**5.4. Fatty acids**

and phos-

amounts of fiber supplements (4–19 g/day) achieved little improvement in glycemic control or CVD risk factors [96]. It has been reported that increased intake of dietary fiber and low GI diet with legumes reduced blood pressure compared with wheat fiber diet in T2DM patients [95]. A cross-sectional study in adults men and women indicated that the highest total dietary fiber and insoluble dietary fiber intakes were associated with a significantly lower risk of overweight, high blood pressure, plasma apolipoprotein (apo) B, apo B, apo A–I, cholesterol, triacylglycerols, and homocysteine [97]. The fiber intake should, ideally, be 40 g/day (or 20 g/1000 kcal/day) or more and about half should be of the water-soluble type. People with T2DM are encouraged to choose ≥5 servings of fiber-rich vegetables or fruit and ≥4 servings of legumes per week to achieve the fiber intake goals set for the general population [98].

A number of antioxidants showed beneficial effect in experimental models of atherosclerosis and CVD [99, 100]. The main polyphenol dietary sources are fruit and beverages (fruit juice, wine, tea, coffee, chocolate, and beer), dry legumes, and cereals [101]. Dietary polyphenols have been shown to possess cardioprotective effects. Oleuropein inhibits the oxidation of LDL-C in vitro [102]. Dietary quercetin decreases lipid peroxidation and upregulates the expression of serum HDL-associated paraoxonase-1 (PON-1) in the liver [101]. PON-1 may mediate anti-atherogenic properties by protecting LDL-C from oxidation. Several studies have indicated that red wine polyphenolic compounds (RWPCs) were able to inhibit proliferation and migration of vascular cells. RWPCs induced NO-mediated endothelium-dependent

relaxations in isolated arteries. The activation of eNOS led to an increase in [Ca2+]i

phorylation of eNOS by the PI3-kinase/Akt pathway [103]. RWPCs also increased endothelial prostacyclin release and inhibited the synthesis and the effects of endothelin-1 in endothelial

Lycopene is a natural carotenoid found in tomatoes, which has biochemical functions as an antioxidant scavenger, hypolipidemic agent, and inhibitor of pro-inflammatory and prothrombotic factors [104]. Red fruits and vegetables, including tomatoes, watermelons, pink grapefruits, apricots, and pink guavas, contain lycopene. Processed tomato products are good dietary sources of lycopene [105]. Two major hypotheses have been proposed to explain the anti-atherogenic activities of lycopene. The non-oxidative action of lycopene results in an increase of gap-junction communication between cells and modulation of immune function [106] .The oxidative hypothesis supports the prevention of the oxidization of LDL-C as the initial step leading to its uptake by the macrophages inside the arterial wall and the formation of foam cells and atherosclerotic plaque [105]. A possible mechanism for the protective role of lycopene in CVD is via the inhibition of cellular 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis [107]. Results from the Harvard Medical School's Women's Health Study showed that women with the highest intake of tomato-based foods rich in lycopene had a reduced risk for CVD compared to women with a low intake of these foods [108]. The European multicenter case-control study on antioxidants,

**5.2. Polyphenols**

40 Diabetes Food Plan

cells [101].

**5.3. Lycopene**

N−3 fatty acids including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have a significant role in the prevention of CVD [116]. The evidence supports a dietary recommendation of ≈500 mg/day of eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) for CVD risk reduction [117]. A meta-analysis suggests that ALA consumption may also confer cardiovascular benefits, and each 1 g/d increment in ALA intake was associated with a 10% lower risk of CVD death [118]. Dietary sources of ALA include flaxseeds and flaxseed oil, walnuts and walnut oil, soybeans and soybean oil, pumpkin seeds, rapeseed oil, and olive oil [119]. In the GISSI Prevention Study, treatment with n-3 PUFA significantly lowered the risk of the primary endpoint (death, non-fatal MI, and stroke) [120]. Several mechanisms explaining the cardioprotective effect of the n-3 PUFA have been suggested including antiarrhythmic and antithrombotic roles [119].

#### **5.5. Ethanol and non-ethanolic components of wine**

Several groups are now beginning to use animal models of myocardial ischemia and reperfusion to explore whether certain nutrients, including ethanol and non-ethanolic components of wine, may have a specific protective effect on the myocardium, independently from the classical risk factors for coronary disease involved in vascular atherosclerosis and thrombosis [121]. Most epidemiological studies have suggested an inverse association between regular light to moderate drinking and the risks of CVD [122]. Researchers have wondered whether moderate alcohol consumption mediates some of its cardioprotective effects by stimulating NO, and conversely, whether binge drinking diminishes NO availability [123]. In a swine model of chronic ischemia, alcohol administration promoted angiogenesis, increased capillary and arteriolar density in non-ischemic myocardium [122]. Numerous studies indicate that moderate red wine consumption is associated with a protective effect on the cardiovascular system, which has largely been attributed to the rich content of phenolic compounds [124, 125]. Polyphenolic antioxidants scavenge the free radicals, inhibit lipid peroxidation (lipoproteins, membranes), attenuate platelet aggregation, produce coronary vasorelaxation, and protect from cellular injury [126]. Sudden death was examined in US males who participated in the Physicians' Health Study over 12 years of follow-up. Men who consumed light to moderate amounts of alcohol (2–6 drinks/week) had a significantly reduced risk of CVD compared to those who never or rarely consumed alcohol [127]. Daily intake of red wine decreased plasma malondialdehyde and oxidized LDL-C, indicating the antioxidant activity of wine polyphenols [128]. The NO-mediated vasorelaxant effects of red wine phenolic extracts acted mainly through activating endothelial NO synthase [129]. Mild to moderate beer drinking (12.5–25 g/day) provides cardiac protection, improves endothelial function by inhibiting vascular oxidative damage and modulating the Akt/eNOS pathway, which should be attributed to the non-alcohol components in beer [130]. PPARγ plays an important role in glucose and lipid metabolism [131]. Ellagic acid and epicatechin gallate, active components of wine, were reported to have similar affinity to PPARγ of rosiglitazone, which is a standard drug for the treatment of T2DM [132]. Xanthohumol is a flavonoid which was reported to exist in hops and beer could decrease the activity of alpha glucosidase in a non-competitive and reversible way via directly binding to the enzyme and triggering conformational alterations [131].

glycemic control [137]. A two-year international Dietary Intervention Randomized Controlled (DIRECT) study found that compared to the other diets, the low-carbohydrate diet was most effective for weight loss, and changes in biomarkers (TG, HDL-C, glucose, and insulin) [138].

Dietary Recommendations for Patients with Cardiovascular Disease and Diabetes

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A Mediterranean diet characterized by a relatively high fat intake (40–50% of total daily calories), of which SFA comprises ≤8%, and MUFA 5–25% of calories is associated with a higher life expectancy in healthy people, as well as with lower rates of stroke, coronary heart disease, and diabetes [77]. Mediterranean-style diets are preferable to a low-fat diet in reducing cardiovascular events, increasing blood HDL-C levels, decreasing plasma TG levels, and improving insulin sensitivity [77]. This diet is characterized by abundant legumes, unrefined cereals, vegetables, fresh fruit, olive oil as the principal source of fat, moderate to high consumption of fish, dairy products (mostly as cheese and yogurt), wine consumed in low to moderate amounts, and red meat consumed in low amounts [139]. The Mediterranean-style eating pattern has been observed to improve cardiovascular risk factors in individuals with diabetes [140]. Interventional studies demonstrate the beneficial role of the Mediterranean diet in T2DM management, greater improvements in glycemic control, and reduction of CVD risk factors [141]. The Mediterranean diet is associated with a lower incidence of all-cause mortality [142].

The dietary approach to stop hypertension (DASH) diet is a dietary pattern to prevent and control hypertension. Its main target is to lower blood pressure, and therefore CVD incidence, by dietary means [77]. The DASH diet includes a relatively high daily content of fruit, vegetables, and grain; moderate amounts of low-fat dairy products, fats, and oils; a decreased content of meat, regular-fat dairy products, snacks, and sweets. All meals have similar sodium content (approximately 3000 mg/day) [77, 143]. Several observational studies in adults have shown that adherence to a DASH-like diet has positive effects on cardiovascular health, including reduced risk of hypertension, T2DM, heart failure, coronary heart disease, stroke [144]. The PREMIER trial reported that standard dietary treatment of hypertensive patients often showed unfavorable control of lipid profile and other cardiovascular risk factors [145]. In the Diabetes Control and Complications Trial, intensive glucose control significantly reduced total cholesterol and LDL-C and TG. The DASH-sodium results indicate that low sodium levels are correlated with the largest reductions in blood pressure for participants at

To maintain a healthy weight, diet should include a variety of foods, increased intake of fruits and vegetables, whole grains, olive oil, and nuts. Moderate intake of fish, poultry, and red wine is recommended. Consumption of foods high in sodium and sugar should be minimized. The Mediterranean diet has been shown to reduce the incidence of major cardiovascular events

**6.4. The dietary approach to stop hypertension (DASH) diet**

both pre-hypertensive and hypertensive levels [146].

**7. Conclusions**

**6.3. A Mediterranean diet**
