Showing papers in "Nutrition Metabolism and Cardiovascular Diseases in 2019"

Ultra-processed food consumption and its effects on anthropometric and glucose profile: A longitudinal study during childhood.

Abstract: Background and aims Obesity and insulin resistance development are related to known risk factors (such as diet) that begin in childhood. Among dietary factors, the consumption of ultra-processed foods has received attention. The present study investigated the association between ultra-processed foods consumption at preschool age and changes in anthropometric measurements from preschool to school age and glucose profile at school age. Methods and results The present study was a follow-up of a randomized controlled trial, conducted with 307 children of low socioeconomic status from Sao Leopoldo, Brazil. At ages 4 and 8 years, children's anthropometric assessments were collected from preschool to school age including body-mass index (BMI) for-age, waist circumference (WC), waist-to-height ratio (WHtR) and skinfold. At the age 8 years, blood tests were performed to measure glucose profile. Dietary data were collected through 24-h recalls and the children's ultra-processed food intake was assessed. Linear regression analysis was used to assess the relationship between ultra-processed food consumption and the outcomes. The percentage of daily energy provided by ultra-processed foods was 41.8 ± 8.7 (753.8 ± 191.0 kcal) at preschool age and 47.8 ± 8.9 (753.8 ± 191.0 kcal) at school age, on average. The adjusted linear regression analyses showed that ultra-processed food consumption at preschool age was a predictor of an increase in delta WC from preschool to school age (β = 0.07; 95%CI 0.01–0.14; P = 0.030), but not for glucose metabolism. Conclusion Our data suggest that early ultra-processed food consumption played a role in increasing abdominal obesity in children. These results reinforce the importance of effective strategies to prevent the excessive consumption of ultra-processed foods, especially in early ages.

Diabetic kidney disease: new clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on “The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function”

Abstract: This joint document of the Italian Diabetes Society and the Italian Society of Nephrology reviews the natural history of diabetic kidney disease (DKD) in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents. Recent epidemiological studies have disclosed a wide heterogeneity of DKD. In addition to the classical albuminuric phenotype, two new albuminuria-independent phenotypes have emerged, i.e., “nonalbuminuric renal impairment” and “progressive renal decline”, suggesting that DKD progression toward end-stage kidney disease (ESKD) may occur through two distinct pathways, albuminuric and nonalbuminuric. Several biomarkers have been associated with decline of estimated glomerular filtration rate (eGFR) independent of albuminuria and other clinical variables, thus possibly improving ESKD prediction. However, the pathogenesis and anatomical correlates of these phenotypes are still unclear. Also the management of hyperglycemia in patients with type 2 diabetes and impaired renal function has profoundly changed during the last two decades. New anti-hyperglycemic drugs, which do not cause hypoglycemia and weight gain and, in some cases, seem to provide cardiorenal protection, have become available for treatment of these individuals. In addition, the lowest eGFR safety thresholds for some of the old agents, particularly metformin and insulin secretagogues, have been reconsidered. The heterogeneity in the clinical presentation and course of DKD has important implications for the diagnosis, prognosis, and possibly treatment of this complication. The therapeutic options for patients with type 2 diabetes and impaired renal function have substantially increased, thus allowing a better management of these individuals.

Dietary patterns and management of type 2 diabetes: A systematic review of randomised clinical trials

Abstract: Background and aim The aim of the present review is to examine evidence from published studies on the effectiveness of six or more months of low carbohydrate, macrobiotic, vegan, vegetarian, Mediterranean and intermittent fasting (IF) diets compared to low fat diets on diabetes control and management. Methods and results In accordance with PRISMA guidelines, Cochrane CENTRAL, PubMed and Scopus databases were systematically searched for relevant studies. Twenty randomised controlled trials (RCTs) > 6 months that investigated the effectiveness of various dietary patterns on type 2 diabetes mellitus (T2DM) were included. Risk of bias was assessed using the Cochrane tool. There were no significant differences in glycemic control, weight and lipids for the majority of low carbohydrate diets (LCDs) compared to low fat diets (LFDs). Four out of fifteen LCD interventions showed better glycemic control while weight loss was greater in one study. The Mediterranean dietary pattern demonstrated greater reduction in body weight and HbA1c levels and delayed requirement for diabetes medications. The vegan and macrobiotic diet demonstrated improved glycemic control, while the vegetarian diet showed greater body weight reduction and insulin sensitivity. Conclusions Although more long-term intervention trials are required, mounting evidence supports the view that vegan, vegetarian and Mediterranean dietary patterns should be implemented in public health strategies, in order to better control glycemic markers in individuals with T2DM.

Total polyphenol intake, polyphenol subtypes and incidence of cardiovascular disease: The SUN cohort study

Abstract: Background and aims Polyphenol-rich diets have been associated with reduced risk of cardiovascular disease (CVD). However, few prospective epidemiological studies have examined the relationship between classes of ingested polyphenols and risk of CVD. Our aim was to evaluate the association between polyphenol intake and risk of major cardiovascular events in a prospective Spanish cohort. Methods and results We included 17,065 university graduates (60.7% women, mean age: 37.2 years, age range: 20–89) followed-up for a mean of 10.1 years. Polyphenol intake was assessed at baseline using a validated semi-quantitative 136-item food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for incident cardiovascular events (myocardial infarction, stroke or cardiovascular death). Cherries, chocolate, coffee, apples, and olives were the major sources of variability in polyphenol intake. Participants with higher flavonoids intake (fifth quintile) had a 47% lower incidence of cardiovascular events compared to those in the lowest quintile (HR: 0.53, 95% CI: 0.29–0.98; P for trend = 0.09) after adjusting for potential confounders. The results were non-significant for other polyphenol types. Conclusion The intake of flavonoids showed an inverse association with risk of cardiovascular events in a prospective cohort of Spanish middle-aged adult university graduates. Registration number for clinical trials NCT02669602 in Clinical Trials.

Dietary fat intake and metabolic syndrome in adults: A systematic review

Abstract: Background and aims The metabolic syndrome (MetS) is a cluster of coexisting cardiovascular risk factors. The role of specific dietary fats was reemphasized by dietary recommendations. This systematic review aims to assess evidence for the effect of dietary fat intake on MetS occurrence and reversion in adults. Methods and Results The MEDLINE database was used to search the existing literature. We included observational studies that analyzed dietary fat intake in adults with MetS and clinical trials that compared the effects of different dietary fat diets on MetS and/or its components. Thirty articles were selected (14 observational and 16 clinical trials), and we included information of dietary fat and fatty acids as well as MetS, body mass index, cholesterol, hypertension, and diabetes in adults. SFA intake was found to be positively associated with MetS components. Most of the observational reviewed studies found beneficial associations between MUFA and PUFA (including n-3 and n-6 subtypes) intake and MetS components. Clinical trials also supported the benefits of MUFA- or PUFA-enriched diets (including low-fat diets) in reducing MetS. Conclusions The effects of dietary SFAs on MetS will be influenced by other specific nutrients. Replacement of SFA by MUFA and PUFA has been associated with a decrease in MetS. Dietary recommendations should emphasize on different qualities of fat intake, not only to reduce total fat intake, to obtain health benefits in adults.

Effect of synbiotic pomegranate juice on glycemic, sex hormone profile and anthropometric indices in PCOS: A randomized, triple blind, controlled trial.

Abstract: Background and Aims Polycystic Ovarian Syndrome is a common reproductive, endocrine, and metabolic disease in women. Pomegranate juice, known as a rich source of phytochemicals with high antioxidant activity, enriched with probiotic may improve PCOS. Methods and Results A randomized, controlled, triple-blinded, parallel trial study was performed in PCOS patients (n = 92). Three treatment groups (23 patients each) received 2 L of synbiotic pomegranate juice (SPJ), pomegranate juice (PJ), and synbiotic beverage (SB) weekly. The control group (23 patients) received 2 L of placebo beverage weekly. Primary outcome was any change in insulin resistance and secondary outcomes were fasting blood sugar (FBS), insulin sensitivity, testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), body mass index (BMI), waist and hip circumference, from baseline to the end of the trial. At the end of the study, 86 patients were analyzed. There was significant change in insulin resistance in the SPJ and SB groups. Insulin sensitivity increased significantly in the SPJ and SB groups. Insulin also changed significantly in the SPJ and SB groups. BMI, weight and waist circumference decreased significantly in the SPJ and SB groups. Testosterone level also decreased significantly in the SPJ and SB groups. There was no significant change in FPG, LH and FSH in any of the groups. Conclusion SPJ in the form of a new beverage can improve insulin resistance, insulin, testosterone level, BMI, weight and waist circumference in PCOS. This trial was registered in Iranian Registry of Clinical Trials, with number: 25272.

Population dietary salt reduction and the risk of cardiovascular disease. A scientific statement from the European Salt Action Network.

Abstract: The publication in the last few years of a number of prospective observational studies suggesting a J-shaped association between levels of salt (sodium) consumption and cardiovascular outcomes has opened a debate on the pertinence of population-wide salt reduction policies to reduce cardiovascular disease burden, and some have even questioned the global World Health Organization guidelines, that recommend a 30% reduction in salt consumption by 2025, aiming at an ideal target of no more than 5 g of salt consumption per day. In September 2018 the European Salt Action Network (E.S.A.N.), after appraising the quality of publications questioning the appropriateness of population salt reduction, discussed the scientific evidence and identified the pitfalls of recent data. The new evidence was deemed inadequate and, in places, biased by flawed methodology. These were identified in the biased assessment of sodium intake from spot urine and the use of the Kawasaki formula, the biased assessment of the sodium–outcome relationships in prospective observational studies using spot urine samples, the impact of reverse causality in such studies, the inadequate analytical approaches to data analysis, the lack of biological plausibility and the lack of precision in assessing long-term salt consumption, as recently demonstrated in studies using more stringent quality features in their study designs. On the basis of such appraisal, the E.S.A.N. agreed a statement confirming the support to the implementation of national and regional programmes of moderate reduction in salt intake, as recommended by the World Health Organization.

Dietary habits of adolescents living in North America, Europe or Oceania: A review on fruit, vegetable and legume consumption, sodium intake, and adherence to the Mediterranean Diet.

Abstract: Aims This review aimed at investigating fruit, vegetable and legume consumption, salt/sodium intake, and the adherence to the Mediterranean dietary pattern in adolescents, three key aspects towards the adoption of a healthy diet. Data synthesis Three separate searches were carried out on PubMed and Scopus, using the same procedure, searching for studies published in the previous decade with data on fruit and/or vegetable or legume consumption, salt or sodium intake, and adherence to the Mediterranean Diet assessed using the KIDMED questionnaire. The review included a total of 58 papers, which describe original investigations on healthy adolescents (10–19 years old) living in North America, Europe or Oceania, with a sample size >150 participants. The average fruit and vegetable consumption has been found strongly below the recommended values of 400 grams or 5 portions per day in almost all the examined populations. Very little is known about adolescents' legume consumption. Few available data have been found also for sodium intake and, for the majority of the screened populations, levels were far above the recommended 5 grams per day. Lastly, a medium–low adherence to the Mediterranean Diet has been found for adolescents living in Mediterranean Countries. Conclusions Adolescents living in North America, Europe or Oceania are far from being compliant with the nutritional recommendations for fruit, vegetables, legumes, and sodium, and they do not follow the principles of the Mediterranean Diet. Educational and behavioural interventions are required to improve adolescents' dietary patterns.

Impact of severe and symptomatic hypoglycemia on quality of life and fear of hypoglycemia in type 1 and type 2 diabetes. Results of the Hypos-1 observational study.

Abstract: Background and aims Hypoglycemia represents a relevant burden in people with diabetes. Consequences of hypoglycemia/fear of hypoglycemia on quality of life (QoL) and behaviors of patients with T1DM and T2DM were assessed. Methods and results HYPOS-1 was an observational retrospective study. Fear of hypoglycemia (Fear of Hypoglycemia Questionnaire, FHQ), general health status (visual analog scale of EuroQol questionnaire, EQ5D-VAS) psychological well-being (WHO-5 well being index, WHO-5), diabetes related distress (Problem Areas in Diabetes 5, PAID-5), and corrective/preventive behaviors following hypoglycemia were compared between people with and without previous experience of severe and symptomatic hypoglycemia and by tertiles of FHQ scores. A multivariate analysis was performed to identify factors associated with the likelihood of being in the third tertile of FHQ score. Overall, 2229 patients were involved. Severe hypoglycemia had statistically significant and clinically relevant (measured as effect sizes) negative impact on EQ5D-VAS, WHO-5, PAID-5, and FHQ both in T1DM and T2DM. In T2DM, symptomatic episodes had similar impact of severe hypoglycemia. Moving from the first to the third FHQ tertile, lower scores of EQ-5D VAS and WHO-5, and higher levels of PAID-5 were found. Patients in the third tertile performed more frequently corrective/preventive actions that negatively impact on metabolic control. Previous hypoglycemia, insulin treatment, female gender, age, and school education were the independent factors associated with increased likelihood to be in the third tertile. Conclusion Not only severe but also symptomatic hypoglycemia negatively affect patient QoL, especially in T2DM. Addressing fear of hypoglycemia should be a goal of diabetes education.

High plasma glutamate and low glutamine-to-glutamate ratio are associated with type 2 diabetes: Case-cohort study within the PREDIMED trial

Abstract: Background and aims Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD). Methods and results The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95% CI, 1.43–5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36–1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16–0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01). Conclusion Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com , ISRCTN35739639.

Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis

Abstract: Background and aim This network meta-analysis (NMA) compares the effects of different types of olive oil (OO) on cardiovascular risk factors. Methods and results Literature search was conducted on three electronic databases (Medline, Web of Science, and Cochrane Central). Inclusion criteria: Randomized controlled trials (RCTs) (≥3 weeks duration of intervention) comparing at least two of the following types of OO: refined OO (ROO), mixed OO (MOO), low phenolic (extra) virgin OO (LP(E)VOO), and high phenolic (extra) virgin OO (HP(E)VOO). Random-effects NMA was performed for seven outcomes; and surface under the cumulative ranking curve (SUCRA) was estimated, using an analytical approach (P-score). Thirteen RCTs (16 reports) with 611 mainly healthy participants (mean age: 26–70 years) were identified. No differences for total cholesterol, HDL-cholesterol, triacylglycerols, and diastolic blood pressure were observed comparing ROO, MOO, LP(E)VOO and HP(E)VOO. HP(E)VOO slightly reduce LDL-cholesterol (LDL-C) compared to LP(E)VOO (mean difference [MD]: −0.14 mmol/L, 95%–CI: −0.28, −0.01). Both, HP(E)VOO and LP(E)VOO reduces SBP compared to ROO (range of MD: −2.99 to −2.87 mmHg), and HP(E)VOO may improve oxidized LDL-cholesterol (oxLDL-C) compared to ROO (standardized MD: −0.68, 95%–CI: −1.31, −0.04). In secondary analyses, EVOO may reduce oxLDL-C compared to ROO, and a dose-response relationship between higher intakes of phenolic compounds from OO and lower SBP and oxLDL-C values was detected. HP(E)VOO was ranked as best treatment for LDL-C (P-score: 0.83), oxLDL-C (0.88), and SBP (0.75). Conclusions HP(E)VOO may improve some cardiovascular risk factors, however, public health implications are limited by overall low or moderate certainty of evidence.

Differential effect of short-term popular diets on TMAO and other cardio-metabolic risk markers

Abstract: Background Dietary nutrient intake and its metabolism by the gut microbiome have recently been implicated in cardiovascular disease (CVD) risk. In particular, trimethylamine N-oxide (TMAO), a metabolite of the gut microbiota, has been shown to be a predictor of incident CVD events. Elevated levels of branched-chain amino acids (BCAA) have also been associated with an increased propensity for insulin resistance. Methods To study the association of dietary intake with systemic TMAO, its nutrient precursors, and BCAA levels on fasting plasma levels of TMAO and its nutrient precursors and BCAA, we conducted an exploratory post-hoc analysis of 3 popular diets – high fat (Atkins), Mediterranean (South Beach), and very low fat (Ornish) – using plasma samples from a prior randomized, crossover study, with each isocaloric dietary phase lasting 4 weeks. Metabolites were quantified using stable isotope dilution HPLC with on-line tandem mass spectrometry. Results Compared to the low fat Ornish phase, the high fat Atkins dietary phase was characterized by increased levels of TMAO (3.3 vs. 1.8 μM, p = 0.01), and the BCAA valine (272.8 vs. 235.8 μM, p = 0.005) and leucine (105.9 vs. 96.4 μM, p = 0.01). The high fat Atkins dietary phase was also associated with higher levels of TMAO (3.3 vs 1.6 μM, p = 0.04), valine (272.8 vs. 240.7 μM, p = 0.004), and leucine (105.9 vs. 96.4 μM, p = 0.01) compared to baseline. Conclusions These data suggest that over a 4-week interval, a saturated fat diet that is predominantly animal-based, compared to an isocaloric, low fat, predominantly plant-based diet, is associated with heightened risk for cardiometabolic derangements, as monitored by a higher plasma levels of both TMAO and BCAA.

Gender differences in homocysteine concentrations, a population-based cross-sectional study.

Abstract: Background and aims High concentrations of homocysteine are considered a risk factor for atherosclerosis and coronary artery disease. The aim of this study was to assess whether or not there are gender differences in the plasma concentrations of homocysteine. Methods and results Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000–2014. Cross sectional analysis was carried out on 9237 men and 4353 women. Mean (SD) age of the study sample was 48.4 (9.7) and 47.7 (9.7) years for men and women respectively. Average homocysteine concentrations were 12.6 (5.9) and 9.6 (3.2) μmol/L in men and women respectively (p Conclusion Plasma homocysteine concentrations are higher in men than in women. This may be a contributing factor to gender differences for developing atherosclerosis and coronary artery disease.

The use of real time continuous glucose monitoring or flash glucose monitoring in the management of diabetes: A consensus view of Italian diabetes experts using the Delphi method

Abstract: Until recently, in Italy, the use of continuous glucose monitoring (CGM) systems has been limited, but is now rapidly increasing, including the so-called real-time CGM (rtCGM) and the intermittently viewed CGM (iCGM), also called Flash Glucose Monitoring (FGM). These technologies overcome many of the limitations of self-monitoring of blood glucose (SMBG) by fingerprick and allow to go beyond HbA1c to check glucose control in diabetes. However, standardized protocols for applying and interpreting rtCGM and FGM data are lacking. In this paper, we delineate a consensus amongst Italian diabetes physicians on the attributes of rtCGM and FGM technologies, and introduce a consistent approach for their use by Italian healthcare professionals. Most experts consider rtCGM and FGM as two separate categories of interstitial subcutaneous fluid (ISF) sensing technologies, and see them as superior to SMBG. Furthermore, there is strong consensus that rtCGM and FGM reduce hypoglycemia risk, increase the amount of time in the target glucose range and augment treatment satisfaction. However, there is still no agreement on the indication of the FGM for subjects who suffer asymptomatic hypoglycemia. Consensus on the role of education in initiating and optimizing use of rtCGM/FGM and about the interpretation of glucose trends was near unanimous, whereas no consensus was reached on the statement that there are no disadvantages/risks of rtCGM/FGM. Some issues remain in rtCGM/FGM management: a) risk of excessive correction of high or low glucose; b) risk of alert fatigue leading to alert silencing or rtCGM termination; c) allergic reaction to the adhesive keeping rtCGM or FGM sensors in place. The panel almost unanimously agreed that sensor accuracy depends on multiple variables, that alarm setting should be individualized, and that global glycemic profile represent an useful tool in interpreting glucose data. More clinical studies and a wider use of these devices will increase the efficacy and effectiveness of continuous glucose monitoring in Italy.

The probiotic Lactobacillus fermentum 296 attenuates cardiometabolic disorders in high fat diet-treated rats.

Abstract: Background and aim High-fat (HF) diet consumption has been associated with gut dysbiosis and increased risk of dyslipidemia, type 2 diabetes mellitus and hypertension. Probiotic administration has been suggested as a safe therapeutic strategy for the treatment of cardiometabolic disorders. This study was designed to assess the effects of probiotic Lactobacillus (L.) fermentum 296, a fruit-derived bacteria strain, against cardiometabolic disorders induced by HF diet. Methods and results Male Wistar rats were divided into control diet (CTL); HF diet; and HF diet treated with Lactobacillus fermentum 296 (HF + Lf 296). The L. fermentum 296 strain at 1 × 109 colony forming units (CFU)/ml were daily administered by oral gavage for 4 weeks. The results showed that rats fed with HF diet displayed insulin resistance, reduced Lactobacillus spp. counts in feces, serum lipids, and oxidative profile. Rats fed on HF diet also demonstrated augmented blood pressure associated with sympathetic hyperactivity and impaired baroreflex control. The administration of L. fermentum 296 for 4 weeks recovered fecal Lactobacillus sp. counts and alleviated hyperlipidemia, sympathetic hyperactivity, and reduced systolic blood pressure in HF rats without affecting baroreflex sensibility. Conclusion Our results suggest the ability of L. fermentum 296 improve biochemical and cardiovascular parameters altered in cardiometabolic disorders.

Blood pressure levels and hypertension prevalence in a high selenium environment: results from a cross-sectional study

Abstract: Background and aims Recent human and laboratory studies have suggested the possibility that selenium overexposure may increase blood pressure. We sought to ascertain whether adults living in a seleniferous area exhibit an association between selenium exposure and both blood pressure levels as well as prevalence of hypertension. Methods and results We measured selenium levels in blood (serum), hair and nail samples obtained from 680 adult volunteers (267 men and 413 women), living in seven Punjabi villages in a seleniferous area and related them to health outcomes, including systolic and diastolic blood pressure and presence of hypertension. In a multivariable restricted cubic spline regression model, adjusted for age, sex and history of hypertension, we found a positive association between systolic blood pressure and both serum (P = 0.004) and hair (P = 0.058) selenium levels, but not with nail selenium content. Little association emerged between the three selenium biomarkers and diastolic blood pressure. Hypertension prevalence was positively associated with the three exposure indicators (P Conclusions Overall, these findings suggest that chronic overexposure to environmental selenium may increase blood pressure, though there were inconsistencies for this association according to the choice of exposure indicator, the study endpoint and the sex.

Effects of Ramadan intermittent fasting on lipid and lipoprotein parameters: An updated meta-analysis.

Abstract: Aims This systematic review and meta-analysis aimed to clarify several aspects of intermittent fasting during the month of Ramadan on lipid and lipoprotein levels in apparently healthy subjects. Data synthesis We searched PubMed, Scopus, and Embase databases and the reference lists of previous reviews, up to Feb 2019 for studies that investigated the effects of Ramadan fasting on fasting levels of triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C, and VLDL-C among healthy subjects including pregnant women and athletic subjects. Studies were selected for quality assessment, meta-analyses, subgroup analyses, and meta-regressions; data of 33 eligible studies, conducted between 1978 and 2019, were included in the analysis. Results Intermittent fasting showed no significant effect on circulating TG (WMD = −0.38 mg/dl, 95% CI = −5.33, 4.57), TC (WMD = −1.58 mg/dl, 95% CI = −6.04, 2.88), and LDL-C levels (WMD = 1.85 mg/dl, 95% CI = 0.77, 2.92). Overall, HDL-C (WMD = −2.97 mg/dl; 95% CI = −6.43, 0.48 mg/dl) and VLDL-C (WMD = −1.41 mg/dl; 95% CI = −2.73, −0.10 mg/dl) significantly decreased after Ramadan fasting. A significant increase in LDL-C levels was observed in athletic subjects (WMD = 2.97 mg/dl; 95% CI = 0.80, 5.13) and apparently healthy subjects (WMD = 1.81 mg/dl; 95% CI = 0.55, 3.07). Change in TG levels was associated with age (β = −0.94, P = 0.043), its baseline values (β = −0.44, P = 0.001), and weight change during the fasting period (β = −0.57, P = 0.032). Conclusion Ramadan fasting may be accompanied by a moderate improvement of lipid and lipoprotein parameters, especially HDL-C levels; fasting appears to be more beneficial for men and athletic subjects.

The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia - A systematic review and meta-analysis.

Abstract: Background and aims Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia. Methods and results PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24–2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30–085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55–0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76–0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00–1.67, P = 0.05) after the CARES study was included. Conclusion Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia. Registration number PROSPERO(CRD42018091657).

Association between long-term exposure of ambient air pollutants and cardiometabolic diseases: A 2012 Korean Community Health Survey.

Abstract: Background and aim The associations of long-term exposure to particulate matter Methods and results We selected 100,867 adults aged 19 years or older who had lived in the same domicile for ≥10 years and surveyed them to collect data on socioeconomic characteristics; health-related behaviors; obesity; and physician-diagnosed CMD history, including hypertension, diabetes mellitus, dyslipidemia, stroke, myocardial infarction, and ischemic heart disease. We calculated interquartile ranges for PM10, NO2, CO, SO2, and O3 from the 10 year average concentrations (2003–2012). Hypertension, diabetes mellitus, and dyslipidemia were positively associated with PM10, NO2, CO, SO2, and O3 after adjusting for confounding factors. Obesity was positively associated with PM10, NO2, SO2, and O3. On the other hand, we found no associations between stroke, myocardial infarction, and ischemic heart disease and exposure to PM10, NO2, CO, SO2, and O3 in these subjects. In subjects aged ≥65 years, the risk of dyslipidemia was markedly increased under exposure to NO2 and CO compared to subjects aged Conclusion Long-term exposure to PM10, NO2, CO, SO2, and O3 may be a risk factor of CMD in Korean adults.

GDF15 reflects beta cell function in obese patients independently of the grade of impairment of glucose metabolism.

Abstract: Background and aims Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function. Methods and results In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35–63 kg/m2, age 39.4 ± 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated. GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups. Conclusion We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options.

Betulinic acid inhibits high-fat diet-induced obesity and improves energy balance by activating AMPK.

Abstract: Background and aim Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity. Methods and results Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA. Conclusions The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.

Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese.

Abstract: Background and aims It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese. Methods and results As many as 70,303 subjects with a body mass index (BMI) Conclusions In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.

Carbohydrate intake and risk of metabolic syndrome: A dose-response meta-analysis of observational studies.

Abstract: Background and aims Epidemiological association studies have reported inconsistent findings on the relationship between carbohydrate intake and risk of metabolic syndrome (MetS). Therefore, we aimed to conduct the first dose–response meta-analysis to investigate this effect. Methods and results A systematic search in PubMed and Web of Science databases from their inception to June 01, 2019, together with relevant literature scrutiny, was performed to identify related studies for inclusion into the meta-analysis. We calculated the odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Furthermore, subgroup, sensitivity, heterogeneity, and publication bias analyses were performed. This meta-analysis included 14 cross-sectional and four cohort studies, totaling 284,638 participants and 69,554 MetS cases. The highest versus the lowest carbohydrate intake values were associated with an increased risk of MetS (OR: 1.253, 95% CI: 1.147–1.368), with moderate heterogeneity (I2 = 54.5%). Using dose–response analysis, we found a linear association between carbohydrate consumption and MetS risk with a corresponding OR of 1.026 (95% CI, 1.004–1.048) and with significant heterogeneity (I2 = 82.0%) at 5% energy intake from carbohydrates. We have found similar results using subgroup analyses for major study characteristics and adjustment for confounders. Sensitivity analysis further enhanced the robustness of the results, and no publication bias was detected. Conclusion Carbohydrate intake is associated with an increased risk of developing MetS. Therefore, additional large prospective cohort studies are warranted to confirm our findings.

Relationship between albuminuric CKD and diabetic retinopathy in a real-world setting of type 2 diabetes: Findings from No blind study.

Abstract: Background and aims Recently, the albuminocentric view of diabetic kidney disease (DKD) in type 2 diabetes (T2DM) has been changing. Therefore, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) has to be addressed according to this new clinical presentation of DKD. The aim of this study was to evaluate, in a real-world setting, the correlation DR–DKD in T2DM. Methods and results A total of 2068 type 2 diabetic patients enrolled in a multicenter cross-sectional study were investigated. Albuminuric subjects were largely prevalent among subjects with DR (p = 0.019). In the whole study population, no difference in albumin excretion rate (AER) was observed between presence/absence of DR; instead, AER was significantly higher among patients with glomerular filtration rate (eGFR) Conclusion In T2DM with DKD, the AER seems to be related to the presence of DR. This association is confirmed above all in those with more severe DR.

Efficacy of l-carnitine supplementation for management of blood lipids: A systematic review and dose-response meta-analysis of randomized controlled trials.

Abstract: Background and aim l -carnitine has an important role in fatty acid metabolism and could therefore act as an adjuvant agent in the improvement of dyslipidemia. The purpose of present systematic review and meta-analysis was to critically assess the efficacy of l -carnitine supplementation on lipid profiles. Methods and results We performed a systematic search of all available randomized controlled trials (RCTs) in the following databases: Scopus, PubMed, ISI Web of Science, The Cochrane Library. Mean difference (MD) of any effect was calculated using a random-effects model. In total, there were 55 eligible RCTs included with 58 arms, and meta-analysis revealed that l -carnitine supplementation significantly reduced total cholesterol (TC) (56 arms-MD: −8.53 mg/dl, 95% CI: −13.46, −3.6, I2: 93%), low-density lipoprotein-cholesterol (LDL-C) (47 arms-MD: −5.48 mg/dl, 95% CI: −8.49, −2.47, I2: 94.5) and triglyceride (TG) (56 arms-MD: −9.44 mg/dl, 95% CI: −16.02, −2.87, I2: 91.8). It also increased high density lipoprotein-cholesterol (HDL-C) (51 arms-MD:1.64 mg/dl, 95% CI:0.54, 2.75, I2: 92.2). l -carnitine supplementation reduced TC in non-linear fashion based on dosage (r = 21.11). Meta-regression analysis indicated a linear relationship between dose of l -carnitine and absolute change in TC (p = 0.029) and LDL-C (p = 0.013). Subgroup analyses showed that l -carnitine supplementation did not change TC, LDL-C and TG in patients under hemodialysis treatment. Intravenous l -carnitine and lower doses (>2 g/day) had no effect on TC, LDL-C and triglycerides. Conclusion l -carnitine supplementation at doses above 2 g/d has favorable effects on patients' lipid profiles, but is modulated on participant health and route of administration.

Moderate alcohol consumption and lower total mortality risk: Justified doubts or established facts?

Abstract: For almost a century, the scientific community is aware of the J-shaped curve between alcohol consumption and all-cause mortality. Moderate drinkers seem to live longer than both abstainers and heavy drinkers. These epidemiological observations regarding moderate alcohol consumption and beneficial health effects have been incessantly scrutinised for confounding and bias. This viewpoint discusses previous and recent criticisms regarding the J-shaped curve between alcohol consumption and total mortality risk. The controversies regarding the J-shaped curve between alcohol consumption and mortality are ongoing, as well as the debate among scientists in this area of research, resulting in conflicting messages in media and in different alcohol guidelines. Although it appears quite difficult to come up with a position statement only based on the currently available scientific data, it is imperative to fairly inform the public, without creating confusion and, worst case, disbelief in science.

Lipoprotein-X fifty years after its original discovery.

Abstract: Aims To review the formation, catabolism, and the possible atherogenic properties of Lp-X. Data Synthesis The conversion of cholesterol to bile acids is regulated by several mechanisms including cholesterol 7 alpha hydroxylase, fibroblast growth factor 19, and farnesoid X receptors. During cholestasis these mechanisms are altered and there is an accumulation of bile acids and cholesterol in plasma. The hypercholesterolemia observed in cholestasis is due to the presence of an anomalous lipoprotein called lipoprotein-X (Lp-X). Lp-X is a lipoprotein rich in phospholipid and free cholesterol present in plasma of patients with cholestasis and, with some variations, in patients with lecithin-cholesterol-acyl-transferase deficiency (LCAT), and after lipid infusion. Lp-X is formed from a bile lipoprotein moving to the blood vessels where it incorporates small quantities of triglycerides, apo-C and esterified cholesterol and becomes a “mature” Lp-X. The activity of the phosphatidilcholine canalicular transporter Mdr2 P-glycoprotein (homologous to the human ABCB4) is essential for LpX appearance, since its suppression abolishes Lp-X formation. However, the concentration of Lp-X in plasma is determined also by the degree of the cholestasis, the residual liver function, and the LCAT deficiency. The Lp-X catabolism seems to be mediated by the reticuloendothelial system and possibly the kidney. Conclusions Lp-X might be considered a defense mechanism against the toxic effect of free cholesterol in cholestasis. The frequency of cardiovascular events in patients affected by primary biliary cholangitis, in whom the Lp-X is present in high concentration, are not increased. Further studies could now clarify the remaining open questions on the role of Lp-X in the dyslipidemia of cholestasis.

Mediterranean alcohol-drinking pattern, low to moderate alcohol intake and risk of atrial fibrillation in the PREDIMED study

Abstract: Background and aims There is ongoing controversy about the effect of a low to moderate alcohol consumption on atrial fibrillation (AF). Our aim is to assess the association between adherence to a Mediterranean alcohol drinking pattern and AF incidence. Methods and results A total 6527 out of the 7447 participants in the PREDIMED trial met our inclusion criteria. A validated frequency food questionnaire was used to measure alcohol consumption. Participants were classified as non-drinkers, Mediterranean alcohol drinking pattern (MADP) (10–30 g/d in men and 5–15 g/day in women, preferably red wine consumption with low spirits consumption), low-moderate drinking ( Conclusions In a high cardiovascular risk adult population, a Mediterranean alcohol consumption pattern (low to moderate red wine consumption) was not associated with an increased incidence of AF. Clinical trials URL: http://www.controlled-trials.com . Unique identifier: ISRCTN35739639.

Association of metabolic syndrome with atherogenic index of plasma in an urban Chinese population: A 15-year prospective study.

Abstract: Background and aims The metabolic syndrome(Mets) is a multiplex risk factor for atheroselerotie cardiovascular disease. The aims of the study were to assess the association of the Mets with atherogenic index of plasma(AIP) and other atherogenic parameters in an urban Chinese population. Methods and results The data were collected in 1992 and then again in 2007 from the same group of 582 individuals(359 men and 223 women) without Mets in 1992. During 15 years’ follow-up, AIP was the lipid parameter that was most strongly associated with Mets, with an unadjusted odds ratio of 5.66 (95% CI:1.76–18.23, P = 0.004) in the univariate logistic regression analysis. Multivariate logistic regression analyses also revealed that AIP was an independent risk factor for Mets. AIP significantly predicted Mets in men, with an unadjusted odds ratio of 30.73 (95% CI: 5.62, 168.12 P = 0.012) in a univariate model. Associations remained significant after adjustment for smoking, drinking, physical exercise and components of Mets. The incidences of Mets adjusted for age according to the quartiles of AIP showed a statistical linear trend in men(P for trend = 0.007) rather than in women(P for trend = 0.529). Conclusions AIP might be a strong and independent predictor for Mets in an urban Chinese population. The incidence of Mets increased with AIP elevated in men while not in women.

Temporal relationship between body mass index and triglyceride-glucose index and its impact on the incident of hypertension.

Abstract: Background and aims Obesity and insulin levels can influence each other by metabolism However, their temporal sequences and influence on hypertension are generally unknown, especially in Chinese adults Recently, some scholars have proposed that triglycerides-glucose index (TyG) is an important indicator of insulin resistance The study aims to describe the relationship between body mass index (BMI) and TyG index and its impact on hypertension Methods and results A total of 4081 adults (5633% women) without antihypertensive, hypoglycemic or lipid-lowering medications were selected for the present study Measurements of BMI and TyG index were obtained twice from 2012 to 2017 Cross-lagged panel analysis was used to describe the temporal sequences between BMI and TyG index, and the effect of their temporal relationship patterns on hypertension was explored through mediation analysis After adjusting for confounding factors (age, sex, ethnicity et al), the cross-lagged path coefficient from baseline BMI to follow-up TyG (ρ2 = 0135, P Conclusion These results provided evidence that the temporal relationship between BMI and insulin resistance is reciprocal and a higher BMI precedes hyperinsulinemia in Chinese adults This relationship plays an essential role in the development of hypertension, while there is a difference between women and men