Dietary Patterns and Metabolic Syndrome in Adult Subjects: A Systematic Review and Meta-Analysis

Metabolic Syndrome (MetS) constitutes a relevant public health burden. Several studies have demonstrated the association between diet and MetS. We performed a systematic review and meta-analysis to provide an estimate of the association between dietary patterns defined through a posteriori methods and MetS. A literature search on PubMed, Web of Science, and Scopus databases, up to March 2019, was conducted to identify all eligible case-control, prospective, or cross-sectional studies involving adult subjects of both sexes. Random-effects models were used. Heterogeneity and publication bias were evaluated. Stratified analyses were conducted on study characteristics. Forty observational studies were included in the meta-analysis, which identified the “Healthy” and the “Meat/Western” dietary patterns. The “Healthy” pattern was associated with reduced MetS risk (OR = 0.85; 95% confidence interval (CI): 0.79–0.91) and significantly decreased the risk in both sexes and in Eastern countries, particularly in Asia. Adherence to the “Meat/Western” pattern increased MetS risk (OR = 1.19; 95% CI: 1.09–1.29) and the association persisted in the stratified analysis by geographic area (Asia, Europe, America) and study design. Lifestyle is linked to risk of developing MetS. The “Healthy” and “Meat/Western” patterns are significantly associated with reduced and increased MetS risk, respectively. Nutrition represents an important modifiable factor affecting MetS risk.


Introduction
Metabolic Syndrome (MetS) has become a relevant public health concern [1] because of its increased prevalence partially explained by aging population and lifestyle factors, including diet [2,3].
MetS is a pathophysiological state and a cluster of interrelated factors including abdominal obesity, insulin resistance, dysglycemia, hypertension, and dyslipidemia (triglycerides and HDL-C-high-density lipoprotein cholesterol) [4]. The diagnosis of MetS requires three or more of the following criteria: (i) waist circumference >102 cm in men and >88 cm in women; (ii) HDL-C <40 mg/dL (<1.04 mmol/L) in men and <50 mg/dL (<1.29 mmol/L) in women; (iii) triglycerides ≥150 mg/dL (≥1.7 mmol/L); (iv) blood pressure ≥130/85 mmHg and (v) fasting glucose ≥110 mg/dL (≥6.1 mmol/L) [4,5]. A harmonization of the diagnostic criteria has been proposed, as the reference thresholds for abdominal obesity vary considerably among countries and international organizations [4]. In particular, the recommended waist circumference cutoff points are lower for both men and women in Asia, Sub-Saharan Africa, and Central and South America [4].
According to literature, the consumption of specific foods or nutrients is strongly related to the risk of developing MetS [6][7][8][9]. Nutritional epidemiology currently applies dietary patterns to analyze Among these, 236 articles were excluded as not investigating the association between dietary patterns and the outcome of interest. Sixty-five articles were subjected to full-text revision. Hand searching of reference lists of both selected articles and recent relevant reviews led to the identification of seven additional items. Subsequently, 32 papers were excluded because they did not meet the inclusion criteria as follows: 9 studies considered a different dietary pattern as the comparison reference; 6 studies were carried out on adolescents; 5 studies reported the MetS risk combined with genotype; 4 studies derived the dietary patterns considering nutrients instead of food Among these, 236 articles were excluded as not investigating the association between dietary patterns and the outcome of interest. Sixty-five articles were subjected to full-text revision. Hand searching of reference lists of both selected articles and recent relevant reviews led to the identification of seven additional items. Subsequently, 32 papers were excluded because they did not meet the inclusion criteria as follows: 9 studies considered a different dietary pattern as the comparison reference; 6 studies were carried out on adolescents; 5 studies reported the MetS risk combined with genotype; 4 studies derived the dietary patterns considering nutrients instead of food items; 3 studied reported the correlation instead of risk estimate; one study used a control group (no MetS) as reference; one study was carried out on transplant recipients; and one study was carried out on type 2 diabetes. Therefore, at the end of the selection process, 40 studies were enclosed for the identification of the different dietary patterns in the systematic review and meta-analysis .

Study Characteristics and Quality Assessment
General characteristics of the 40 studies evaluating the association between adherence to a posteriori dietary patterns with MetS risk are shown in Table 1.

Meta-Analysis
We identified two common dietary patterns with similar factor loading of principle components: "Healthy" and "Meat/Western" patterns. Thirty-eight out of 40 articles included in the systematic review were used for the overall risk estimation. Two studies [41,48] were excluded because they reported dietary patterns that could not be clearly assumed in "Healthy" nor in "Meat/Western" patterns. In the studies by Agodi et al. [31] and by Wang et al. [23], the "Healthy" dietary pattern was the only pattern identified, whereas in the study by Cattafesta et al. [42] the "Meat/Western" was the only pattern selected. The meta-analyses on the MetS risk in association with "Healthy" and "Meat/Western" dietary patterns (studies comparing the highest intake to the lowest intake) are shown in Figure 2A,B, respectively.    reported dietary patterns that could not be clearly assumed in "Healthy" nor in "Meat/Western" patterns. In the studies by Agodi et al. [31] and by Wang et al. [23], the "Healthy" dietary pattern was the only pattern identified, whereas in the study by Cattafesta et al. [42] the "Meat/Western" was the only pattern selected. The meta-analyses on the MetS risk in association with "Healthy" and "Meat/Western" dietary patterns (studies comparing the highest intake to the lowest intake) are shown in Figure 2A  The overall analysis showed that the MetS risk significantly decreased in association with the adherence to the "Healthy" pattern (OR = 0.85; 95% CI: 0.79-0.91) and significantly increased in association with the adherence to the "Meat/Western" pattern (OR = 1.19; 95% CI: 1.09-1.29). These results did not essentially change when the studies [27,33,52] not comparing the highest vs. the lowest dietary pattern adherence values were excluded ( Table 2). In the "Healthy" pattern meta-analysis, the stratification by study design showed a significant reduced MetS risk in the cross-sectional studies only (Table 2). Stratifying the analysis by geographic area, MetS risk decreased significantly in Eastern countries (OR = 0.78; 95% CI: 0.71-0.86), particularly in Asia (OR = 0.77; 95% CI: 0.70-0.85). The preventive effect of the "Healthy" pattern resulted statistically significant in both sexes (Table 2).
In the "Meat/Western" pattern meta-analysis, the stratification by study design showed a significantly higher MetS risk in both cohort and cross-sectional studies (Table 2). Similarly, when stratifying the analysis by the geographic area the MetS risk significantly increased in Asia, America and Europe, and in Eastern and Western countries ( Table 2). No significant association was found when stratifying by sex ( Table 2).
The high heterogeneity in the pooled analysis of both "Healthy" and "Meat/Western" patterns was slightly reduced in the stratification by geographic area.
In the meta-analysis on the "Healthy" pattern, a significant publication bias was detected by the Egger's test in the overall analysis (p = 0.005) and in cross-sectional studies (p = 0.016), but not by the Begg's method (Table 2). In the analysis performed excluding the studies by Bell et al. [27], by Arisawa et al. [33] and by Panagiotakos et al. [52], the publication bias, although reduced, remained significant (p = 0.011) ( Table 2). In the meta-analysis on "Meat/Western" pattern, a significant publication bias was detected by Egger's method in the Eastern countries (p = 0.021) and by the Begg's test in men (p = 0.042) ( Table 2).
In the meta-analysis on the "Healthy" pattern, a significant publication bias was detected by the Egger's test in the overall analysis (p = 0.005) and in cross-sectional studies (p = 0.016), but not by the Begg's method (Table 2). In the analysis performed excluding the studies by Bell et al. [27], by Arisawa et al. [33] and by Panagiotakos et al. [52], the publication bias, although reduced, remained significant (p = 0.011) ( Table 2). In the meta-analysis on "Meat/Western" pattern, a significant publication bias was detected by Egger's method in the Eastern countries (p = 0.021) and by the Begg's test in men (p = 0.042) ( Table 2).
The funnel plots of the meta-analyses on the "Healthy" pattern and on the "Meat/Western" pattern are shown in Figure 3A,B, respectively.

Discussion
Our systematic review and meta-analysis investigated the effect of dietary patterns extracted via a posteriori methods on MetS risk. According to literature, several different health outcomes are associated with unhealthy and healthy dietary patterns. In particular, the Western/unhealthy pattern increases the risk of cancer in different sites [63][64][65][66][67][68] and the risk of low bone mineral density and osteoporotic fracture [69]. Moreover, the prudent/healthy pattern is associated with lower risk of cardiovascular disease and coronary heart disease [70], diabetes mellitus [71,72], and cognitive decline and dementia [73].
Considering the 40 included articles, we identified two prevalent dietary patterns: "Healthy" and "Meat/Western". The "Healthy" pattern was associated with a lower MetS risk and significantly decreased the risk in both sexes and in Eastern countries, particularly in Asia. Adherence to the "Meat/Western" pattern was positively associated with MetS risk and this association persisted in the stratified analysis by geographic area and study design. Similarly, the recent meta-analyses by Shab-Bidar et al. [15] and Rodríguez-Monforte et al. [16] showed that a Western/unhealthy pattern significantly increased MetS risk, whereas a prudent/healthy pattern significantly lowered MetS risk. In our study, MetS risk through unhealthy dietary patterns increased by 19%, while it increased by 22% in the study by Shab-Bidar et al. [15] and by 28% in the study by Rodríguez-Monforte et al. [16]. Healthy dietary patterns significantly decreased MetS risk by 15% in our analysis, by 11% in the meta-analysis by Shab-Bidar et al. [15] and by 17% in the meta-analysis by Rodríguez-Monforte et al. [16]. It should be noted that the meta-analysis of Shab-Bidar et al. [15] was performed on cross-sectional studies only and that Rodríguez-Monforte et al. [16] selected 31 studies including those which identified the dietary patterns via cluster analysis (a priori method).
According to our findings, the "Meat/Western" pattern significantly increased MetS risk of 20% in Asia, 15% in Europe and 33% in America. In dietary patterns derived a posteriori, the factor loadings indicate the most commonly consumed foods, reflecting the cultural influence on food consumption [74,75]. It is noteworthy that the usual diet of European populations, especially in Mediterranean countries, tend to include the consumption of healthy foods, such as seafood, vegetables, and fruit, whereas American populations mostly adhere to Westernized dietary patterns, containing high pro-inflammatory foods [76]. As reported in the study by Calton et al. [77], other pre-defined representative dietary patterns exist worldwide, such as the Dietary Approaches to Stop Hypertension (DASH) diet, which is characterized by high intake of fruit, vegetables, whole grains and dairy [78], and the Northern Europe dietary pattern, which is characterized by high intake of fruit, vegetables, legumes, low-fat dairy, fatty fish, oats, barley and almonds [79]. These patterns can affect MetS risk and should be evaluated when investigating the effect of the dietary patterns on developing MetS, as culture and society influence adherence to healthy or unhealthy dietary pattern [77]. Our study combined dietary patterns derived a posteriori from world countries with very different eating habits, in particular, traditional dietary patterns from Eastern Asian countries (Japan [33,35], China [25,30,56], Korea [24,28,34,36,39,40,43,45]), from Western Asian countries (Iran [19,46,51,54,55,58]), from the Mediterranean area (Greece [52], Lebanon [21,38]), from Northern Europe (Sweden [53]), from Middle Europe (Germany [44], Czech Republic [31] and Poland [20,22,32]), from North America (USA [29,37,49,50]), from South America (Brazil [42,57]), and from Australia [27]. Indeed, the traditional dietary pattern in Asian countries is characterized by high intake of rice and/or kimchi, fish and sea food, soybean and soybean products, mushrooms, vegetables, and fruit [24,28,34,39,40,43,56], in Poland by red meat, fish, potatoes, soup, refined grains and sugars, and high-fat milk [20,22], and in Iran by refined grains, nuts, eggs, vegetables and legumes, potatoes, and hydrogenated fats [51,58].
Despite the influence of sex-related factors on MetS [80], we observed no sex-related difference on the association of dietary pattern with MetS, but, notably, the "Healthy" pattern showed a stronger protective effect in women.
The "Meat/Western" pattern, characterized by high intake or red and processed meat, eggs, refined grains, and sweets, resulted associated with an increased (+19%) MetS risk. These foods plausibly represent the main cause of the observed effect on MetS risk, particularly meat [81,82], since refined carbohydrates, red and processed meats, and fried foods have pro-inflammatory properties and can increase inflammatory cytokines [83]. Indeed, although the meta-analysis by Namazi et al. [14] found no significant association between the most pro-inflammatory diet and MetS, inflammatory factors are involved in insulin resistance and lipid disorders [83].
Our results showed the association of the "Healthy" pattern with a lower (−15%) MetS risk. The healthy patterns are characterized by the consumption of foods with high content of vitamins, minerals, antioxidants, fiber, MUFA and n-3 fatty acids, which could contribute to explain the protective effect of the "Healthy" pattern on MetS. Indeed, higher adherence to healthy dietary patterns is associated with a lower risk of glucose intolerance, weight gain, inflammation, insulin resistance and a higher level of HDL cholesterol [84].

Limitations
The main limitation of our study is that the risk of developing MetS could be associated with dietary patterns other than the two ("Healthy" and "Meat/Western") discussed in this meta-analysis. Differences in the populations in study and in the referral values for MetS diagnosis represent another study limitation and result in heterogeneity. Indeed, the high heterogeneity may be related to the wide variability in dietary data collection and analysis, in the various and not uniformly adjusted confounding factors, and in the identification of the dietary patterns. Heterogeneity is more evident in the analysis on "Meat/Western" pattern, as a possible consequence of the difficulty in characterizing this pattern across the selected studies. Another limitation is that pooled data were directly driven by the included studies, presenting their own weaknesses in study design. Moreover, the cross-sectional nature of many included studies precludes causal inference and the dietary pattern may represent a post hoc event. Only the OR of the highest and the lowest quantile of healthy or unhealthy dietary patterns were included in our analysis, limiting the evaluation of the presence of any trend. Finally, some studies reported risk estimates for quintiles, others for quartiles, and others for tertiles. As dietary intakes are influenced by sex, race/ethnicity, and societal factors, our findings should be considered in the different geographic contexts. Thus, these aspects may have affected the reproducibility of the association between dietary patterns and MetS.
To further advance this field of research, future studies are needed to examine the association between dietary patterns in geographic context not yet described and MetS, and to evaluate the impact of dietary patterns on the determinants of MetS.

Conclusions
A protective effect on MetS is attributed to adherence to the "Healthy" pattern, which is characterized by high consumption of fruit, vegetables, whole grains, poultry, fish, nuts, legumes, and low-fat dairy products, whereas the "Meat/Western" pattern is positively associated with MetS. Nutrition is one of the most important modifiable factors affecting health. Public health efforts should aim to adopt healthy dietary patterns and to reduce the burden of MetS, providing guidance for nutritional intervention. For further advance in research, more prospective studies are needed to investigate the association between dietary patterns and MetS in each gender and in different geographic context.