Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity

Interaction of the receptor for advanced glycation endproducts (RAGE) with its ligands results in expression of inflammatory mediators, activation of NF-κB, and induction of oxidative stress, all of which have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Soluble receptor for advanced glycation endproducts (sRAGE) has recently emerged as a reliable biomarker of inflammation in numerous RAGE-mediated disorders.

Objective

To assess sRAGE levels in adult patients with IBD.

Method

Serum was collected from adult patients with Crohn's disease (CD, 56 patients), ulcerative colitis (UC, 60 patients), and healthy controls (HC, 113 subjects). Levels of sRAGE were determined by enzyme-linked immunosorbent assay.

Results

Serum sRAGE levels were elevated in IBD compared to HC and were higher in UC patients compared to CD and HC. Levels of sRAGE were significantly higher in the serum of UC patients with active disease compared to patients with inactive disease, but no association with the Montreal Classification was evident. Serum sRAGE was lower in CD patients with biological therapies.

Conclusions

These findings suggest that serum levels of sRAGE are altered in patients with intestinal inflammation and may reflect distinct immunoinflammatory pathogenesis of UC and CD.     

Genome-wide association studies of obesity and metabolic syndrome

Until just a few years ago, the genetic determinants of obesity and metabolic syndrome were largely unknown, with the exception of a few forms of monogenic extreme obesity. Since genome-wide association studies (GWAS) became available, large advances have been made. The first single nucleotide polymorphism robustly associated with increased body mass index (BMI) was in 2007 mapped to a gene with for the time unknown function. This gene, now known as fat mass and obesity associated (FTO) has been repeatedly replicated in several ethnicities and is affecting obesity by regulating appetite. Since the first report from a GWAS of obesity, an increasing number of markers have been shown to be associated with BMI, other measures of obesity or fat distribution and metabolic syndrome. This systematic review of obesity GWAS will summarize genome-wide significant findings for obesity and metabolic syndrome and briefly give a few suggestions of what is to be expected in the next few years.     

The Framingham Heart Study: Impact on the Prevention and Control of Cardiovascular Diseases in India

India is in the middle of the epidemiological transition, with the burden of disease shifting towards chronic conditions, of which cardiovascular diseases (CVDs) form a major part. Findings from the Framingham Heart Study (FHS) have tremendous potential to circumvent the projected increase in CVD burden in India, as they highlight the importance of measuring risk in individuals and populations, and preventing future onset of disease. The findings of the FHS have stimulated several cross-sectional studies in India documenting a high and increasing burden of CVD risk factors. These have led to policy level changes in the country, in the form of Framework Convention on Tobacco Control ratification, and the National Program on Diabetes, CVD, and Stroke. There is now need for an Indian cohort study on the lines of the FHS, which can more closely evaluate the use of the FHS risk score among Indians and translate FHS findings into the Indian context.     

Metabolic syndrome may be associated with increased arterial stiffness even in the absence of hypertension: A study in 84 cases and 82 controls

Objective

To evaluate the hemodynamic characteristics of metabolic syndrome (MetS) in the absence and presence of hypertension.

Materials/Methods

Altogether 166 subjects without previously diagnosed cardiovascular disease, diabetes, or antihypertensive medication, were allocated to four groups: control, hypertension only, MetS without hypertension, and MetS with hypertension (mean age 44–46 years). Cut-point for hypertension was blood pressure ≥ 140/90 mmHg. Other criteria of MetS were as defined by Alberti et al. 2009. Hemodynamic variables were measured using whole-body impedance cardiography and pulse wave analysis.

Results

Pulse wave velocity was higher in hypertensive and normotensive subjects with MetS than controls (p < 0.05), and in the hypertensive MetS group than subjects with hypertension only (p < 0.05). Aortic pulse pressure was higher in the two hypertensive groups than the two normotensive groups (p < 0.05). Systemic vascular resistance index was higher in the hypertensive than normotensive MetS group (p < 0.05), and in the group with hypertension alone than in controls (p < 0.05). Heart rate was higher in the hypertensive Mets group than in controls and subjects with hypertension only (p < 0.05). Cardiac index did not differ, while stroke index was lower in both groups with MetS than groups without MetS. Augmentation pressure was higher in the hypertensive MetS group than in controls and normotensive MetS group (p < 0.05).

Conclusions

Pulse wave velocity, an acknowledged marker of arterial stiffness, was associated with MetS even in the absence of hypertension. This emphasizes the importance of the prevention and treatment of MetS.     

Visceral obesity,but not central obesity,is associated with cardiac remodeling in subjects with suspected metabolic syndrome

Background and aims

Metabolic syndrome (MetS) is a cluster of multiple risk factors including central obesity that may lead to cardiac damage and cardiovascular events. We investigated whether visceral obesity induces cardiac structural and functional remodeling independently from central obesity and other risk factors in subjects with suspected MetS.

Serum Bisphenol A is an independent risk factor of hyperuricemia: A 6-year prospective study

Objective

This study aims to evaluate whether serum Bisphenol A (BPA) is a risk factor for hyperuricemia.

Risk of metabolic syndrome in adolescents with polycystic ovarian syndrome: A systematic review and meta-analysis

Background

Polycystic ovarian syndrome (PCOS) is the commonest reproductive disorder in women and is closely associated with the development of metabolic syndrome (MetS). The objective of this systematic review and meta-analysis was to describe the risk of MetS in adolescent with PCOS to help diagnosing and preventing of morbidity and mortality later in life.

Visceral adiposity index and 10-year cardiovascular disease incidence: The ATTICA study

Background and aims

Visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue accumulation/dysfunction. Our aim was to evaluate potential associations between the VAI and the 10-year cardiovascular disease (CVD) incidence.

Association of vitamin D status with metabolic syndrome and its components: A cross-sectional study in a population of high educated Iranian adults

Aim

We aimed to assess the association of vitamin D status with metabolic syndrome and its components among high educated Iranian adults.

The role of serum and dietary advanced glycation endproducts in relation to cardiac function and structure: The Hoorn Study

Background and aimsThis study aims to investigate the relationship of serum and dietary advanced glycation endproducts (AGEs) with cardiac function and structure after eight years of follow-up.Methods and resultsWe included 370 Hoorn Study participants (aged 66.4 ± 6.1, 47% women). Serum protein-bound AGEs [N^ε-(carboxymethyl)lysine, N^ε-(carboxyethyl)lysine, and pentosidine], as well as echocardiography to assess left atrium volume index (LAVI), left ventricle ejection fraction (LVEF), and left ventricle mass index (LVMI), were measured at baseline and after 8 years of follow-up. Dietary AGEs [N^ε-(carboxymethyl)lysine and N^ε-(carboxyethyl)lysine] were estimated at baseline with a validated food-frequency questionnaire and an AGEs database. Increased pentosidine [-1.4% (−2.6;-0.2)] and overall serum AGEs Z-scores over time [-2.1% (−3.8;-0.5)] were associated with decreased LVEF at follow-up, adjusted for confounders. Glucose metabolism status was an effect modifier (P-for-interaction = 0.04). In participants with impaired glucose metabolism, but not type 2 diabetes, increased pentosidine was associated with decreased LVEF [-4.2 (−8.0;-0.3)%]. Higher dietary N^ε-(carboxyethyl)lysine [1.9 (0.1; 3.7)%] and overall dietary AGEs Z-scores [2.1 (0.1; 4.2)%] were associated with higher LVEF at follow-up. However, prior cardiovascular disease (CVD) was an effect modifier (P = 0.02). We found a stronger, non-significant, association of higher dietary (carboxyethyl)lysine with higher LVEF at follow-up in participants without CVD [2.3 (−0.1; 4.7)%] compared to participants with CVD [0.6 (−2.1; 3.4)%].ConclusionOverall serum AGEs were longitudinally associated with impaired systolic function. Future research should focus on including changes in dietary AGEs intake over time and the relation of dietary AGEs with cardiac measures needs to be established in intervention studies using low AGEs diets.     

Glucometabolic characteristics and higher vascular complication risk in Korean patients with type 2 diabetes with non-albumin proteinuria

ObjectiveWe investigated the clinical relevance of non-albumin proteinuria (NAP) in Korean patients with type 2 diabetes (T2D).Research design and methodsWe enrolled 883 T2D patients who had both their urinary albumin-to-creatinine ratio (uACR) and protein-to-creatinine ratio (uPCR) measured. We classified the patients into non-proteinuria (NP; uPCR <150 mg/g and uACR <30 mg/g), isolated NAP (iNAP; uPCR ≥150 mg/g and uACR <30 mg/g), and albuminuria (uACR ≥30 mg/g) groups. The associations between uPCR, uACR, and several indices of glucose metabolism were investigated.ResultsThe glucometabolic pathophysiology of iNAP (96 [10.9%]) group was more associated with a decrease in homeostatic model assessment (HOMA)-beta value (aOR 1.89 [95% CI, 1.21–2,96]) than with an increase in HOMA-insulin resistance (aOR 1.29 [95% CI, 0.83–2.01]). uPCR ≥150 mg/g was also found to have more consistent and stronger association with vascular complications than uACR ≥30 mg/g (aOR 1.44 [95% CI, 1.03–2.02] vs. 1.26 [95% CI, 0.89–1.79]).ConclusionsThe nephropathy of iNAP may be mainly attributed to decreased beta cell function. Furthermore, uPCR might be a more sensitive urinary biomarker than uACR for the detection of vascular complications in T2D patients.     

Association between serum uric acid (SUA) levels and metabolic syndrome (MetS) components in personnel of Shahroud University of Medical Sciences

AimsSerum uric acid level has been suggested to be associated with metabolic syndrome risk factors. However, the association between metabolic syndrome and serum uric acid is still controversial and challenging. This study was aimed to investigate the association between serum uric acid levels and metabolic syndrome components in personnel of the Shahroud University of Medical Sciences.Material and methodsThis case–control study was conducted on 499 personnel aged 30–60 years old who were working in Shahroud University of Medical Sciences, in 2015. MetS was defined according to the National Cholesterol Education Program (NCEP) criteria. The relationship between serum UA level and the number of metabolic components was determined by linear regression analysis.ResultIn this study, the mean concentration of serum uric acid in men with the syndrome was higher than that in women. Mean serum UA level increased as the number of metabolic factors increased. The mean serum uric acid levels was 4.98 ± 1.64 in patients with metabolic syndrome and 4.5 ± 1.28 in non-patients (p = 0.005). Subject with abnormal uric acid were almost 2.62 times more likely than other subject to develop the syndrome.ConclusionsThe results of this study showed that only hypertriglyceridemia is a component which increases the risk of hyperuricemia. In addition, hyperuricemia increases the risk of metabolic syndrome by more than two fold. It seems that high uric acid can be considered as a predisposing factor for metabolic syndrome; thus, it is recommended to measure serum uric acid in routine tests.     

The clinical usefulness of glycated albumin in patients with diabetes and chronic kidney disease: Progress and challenges

Prolonged hyperglycemia leads to a non-enzymatic glycation of proteins, and produces Amadori products, such as glycated albumin (GA) and glycated hemoglobin (HbA1c). The utility of HbA1c in the setting of chronic kidney disease (CKD) may be problematic since altered lifespan of red blood cells, use of iron and/or erythropoietin therapy, uremia and so on. Therefore, as an alternative marker, GA has been suggested as a more reliable and sensitive glycemic index in patients with CKD. In addition to the mean plasma glucose concentration, GA also reflects postprandial plasma glucose and glycemic excursion. Besides, with a half-life of approximately 2–3?weeks, GA may reflect the status of blood glucose more rapidly than HbA1c. GA is also an early precursor of advanced glycation end products (AGEs), which cause alterations in various cellular proteins and organelles. Thus, high GA levels may correlate with adverse outcomes of patients with CKD. In this review, the clinical usefulness of GA was discussed, including a comparison of GA with HbA1c, the utility and limitations of GA as a glycemic index, its potential role in pathogenesis of diabetic nephropathy and the correlations between GA levels and outcomes, specifically in patients with diabetes and CKD.     

Dose–response relationship between distinct serum uric acid trajectories and metabolic syndrome risk: A 5-year prospective cohort study

Background and aimsAlthough high serum uric acid (SUA) at baseline has been linked to increased risk for metabolic syndrome (MetS), the association of longitudinal SUA changes with MetS risk is unclear. We aimed to examine the effect of distinct SUA trajectories on new-onset MetS risk by sex in a Chinese cohort.Methods and resultsA total of 2364 women and 2770 men who were free of MetS in 2013 were enrolled in this study and followed up to 2018. Group-based trajectory modeling was applied to identify SUA trajectories. Cox proportional hazards model was used to evaluate the association between SUA trajectory and new-onset MetS. The dose–response relationship between SUA trajectories and MetS risk was examined by treating trajectory groups as a continuous variable. During a median follow-up of 48.0 months, 311 (13.16%) women and 950 (34.30%) men developed MetS. SUA trajectories (2013–2018) were defined as four distinct patterns in both women and men: “low”, “moderate”, “moderate-high”, and “high”. Compared with “low” SUA trajectory, the adjusted hazard ratio for incident MetS among participants with “moderate”, “moderate-high” and “high” trajectory was in a dose–response manner: 1.75 (95% CI: 1.08–2.82), 1.94 (95% CI: 1.20–3.14), and 3.05 (95% CI: 1.81–5.13), respectively, for women; 1.20 (95% CI: 0.97–1.49), 1.48 (95% CI: 1.19–1.85), and 1.66 (95% CI: 1.25–2.21), respectively, for men.ConclusionsElevated SUA trajectories are associated with increased risk for new-onset MetS in women and men. Monitoring SUA trajectories may assist in identifying subpopulations at higher risk for MetS.     

Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular,but not macrovascular,disease in individuals with and without (pre)diabetes: The Maastricht Study

AimsReactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown.MethodsSubjects with normal glucose metabolism (n = 1796; age: 57.9 ± 8.2 years; 43.3% men), prediabetes (n = 478; age: 61.6 ± 7.6 years; 54.0% men) and T2DM (n = 669; age: 63.0 ± 7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2 h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA_1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO.ResultsFasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥ 30 mg/24 h [fasting: 1.12 (95% CI: 0.97–1.29); post-OGTT: 1.19 (1.01–1.41)], eGFR < 60 mL/min/1.73 m² [fasting: 1.58 (95% CI: 1.38–1.82), post-OGTT: 1.57 (1.34–1.83)] and retinopathy [fasting: 1.59 (95% CI: 1.01–2.53), post-OGTT: 1.38 (0.77–2.48)]. No associations with prior CVD were found.ConclusionFasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.     

Addition of fenofibrate to statins is associated with risk reduction of diabetic retinopathy progression in patients with type 2 diabetes and metabolic syndrome: A propensity-matched cohort study

AimThis study aimed to determine the association between fenofibrate added to statin therapy and diabetic retinopathy progression.MethodsIn this propensity-matched study using the Korean National Health Insurance Service cohort (2002–2019), patients with type 2 diabetes and metabolic syndrome (≥ 30 years) receiving statin therapy were matched 1:2 by propensity score into the statin plus fenofibrate group (n = 22,395) and statin-only group (n = 43,191). The primary outcome was a composite of diabetic retinopathy progression including vitreous hemorrhage, vitrectomy, laser photocoagulation, intravitreous injection therapy and retinal detachment.ResultsThe median (quartiles) follow-up duration was 44.0 (27.6–70.6) months. For the primary outcome, the incidence rate per 1,000 person-years was 9.66 in the statin-only group and 8.68 in the statin-plus-fenofibrate group. The risk of the primary outcome was significantly lower (hazard ratio [HR]=0.88; 95% confidence interval [0.81;0.96] P = 0.005) in the statin-plus-fenofibrate group than in the statin-only group. Only patients with pre-existing retinopathy showed benefits from fenofibrate treatment (HR=0.83 [0.73;0.95] P = 0.006). In addition, the statin plus fenofibrate group exhibited significantly lower risks of vitreous hemorrhage (HR= 0.86 [0.75;0.995] P = 0.042), laser photocoagulation (HR=0.86 [0.77;0.96] P = 0.009) and intravitreous injection therapy (HR=0.73 [0.59;0.90] P = 0.003) than those in the statin-only group. There was no significant interaction between the different characteristics at baseline and the treatment effect.ConclusionThe addition of fenofibrate to statins was associated with significantly lower risk of diabetic retinopathy progression than statin therapy alone in patients with type 2 diabetes and metabolic syndrome.