BACKGROUND: Nutritional management plays a crucial role in treating patients with type 2 diabetes (T2D), working to prevent and control the progression of chronic non-communicable diseases.
OBJECTIVE: To evaluate the effects of individualized nutritional interventions on weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)} over 12 months and subsequently at follow-up (15 months).
METHODS: This longitudinal experimental study (without randomization and blinding) enrolled 84 sedentary participants with T2D (both sexes, aged 18-80 years). They were divided into a control group of 40 participants who received only medical consultations, and an intervention group of 44 participants who received the same medical care along with a nutritional assessment. Consultations occurred quarterly from August 2020 to November 2022 (first-twelfth month), with six to nine patients per session. Subsequently, a follow-up was conducted from December 2022 to November 2023, during which the intervention group had only medical care (during the 12th-15th months). Personalized dietary planning was inspired by the Mediterranean/DASH diets adapted to Brazilian foods and socioeconomic cultures.
METHODS: Normal variables were compared between groups for each time point and also within each group across different time points using a two-way ANOVA (repeated measures for intragroup) followed by the Šídák post hoc test. Non-normal variables were compared between groups for each time point using Kruskal-Wallis followed by the Dunn post hoc test, and within each group across different time points using Friedman followed by the Dunn post hoc test. Data with a Gaussian distribution were presented as mean ± standard deviation (SD), and data with a non-Gaussian distribution were presented as median ± interquartile range (IQR). For all cases, α < 0.05 and p < 0.05 were adopted.
RESULTS: In the intervention group, significant reductions were observed between the first and twelfth month for all parameters (p < 0.05), (except for TC), along with an increase in HDL-C (p = 0.0105). Conversely, in the control group, there was a significant increase in HbA1c, weight, BMI, FBG, and WHR (p < 0.05) between the first and twelfth months. Regarding the comparison between groups, there was a significant difference for all analyzed parameters (p < 0.05) from the first to the twelfth month. In the follow-up, differences were also observed (p < 0.05), except for BMI (p > 0.05).
CONCLUSIONS: The individualized nutritional intervention improved eating habits, anthropometric, biochemical, and cardiovascular markers in T2D over 12 months, with sustained results during follow-up. The dietary plan inspired by the Mediterranean and DASH diets demonstrated good adaptation to the Brazilian food culture and the patients\' socioeconomic contexts. Consistent monitoring and personalized nutritional management are essential for optimizing long-term outcomes. However, more clinical trials are necessary in order to optimize the level of evidence for longitudinal interventions.

Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically relevant analyses, stable isotope-labeled (SIL) internal standards (ISs) represent the \"gold standard\" for quantitation due to their similar physiochemical properties to the analyte, wide availability, and ability to multiplex to several peptides. However, the purchase of SIL-ISs is a resource-intensive step in terms of cost and time, particularly for screening putative biomarker panels of hundreds of proteins. We demonstrate an alternative strategy utilizing nonhuman sera as the IS for quantitation of multiple human proteins. We demonstrate the effectiveness of this strategy using two high abundance clinically relevant analytes, vitamin D binding protein [Gc globulin] (DBP) and albumin (ALB). We extend this to three putative risk markers for cardiovascular disease: plasma protease C1 inhibitor (SERPING1), annexin A1 (ANXA1), and protein kinase, DNA-activated catalytic subunit (PRKDC). The results show highly specific, reproducible, and linear measurement of the proteins of interest with comparable precision and accuracy to the gold standard SIL-IS technique. This approach may not be applicable to every protein, but for many proteins it can offer a cost-effective solution to LC-MS/MS protein quantitation.

Prospective studies have failed to establish a causal relationship between animal fat intake and cardiovascular diseases in humans. Furthermore, the metabolic effects of different dietary sources remain unknown. In this four-arm crossover study, we investigated the impact of consuming cheese, beef, and pork meat on classic and new cardiovascular risk markers (obtained from lipidomics) in the context of a healthy diet. A total of 33 young healthy volunteers (23 women/10 men) were assigned to one out of four test diets in a Latin square design. Each test diet was consumed for 14 days, with a 2-week washout. Participants received a healthy diet plus Gouda- or Goutaler-type cheeses, pork, or beef meats. Before and after each diet, fasting blood samples were withdrawn. A reduction in total cholesterol and an increase in high density lipoprotein particle size were detected after all diets. Only the pork diet upregulated plasma unsaturated fatty acids and downregulated triglycerides species. Improvements in the lipoprotein profile and upregulation of circulating plasmalogen species were also observed after the pork diet. Our study suggests that, within the context of a healthy diet rich in micronutrients and fiber, the consumption of animal products, in particular pork meat, may not induce deleterious effects, and reducing the intake of animal products should not be regarded as a way of reducing cardiovascular risk in young individuals.

Cardiovascular disease (CVD) is highly prevalent and can lead to disability and premature mortality. Sedentary behaviour, defined as a low energy expenditure while sitting or lying down, has been identified as an independent risk factor for CVD. This article discusses (1) the association of total sedentary time and patterns of accumulating sedentary time with CVD risk markers, CVD incidence and mortality; (2) acute experimental evidence regarding the acute effects of reducing and breaking up sedentary time on CVD risk markers; and (3) the effectiveness of longer-term sedentary behaviour interventions on CVD risk. Findings suggest that under rigorously controlled laboratory and free-living conditions, breaking up sedentary time improves cardiovascular risk markers in individuals who are healthy, overweight or obese, or have impaired cardiovascular health. Breaking up sedentary time with walking may have the most widespread benefits, whereas standing breaks may be less effective, especially in healthy individuals. There is also growing evidence that sedentary behaviour interventions may benefit cardiovascular risk in the longer term (i.e., weeks to months). Reducing and breaking up sedentary time may, therefore, be considered a target for preventing and managing CVD. Further research is needed to determine the effectiveness of sedentary behaviour interventions over the long-term to appropriately inform guidelines for the management of CVD.

OBJECTIVE: Ambient particle matter is a risk factor for cardiovascular disease (CVD). However, little is known about associations between particles in occupational settings and risk of CVD. We investigated associations between occupational dust exposure and biomarkers of CVD, and potential recovery effects after vacation.
METHODS: Personal dust exposure measurements (respirable silica, respirable dust < 4 µm, and particles of 0.1-10 µm (PM 0.1-10) were conducted once, and biological sampling were performed twice on non-smoking, male construction workers in Stockholm county, Sweden; during work and immediately after summer vacation. Linear regressions with adjustments for confounders and covariates were performed evaluating associations between occupational dust exposure and biomarkers. Paired t tests were performed evaluating changes before and after vacation.
RESULTS: Sixty-five workers participated. Homocysteine concentrations were significantly higher with increasing concentrations (mg/m3) of respirable silica, respirable dust, and PM 0.1-10, and pulse rate with higher levels of respirable dust and dust of PM 0.1-10. Homocysteine levels were also positively correlated to number of years of dust exposure, as were low-density lipoprotein (LDL) levels. A clear recovery effect was present for LDL after vacation, but not for homocysteine.
CONCLUSIONS: Occupational dust exposure was associated with some CVD risk markers, even at mean exposure concentrations below the Swedish occupational exposure limits for respirable silica and respirable dust, respectively. Vacation resulted in recovery for some risk markers. However, the change of the homocysteine and LDL levels suggest a long-term effect. Reduction of occupational exposure to dust may decrease the risk of CVD among exposed workers.

UNASSIGNED: Extracellular vesicles (EVs) are submicron membrane-bound vesicles released from various cells, which are emerging as a potential novel biomarker in cardiovascular diseases (CVDs) due to their procoagulatory and prothrombotic properties. However, there is little information about the relationships between circulating EVs and conventional and thrombogenic risk markers of CVDs.
UNASSIGNED: To investigate the relationships between circulating EVs, conventional cardiovascular risk markers and thrombogenic markers in subjects with moderate risk of CVDs.
UNASSIGNED: Subjects (n = 40) aged 40-70 years with moderate risk of CVDs were recruited and assessed for body mass index, blood pressure and plasma lipid profile, as well as platelet aggregation, clot formation, thrombin generation and fibrinolysis. Numbers of circulating EVs were assessed by Nanoparticle Tracking Analysis and flow cytometry. A range of assays were used to assess the procoagulatory activity of plasma and circulating EVs.
UNASSIGNED: Circulating EV numbers were positively associated with body mass index, blood pressure, plasma triacylglycerol concentration and overall CVD risk. Higher circulating EV numbers were also associated with increased thrombin generation and enhanced clot formation, and EVs isolated from subjects with moderate CVD risk promoted thrombin generation ex vivo. Higher numbers of endothelial-derived EVs were associated with a greater tendency for clot lysis. Plasma triacylglycerol concentration and diastolic blood pressure independently predicted circulating EV numbers, and EV numbers independently predicted aspects of thrombin generation and clot formation and 10-year CVD risk.
UNASSIGNED: Circulating EVs were strongly associated with both conventional and thrombogenic risk markers of CVDs, and also with overall CVD risk, highlighting a potentially important role for EVs in CVDs.

OBJECTIVE: Replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers.
METHODS: In an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25-70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups.
RESULTS: PLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia.
CONCLUSIONS: The serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants\' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT01679496 on September 6th 2012.

Childhood hypertension drives hypertension in later life; hence, assessing blood pressure in children is an important measure to determine current and future cardiovascular health. There is, however, a paucity of childhood blood pressure data, particularly for sub-Saharan Africa. This study explores blood pressure and associations with age, sex, socioeconomic status, physical activity, fitness, and cardiovascular risk markers. In the \'Disease, Activity and Schoolchildren\'s Health\' (DASH) study, a cross-sectional analysis was conducted in disadvantaged neighbourhoods in the Eastern Cape province of South Africa. Assessments included blood pressure, accelerometer-measured physical activity, physical fitness, and cardiovascular risk markers. The study consisted of 785 children (383 boys, 402 girls, M = 12.4±0.9 years). Overall, 18% of the children were classified as hypertensive, while 20% were either overweight/obese, and almost four out of ten children did not meet global daily physical activity recommendations. Hypertensive children were more likely to be overweight/obese, χ2 (2,785) = 14.42, p < 0.01, but only if they did not meet physical activity recommendations, χ2 (2,295) = 11.93, p < 0.01. Considering the moderating effect which sufficient activity has on the relationship between hypertension and body weight, more emphasis should be placed on early primary health intervention and education strategies.

BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world\'s largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa.
METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free.
RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV.
CONCLUSIONS: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.

Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor that has been developed as oral glucose lowering drug. The original dosefinding studies focused on optimal glycaemic effects. However, dapagliflozin also affects various cardiorenal risk markers and provides cardiorenal protection. To evaluate whether the currently registered doses of 5 and 10 mg are optimal for cardiorenal efficacy and safety, we characterized the relationship between dapagliflozin exposure and nonglycaemic cardiorenal risk markers as well as adverse events.
Data were obtained from a pooled database of 13 24-week randomized controlled clinical trials of the clinical development programme of dapagliflozin. The exposure-response relationship was quantified using population pharmacodynamic and repeated time-to-event models.
A dose of 10 mg dapagliflozin resulted in an average individual exposure of 638 ng h/mL (95% prediction interval [PI]: 354-1061 ng h/mL), which translated to 71.2% (95% PI: 57.9-80.5%), 61.1% (95% PI: 58.0-64.8%), 91.3% (95% PI: 85.4-94.6%) and 25.7% (95% PI: 23.5-28.3%) of its estimated maximum effect for fasting plasma glucose, haematocrit, serum creatinine and urinary albumin-creatinine ratio, respectively.
We demonstrate that doses higher than 10 mg could provide additional beneficial effects in haematocrit, systolic blood pressure, urinary albumin-creatinine ratio and uric acid, without obvious increases in the rate of adverse events. These results raise the question whether future outcome studies assessing the benefits of higher than currently registered dapagliflozin doses are merited.