Development of synthetic lipoxin-A4 mimetics (sLXms): New avenues in the treatment of cardio-metabolic diseases.

Resolution of inflammation is a complex, dynamic process consisting of several distinct processes, including inhibition of endothelial activation and leukocyte trafficking; promotion of inflammatory cell apoptosis and subsequent non-phlogistic scavenging and degradation; augmentation of pathogen phagocytosis; modulation of stromal cell phenotype coupled to the promotion of tissue regeneration and repair. Among these tightly regulated processes, the clearance and degradation of apoptotic cells without eliciting an inflammatory response is a crucial allostatic mechanism vital to developmental processes, host defence, and the effective resolution of inflammation. These efferocytic and subsequent effero-metabolism processes can be carried out by professional and non-professional phagocytes. Defective removal or inadequate processing of apoptotic cells leads to persistent unresolved inflammation, which may promote insidious pathologies including scarring, fibrosis, and eventual organ failure. In this manuscript, the well-established role of endothelial activation and leukocyte extravasation, as classical vascular targets of the 'inflammation pharmacology', will be briefly reviewed. The main focus of this work is to bring attention to a less explored aspect of the 'resolution pharmacology', aimed at tackling defective efferocytosis and inefficient effero-metabolism, as key targeted mechanisms to prevent or pre-empt vascular complications in cardio-metabolic diseases. Despite the use of gold standard lipid-lowering drugs or glucose-lowering drugs, none of them are able to tackle the so called residual inflammatory risk and/or the metabolic memory. In this review, the development of synthetic mimetics of endogenous mediators of inflammation is highlighted. Such molecules finely tune key components across the whole inflammatory process, amongst various other novel therapeutic paradigms that have emerged over the past decade, including anti-inflammatory therapy. More specifically, FPR2-agonists in general, and Lipoxin analogues in particular, greatly enhance the reprogramming and cross-talk between classical and non-classical innate immune cells, thus inducing both termination of the pro-inflammatory state as well as promoting the subsequent resolving phase, which represent pivotal mechanisms in inflammatory cardio-metabolic diseases.

Multiplex proteomics identifies inflammation-related plasma biomarkers for aging and cardio-metabolic disorders.

BACKGROUND: Cardio-metabolic disorders (CMDs) are common in aging people and are pivotal risk factors for cardiovascular diseases (CVDs). Inflammation is involved in the pathogenesis of CVDs and aging, but the underlying inflammatory molecular phenotypes in CMDs and aging are still unknown. METHOD: We utilized multiple proteomics to detect 368 inflammatory proteins in the plasma of 30 subjects, including healthy young individuals, healthy elderly individuals, and elderly individuals with CMDs, by Proximity Extension Assay technology (PEA, O-link). Protein-protein interaction (PPI) network and functional modules were constructed to explore hub proteins in differentially expressed proteins (DEPs). The correlation between proteins and clinical traits of CMDs was analyzed and diagnostic value for CMDs of proteins was evaluated by ROC curve analysis. RESULT: Our results revealed that there were 161 DEPs (adjusted p < 0.05) in normal aging and EGF was the most differentially expressed hub protein in normal aging. Twenty-eight DEPs were found in elderly individuals with CMDs and MMP1 was the most differentially expressed hub protein in CMDs. After the intersection of DEPs in aging and CMDs, there were 10 overlapping proteins: SHMT1, MVK, EGLN1, SLC39A5, NCF2, CXCL6, IRAK4, REG4, PTPN6, and PRDX5. These proteins were significantly correlated with the level of HDL-C, TG, or FPG in plasma. They were verified to have good diagnostic value for CMDs in aging with an AUC > 0.7. Among these, EGLN1, NCF2, REG4, and SLC39A2 were prominently increased both in normal aging and aging with CMDs. CONCLUSION: Our results could reveal molecular markers for normal aging and CMDs, which need to be further expanded the sample size and to be further investigated to predict their significance for CVDs.

Cross-sectional and longitudinal associations of Iron biomarkers and cardiovascular risk factors in pre- and postmenopausal women: leveraging repeated measurements to address natural variability.

BACKGROUND: The association between iron biomarkers and cardiovascular disease risk factors (CVD-RFs) remains unclear. We aimed to (1) evaluate the cross-sectional and longitudinal associations between iron biomarkers (serum ferritin, transferrin saturation (TSAT), transferrin) and CVD-RFs among women, and (2) explore if these associations were modified by menopausal status. METHOD: Cross-sectional and longitudinal analyses including 2542 and 1482 women from CoLaus cohort, respectively. Multiple linear regression and multilevel mixed models were used to analyse the associations between Iron biomarkers and CVD-RFs. Variability of outcomes and iron markers between surveys was accessed using intraclass correlation (ICC). RESULTS: After multivariable adjustment, elevated serum ferritin levels were associated with increased insulin and glucose levels, while higher transferrin levels were linked to elevated glucose, insulin and total cholesterol, and systolic and diastolic blood pressure (p < 0.05). No association was observed between CVD-RFs and TSAT (p > 0.05). Iron biomarkers demonstrated low reliability across reproductive stages but exhibited stronger associations in the perimenopausal group. In longitudinal analysis, we found association only for transferrin with lower glucose levels [ß = - 0.59, 95% CI (- 1.10, - 0.08), p = 0.02] and lower diastolic blood pressure [ß = - 7.81, 95% CI (- 15.9, - 0.56), p = 0.04]. CONCLUSION: In cross-sectional analysis, transferrin was associated with several CVD-RFs, and the associations did not change according to menopausal status. Conversely, in the longitudinal analyses, changes in transferrin were associated only with lower glucose and diastolic blood pressure levels. These differences might stem from the substantial longitudinal variation of iron biomarkers, underscoring the need for multiple iron measurements in longitudinal analyses.

ProtecT-2-D trial protocol: cardiovascular protection in patients with type 2 diabetes and established heart and/or vascular disease at a cardio-metabolic clinic-a randomized controlled trial.

BACKGROUND: Cardiovascular disease remains the primary cause of morbidity and mortality despite advancements in the treatment of patients with type 2 diabetes. Effective diabetes management extends beyond blood glucose control and includes cardiovascular prevention and treatment. However, the conventional healthcare model often emphasizes single-disease-specific management, leading to fragmented care. We aim to establish an affordable Cardio-Metabolic Clinic (CMC) that can provide comprehensive assessment and specialized care with a focus on cardiovascular protection. METHODS: The ProtecT-2-D study is a prospective, randomized control trial at the Cardiovascular Research Unit, Odense University Hospital Svendborg, Denmark. In this study, 1500 participants with type 2 diabetes and cardiovascular disease will be randomly assigned in a 2:1 ratio to receive either the intervention: treatment in the CMC, or the control: standard of care. The Cardio-Metabolic Clinic applies a decision-making algorithm coded with the latest guidelines to evaluate lifestyle factors and manage medical treatment. Health examinations are conducted at baseline and after three years, and clinical events will be assessed through registry and journal audits after five and ten years. The primary outcome is the time to the first occurrence of a composite of cardiovascular deaths, non-fatal acute myocardial infarctions, non-fatal stroke, or hospitalization due to heart failure at a time frame of five years. DISCUSSION: The Cardio-Metabolic Clinic represents a pioneering approach to diabetes management that aims to improve patient outcomes by reducing the cardiovascular disease burden. This study could transform diabetes care and offer a multidisciplinary, cost-effective, and specialized treatment. We need to establish the efficacy and feasibility of a CMC to integrate comparable clinics into broader healthcare systems, and potentially enhance cardiovascular health in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT06203860.

Frequency of Consumption of Food Groups and Cardio-Metabolic Risk Factors: A Genetically Informative Twin Study in Sri Lanka.

Low- and middle-income countries (LMICs) globally have undergone rapid urbanisation, and changes in demography and health behaviours. In Sri Lanka, cardio-vascular disease and diabetes are now leading causes of mortality. High prevalence of their risk factors, including hypertension, dysglycaemia and obesity have also been observed. Diet is a key modifiable risk factor for both cardio-vascular disease and diabetes as well as their risk factors. Although typically thought of as an environmental risk factor, dietary choice has been shown to be genetically influenced, and genes associated with this behaviour correlate with metabolic risk indicators. We used Structural Equation Model fitting to investigate the aetiology of dietary choices and cardio-metabolic phenotypes in COTASS, a population-based twin and singleton sample in Colombo, Sri Lanka. Participants completed a Food Frequency Questionnaire (N = 3934) which assessed frequency of intake of 14 food groups including meat, vegetables and dessert or sweet snacks. Anthropometric (N = 3675) and cardio-metabolic (N = 3477) phenotypes were also collected including weight, blood pressure, cholesterol, fasting plasma glucose and triglycerides. Frequency of consumption of most food items was found to be largely environmental in origin with both the shared and non-shared environmental influences indicated. Modest genetic influences were observed for some food groups (e.g. fruits and leafy greens). Cardio-metabolic phenotypes showed moderate genetic influences with some shared environmental influence for Body Mass Index, blood pressure and triglycerides. Overall, it seemed that shared environmental effects were more important for both dietary choices and cardio-metabolic phenotypes compared to populations in the Global North.

Dietary amino acid patterns and cardiometabolic risk factors among subjects with obesity; a cross-sectional study.

BACKGROUND: The prevalence of obesity is a growing global public health concern. Certain dietary amino acids have been shown to have a potential therapeutic role in improving metabolic syndrome parameters and body composition in individuals with obesity. However, some amino acids have been linked to an increased risk of cardiometabolic disorders. This cross-sectional study aims to investigate the association between dietary amino acid patterns and cardiometabolic risk factors in individuals with obesity. METHODS: This cross-sectional study included 335 participants with obesity (57.9% males and 41.5% females) from Tabriz and Tehran, Iran. The participants were between the ages of 20-50, with a body mass index (BMI) of 30 kg/m2 or higher, and free from certain medical conditions. The study examined participants' general characteristics, conducted anthropometric assessments, dietary assessments, and biochemical assessments. The study also used principal component analysis to identify amino acid intake patterns and determined the association between these patterns and cardiometabolic risk factors in individuals with obesity. RESULTS: Upon adjusting for potential confounders, the study found that individuals in the third tertiles of pattern 1 and 2 were more likely to have lower LDL levels (OR = 0.99 and 95% CI (0.98-0.99)) for both. Additionally, a significant decrease in total cholesterol was observed in the third tertiles of pattern 2 in model II (OR = 0.99, 95% CI (0.98-0.99)). These findings suggest a potential cardioprotective effect of these amino acid patterns in managing cardiometabolic risk factors in individuals with obesity. CONCLUSIONS: This study found that two identified amino acid patterns were associated with lower serum LDL and total cholesterol levels, while a third pattern was associated with higher serum triglycerides. The specific amino acids contributing to these patterns highlight the importance of targeted dietary interventions in managing cardiometabolic risk factors in individuals with obesity.

The association between dietary inflammatory index with some cardio-metabolic risk indices among the patients with type 2 diabetes from Hoveyzeh cohort study: a cross-sectional study.

BACKGROUND: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. METHODS: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. RESULTS: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). CONCLUSION: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications.

A Comprehensive Pilot Study to Elucidate the Distinct Gut Microbial Composition and Its Functional Significance in Cardio-Metabolic Disease.

Cardio-metabolic disease is a significant global health challenge with increasing prevalence. Recent research underscores the disruption of gut microbial balance as a key factor in disease susceptibility. We aimed to characterize the gut microbiota composition and function in cardio-metabolic disease and healthy controls. For this purpose, we collected stool samples of 18 subjects (12 diseased, 6 healthy) and we performed metagenomics analysis and functional prediction using QIIME2 and PICRUSt. Furthermore, we carried out assessments of microbe-gene interactions, gene ontology, and microbe-disease associations. Our findings revealed distinct microbial patterns in the diseased group, particularly evident in lower taxonomic levels with significant variations in 14 microbial features. The diseased cohort exhibited an enrichment of Lachnospiraceae family, correlating with obesity, insulin resistance, and metabolic disturbances. Conversely, reduced levels of Clostridium, Gemmiger, and Ruminococcus genera indicated a potential inflammatory state, linked to compromised butyrate production and gut permeability. Functional analyses highlighted dysregulated pathways in amino acid metabolism and energy equilibrium, with perturbations correlating with elevated branch-chain amino acid levels-a known contributor to insulin resistance and type 2 diabetes. These findings were consistent across biomarker assessments, microbe-gene associations, and gene ontology analyses, emphasizing the intricate interplay between gut microbial dysbiosis and cardio-metabolic disease progression. In conclusion, our study unveils significant shifts in gut microbial composition and function in cardio-metabolic disease, emphasizing the broader implications of microbial dysregulation. Addressing gut microbial balance emerges as a crucial therapeutic target in managing cardio-metabolic disease burden.

Dietary glycemic index and glycemic load predict longitudinal change in glycemic and cardio-metabolic biomarkers among old diabetic adults living in a resource-poor country.

This study aims to investigate longitudinal associations between the dietary glycemic index (GI) and glycemic load (GL) and changes in glycemic and cardio-metabolic outcomes. A 28-month retrospective cohort study included 110 Vietnamese diabetic patients, collecting their dietary GI and GL values along with blood biochemical data from baseline 24-h dietary recall and medical records. Latent class growth modelling identified three distinct HbA1c trajectories during the follow-up period, with 51% of patients achieving good glycemic control. The adjusted linear mixed-effect model showed that 1 unit increase in logarithms in dietary GL was associated with a 0.14% increase in the log-HbA1c. Among poorly controlled diabetic patients, baseline GL values were positively correlated with increases in HbA1c; GI showed effects on changes in fasting plasma glucose and the triglyceride-glucose (TyG) index. No significant association was observed in patients with good glycemic control.

[Epidemiological characteristics of cardio-metabolic risk factors in women aged 15-49 years in 4 provinces of China in 2018].

OBJECTIVE: To analyze the prevalence of cardio-metabolic(CM) risk in women aged 15-49 years in 4 provinces of China and the influence of socioeconomic factors on them. METHODS: A total of 2851 women aged 15-49 years from Community-based Cohort Study on Nervous System Disease in 2018 were selected. Obesity, central obesity, elevated triglyceride(TG), elevated total cholesterol(TC), decreased high-density lipoprotein cholesterol(HDL-C), elevated low-density lipoprotein cholesterol(LDL-C), elevated blood pressure, elevated blood glucose and risk factor aggregation were analyzed. χ~2 test was used for univariate analysis, multinomial Logit model was used to evaluate the relationship between socioeconomic factors and CM risk factors, and Cochran-Armitage trend test was used for trend analysis. RESULTS: The detection rate of CM risk factors in this study from high to low were central obesity(26.76%), overweight(22.41%), pre central obesity(17.47%), decreased HDL-C(15.36%), elevated TG(11.78%), borderline elevated TC(11.40%), borderline elevated TG(11.12%), elevated blood pressure(9.71%) and hypertension(9.12%). The prevalence rates of CM risk factors were different among different age groups, income groups and education levels(P<0.05). In addition to decreased HDL-C, the prevalence of other metabolic risk factors increased with age(P_(trend)<0.05). With the improvement of educational level, the prevalence rates of overweight, obesity, central obesity, central obesity, elevated TG, decreased HDL-C, elevated blood pressure, hypertension, elevated blood pressure and diabetes showed a downward trend(P_(trend)<0.05). Multinomial Logit model showed that the rick of metabolic risk factors in the age group of 40 to 49 years old was higher than that in the younger age group aged 15-29 years, and was more significant in hypertension, elevated blood pressure and elevated blood glucose, which were 8.51 times(95% CI 5.45-13.27), 3.14 times(95%CI 2.20-4.48)and 2.66(95% CI 1.52-4.66)times of the younger age group, respectively. Women with high-income level have a higher risk of borderline elevated TC, elevated TC and borderline elevated LDL-C(OR=1.85, 95% CI 1.44-2.38;OR=2.01, 95% CI 1.25-3.22;OR=2.16, 95% CI 1.61-2.90), but the lower risk of overweight and elevated blood pressure(OR=0.79, 95% CI 0.64-0.98;OR=0.69, 95% CI 0.50-0.94). The risk of obesity, hypertension and diabetes of people with college degree or above was about 50% lower than those with junior high school education or below(OR=0.52, 95% CI 0.35-0.78;OR=0.43, 95% CI 0.27-0.67; OR=0.52, 95% CI 0.28-0.96). CONCLUSION: Central obesity, overweight, pre central obesity and HDL-C decrease were prominent CM risk factors in women aged 15-49 years in four provinces of China in 2018. The detection rate of CM risk factors is higher in women of high age group or low education level.

Targeting ferroptosis in cardio-metabolic-diseases: Mechanisms and therapeutic prospects.

Cardio-metabolic-diseases (cardio-metabolic-diseases) are leading causes of death and disability worldwide and impose a tremendous burden on whole society as well as individuals. As a new type of regulated cell death (RCD), ferroptosis is distinct from several classical types of RCDs such as apoptosis and necroptosis in cell morphology, biochemistry, and genetics. The main molecular mechanisms of ferroptosis involve iron metabolism dysregulation, mitochondrial malfunction, impaired antioxidant capacity, accumulation of lipid-related peroxides and membrane disruption. Within the past few years, mounting evidence has shown that ferroptosis contributes to the pathophysiological process in cardio-metabolic-diseases. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This review comprehensively summarizes the mechanism of ferroptosis in the development and progression of cardio-metabolic-diseases, so as to provide new insights for cardio-metabolic-diseases pathophysiology. Moreover, we highlight potential druggable molecules in ferroptosis signaling pathway, and discuss recent advances in management strategies by targeting ferroptosis for prevention and treatment of cardio-metabolic-diseases.

Trajectory patterns of metabolic syndrome severity score and risk of type 2 diabetes.

BACKGROUND: The available evidence indicates that the severity of metabolic syndrome tends to worsen progressively over time. We assessed the trajectory of age and sex-specific continuous MetS severity score (cMetS-S) and its association with the development of diabetes during an 18-year follow-up. METHODS: In a prospective population-based Tehran Lipid and Glucose Study, 3931 eligible participants free of diabetes, aged 20-60 years, were followed at three-year intervals. We examined the trajectories of cMetS-S over nine years using latent growth mixture modeling (LGMM) and subsequent risks of incident diabetes eight years later. The prospective association of identified trajectories with diabetes was examined using the Cox proportional hazard model adjusting for age, sex, education, and family history of diabetes, physical activity, obesity (BMI ≥ 30 kg/m2), antihypertensive and lipid-lowering medication, and baseline fasting plasma glucose in a stepwise manner. RESULTS: Among 3931 participants, three cMetS-S trajectory groups of low (24.1%), medium (46.8%), and high (29.1%) were identified during the exposure period. Participants in the medium and high cMetS-S trajectory classes had HRs of 2.44 (95% CI: 1.56-3.81) and 6.81 (95% CI: 4.07-10.01) for future diabetes in fully adjusted models, respectively. Normoglycemic individuals within the high cMetS-S class had an over seven-fold increased risk of diabetes (HR: 7.12; 95% CI: 6.05-12.52). CONCLUSION: Although most adults exhibit an unhealthy metabolic score, its severity usually remains stable throughout adulthood over ten years of follow-up. The severity score of metabolic syndrome has the potential to be utilized as a comprehensive and easily measurable indicator of cardiometabolic dysfunction. It can be employed in clinical settings to detect and track individuals at a heightened risk of developing T2DM, even if their glucose levels are normal.

Adipose tissue distribution is associated with cardio-metabolic alterations in adult patients with juvenile-onset dermatomyositis.

OBJECTIVES: Primary aims were to compare adipose tissue distribution in adult patients with juvenile-onset DM (JDM), with matched controls. Secondary aims were to explore how adipose tissue distribution is associated with cardio-metabolic status (cardiac dysfunction and metabolic syndrome) in patients. METHODS: Thirty-nine JDM patients (all aged ≥18 y, mean age 31.7 y and 51% female) were examined mean 22.7 y (s.d. 8.9 y) after disease onset and compared with 39 age/sex-matched controls. In patients, disease activity and lipodystrophy were assessed by validated tools and use of prednisolone noted. In all participants, dual-energy X-ray absorptiometry (DXA) and echocardiography were used to measure visceral adipose tissue (VAT)(g) and cardiac function, respectively. Risk factors for metabolic syndrome were measured and associations with adipose tissue distribution explored. For primary and secondary aims, respectively, P-values ≤0.05 and ≤0.01 were considered significant. RESULTS: Patients exhibited a 2.4-fold increase in VAT, and reduced HDL-cholesterol values compared with controls (P-values ≤ 0.05). Metabolic syndrome was found in 25.7% of the patients and none of the controls. Cardiac dysfunction (systolic and/or diastolic) was found in 23.7% of patients and 8.1% of controls (P = 0.07). In patients, VAT levels were correlated with age, disease duration and occurrence of metabolic syndrome and cardiac dysfunction. Occurrence of lipodystrophy (P = 0.02) and male sex (P = 0.04) tended to be independently associated with cardiac dysfunction. CONCLUSION: Adults with JDM showed more central adiposity and cardio-metabolic alterations than controls. Further, VAT was found increased with disease duration, which was associated with development of cardio-metabolic syndrome.

Effect of zinc supplementation in the management of type 2 diabetes: A grading of recommendations assessment, development, and evaluation-assessed, dose-response meta-analysis of randomized controlled trials.

The question of whether zinc supplementation may improve cardio-metabolic health in patients with type 2 diabetes mellitus (T2DM) remains controversial and require further evaluation. This study aimed to summarize the effectiveness of oral zinc supplementation in improving cardio-metabolic risk markers in people with T2DM. We searched PubMed, Scopus, and Web of Science from inception to April 2023, for randomized controlled trials (RCTs). RCTs of type 2 diabetic adults (aged ≥18 years) comparing zinc supplementation with placebo were included. We excluded studies if not randomized, involved co-supplementation, and were conducted in children or pregnant women. Glycemic indices, lipid profiles, blood pressure, anthropometric measure, c-reactive protein (CRP), creatinine, and serum zinc were extracted. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methods. We used a random-effect model to perform the dose-response analysis. Effect sizes were presented as mean difference (MD) and 95% confidence interval (CI). 22 studies (n = 1442 participants) were included. The certainty of the evidence was rated as moderate to high. Zinc supplementation significantly reduced glycemic indices: including two-hour postprandial glucose (2hpp) (mean difference (MD): -34.34 mg/dl; 95%CI: -51.61∼ -17.07), fast blood sugar (FBS) (MD: -23.32 mg/dl; 95% CI: -33.81∼ -12.83), and hemoglobin A1c (HbA1c) (MD: -0.47; 95% CI: -0.71∼ -0.23). Zinc had a favorable effect on lipid profiles low-density lipoprotein (LDL) (MD: -10.76 mg/dl; CI: -17.79∼-3.73), triglyceride (TG) (MD: -18.23 mg/dl; CI: -32.81∼-3.65), total cholesterol (TC) (MD: -12.74 mg/dl; CI: -21.68∼-3.80), VLDL (MD: -5.39 mg/dl; CI: -7.35∼-3.43) and high-density lipoprotein (HDL) (MD: 4.04 mg/dl; CI: 0.96 ∼ 7.12). Systolic blood pressure (SBP) (MD): -3.64 mmHg; 95% CI: -6.77∼ -0.52), weight (MD: 1.00 kg; 95% CI: 0.34∼1.66), CRP (MD: -3.37 mg/l, 95% CI: -4.05∼ -2.70), and serum zinc (MD: 15.38 µg/dl; 95% CI: 10.74∼ 20.02) changed to a statistically significant extent with zinc supplementation. There was also a linear association between additional 10 mg/d zinc treatment with FBS, HbA1c, HDL, LDL, TG, TC, and serum zinc. A non-linear dose-response gradient was seen for FBS, HDL, and SBP (p < 0.05). Egger's test showed no substantial publication bias. Our findings strongly suggest a potential beneficial effect of zinc supplementation on type 2 diabetic patients. Further high-quality research is needed to determine the optimal form, dosage, and duration of zinc supplementation for this population.

Urban design and cardio-metabolic risk factors.

Accumulating evidence suggests that the built environment may be associated with cardiovascular disease via its influence on health behaviours. The aim of this study was to estimate the associations between traditional and novel neighbourhood built environment metrics and clinically assessed cardio-metabolic risk factors among a sample of adults in Canada. A total of 7171 participants from Albertas Tomorrow Project living in Alberta, Canada, were included. Cardio-metabolic risk factors were clinically measured. Two composite built environment metrics of traditional walkability and space syntax walkability were calculated. Among men, space syntax walkability was negatively associated with systolic and diastolic blood pressure (b = -0.87, 95% CI -1.43, -0.31 and b = -0.45, 95% CI -0.86, -0.04, respectively). Space syntax walkability was also associated with lower odds of overweight/obese among women and men (OR = 0.93, 95% CI 0.87, 0.99 and OR = 0.88, 95% CI 0.79, 0.97, respectively). No significant associations were observed between traditional walkability and cardio-metabolic outcomes. This study showed that the novel built environment metric based on the space syntax theory was associated with some cardio-metabolic risk factors.

The effect of traditional diet on glucose homoeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: a randomised crossover study.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (-0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

Twenty-year trajectories of cardio-metabolic factors among people with type 2 diabetes by dementia status in England: a retrospective cohort study.

To assess 20-year retrospective trajectories of cardio-metabolic factors preceding dementia diagnosis among people with type 2 diabetes (T2D). We identified 227,145 people with T2D aged > 42 years between 1999 and 2018. Annual mean levels of eight routinely measured cardio-metabolic factors were extracted from the Clinical Practice Research Datalink. Multivariable multilevel piecewise and non-piecewise growth curve models assessed retrospective trajectories of cardio-metabolic factors by dementia status from up to 19 years preceding dementia diagnosis (dementia) or last contact with healthcare (no dementia). 23,546 patients developed dementia; mean (SD) follow-up was 10.0 (5.8) years. In the dementia group, mean systolic blood pressure increased 16-19 years before dementia diagnosis compared with patients without dementia, but declined more steeply from 16 years before diagnosis, while diastolic blood pressure generally declined at similar rates. Mean body mass index followed a steeper non-linear decline from 11 years before diagnosis in the dementia group. Mean blood lipid levels (total cholesterol, LDL, HDL) and glycaemic measures (fasting plasma glucose and HbA1c) were generally higher in the dementia group compared with those without dementia and followed similar patterns of change. However, absolute group differences were small. Differences in levels of cardio-metabolic factors were observed up to two decades prior to dementia diagnosis. Our findings suggest that a long follow-up is crucial to minimise reverse causation arising from changes in cardio-metabolic factors during preclinical dementia. Future investigations which address associations between cardiometabolic factors and dementia should account for potential non-linear relationships and consider the timeframe when measurements are taken.

Evaluating the association between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, mental health, and cardio-metabolic risk factors among individuals with obesity.

BACKGROUND: Several previous investigations have examined the brain-protective role of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. However, more knowledge is needed about the MIND diet's other favorable impacts. The purpose of this study was to examine the relationship between the MIND diet, mental health, and metabolic markers in individuals with obesity. METHODS: In this cross-sectional study, we included 339 individuals with obesity (BMI ≥ 30 kg/m2) aged 20-50 years. We utilized a semi-quantitative Food Frequency Questionnaire (FFQ), we assessed dietary intake, including 168 food items, and calculated the value of MIND. Metabolic syndrome (MetS) was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines. We assessed biochemical parameters using Enzymatic methods. Blood pressure and body composition were also determined. RESULTS: Higher tertiles of the MIND diet score were associated with significantly higher energy intake, macronutrients, and brain-healthy food intakes (P < 0.001). Among the brain-unhealthy foods, only the intake of sweets and pastries was significantly lower in the highest versus lowest MIND tertiles. We also observed lower odds of stress (P < 0.05) and higher insulin sensitivity (P < 0.05) in the highest versus lowest MIND diet tertiles. We witnessed no significant changes in other parameters. CONCLUSION: Lower stress levels and higher insulin sensitivity independent of some confounders like age, BMI, sex, and physical activity were associated with the highest tertile of MIND diet score.

Dietary energy density, metabolic parameters, and blood pressure in a sample of adults with obesity.

BACKGROUND: Several previous studies revealed the role of dietary energy density (DED) in developing obesity and related disorders. However, the possible role of DED in triggering cardiometabolic risk factors of individuals with obesity has not been studied yet. This study aimed to evaluate the association between DED and anthropometric parameters, blood pressure, and components of metabolic syndrome (MetS) (such as glycemic markers, lipid profile, and blood pressure) among individuals with obesity. METHODS: In this cross-sectional study, we included 335 adults with obesity (BMI ≥ 30 kg/m2) aged 20-50 years in Tabriz and Tehran, Iran. Dietary intake was assessed by a validated semi-quantitative Food Frequency Questionnaire (FFQ), including 168 food items; then, DED was calculated. MetS was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Enzymatic methods were used to assess serum lipids, glucose, and insulin concentrations. Blood pressure was measured by sphygmomanometer and body composition by bioelectrical impedance analysis (BIA). RESULTS: Participants in the higher tertiles of DED had more intake of carbohydrate, dietary fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and meat, fish, poultry (MFP). Increasing the DED in both methods had no association with systolic blood pressure (SBP), fasting blood sugar (FBS), low-density lipoprotein cholesterol (LDL-C), insulin, triglyceride (TG), and homeostatic model assessment of insulin resistance (HOMA-IR) even after adjustment for confounders. However, diastolic blood pressure (DBP) decreased in second tertile of DED I (ß = 0.921, P = 0.004). The quantitative insulin-sensitivity check index (QUICKI) in second tertile of both DED methods had significant positive association with DED. In the second tertile of DED II, while total cholesterol (TC) significantly decreased (P crude = 0.036, P adjusted = 0.024), high-density lipoprotein cholesterol (HDL-C) increased (ß = 1.096, p = 0.03). There was no significant changes in biochemical parameters in third tertile of DED I and II even after adjustment for covariates. Also, higher tertiles of DED was associated with reduced prevalence of MetS. CONCLUSION: High DED was associated with lower levels of blood pressure and TC but elevated levels of HDL and QUICKI independent of such confounders as age, BMI, sex, and physical activity. Further longitudinal studies are warranted to better elucidate casual associations.

Dietary Antioxidant Quality Score (DAQS), serum lipids, markers of glucose homeostasis, blood pressure and anthropometric features among apparently metabolically healthy obese adults in two metropolises of Iran (Tabriz and Tehran): a cross-sectional study.

BACKGROUND: Oxidative stress (OS) is associated with a variety of non-communicable diseases, including MetS, diabetes mellitus, metabolic syndrome, and cardiovascular disease through increased production of reactive oxygen species (ROS) and impairment of antioxidant defense mechanisms. Antioxidants can protect cells against free radical damage, so it seems important to determine the relationship between the quality of dietary antioxidants intake and chronic diseases. The Dietary Antioxidant Quality Score (DAQS) is obtained by adding the daily intake of known dietary vitamins and minerals, including selenium, zinc, vitamin A, vitamin C, and vitamin E, compared to the recommended daily intake (RDI). Therefore, this study aims to determine the relationship between DAQS, serum lipids, markers of glucose homeostasis, blood pressure and anthropometric features among obese adults. METHODS: In the present cross-sectional study, 338 individuals who were obese (BMI ≥ 30 kg/m2) aged 20-50 years were recruited from Tabriz and Tehran, Iran. A validated semi-quantitative Food Frequency Questionnaire (FFQ) with 168 food items was used to quantify dietary consumption; accordingly, DAQS was computed. Blood biomarkers were measured using enzyme-linked immunosorbent assay (ELISA) kits. A standard mercury sphygmomanometer was used to assess blood pressure, and bioelectrical impedance analysis (BIA) was performed to determine body composition. The association between the DAQS tertiles and biochemical variables was investigated using multinomial logistic regression. RESULTS: Participants in the highest tertile of DAQS have a lower diastolic blood pressure (DBP) values in all of the adjusted models [odds ratio (OR) = 0.920; confidence interval (CI)= 0.852-0.993, P-value = 0.03] in the analysis of co-variance (ANCOVA) model. Similarly, subjects at the second tertile of DAQS had lower DBP compared with the first tertile in age and sex-adjusted model [OR= 0.937; CI= 0.882-0.997]. There was no statistically significant difference for other metabolic parameters in different DAQS tertiles. CONCLUSION: According to our findings, higher DAQS was associated with lower DBP among obese adults with obesity in two major cities of Iran (Tehran and Tabriz). Other studies with interventional design are needed to better elucidate these associations and underlying mechanisms.