Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk.

Randomized clinical trials with statins and other lipid-lowering drugs have shown the presence of a "residual cardiovascular risk" in those treated to "target" for LDL-cholesterol. This risk is mainly associated to lipid components other than LDL and in particular to remnant cholesterol (RC) and to lipoproteins rich in triglycerides in fasting and non-fasting conditions. During fasting, RCs correspond to the cholesterol content of the VLDL and their partially depleted triglyceride remnant containing apoB-100. Conversely, in non-fasting conditions, RCs include also cholesterol present in chylomicrons containing apoB-48. Therefore, RCs refer to total plasma cholesterol minus HDL-cholesterol and LDL-cholesterol, that is, all the cholesterol present in the VLDL, chylomicrons and in their remnants. A large body of experimental and clinical data suggests a major role of RCs in the development of atherosclerosis. In fact, RCs easily pass the arterial wall and bind to the connective matrix stimulating the progression of smooth muscle cells and the proliferation of resident macrophages. RCs are a causal risk factor for cardiovascular events. Fasting and non-fasting RCs are equivalent for predicting vascular events. Further studies on drugs effect on RC levels and clinical trials to evaluate the efficacy of RC reduction on cardiovascular events are needed.

Diet and metabolic syndrome: a narrative review.

Metabolic syndrome (MetS) is a highly prevalent condition defined by the presence of at least three out of five risk factors including central obesity, increased fasting glucose, high blood pressure, and dyslipidaemia. Metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality. Excess energy intake and Western dietary pattern may influence the development of metabolic syndrome. By contrast, both Mediterranean diet (Med-diet) and Dietary Approaches to Stop Hypertension (DASH) diet, with or without calorie restriction, have positive effects. For the prevention and management of MetS, it is recommended to increase the daily intake of fiber-rich and low-glycaemic-index foods and the consumption of fish and dairy products, especially yogurt and nuts. Moreover, it is advisable to consume a large variety of unprocessed cereals, legumes, and fruit. Finally, it is suggested to replace saturated fatty acids with monounsaturated and polyunsaturated fatty acids and to limit the consumption of free sugars to less than 10% of the total energy intake. The aim of this narrative review is to analyze current evidence on the different dietary patterns and nutrients that may affect prevention and treatment of MetS and to discuss the underlying pathophysiological mechanisms.

Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review.

Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease and it is considered the hepatic manifestation of metabolic syndrome (MetS). Diet represents the key element in NAFLD and MetS treatment, but some nutrients could play a role in their pathophysiology. Among these, fructose added to foods via high fructose corn syrup (HFCS) and sucrose might participate in NAFLD and MetS onset and progression. Fructose induces de novo lipogenesis (DNL), endoplasmic reticulum stress and liver inflammation, promoting insulin resistance and dyslipidemia. Fructose also reduces fatty acids oxidation through the overproduction of malonyl CoA, favoring steatosis. Furthermore, recent studies suggest changes in intestinal permeability associated with fructose consumption that contribute to the risk of NAFLD and MetS. Finally, alterations in the hunger-satiety mechanism and in the synthesis of uric acid link the fructose intake to weight gain and hypertension, respectively. However, further studies are needed to better evaluate the causal relationship between fructose and metabolic diseases and to develop new therapeutic and preventive strategies against NAFLD and MetS.

Prevention and Management of Type II Diabetes Chronic Complications: The Role of Polyphenols (Mini-Review).

The numerous complications of diabetes may be at least in part generated by the oxidative stress associated with the constant state of hyperglycemia. Polyphenols are plant-based secondary metabolites that have high potentials in the prevention and treatment of some diseases, in particular those that involve oxidative stress, such as complications of diabetes. The purpose of this narrative review is to show the main evidence regarding the role of polyphenols in treating and preventing these complications. For the bibliographic research, the papers published up to March 15, 2021, were considered, and the search terms included words relating to polyphenols, their classes and some more known compounds in association with the complications of diabetes. There are numerous studies showing how polyphenols are active against endothelial damage induced by diabetes, oxidative stress and hyperinflammatory states that are at the origin of the complications of diabetes. Compounds such as flavonoids, but also anthocyanins, stilbenes or lignans slow the progression of kidney damage, prevent ischemic events and diabetic nephropathy. Many of these studies are preclinical, in cellular or animal models. The role of polyphenols in the prevention and treatment of diabetes complications is undoubtedly promising. However, more clinical trials need to be implemented to understand the real effectiveness of these compounds.

High Compliance to Mediterranean Diet Associates with Lower Platelet Activation and Liver Collagen Deposition in Patients with Nonalcoholic Fatty Liver Disease.

The Mediterranean diet (Med-Diet) is considered the most effective dietary patterns to obtain weight loss in NAFLD patients. Previous evidence suggested that Med-Diet adherence could reduce cardiovascular risk and have a beneficial effect on NAFLD severity. Aim of the study was to investigate the relationship between Med-Diet adherence, platelet activation (PA), and liver collagen deposition. The study was performed in 655 consecutive NAFLD outpatients from the PLINIO study, a prospective observational cohort study aimed to identify non-conventional predictors of liver fibrosis progression in NAFLD. PA was measured by the serum thromboxane B2 (TxB2), and liver collagen deposition by N-terminal propeptide of type III collagen (Pro-C3). Adherence to the Med-diet was investigated by a short nine-item validated dietary questionnaire. Patients with high Med-Diet adherence were older and had less metabolic syndrome and lower serum triglycerides, GGT, TxB2, and Pro-C3. At multivariate regression analyses, in the linear model, the Med-Diet score negatively correlated with both TxB2 (Beta = −0.106; p = 0.009) and Pro-C3 (Beta = −0.121; p = 0.002) and in the logistic model high adherence inversely correlated with higher TxB2 tertiles (II tertile: OR = 0.576, p = 0.044; III tertile: OR = 0.556, p = 0.026) and Pro-C3 tertile (III tertile: OR = 0.488, p = 0.013). Low consumption of red meat inversely correlated with higher TxB2 tertile (II tertile: OR = 0.448, p < 0.001, III tertile: OR = 0.567, p = 0.004). In conclusion, NAFLD patients with high adherence to the Med-Diet show lower PA and liver collagen deposition, suggesting a protective role of the Med-Diet against NAFLD progression and cardiovascular risk. In addition, the correlation between TxB2 and Pro-C3 suggests a link between NAFLD severity and cardiovascular risk.

Open Issues in the Transition from NAFLD to MAFLD: The Experience of the Plinio Study.

Metabolic associated fatty liver diseases (MAFLD) definition was proposed to identify fatty liver condition associated to metabolic disorders and to replace non-alcoholic fatty liver disease (NAFLD). We aimed to explore the effect of the application of the new MAFLD criteria on a pre-existing cohort of NAFLD patients. The consequences of the reclassification were investigated by applying the MAFLD criteria to a prospective cohort (The Plinio Study) of dysmetabolic patients examined for the presence of NAFLD. In the Plinio cohort, 795 patients had NAFLD and 767 of them (96.5%) were reclassified as MAFLD patients. Out of these, 94.9% had overweight/obesity or diabetes, while the remaining were lean and had metabolic dysregulation defined by the presence of at least two metabolic risk abnormalities. By contrast, 3.5% of the NAFLD patients were reclassified as no-MAFLD due to the absence of overweight/obesity, diabetes, or metabolic risk abnormalities. The only significant difference between the NAFLD and MAFLD groups was the higher prevalence of subjects with BMI ≥ 25 kg/m2 in the latter (88.6% vs. 92%; p = 0.018). In the cohort, 68 subjects were defined as "lean NAFLD". Of these, 40 were reclassified as MAFLD and 28 as no-MAFLD. In conclusion, when applying MAFLD criteria to the Plinio cohort, there is a substantial overlap between NAFLD and MAFLD diagnosis. However, some specific subgroups of patients, such as those currently defined as lean NAFLD, were excluded by the new MAFLD definition.