributes,
including a lower content of refined carbohydrate, a
high-fibre content, a moderate fat content (mostly
monounsaturated) and a moderate to high content of
vegetables and protein. Such Mediterranean diet is per-
haps best described by the word ‘frugal’ (from the Latin
fruges, used in reference to products of the earth) [49].
Adhering to healthful practices, including healthful die-
tary patterns such as Mediterranean diet, may delay the
process of non-communicable diseases, including type 2
diabetes, that are communicated by means of the global
promotion of unhealthy lifestyles. Needless to say, living
in a neighbourhood rich in resources for physical activity
and healthful foods compared with living in an environ-
ment not encouraging a healthy lifestyle is associated
with a 38% lower incidence of type 2 diabetes [50].
Conflicts of interest
The authors have no conflicts of interest to declare.

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