Mediterranean Diet and Cardiodiabesity: A Systematic Review through Evidence-Based Answers to Key Clinical Questions

nutrients
Review
Mediterranean Diet and Cardiodiabesity: A
Systematic Review through Evidence-Based
Answers to Key Clinical Questions
Marcella Franquesa 1,2 , Georgina Pujol-Busquets 1,3 , Elena García-Fernández 1 , Laura Rico 1 ,
Laia Shamirian-Pulido 1 , Alicia Aguilar-Martínez 4 , Francesc Xavier Medina 4 ,
Lluís Serra-Majem 5,6 and Anna Bach-Faig 4,7, *
1 Faculty of Health Sciences, Universitat Oberta de Catalunya (Open University of Catalonia, UOC),
08018 Barcelona, Spain; (M.F.); (G.P.-B.);
(E.G.-F.); (L.R.); (L.S.-P.)
2 REMAR-IVECAT Group, Health Science Research Institute Germans Trias i Pujol, Can Ruti Campus,
08916 Badalona, Spain
3 Division of Exercise Science and Sports Medicine, Department of Human Biology, Faculty of Health Sciences,
University of Cape Town, 7725 Cape Town, South Africa
4 FoodLab Research Group (2017SGR 83), Faculty of Health Sciences, Universitat Oberta de Catalunya
(Open University of Catalonia, UOC), 08018 Barcelona, Spain; (A.A.-M.);
(F.X.M.)
5 CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III,
28029 Madrid, Spain;
6 Research Institute of Biomedical and Health Sciences, University of Las Palmas de Gran Canaria,
35001 Las Palmas de Gran Canaria, Spain
7 Food and Nutrition Area, Barcelona Official College of Pharmacists, 08009 Barcelona, Spain
* Correspondence:




Received: 3 February 2019; Accepted: 13 March 2019; Published: 18 March 2019



Abstract: The Mediterranean Diet (MedDiet) has been promoted as a means of preventing and
treating cardiodiabesity. The aim of this study was to answer a number of key clinical questions (CQs)
about the role of the MedDiet in cardiodiabesity in order to provide a framework for the development
of clinical practice guidelines. A systematic review was conducted to answer five CQs formulated
using the Patient, Intervention, Comparison, and Outcome (PICO) criteria. Twenty articles published
between September 2013 and July 2016 were included, adding to the 37 articles from the previous
review. There is a high level of evidence showing that MedDiet adherence plays a role in the primary
and secondary prevention of cardiovascular disease (CVD) and improves health in overweight and
obese patients. There is moderate-to-high evidence that the MedDiet prevents increases in weight and
waist circumference in non-obese individuals, and improves metabolic syndrome (MetS) and reduces
its incidence. Finally, there is moderate evidence that the MedDiet plays primary and secondary
roles in the prevention of type 2 diabetes mellitus (T2DM). The MedDiet is effective in preventing
obesity and MetS in healthy and at-risk individuals, in reducing mortality risk in overweight or obese
individuals, in decreasing the incidence of T2DM and CVD in healthy individuals, and in reducing
symptom severity in individuals with T2DM or CVD.

Keywords: Mediterranean Diet; diabetes mellitus; cardiovascular disease; metabolic syndrome;
obesity; cardiodiabesity; review; PICO




Nutrients 2019, 11, 655; doi:10.3390/nu11030655 www.mdpi.com/journal/nutrients

,Nutrients 2019, 11, 655 2 of 20



1. Introduction
A growing body of scientific evidence shows that the Mediterranean Diet (MedDiet) has a beneficial
effect on obesity, metabolic syndrome (MetS), cardiovascular disease (CVD), and type 2 diabetes mellitus
(T2DM) [1–4]. These four diseases are so inherently linked that a new umbrella term, cardiodiabesity,
has been adopted to reflect their coexistence and interrelationship [5,6] (Figure 1). According to the
International Diabetes Federation, T2DM is expected to become the seventh leading cause of death by
2030 [7]. One of the main causes of T2DM is obesity, which is now a worldwide epidemic despite efforts
by the World Health Organization to meet the target of a 25% relative reduction in premature mortality
from non-communicable diseases [7]. If the current trend continues, by 2025, approximately 18% of men
and over 21% of women will be obese, up from the current rates of 10.8% and 14.9%, respectively [8].
The potential rise in the global incidence of cardiodiabesity is alarming, as central obesity and visceral
adiposity have already been identified as causative agents of T2DM and CVD [8].




Figure 1. Summary of cardiodiabesity and standard diagnostic criteria. Cardiodiabesity encompasses
cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS), and obesity.
Note: Reproduced with permission from García-Fernández et al. [6]. Abbreviations not previously
defined: HDL-Chol, high-density lipoprotein cholesterol.

The word diet comes from the original Greek term diaita (way of living), and the
MedDiet [9]—describing traditional dietary and lifestyle habits in the Mediterranean region—has
attracted international interest as a healthy, prudent dietary pattern [10] that can, as shown by extensive
evidence, contribute to the prevention of chronic diseases [11].
Dietary recommendations can play an important role in the prevention of certain diseases.
Not all physicians, however, are willing to offer nutritional advice, as they feel that they lack the
necessary knowledge to confidently discuss these issues with their patients [12]. The main reasons
for this reluctance include a lack of time or information, the need for cultural adaptations to dietary
patterns and guidelines, and the complexity and contradictions of existing recommendations [13–15].
Even physicians themselves do not have high levels of MedDiet adherence, probably due in part to
away-from-home eating, which is associated with poor health outcomes [15]. Health professionals
could benefit from clinical practice guidelines (CPGs), which have been defined as recommendations
developed systematically to help professionals and patients make decisions about the most appropriate
health care and to select the diagnostic or therapeutic options that are best suited to addressing a
health problem or a specific clinical condition [15].
According to the Appraisal of Guidelines for Research and Evaluation (AGREE) tool, the first step
in drawing up CPGs is to define a clear set of clinical questions (CQs) using the Patient, Intervention,
Comparison, and Outcome (PICO) criteria [16–18]. The next step is to establish systematic and explicit
criteria for reviewing and assessing the available scientific evidence to provide answers to these
questions. The aim of this study was to establish a theoretical framework for the development of
CPGs on the application of the MedDiet in patients with conditions grouped under the umbrella
term cardiodiabesity. To do this, existing evidence on the association between MedDiet adherence and
collective cardiodiabesity risk was updated [6]. The findings presented in this paper should provide

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experts with the basis for developing CPGs to promote the provision of evidence-based nutrition
information and advice to patients with obesity, MetS, CVD, and T2DM.

2. Materials and Methods

2.1. Literature Search
A thorough search of prospective cohort, cross-sectional, and clinical trial studies in the scientific
literature was conducted to gather evidence on the ability of the MedDiet to modulate or prevent
diseases encompassed by the term cardiodiabesity. Using the same search strategies as García-Fernández
et al. [6], the available evidence on the association between the MedDiet and cardiodiabesity was
updated by reviewing studies published between September 2013 and July 2016. The literature search
was performed in PubMed using the search term Mediterranean Diet and the key words Diabetes Mellitus,
Coronary Disease, Myocardial Ischemia, Heart Disease, Metabolic Syndrome, and Obesity.

2.2. Inclusion Criteria
Five CQs were defined using the PICO framework (Table 1) [16–18]. As in the earlier review by
García-Fernández et al. [6], only those studies relating to T2DM, obesity, MetS, and CVD were eligible
for inclusion. In this study, we applied more stringent selection criteria (Table 2) to the articles from
the previous study and to the new ones. The studies included were assigned one of three levels of
evidence (Table 3) to answer the formulated CQs and to establish recommendations for the CPGs.

Table 1. Clinical questions (CQs) based on the Patient, Intervention, Comparison, and Outcome
(PICO) method.

P: Who Are the I: What C: Against What is the O: What Are the
Patients/Participants Intervention Is Intervention of Interest Measured Results CQs
in the Study? Being Examined? Being Compared? (Outcomes)?
Application of CQ 1: What effect does the
Men and women with Epidemiologically similar Reduction in
MedDiet and/or MedDiet have on weight
overweight or obesity control group that does weight, BMI,
monitoring of reduction in overweight and
and/or MetS not follow the MedDiet and/or WC
MedDiet adherence obese patients?
Reduction in risk of
Application of
Epidemiologically similar all-cause mortality CQ 2: What effect does the
Men and women with MedDiet and/or
control group that does and mortality due MedDiet have on the incidence
or at risk of T2DM monitoring of
not follow the MedDiet to CVD, heart and prevention of T2DM?
MedDiet adherence
attack, or T2DM
Application of CQ 3: What effect does the
Healthy men and Epidemiologically similar Reduction in
MedDiet and/or MedDiet have on established
women with MetS or control group that does incidence or
monitoring of MetS or on the risk of
risk factors for MetS not follow the MedDiet severity of MetS
MedDiet adherence developing MetS?
Application of CQ 4: What effect does the
Epidemiologically similar Reduction in CVD
MedDiet and/or MedDiet have on the prevention
Men and women control group that does incidence or
monitoring of of CVD and the modulation of
not follow the MedDiet mortality
MedDiet adherence disease course?
CQ 5: What effect does the
Application of
Epidemiologically similar Reduction in MedDiet have on weight gain and
MedDiet and/or
Men and women control group that does weight gain, BMI, abdominal adiposity in healthy
monitoring of
not follow the MedDiet or WC individuals and individuals
MedDiet adherence
without overweight?
Abbreviations not previously defined: BMI, body mass index; WC, waist circumference.