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Background: Type 2 diabetes mellitus (T2DM) patients are predisposed to several diabetes-related complications. Dysregulation of the haemostatic mechanisms have been implicated. There are however no current studies assessing the levels and activity of protein C (PC), protein S (PS), and antithrombin III (AT III), which are essential in haemostatic regulation, in a single cohort of T2DM patients. This study evaluated the effect of poorly-managed T2DM on the levels and activity of PC, PS, and AT III. Methods: This cross-sectional study was conducted at the Diabetes Clinic, Cocoa Clinic in Kumasi, Ghana. A total of 242 T2DM patients, comprising 152 patients with poorly-managed diabetes and 90 well-managed diabetes patients, were recruited for the study. Fasting blood glucose, liver function tests and lipid profile were performed for each respondent. Glycated haemoglobin (HbA1c) was estimated by turbidimetric inhibition immunoassay. The levels and activity of PC, PS and AT III were measured by solid phase sandwich ELISA method. Results: There was a negative correlation between HbA1c and the levels and activity of PC, PS and AT III. The levels and activity of PC [(5.78 vs 4.64 μg/ml, p<0.0001) and (42.22 vs 36.21 U/ml, p = 0.01) respectively], PS [(22.55 vs 20.29 μg/ml, p = 0.010) and (235.94 vs 211.67 U/ml, p<0.0001) respectively] and AT III [(16.28 vs 14.41μg/ml, p<0.0001) and (176.01 vs 160.09 U/ml, p = 0.03) respectively] were significantly increased in patients with well-managed T2DM compared to the poorly-managed diabetes patients. Likewise, the levels and activity of PC, PS, and AT III was higher among T2DM patients using statins than patients who were statin-naïve. Among patients with well-managed T2DM, those who were on statins had significantly higher levels and activities of PC, PS, and AT III compared to well-managed T2DM patients not on statins. However, there no statistically significant differences between the level and activity of PC, PS, and AT III among poorly-managed T2DM patients with respect to statin status. Conclusion: Poorly-managed type 2 diabetes mellitus is associated with reduced levels and activity of PC, PS and AT III compared to well-managed T2DM. Though use of statins may improve the levels and activity of the PC, PS and AT III in T2DM, their effect is limited in the presence of poorly-controlled T2DM. Proper management of diabetes is essential to reduce the likelihood of thrombotic events among T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Frequency of insulin pen use, despite its higher costs, is increasing to substitute the traditional use of insulin vials. This study aims to report insulin pen use frequency and its associated factors among participants of the STEPS survey 2016 in Iran, which was conducted based on the World Health Organization (WHO) STEPS methodology. Methods: In this cross-sectional study, 19,503 (mean age of 46.03±0.13) out of 30,541 participants of the Iran STEPS survey were included (Inclusion criteria: aged >25 years old and availability of their demographic, clinical, and laboratory results for serum glucose, HbA1c, and lipid profile). Clinical and demographic characteristics, a frequency of use of each diabetes mellitus treatment type, and the association of insulin pen use with health outcomes are reported using descriptive analysis and propensity score modeling. Results: There were 1,999(10.85%) individuals diagnosed with diabetes in the population, while 1,160(56.87%) cases were taking antihyperglycemic treatments. In this subset, 240(21.14%) individuals administered insulin with or without using oral agents at the same time. 52.28% of participants who were under insulin therapy used insulin pens. None of the socioeconomic determinants, including gender (p-value = 0.11), type of residential areas (p-value = 0.52), years of schooling (p-value = 0.27), wealth index (p-value = 0.19), marital status (p-value = 0.37), and insurance types (p-value = 0.72) were significantly different among groups using insulin pens and insulin vials. Moreover, in the propensity score modeling, pen usage was not associated with a lower heart attack and ischemic stroke histories, systolic blood pressure, serum lipid profile, blood glucose, or HbA1c levels. Conclusion: Results showed that the use of the higher-costing insulin pens compared to traditional vials and syringes is not associated with improved glycemic control and better lipid profile in our sample. Future studies are needed to confirm these findings and to compare other aspects of insulin pen use, including adherence to treatment and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes. Methods: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation. Results: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial. Conclusions: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is featured by increased plasma very low density lipoproteins (VLDL). The extent to which plasma apolipoprotein E (ApoE) levels are elevated in NAFLD is unclear. We determined whether plasma ApoE is elevated in subjects with suspected NAFLD. Plasma ApoE and genotypes were determined in 6,762 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. A Fatty Liver Index (FLI) ≥ 60 was used as a proxy of NAFLD. A total of 1,834 participants had a FLI ≥ 60, which coincided with increased triglycerides, non-HDL cholesterol, ApoB and ApoE (all P<0.001). In multivariable linear regression analysis, plasma ApoE levels were positively associated with an elevated FLI when taking account of ApoE genotypes and other clinical and laboratory covariates (fully adjusted model: β = 0.201, P<0.001). Stratified analysis for ApoE genotypes (ApoE ε3ε3 homozygotes, ApoE ε2 carriers, and ApoE ε3ε4 and ε4ε4 carriers combined), also showed positive associations of plasma ApoE levels with an elevated FLI in each group (all P<0.001). In conclusion, it is suggested that NAFLD is characterized by increased plasma ApoE levels, even when taking account of the various ApoE genotypes. Increased plasma ApoE may contribute to altered VLDL metabolism and to increased atherosclerosis susceptibility in NAFLD. [ABSTRACT FROM AUTHOR]

We aimed to investigate the clinical factors affecting the therapeutic effectiveness of the sodium–glucose cotransporter-2 inhibitor empagliflozin in patients with type 2 diabetes mellitus (T2DM). We reviewed the medical records of 374 T2DM patients aged between 20 and 75 years who were prescribed empagliflozin 10 mg or 25 mg as add-on therapy for more than 90 consecutive days. Changes in hemoglobin A1c (HbA1c) from baseline levels and the reduction in body weights of the study participants were assessed. We found that younger patients (≤ 50 years), patients with the highest levels of HbA1c (>9%) at baseline, patients with an estimated glomerular filtration rate (eGFR) of >90 mL/min/1.73 m2, and patients with a shorter duration of T2DM (< 10 years) were more likely to exhibit a better glycemic response. Multivariate linear regression analysis revealed that a shorter duration of T2DM, higher baseline levels of HbA1c, and higher eGFR were positively associated with HbA1c reduction. Higher BMI and lower HbA1c levels were predictors of a more significant reduction in body weight among patients taking empagliflozin. The glucose-lowering effect of empagliflozin was more evident in T2DM patients with higher baseline HbA1c levels, better renal function, and shorter duration of T2DM. [ABSTRACT FROM AUTHOR]

Background: Low-grade albuminuria has been considered a predictor of cardiovascular mortality. We investigated the relationship between high-normal albuminuria and subclinical atherosclerosis in non-diabetic men with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. Methods: In this cross-sectional study, 1,756 men with eGFR ≥60 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) <30 mg/g, who attended general health checkups between April 2012 and March 2015, underwent blood sampling, urinalysis, and carotid ultrasonography. We excluded the subjects who were diabetic and/or received an anti-hypertensive drug. Carotid intima-media thickness (IMT) and the number of focal atheromatous plaques were used as indicators of subclinical atherosclerosis. Multiple linear regression analysis was performed to identify clinical factors associated with carotid IMT. Poisson regression analysis was used to assess the determinants of the carotid plaque number. Results: Median UACR was 4.8 mg/g (interquartile range, 3.6–6.9 mg/g). Compared with subjects with low-normal UACR (<10.0 mg/g), subjects with high-normal UACR (10.0–29.8 mg/g) had greater IMT and higher carotid plaque number. High-normal UACR was independently associated with thickened IMT in the model adjusted for conventional cardiovascular disease risk factors. Moreover, participants with high-normal UACR were also more likely to be associated with increased plaque count (prevalence ratio: 1.06; 95% confidence interval: 1.01–1.14) after adjustment for conventional cardiovascular disease risk factors. Conclusions: Our results indicate that high-normal albuminuria is associated with both carotid IMT and plaque formation in the non-diabetic male population with eGFR ≥60 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background: The incidence of type 2 diabetes (T2DM) in children has increased dramatically. However, limited published information is known about the glycemic control and lipid outcomes in pediatric T2DM outside of clinical trials. Objectives: To determine the glycemic control and lipid measure outcomes at one and three- year follow-up in children with T2DM. Methods: A retrospective electronic medical record review of children with T2DM at the Children’s Hospital of Alabama over a 12-year period. Results: There were 301 patients with a diagnosis of T2DM who had a 1-year follow-up visit, of which 184 also had a 3-year follow-up. Most patients (78%) received either insulin with metformin or insulin alone at diagnosis. At one year, 37% of the cohort achieved ‘optimal glycemic control’ (HbA1C ≤6.5%) and 58% of patients achieved durable glycemic control (HbA1C ≤8%). Optimal glycemic control was seen in 48 patients at 3 years. The patients treated with insulin (alone or in combination with metformin) tended to have higher HbA1C at diagnosis, but had improved lipid and glycemic outcomes at follow-up. The group treated with insulin along with metformin had significant improvements in non-HDL, HDL and TC/HDL ratios. The effects of insulin treatment on glycemic control at 3 years were not statistically significant. Conclusion: With the current modality of treatment, only a minority of patients achieve optimal glycemic control at 1 and 3 years of follow-up. Studies are warranted to further elucidate the optimal therapies in the management of pediatric T2DM. [ABSTRACT FROM AUTHOR]

Background: High-density lipoprotein (HDL) functionality and low-density lipoprotein (LDL) atherogenic traits can describe the role of both particles on cardiovascular diseases more accurately than HDL- or LDL-cholesterol levels. However, it is unclear how these lipoprotein properties are particularly affected by different cardiovascular risk factors. Objective: To determine which lipoprotein properties are associated with greater cardiovascular risk scores and each cardiovascular risk factor. Methods: In two cross-sectional baseline samples of PREDIMED trial volunteers, we assessed the associations of HDL functionality (N = 296) and LDL atherogenicity traits (N = 210) with: 1) the 10-year predicted coronary risk (according to the Framingham-REGICOR score), and 2) classical cardiovascular risk factors. Results: Greater cardiovascular risk scores were associated with low cholesterol efflux values; oxidized, triglyceride-rich, small HDL particles; and small LDLs with low resistance against oxidation (P-trend<0.05, all). After adjusting for the rest of risk factors; 1) type-2 diabetic individuals presented smaller and more oxidized LDLs (P<0.026, all); 2) dyslipidemic participants had smaller HDLs with an impaired capacity to metabolize cholesterol (P<0.035, all); 3) high body mass index values were associated to lower HDL and LDL size and a lower HDL capacity to esterify cholesterol (P<0.037, all); 4) men presented a greater HDL oxidation and lower HDL vasodilatory capacity (P<0.046, all); and 5) greater ages were related to small, oxidized, cytotoxic LDL particles (P<0.037, all). Conclusions: Dysfunctional HDL and atherogenic LDL particles are present in high cardiovascular risk patients. Dyslipidemia and male sex are predominantly linked to HDL dysfunctionality, whilst diabetes and advanced age are associated with LDL atherogenicity. [ABSTRACT FROM AUTHOR]

Context: While the role of overt hypothyroidism in lipid disorders is clear, the association between dyslipidemia and subclinical thyroid diseases remains unclarified. Objective: To examine lipid trends based on thyroid function over a 10-year period. Design: This is a prospective population based cohort study. Setting: General community. Participants: 2383 euthyroid participants, as well as those with subclinical thyroid diseases, in all residents of district 13 of Tehran were examined. Subjects who were on levothyroxine, anti-hyperthyroid drugs, and glucocorticoids, those with a history of thyroid surgery or RAI and pregnant women were excluded. Main outcome measures: Lipid trends in Model 1 were adjusted for age and follow up duration, and in Model 2 gender-specific multivariate adjustments were performed for thyroid status, diabetes mellitus, smoking status, education, BMI, lipid lowering medications, age and follow up duration by using generalized estimating equations. Results: In every four years of assessments, there were significant decreases in levels of all lipid parameters (all Ps <0.001) except for HDL-C, in which a decrescendo-crescendo trend was observed. The results did not change after adjusting for thyroid status, consumption of lipid lowering drugs during the follow-up period, or other variables. There were significant decreases in the prevalence of hypercholesterolemia and hypertriglyceridemia (all Ps <0.001) during the follow-up period. Conclusion: During a 10 year follow-up, decrescendo trends were observed in levels of total cholesterol, triglycerides, which were not be accounted for by the consumption of lipid lowering drugs and thyroid status. [ABSTRACT FROM AUTHOR]

Objective: Patients with persistent poorly-controlled diabetes mellitus (PPDM) despite engagement in clinic-based care are at particularly high risk for diabetes complications and costs. Understanding this population’s demographics, comorbidities and care utilization could guide strategies to address PPDM. We characterized factors associated with PPDM in a large sample of Veterans with type 2 diabetes. Methods: We identified a cohort of Veterans with medically treated type 2 diabetes, who received Veterans Health Administration primary care during fiscal years 2012 and 2013. PPDM was defined by hemoglobin A1c levels uniformly >8.5% during fiscal year (FY) 2012, despite engagement with care during this period. We used FY 2012 demographic, comorbidity and medication data to describe PPDM in relation to better-controlled diabetes patients and created multivariable models to examine associations between clinical factors and PPDM. We also constructed multivariable models to explore the association between PPDM and FY 2013 care utilization. Results: In our cohort of diabetes patients (n = 435,820), 12% met criteria for PPDM. Patients with PPDM were younger than better-controlled patients, less often married, and more often Black/African-American and Hispanic or Latino/Latina. Of included comorbidities, only retinopathy (OR 1.68, 95% confidence interval (CI): 1.63,1.73) and nephropathy (OR 1.26, 95% CI: 1.19,1.34) demonstrated clinically significant associations with PPDM. Complex insulin regimens such as premixed (OR 10.80, 95% CI: 10.11,11.54) and prandial-containing regimens (OR 18.74, 95% CI: 17.73,19.81) were strongly associated with PPDM. Patients with PPDM had higher care utilization, particularly endocrinology care (RR 3.56, 95% CI: 3.47,3.66); although only 26.4% of patients saw endocrinology overall. Conclusion: PPDM is strongly associated with complex diabetes regimens, although heterogeneity in care utilization exists. While there is evidence of underutilization, inadequacy of available care may also contribute to PPDM. Our findings should inform tailored approaches to meet the needs of PPDM, who are among the highest-risk, highest-cost patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: Protein energy wasting (PEW) is a risk factor for death. However, the cutoff vales for PEW are not optimized for early identification of hemodialysis patients with malnutrition. We evaluated the prognosis of Japanese maintenance hemodialysis patients using nutritional indices optimized for them. Materials and methods: We analyzed data from a nation-wide prospective cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry to develop and validate a nutritional risk index (n = 48349, 48349, respectively). The association of nutritional factors with one-year death was tested using Cox proportional hazards models. Their cutoff levels were determined from the hazard ratios or receiver operating characteristic curves. Then, risk index was developed using scoring models. Results: Male was 61.4%; average age, 65.7±12.2 years; and diabetes mellitus, 32.8%. Four clinical factors were retained in the final model: low BMI (<20kg/m2), yes = 3, no = 0; low serum albumin level (young <3.7g/dL; old <3.5g/dL), yes = 4, no = 0; abnormal serum total cholesterol level, low (<130mg/dL) = 1, high (220≥mg/dL) = 2, no = 0; low serum creatinine level (young female, <9.7mg/dL; old female, <8.0mg/dL; young male, <11.6mg/dL; old male, <9.7mg/dL), yes = 4, no = 0. In the validation dataset, medium- and high-risk groups (total score 8 to 10; 11 or more) showed a higher risk of all-cause death than the low-risk group (0 to 7): medium-risk group (10.5%), hazard ratio adjusted for baseline characteristics 1.96 (95% confidence interval 1.77, 2.16); high-risk group (8.2%), 3.91 (3.57, 4.29). The medium- and high-risk groups also showed a higher risk of cardiovascular disease- and infection-caused deaths than the low-risk group. Conclusion: We developed a new nutritional risk index for hemodialysis patients, which may detect patients with malnutrition with a high-risk of death. [ABSTRACT FROM AUTHOR]

Background: Assessment of infection-related mortality remains inadequate in patients undergoing peritoneal dialysis. This study was performed to develop a risk model for predicting the 2-year infection-related mortality risk in patients undergoing peritoneal dialysis. Methods: The study cohort comprised 606 patients who started and continued peritoneal dialysis for 90 at least days and was drawn from the Fukuoka Peritoneal Dialysis Database Registry Study in Japan. The patients were registered from 1 January 2006 to 31 December 2016 and followed up until 31 December 2017. To generate a prediction rule, the score for each variable was weighted by the regression coefficients calculated using a Cox proportional hazard model adjusted by risk factors for infection-related mortality, including patient characteristics, comorbidities, and laboratory data. Results: During the follow-up period (median, 2.2 years), 138 patients died; 58 of them of infectious disease. The final model for infection-related mortality comprises six factors: age, sex, serum albumin, serum creatinine, total cholesterol, and weekly renal Kt/V. The incidence of infection-related mortality increased linearly with increasing total risk score (P for trend <0.001). Furthermore, the prediction model showed adequate discrimination (c-statistic = 0.79 [0.72–0.86]) and calibration (Hosmer–Lemeshow test, P = 0.47). Conclusion: In this study, we developed a new model using clinical measures for predicting infection-related mortality in patients undergoing peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Spot 14 (S14) protein is primarily expressed in adipogenic tissues. Compared to wild type, S14 knockout mice had better resistance to diet-induced obesity and glucose tolerance. However, the association between serum S14 level and metabolic variables in humans has never been investigated. The objectives of this study were to evaluate the associations between serum S14 concentrations with components of metabolic syndrome (MetS). A total of 327 subjects were recruited in this cross-sectional study and categorized by presence of MetS. The mean serum levels of S14 were significantly lower in subjects with MetS than those without (87.1±26.3 μg/L vs. 107.3±40.2 μg/L, p<0.001). In addition, the subjects with central obesity, low high density lipoprotein-C (HDL-C) or hypertriglyceridemia also had significantly lower S14 levels in comparison to those without. Adjusted with age and sex, diagnosis of MetS (β = -0.227, p<0.001), central obesity (β = -0.176, p = 0.001), low HDL-C (β = -0.149, p = 0.005), and high triglyceride (TG) (β = -0.198, p<0.001) were negatively associated with log transformation of serum S14 levels (logS14). With 25% logS14 increased, the risk of MetS (OR 0.65, 95% CI, 0.51–0.82, p<0.001), central obesity (OR 0.72, 95% CI, 0.58–0.89, p = 0.002), low HDL-C (OR 0.76, 95% CI, 0.61–0.95, p = 0.015) or high TG (OR 0.65, 95% CI, 0.51–0.83, p = 0.001) was reduced with a dose response trend. Our analysis revealed that patients with MetS had lower serum S14 levels than those without. Negative associations existed between MetS, central obesity, high TG, low HDL-C and logS14. [ABSTRACT FROM AUTHOR]

People who develop type 2 diabetes (T2D) are known to have a higher mortality risk. We estimated all-cause, cardiovascular, and cancer mortality-risks in our patient cohort according to categories of impaired glucose metabolism. This 18-year retrospective analysis included a region-wide, representative sample of a population aged 30–75 years. Age- and sex-stratified hazard ratios (HRs) were calculated for 48 participants with diagnosed T2D, 83 with undiagnosed T2D (HbA1c ≥6.5%, fasting glycemia ≥126 mg/dL, or glycemia after 75 g glucose load ≥200 mg/dL); 296 with prediabetes (HbA1c 5.7%-6.4%, fasting glycemia 100–125 mg/dL, or glycemia after 75 g glucose load 140–199 mg/dL), and 607 with normoglycemia. Over 18,612 person-years, 32 individuals with undiagnosed T2D, 30 with diagnosed T2D, 62 with prediabetes, and 80 with normoglycemia died. Total sample crude mortality rate (MR) was 10.96 deaths per 1,000 person-years of follow-up. MR of the diagnosed T2D group was more than 3-times higher and that of newly diagnosed T2D was 2-times higher (34.72 and 21.42, respectively) than total sample MR. Adjusted HR for all-cause mortality was 2.02 (95% confidence interval 1.29–3.16) and 1.57 (95% CI 1.00–2.28) in the diagnosed T2D group and the newly diagnosed T2D group, respectively. Adjusted HR for cardiovascular mortality in the T2D group was 2.79 (95% CI 1.35–5.75); this risk was greatly increased in women with T2D: 6.72 (95% CI 2.50–18.07). In Asturias, age- and sex-standardized all-cause mortality is more than 2-times higher for adults with T2D than for adults without T2D. The HR for cardiovascular mortality is considerably higher in T2D women than in normoglycemic women. [ABSTRACT FROM AUTHOR]

It remains widely perceived that early-onset Type 2 Diabetes (T2D) in children and adolescents is rare and clinically distinct from Type 1 Diabetes (T1D). We studied the challenges of classifying subtypes of early-onset diabetes using clinical features and biomarkers, and management of these patients. We reviewed retrospectively the record of patients < 25 years old who attended the diabetes clinic in Penang General Hospital, Malaysia between 1st December 2012 and 30th June 2015. We examined their clinical features, C-peptide and pancreatic autoantibodies. Comparisons were made between T1D and T2D for magnitude, demographics, metabolic status and complications. We studied 176 patients with a mean age of 20 ± 3.7 years, 43.2% had T1D, 13.6% had T2D, and 13.6% had mixed features of both. When tested, pancreatic autoantibodies were positive in 59.4% of the T1D. T2D presented two years later than T1D at 14.3 years, 20% were asymptomatic at presentation, and 50% required insulin supplementation despite fasting c-peptide of > 250 pmol/L. HbA1C of ≤ 8.0% (64 mmol/mol) was achieved in 30.3% of T1D, 58.3% of T2D on OAD and 16.7% of T2D on insulin. The T2D had greater cardiovascular risk with higher body mass index, more dyslipidaemia, higher blood pressure and earlier onset of nephropathy. The overlapping clinical features, variable autoimmunity, and beta-cell loss complicate classification of young diabetes. Pancreatic autoantibodies and C-peptide did not always predict diabetes subtypes nor respond to insulin. The poor metabolic control and high cardiovascular risk burden among the T2D highlight the need for population-based study and focused intervention. [ABSTRACT FROM AUTHOR]

Studies have demonstrated the adverse effects of smoking on the risk of microvascular complications; however, few have also examined the potential mediating effects of glycemic control. Using data from the Diabetes Control and Complications Trial (DCCT 1983–1993), we describe the acute and long-term risks of smoking on glycemic control and microvascular complications in a well-characterized cohort of participants with type 1 diabetes. The DCCT recorded self-reported smoking behaviors, glycemic exposure based on HbA1c, and complications status. Generalized linear mixed models were used to assess whether time-dependent measurements of smoking predict HbA1c levels. Cox proportional hazard models were used to assess time-dependent smoking exposures as predictors of retinopathy and nephropathy. During a mean of 6.5 years of follow-up, current smokers had consistently higher HbA1c values and were at a higher risk of retinopathy and nephropathy compared with former and never smokers. These risk differences were attenuated after adjusting for HbA1c suggesting that the negative association of smoking on glycemic control is partially responsible for the adverse association of smoking on the risk of complications in type 1 diabetes. These findings support the potential for a beneficial effect of smoking cessation on complications in type 1 diabetes. [ABSTRACT FROM AUTHOR]

C1q complement/tumor necrosis factor (TNF)—related protein (CTRP) family comprises of 15 proteins that posses important implications in energy homeostasis, infection and inflammation. However, their roles in diabetes mellitus (DM) and its vascular complications have not been completely assessed. This works aims to study the association of two CTRPs; 3 and 9, with pro-inflammatory cytokine monocyte chemoattractant protein-1 (MCP-1), and biochemical parameters of type 2 diabetes (T2D), dyslipidemia and coronary artery disease (CAD).Methods: Biochemical markers and serum levels of CTRPs and MCP-1 were measured in 86 postmenopausal females. Subjects were divided over four groups; 13 apparent healthy subjects as control (group I), 29 patients with CAD (group II), 29 patients with T2D ≥5 years (group III) and 15 patients with CAD secondary to T2D (group IV). Serum CTRP3, CTRP9, MCP-1 and insulin were measured by ELISA.Results: Serum CTRP3 levels were found to be significantly higher in group III and IV, whereas, it was significantly lower in group II on comparing to group I. While, CTRP9 levels were significantly decreased in group II, III and IV on comparing to group I. MCP-1 levels were found to be significantly increased in groups II, III and IV on comparison with group I. Both CTRPs were significantly negatively correlated with each other. While MCP-1 was significantly correlated negatively to CTRP9.Conclusion: This study associates the possible role of CTRP3, CTRP9 and MCP-1/CCL2 in the diagnosis/prognosis of CAD complication in T2D postmenopausal females. [ABSTRACT FROM AUTHOR]

Background/Objectives: Previous studies have demonstrated that in acute coronary syndrome (ACS), plaque destabilization and vessel inflammation, represented by vessel edema, often occur simultaneously in multiple coronaries, as well as extend to the cerebrovascular system. Our aim was to determine whether the inflammatory vascular processes occurring within the coronaries during ACS extend simultaneously to the descending aorta. Methods: We prospectively enrolled 111 patients (56 ACS patients and 55 non-ACS patients with known coronary artery disease) to undergo cardiac magnetic resonance of the thoracic aortic wall at presentation and at three-month follow-up. The primary outcome was change in aortic wall area (AWA) and maximal aortic wall thickness (AWT) from baseline to three-month follow-up. Secondary outcomes were baseline and follow-up differences in AWA and AWT, and changes in C-reactive protein (CRP). Results: There was a significant reduction in mean AWA (p = 0.01) and AWT (p = 0.01) between index and follow up scans in ACS group, with no significant changes in non ACS group (both p>0.1) and no difference between ACS and non-ACS groups (p = 0.22). There was no significant difference in AWA and AWT at baseline (p>0.36) and follow-up (p>0.2) between groups. There was a significant reduction in CRP in both groups (p<0.01), with higher reduction in ACS patients (p<0.01) Conclusions: There was a reduction in aortic wall size, aortic wall area, and aortic wall thickness in patients presenting with ACS, and no change in non-ACS patients. There were no interval between-group differences in these measurements. We observed a reduction in C-reactive protein in both groups, with higher reduction noted in ACS patients. [ABSTRACT FROM AUTHOR]

Background and aim: Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and is typically present in older adults with type 1 diabetes (T1D). In young adults, we aimed to assess the impact of T1D on endothelial function as detected by digital peripheral arterial tonometry (PAT) and its relationship with cardiovascular risk factors and long term glycemic control. Materials and methods: Reactive hyperemia index (RHI) as a measure of endothelial function was assessed by PAT in 46 T1D patients and 32 healthy controls. All were participants in the "Atherosclerosis and Childhood Diabetes" study, with baseline values registered five years previously. Annual measurements of HbA1c for assessment of glycemic burden were provided by the Norwegian Childhood Diabetes Registry. Results: The diabetes patients had a mean age of 20.8 years, a median duration of diabetes of 10.0 years and a mean HbA1c of 8.7%. RHI was not significantly decreased in the diabetes group, mean 2.00 (SD = 0.59) vs. 2.21 (SD = 0.56), p = .116. There was no gender difference or any associations with traditional risk factors. Furthermore, there was no significant association between RHI and either HbA1c or long term glycemic burden. Conclusions: RHI as a measure of endothelial function was preserved in young adults with T1D compared with healthy controls. [ABSTRACT FROM AUTHOR]

Accumulating evidence has revealed that both high sensitivity C-reactive protein (hsCRP) and homocysteine (HCY) are associated with increased risk of metabolic syndrome (MetS) and cardiovascular disease. However, it is unclear whether the coexistence of these conditions accelerates the risk of metabolic syndrome (MetS). We hypothesized that the combination of high sensitivity C-reactive protein (hsCRP) and homocysteine (HCY) levels could exacerbate the development of MetS in a large prospective cohort study. We selected data from 3,170 individuals (1,614 men and 1,556 women) who participated in the Korean Genome and Epidemiology Study. Participants with high hsCRP and HCY levels were categorized into quartiles. MetS was defined based on the criteria of the modified National Cholesterol Education Program, Adult Treatment Panel III. The prevalence of MetS was higher in participants with concurrent high hsCRP and HCY compared to those with low hsCRP and HCY levels. The incidence of MetS at the 6-year follow-up was the highest in participants with concomitant high hsCRP and HCY levels, regardless of obesity. Even after adjusting for potential confounding factors including body mass index in a multivariate logistic regression model, subjects with elevated hsCRP and HCY levels had a 2.50-fold increased risk of developing MetS at the six-year follow-up compared to those who did not have high hsCRP and HCY level. MetS is more prevalent in the concurrent presence of elevated hsCRP and HCY levels. The combination of the two conditions may contribute to an increased risk of MetS, but these factors may not be synergistic. [ABSTRACT FROM AUTHOR]

The antinociceptive effects of the carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) during chronic pain are well documented, but most of its possible side-effects remain poorly understood. In this work, we examine the impact of CORM-2 treatment on the lipoprotein profile and two main atheroprotective functions attributed to high-density lipoprotein (HDL) in a mouse model of type 1 diabetes while analyzing the effect of this drug on diabetic neuropathy. Streptozotocin (Stz)-induced diabetic mice treated with CORM-2 (Stz-CORM-2) or vehicle (Stz-vehicle) were used to evaluate the effect of this drug on the modulation of painful diabetic neuropathy using nociceptive behavioral tests. Plasma and tissue samples were used for chemical and functional analyses, as appropriate. Two main antiatherogenic properties of HDL, i.e., the ability of HDL to protect low-density lipoprotein (LDL) from oxidation and to promote reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT), were also assessed. Stz-induced diabetic mice displayed hyperglycemia, dyslipidemia and pain hypersensitivity. The administration of 10 mg/kg CORM-2 during five consecutive days inhibited allodynia and hyperalgesia and significantly ameliorated spinal cord markers (Cybb and Bdkrb1expression) of neuropathic pain in Stz mice, but it did not reduce the combined dyslipidemia shown in Stz-treated mice. Its administration to Stz-treated mice led to a significant increase in the plasma levels of cholesterol (∼ 1.4-fold vs. Ctrl, ∼ 1.3- fold vs. Stz-vehicle; p < 0.05) and was attributed to significant elevations in both non-HDL (∼ 1.8-fold vs. Ctrl; ∼ 1.6-fold vs. Stz-vehicle; p < 0.05) and HDL cholesterol (∼ 1.3-fold vs. Ctrl, ∼ 1.2-fold vs. Stz-vehicle; p < 0.05). The increased HDL in plasma was not accompanied by a commensurate elevation in m-RCT in Stz-CORM-2 compared to Stz-vehicle mice; instead, it was worsened as revealed by decreased [3H]-tracer trafficking into the feces in vivo. Furthermore, the HDL-mediated protection against LDL oxidation ex vivo shown by the HDL isolated from Stz-CORM-2 mice did not differ from that obtained in Stz-vehicle mice. In conclusion, the antinociceptive effects produced by a high dose of CORM-2 were accompanied by antioxidative effects but were without favorable effects on the dyslipidemia manifested in diabetic mice. [ABSTRACT FROM AUTHOR]

Background: Multiple occasions of device-measured physical activity have not been previously examined in relation to metabolic traits. We described associations of total activity, moderate-to-vigorous physical activity (MVPA), and sedentary time from three accelerometry measures taken across adolescence with detailed traits related to systemic metabolism.Methods and Findings: There were 1,826 male and female participants recruited at birth in 1991-1992 via mothers into the Avon Longitudinal Study of Parents and Children offspring cohort who attended clinics in 2003-2005, 2005-2006, and 2006-2008 who were included in ≥1 analysis. Waist-worn uniaxial accelerometers measured total activity (counts/min), MVPA (min/d), and sedentary time (min/d) over ≥3 d at mean age 12y, 14y, and 15y. Current activity (at age 15y), mean activity across occasions, interaction by previous activity, and change in activity were examined in relation to systolic and diastolic blood pressure, insulin, C-reactive protein, and 230 traits from targeted metabolomics (nuclear magnetic resonance spectroscopy), including lipoprotein cholesterol and triglycerides, amino and fatty acids, glycoprotein acetyls, and others, at age 15y. Mean current total activity was 477.5 counts/min (SD = 164.0) while mean MVPA and sedentary time durations were 23.6 min/d (SD = 17.9) and 522.1 min/d (SD = 66.0), respectively. Mean body mass index at age 15y was 21.4 kg/m2 (SD = 3.5). Correlations between first and last activity measurement occasions were low (e.g., r = 0.40 for counts/min). Current activity was most strongly associated with cholesterol and triglycerides in high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) particles (e.g., -0.002 mmol/l or -0.18 SD units; 95% CI -0.24--0.11 for triglycerides in chylomicrons and extremely large very low-density lipoprotein [XL VLDL]) and with glycoprotein acetyls (-0.02 mmol/l or -0.16 SD units; 95% CI -0.22--0.10), among others. Associations were similar for mean activity across 3 occasions. Attenuations were modest with adjustment for fat mass index based on dual-energy X-ray absorptiometry (DXA). In mutually adjusted models, higher MVPA and sedentary time were oppositely associated with cholesterol and triglycerides in VLDL and HDL particles (MVPA more strongly with glycoprotein acetyls and sedentary time more strongly with amino acids). Associations appeared less consistent for sedentary time than for MVPA based on longer-term measures and were weak for change in all activity types from age 12y-15y. Evidence was also weak for interaction between activity types at age 15y and previous activity measures in relation to most traits (minimum P = 0.003; median P = 0.26 for counts/min) with interaction coefficients mostly positive. Study limitations include modest sample sizes and relatively short durations of accelerometry measurement on each occasion (3-7 d) and of time lengths between first and last accelerometry occasions (<4 years), which can obscure patterns from chance variation and limit description of activity trajectories. Activity was also recorded using uniaxial accelerometers which predated more sensitive triaxial devices.Conclusions: Our results support associations of physical activity with metabolic traits that are small in magnitude and more robust for higher MVPA than lower sedentary time. Activity fluctuates over time, but associations of current activity with most metabolic traits do not differ by previous activity. This suggests that the metabolic effects of physical activity, if causal, depend on most recent engagement. [ABSTRACT FROM AUTHOR]

Background: Observations from statin clinical trials and from Mendelian randomization studies suggest that low low-density lipoprotein cholesterol (LDL-C) concentrations may be associated with increased risk of type 2 diabetes mellitus (T2DM). Despite the findings from statin clinical trials and genetic studies, there is little direct evidence implicating low LDL-C concentrations in increased risk of T2DM.Methods and Findings: We used de-identified electronic health records (EHRs) at Vanderbilt University Medical Center to compare the risk of T2DM in a cross-sectional study among individuals with very low (≤60 mg/dl, N = 8,943) and normal (90-130 mg/dl, N = 71,343) LDL-C levels calculated using the Friedewald formula. LDL-C levels associated with statin use, hospitalization, or a serum albumin level < 3 g/dl were excluded. We used a 2-phase approach: in 1/3 of the sample (discovery) we used T2DM phenome-wide association study codes (phecodes) to identify cases and controls, and in the remaining 2/3 (validation) we identified T2DM cases and controls using a validated algorithm. The analysis plan for the validation phase was constructed at the time of the design of that component of the study. The prevalence of T2DM in the very low and normal LDL-C groups was compared using logistic regression with adjustment for age, race, sex, body mass index (BMI), high-density lipoprotein cholesterol, triglycerides, and duration of care. Secondary analyses included prespecified stratification by sex, race, BMI, and LDL-C level. In the discovery cohort, phecodes related to T2DM were significantly more frequent in the very low LDL-C group. In the validation cohort (N = 33,039 after applying the T2DM algorithm to identify cases and controls), the risk of T2DM was increased in the very low compared to normal LDL-C group (odds ratio [OR] 2.06, 95% CI 1.80-2.37; P < 2 × 10-16). The findings remained significant in sensitivity analyses. The association between low LDL-C levels and T2DM was significant in males (OR 2.43, 95% CI 2.00-2.95; P < 2 × 10-16) and females (OR 1.74, 95% CI 1.42-2.12; P = 6.88 × 10-8); in normal weight (OR 2.18, 95% CI 1.59-2.98; P = 1.1× 10-6), overweight (OR 2.17, 95% CI 1.65-2.83; P = 1.73× 10-8), and obese (OR 2.00, 95% CI 1.65-2.41; P = 8 × 10-13) categories; and in individuals with LDL-C < 40 mg/dl (OR 2.31, 95% CI 1.71-3.10; P = 3.01× 10-8) and LDL-C 40-60 mg/dl (OR 1.99, 95% CI 1.71-2.32; P < 2.0× 10-16). The association was significant in individuals of European ancestry (OR 2.67, 95% CI 2.25-3.17; P < 2 × 10-16) but not in those of African ancestry (OR 1.09, 95% CI 0.81-1.46; P = 0.56). A limitation was that we only compared groups with very low and normal LDL-C levels; also, since this was not an inception cohort, we cannot exclude the possibility of reverse causation.Conclusions: Very low LDL-C concentrations occurring in the absence of statin treatment were significantly associated with T2DM risk in a large EHR population; this increased risk was present in both sexes and all BMI categories, and in individuals of European ancestry but not of African ancestry. Longitudinal cohort studies to assess the relationship between very low LDL-C levels not associated with lipid-lowering therapy and risk of developing T2DM will be important. [ABSTRACT FROM AUTHOR]

Background: The long-term trajectories of lipid and glucose levels in subjects who experience a major cardiovascular (CV) event at a young age has not been well studied. Our objective was to investigate lipid, lipoprotein, apolipoprotein (apo), and glucose levels in individuals experiencing a CV event before 50 years of age. Methods and findings: A first CV event [non-fatal myocardial infarction (MI), coronary revascularisation, or CV related death] before age 50 was recorded in 2,939 (cumulative incidence 1.2% in males and 0.3% in females) of 361,353 individuals included in the prospective Swedish AMORIS (Apolipoprotein-related MOrtality RISk) study with health examinations 1985–1996 and follow-up through 2011. In a nested case-control analysis, cases with a CV event were matched to randomly selected controls. Population risk factor trajectories were calculated up to 20 years prior to an event. Total cholesterol (TC), triglyceride (TG), and glucose levels were higher in cases than in controls as early as 20 years prior to the event with differences increasing over time. Low density lipoprotein, apoB, and the apoB/apoA-1 ratio were higher and increased over time, while HDL and apoA-1 were lower in cases compared to controls. The odds ratio was 2.5 (95% confidence interval 1.6–3.7) for TC ≥5 mmol/L and TG ≥1.7 mmol/L in cases versus controls. The adjusted population-attributable fractions including lipids, glucose, diabetes, smoking, hypertension, and obesity indicated that about 50% of CV events before age 50 may be associated with elevated lipid and glucose levels. Conclusions: Elevated TC, TG, LDL, apoB, and glucose levels and high apoB/apo A-1 ratio documented two decades before a CV event in subjects younger than 50 years may account for about half of CV events before age 50, which calls for early recognition and possibly treatment of modifiable CV risk factors in young individuals. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the genetic correlations between type 2 diabetes, obesity and dyslipidemia, and indicated that many genes have pleiotropic effects on them. However, these pleiotropic genes have not been well-defined. It is essential to identify pleiotropic genes using systematic approaches because systematically analyzing correlated traits is an effective way to enhance their statistical power. To identify potential pleiotropic genes for these three disorders, we performed a systematic analysis by incorporating GWAS (genome-wide associated study) datasets of six correlated traits related to type 2 diabetes, obesity and dyslipidemia using Meta-CCA (meta-analysis using canonical correlation analysis). Meta-CCA is an emerging method to systematically identify potential pleiotropic genes using GWAS summary statistics of multiple correlated traits. 2,720 genes were identified as significant genes after multiple testing (Bonferroni corrected p value < 0.05). Further, to refine the identified genes, we tested their relationship to the six correlated traits using VEGAS-2 (versatile gene-based association study-2). Only the genes significantly associated (Bonferroni corrected p value < 0.05) with more than one trait were kept. Finally, 25 genes (including two confirmed pleiotropic genes and eleven novel pleiotropic genes) were identified as potential pleiotropic genes. They were enriched in 5 pathways including the statin pathway and the PPAR (peroxisome proliferator-activated receptor) Alpha pathway. In summary, our study identified potential pleiotropic genes and pathways of type 2 diabetes, obesity and dyslipidemia, which may shed light on the common biological etiology and pathogenesis of these three disorders and provide promising insights for new therapies. [ABSTRACT FROM AUTHOR]

Introduction: Postprandial hyperglycemia plays a pivotal role in cardiovascular disease. However, few studies have investigated associations between the severity of coronary artery disease (CAD) and postprandial glucose levels in angina patients without known diabetes before coronary angiography. Methods: Subjects who were admitted for coronary angiography due to angina and were in stable condition after discharge were recruited. A standard 75-g oral glucose tolerance test (OGTT) was performed at outpatient visits approximately 2–4 weeks after hospital discharge, and fasting and post-challenge blood glucose were measured. Twenty-six volunteers in our hospital staff served as the healthy group. CAD severity was graded using the SYNTAX and Jeopardy scoring systems. Results: The subjects in the angina group had a higher body mass index, higher fasting glucose, and higher 2-h postprandial glucose than those in the healthy group. The SYNTAX and Jeopardy scores were significantly associated with 2-h postprandial blood glucose (correlation coefficients = 0.164 and 0.187, respectively) but not with fasting glucose. Linear regression analyses revealed that SYNTAX and Jeopardy scores were independently associated with glucose levels at 120 min after OGTT (SYNTAX 95%CI = 0.003–0.103; Jeopardy score 0.002–0.027) but not with fasting glucose. Conclusion: CAD severity is associated with blood glucose levels after oral glucose challenge in patients without known diabetes before coronary angiography, suggesting that CAD patients should be routinely screened for post-challenge blood glucose. [ABSTRACT FROM AUTHOR]

Objectives: To determine the risk factors for retinal microvascular impairment on optical coherence tomography angiography (OCT-A) in type 2 diabetic patients without clinical diabetic retinopathy (DR). Methods: This retrospective and cross-sectional study enrolled 74 diabetic patients without clinically evident DR for the study group and 34 healthy subjects for the control group. OCT-A parameters were measured to determine vascular density (VD) and the foveal avascular zone (FAZ) size in the superficial and deep capillary plexuses (SCP/DCP) of the retina. Clinical data were collected on sex, age, diabetes duration, hemoglobin A1c (HbA1c), hypertension, dyslipidemia, low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR) and smoking status. Multiple linear regression analyses were performed to represent the associated clinical variables with OCT-A parameters in diabetic patients. Results: In comparison between the study and control groups, the VD in the SCP and DCP were significantly lower in diabetic patients compared to the controls (P = 0.022 and 0.003, respectively). The FAZ size in the SCP and DCP were significantly greater in diabetic patients compared to the controls (P = 0.035 and <0.001, respectively). In age- and sex-adjusted multiple regression analyses for the diabetic patients, dyslipidemia and hypertension were negatively associated with SCP-VD (β = -0.357, P = 0.002; β = -0.239, P = 0.039, respectively). Current smoking was correlated with lower DCP-VD (β = -0.255, P = 0.043). Greater SCP-FAZ size was associated with dyslipidemia and greater LDL-C (β = 0.254, P = 0.013; β = 0.232, P = 0.029, respectively), and greater DCP-FAZ size, with lower eGFR and greater LDL-C (β = -0.355, P = 0.004; β = 0.235, P = 0.037, respectively). Conclusions: Diabetic patients without clinical DR showed lower VD and greater FAZ size in the SCP and DCP compared to healthy controls. In diabetic patients without clinical DR, dyslipidemia and/or high LDL-C were important risk factors for retinal microvascular impairment. Hypertension, current smoking and lower eGFR also contributed to microvascular impairment. [ABSTRACT FROM AUTHOR]

Purpose: Hypertension is a risk factor of atherosclerotic diseases. However, the importance of prehypertension in Japanese patients with type 2 diabetes mellitus (T2DM) is controversial. The aim of this study was to examine association between prehypertension, hypertension and atherosclerosis in T2DM. Methods: We recruited 179 Japanese patients with T2DM, who never took any medication for diabetes, hypertension, dyslipidemia, or atherosclerosis. Intima-media thickness (IMT) of common carotid artery was evaluated by high-resolution B-mode ultrasonography. Results: Multiple regression analysis adjusted for age, duration of diabetes, body mass index, HbA1c, fasting C-peptide, triglyceride, HDL-cholesterol, LDL-cholesterol, and estimated glomerular filtration rate showed that systolic blood pressure (SBP), but not diastolic BP, was significantly and positively associated with maximum IMT (IMT-max), mean IMT, and plaque score (β = 0.28, p<0.001; β = 0.26, p = 0.047; and β = 0.25, p = 0.006, respectively). ROC analysis showed that the cut-off value of SBP to detect atherosclerosis (IMT-max 1.8mm, the mean of IMT-max of this subjects) was 133.5 (p = 0.008), while DBP was not useful to detect it (p = 0.433). Then, participants were categorized as normotension (SBP <119 mmHg), prehypertension (SBP 120–139 mmHg), and hypertension (>140 mmHg). Multiple logistic regression analysis adjusted for the variables described above plus gender and smoking showed that prehypertension and hypertension were significantly associated with the increased risk of atherosclerosis [prehypertension; odds ratio (OR) 3.45, 95% confidence interval (CI) 1.11–10.76, p = 0.033, and hypertension; OR 7.29, 95%CI 1.99–26.78, p = 0.003]. Conclusion: These findings suggest that prehypertension categorized by SBP is an important risk factor of atherosclerosis independently of conventional risk factors in patients with T2DM. [ABSTRACT FROM AUTHOR]

Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are commonly used perfluorinated chemicals (PFCs). PFCs are mainly excreted by urine. Uremic patients tend to accumulate toxins in their body and have poor functional status. We investigated the associations between PFCs and the clinical profile of uremic patients under hemodialysis (HD). Liquid chromatography tandem mass spectrometry coupled with isotope dilution was used to quantify PFOA and PFOS. We enrolled 126 patients under regular HD. Compared with previous research, the concentration of PFOA was lower, but that of PFOS was higher in uremic patients than in the general population. The levels of PFOA and PFOS in uremic patients before dialysis were 0.52 (ng/ml) and 21.84 (ng/ml) respectively. The PFOA level remained unchanged but that of PFOS decreased to1.85 ng/mL after dialysis. PFOS can be removed by HD. Patients using hypertensive medication had a lower PFOS then those who did not. The PFOS level was negatively correlated with the duration of the HD session and patient performance status, but positively correlated with levels of cholesterol, chloride (an indicator of acidemia), ferritin, and total protein. (p<0.05). The association with serum protein may explain the long half-life of PFCs in humans. This is the first study which investigated PFCs in uremic patients and showed PFCs are associated with adverse effects in this population. [ABSTRACT FROM AUTHOR]

Objective: Despite the common use of non-fasting measurements for lipid profile in children it remains unclear as to the extent non-fasting conditions have on laboratory results of lipids measurements. We aimed to assess the impact of non-fasting lipid profile on the occurrence of dyslipidemia in children. Materials and methods: Basic lipid profile including: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), as well as small, dense-LDL-C (sd-LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)], were measured in 289 presumably healthy children aged 9–11 in both fasting and non-fasting condition. The clinical impact of non-fasting lipid profile was evaluated individually for each child with estimation of false positive (FP) and false negative (FN) results. Results: The highest percentage of FP results in non-fasting condition was observed for TG (42.3%) being significantly higher when compared to FN results (p = 0.003). In contrast, the highest percentage of FN results in a non-fasting state were shown for LDL-C (14.3%), but the difference was statistically insignificant when compared to FP results. When comparing fasting and non-fasting lipid profile a number of significant differences was shown for: TG (p<0.001), HDL-C (p = 0.002) LDL-C (p<0.001) and ApoAI (p<0.001), respectively. The occurrence of dyslipidemia, recognized on the basis of non-fasting lipids was significantly higher (p = 0.010) when compared to fasting lipid profile. Conclusions: A higher occurrence of dyslipidemia, based on the measurement of non-fasting lipids in children, is suggestive of possible disorders in lipid metabolism. However, accurate identification of dyslipidemia by assessment of non-fasting lipids requires the establishment of appropriate cut-off values for children. [ABSTRACT FROM AUTHOR]

Background: Autopsy studies reveal that atherosclerosis lesions can be found as early as two years of age. To slow the development of this early pathology, obesity and dyslipidemia prevention should start from childhood making it urgent to explore new ways to evaluate dyslipidemia risk in children that can be applied widely, such as the non-invasive anthropometric evaluation. Objective: Assess the metabolic profile of a pediatric population at a specific age to describe the association between anthropometric and biochemical cardiovascular disease risk factors; and evaluate selected anthropometric variables as potential predictors for dyslipidemic cardiovascular risk. Design and methods: Anthropometric features, bioimpedance parameters and fasting clinical profile were assessed in Lisbon and the Tagus Valley region pre-pubertal nine-year-old children (n = 1.496) from 2009–2013 in a descriptive, cross-sectional study. Anthropometric variables predictive power was evaluated through regression analysis. Results: At least one abnormal lipid parameter was found in 65% of “normal weight”, 73% of “overweight” and 81% of “obese” children according to the International Obesity Task Force (IOTF) standards. Dyslipidemia was present in 67.8% of children. Waist-hip ratio (WHR) explained 0.4% of total cholesterol (TC) variance. Waist circumference (WC) explained 2.8% of apolipoprotein (APO) A1 variance. Waist-circumference-to-height-ratio (WHtR) explained 2.7%, 2.8% and 1.9% of low-density lipoprotein cholesterol (LDL-c), APO B, and N_HDL-c variance, respectively. Children with abnormally high WHR levels had an increase in risk of 4.49, 3.40 and 5.30 times, respectively, for developing cardiovascular disease risk factors measured as high-risk levels of TC, LDL-c and non-HDL-c (N_HDL-c) (p<0.05). Only 29.9% of “normal weight” children had no anthropometric, bioimpedance or biochemical parameters associated with CV risk. Conclusion: A large proportion of school age children have at least one lipid profile abnormality. BMI, zBMI, calf circumference (CC), hip circumference (HC), WC, and WHR are directly associated with dyslipidemia, whereas HC and calf circumference (CC) adjusted to WC, and mid-upper arm circumference (MUAC), are all inversely associated with dyslipidemia. Selected anthropometric variables are likely to help predict increased odds of having CV risk factors. [ABSTRACT FROM AUTHOR]

Importance: Landmark studies showed that partial clinical remission in new-onset type 1 diabetes is associated with reduced prevalence of long-term complications, but early clinical indicators of this favorable outcome are poorly characterized. Aim: To determine if there were any differences in lipid parameters, especially LDL-cholesterol, between remitters and non-remitters 4 to 5 years after the diagnosis of type 1 diabetes after controlling for hemoglobin A1c, body mass index, and pubertal status. Subjects and methods: A longitudinal retrospective cohort study of 123 subjects of mean age 11.9 ± 2.9 years, [male 11.7 ± 2.9 years, (n = 55); female 12.0 ± 2.9 years, (n = 68), p = 0.60] with type 1 diabetes of 4–5 years duration. Anthropometric and biochemical data were collected at the 4th or 5th year after diagnosis in line with the American Diabetes Association recommendation to initiate screening for complications in children either at the beginning of puberty or 4–5 years after diagnosis. Puberty was defined by Tanner stages II-V. Partial clinical remission was defined by the gold-standard insulin-dose adjusted hemoglobin A1c (IDAA1c) of ≤9. Results: There were 44 (35.8%) remitters (age 13.0 ± 2.5y; male 52.3%). Both the total cholesterol and LDL-cholesterol were significantly lower in remitters compared to non-remitters: LDL-C: 78.8 ± 28.7 mg/dL vs. 91.6 ± 26.5 mg/dL, p = 0.023; and total cholesterol: 151.5 ± 32.6 mg/dL vs. 167.0 ± 29.6 mg/dL, p = 0.015. Other lipid fractions were similar between the groups. There were no differences between the groups for glycemic control, body mass index z score, thyroid function, celiac disease occurrence, or vitamin D status. A greater number of remitters were in puberty compared to non-remitters (86.4% vs. 60.8%, p = 0.006). LDL-C concentration was similar in prepubertal remitters vs. non-remitters (p = 0.93), but was significantly lower in remitters in puberty compared to non-remitters in puberty (p = 0.018) after adjusting for age and duration of diabetes. Conclusions: Children with type 1 diabetes who underwent a honeymoon phase had significantly lower LDL cholesterol 5 years after diagnosis. This early divergence in lipidemia may explain the dichotomy in the prevalence of long-term complication in type 1 diabetes between remitters and non-remitters. It also offers a pathway for targeted lipid monitoring in type 1 diabetes, by establishing non-remission as a non-modifiable risk factor for vascular complication in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Prevalent anuric peritoneal dialysis (PD) patients usually have higher mortality than PD patients with residual urine volume. We aimed to evaluate the predictors of survival in anuric PD patients. Anuric PD patients (n = 505, <100 mL of daily urine) enrolled in Korean nationwide prospective cohort were analyzed. Survived and non-survived anuric PD patients were compared by propensity score matching analysis with a ratio of two to one. The propensity method was used to adjust for patient age, dialysis duration, and presence of diabetes. Among the total anuric PD patients, non-survived patients showed a significantly older age, higher incidence of diabetes, coronary artery disease, and arrhythmia, and lower serum creatinine and albumin. After propensity score matching, multivariate Cox regression analysis for patient survival showed a decreasing risk as serum albumin increased (HR = 0.347, p = 0.0094). Analysis using the receiver-operating-characteristic (ROC) curve showed that survival could be predicted with a sensitivity of 59.4% and a specificity of 63.2% using a cutoff value of 3.6 g/dL of serum albumin in unmatched total PD patients. The beneficial impact of high albumin level on death was significantly greater for patients with older age (≥50 years), no diabetes, low ultrafiltration (UF) volume (<1000 mL/day), and low levels of serum creatinine (<10 mg/dL), total cholesterol (<177.5 mg/dL), ferritin (<100 ng/mL), and high-sensitivity C-reactive protein (hs-CRP) (<0.1 mg/dL). Survival in anuric PD patients was associated with age, comorbidities, and nutritional factors such as creatinine and albumin. After adjustment by propensity score matching, serum albumin level was an independent predictor for survival in anuric PD patients. [ABSTRACT FROM AUTHOR]

Objective: Blood pressure variability (BPV) has been associated with risk of cardiovascular events in observational studies, independently of mean BP levels. In states with higher autonomic imbalance, such as in diabetes, the importance of BP variability may theoretically be even greater. We aimed to investigate the incremental value of BPV for prediction of cardiovascular and all-cause mortality in patients with type 2 diabetes. Methods: We identified 9,855 patients without pre-existing cardiovascular disease who did not change BP-lowering treatment during the observation period from a Swedish primary health care cohort of patients with type 2 diabetes. BPV was summarized as the standard deviation (SD), coefficient of variation (CV), or variation independent of mean (VIM). Patients were followed for a median of 4 years and associations with cardiovascular and all-cause mortality were investigated using Cox proportional hazards models. Results: BPV was not associated with cardiovascular specific or all-cause mortality in the total sample. In patients who were not on BP-lowering drugs during the observation period (n = 2,949), variability measures were associated with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50% increases in SD, CV and VIM, respectively, adjusted for Framingham risk score risk factors, including mean BP. However, the addition of the variability measures in this subgroup only led to very minimal improvement in discrimination, indicating they may have limited clinical usefulness (change in C-statistic ranged from 0.000–0.003 in all models). Conclusions: Although BPV was independently associated with all-cause mortality in diabetes patients in primary care who did not have pre-existing cardiovascular disease or BP-lowering drugs, it may be of minimal clinical usefulness above and beyond that of other routinely measured predictors, including mean BP. [ABSTRACT FROM AUTHOR]

Purpose: Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. Methods: We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay. Using multiple regression analysis we evaluated potential association of circulating ANGPTL3, 4, and 8 levels with general medical status including age, sex, smoking, drinking, obesity, hypertension, impaired glycometabolism, dyslipidemia, hyperuricemia, hepatic impairment, chronic kidney disease, anemia, cardiac abnormality, and inflammation. Results: Circulating ANGPTL3 levels were relatively high in health-related categories of hepatic impairment and inflammation. Circulating ANGPTL4 levels were also significantly high in impaired glycometabolism or hepatic impairment but decreased in inflammation. Finally, increased ANGPTL8 levels were observed in obesity, impaired glycometabolism and dyslipidemia. Particularly, increased levels of circulating ANGPTL8 were positively correlated with circulating triglycerides and LDL-cholesterol levels and inversely correlated with circulating HDL-cholesterol levels. Conclusions: Circulating ANGPTL3, 4, and 8 levels reflect some risk factors for CVD development. [ABSTRACT FROM AUTHOR]

Background: With a cholesterol-lowering focus for diabetic adults and in the age of polypharmacy, it is important to understand how lipid profile levels differ among those with and without diabetes. Objective: Investigate the means, differences, and trends in lipid profile measures [TC, total cholesterol; LDL-c, low-density lipoprotein; HDL-c, high-density lipoprotein; and TG, triglycerides] among US adults by diabetes status and cholesterol-lowering medication. Methods: Population number and proportion of adults aged ≥21 years with diabetes and taking cholesterol-lowering medication were estimated using data on 10,384 participants from NHANES 2003–2012. Age-standardized means, trends, and differences in lipid profile measures were estimated by diabetes status and cholesterol medication use. For trends and differences, linear regression analysis were used adjusted for age, gender, and race/ethnicity. Results: Among diabetic adults, 52% were taking cholesterol-lowering medication compared to the 14% taking cholesterol-lowering medication without diabetes. Although diabetic adults had significantly lower TC and LDL-c levels than non-diabetic adults [% difference (95% confidence interval): TC = -5.2% (-6.8 –-3.5), LDL-c = -8.0% (-10.4 –-5.5)], the percent difference was greater among adults taking cholesterol medication [TC = -8.0% (-10.3 –-5.7); LDL-c = -13.7% (-17.1 –-10.2)] than adults not taking cholesterol medication [TC = -3.5% (-5.2 –-1.6); LDL-c = -4.3% (-7.1 –-1.5)] (interaction p-value: TC = <0.001; LDL-c = <0.001). From 2003–2012, mean TC and HDL-c significantly decreased among diabetic adults taking cholesterol medication [% difference per survey cycle (p-value for linear trend): TC = -2.3% (0.003) and HDL-c = -2.3% (0.033)]. Mean TC, HDL-c, and LDL-c levels did not significantly change from 2003 to 2012 in non-diabetic adults taking cholesterol medication or for adults not taking cholesterol medications. Conclusions: Diabetic adults were more likely to have lower lipid levels, except for triglyceride levels, than non-diabetic adults with profound differences when considering cholesterol medication use, possibly due to the positive effects from clinical diabetes management. [ABSTRACT FROM AUTHOR]

Benefits of cardiovascular disease (CVD) risk factors control are well known, but goals achievement remains low. The objective of this study is to evaluate the prevalence of CVD risk factors among men ina worker’s cohort with no previous CVD, to study control variations across time and the factors associated with poor control. To this end, we conducted a cohort reexamination (2010–2014) within the context of the Aragon Workers Health Study (AWHS). Data from working characteristics, analytical values and pharmacological prescription were included in the analysis. Prevalences of risk factor diagnosis and control were calculated, as well as factors associated with poor control. The prevalence of CVD risk factors was high. In 2014dyslipidaemia was the most prevalent (85.2%) followed by Hypertension (HT) (42.0%). People under treatment increased for the period analysed (p<0.001). The proportion of people treated varied from 72.2% in Diabetes Mellitus to 31.1% in dyslipidaemia in 2014. 46.2% of the workers with HT were controlled, decreasing to 21.9% in Diabetes and 11.0% in dyslipidaemia (2014). Working in a turn different to central shift was associated with poor control, especially for those working at night with HT (Odds Ratio in 2010: 3.6; Confidence Interval 95% 1.8–7.4) and dyslipidaemia (Odds Ratio 2010: 4.7; Confidence Interval 95% 1.3–16.4). We conclude that, although CVD control has increased significantly for the period studied, there are still many people that do not receive any treatment, and control goals are normally not achieved. [ABSTRACT FROM AUTHOR]

Objectives: The body variable associated with the diagnosis of Metabolic Syndrome (MetS) is an elevated waist circumference (WC), although a number of other variables have been suggested. Among these, an elevated waist-to-height ratio (WHtR), ie a value higher than 0.5, that may identify abnormality, independently from height. An elevated WHtR provided the best correlation with MetS in a prior study in a large Italian population. In order to assess the validity of this conclusion, a long-term follow-up study re-examined this population, also in order to detect possible associations with cardiovascular (CV) risk. Methods and results: 1,071 subjects with a complete follow-up of over 6 years were evaluated with a comparative assessment of the three anthropometric variables, namely WHtR, WC and body mass index (BMI). WHtR≥ 0.5 had the highest sensitivity for the identification of MetS, both in males and females (94.1% and 86.7% respectively). WHtR was of reduced specificity, occurring, yet less frequently (17.7% in males and 30% in females), in patients without MetS. By contrast, enlarged WC occurred with a lower frequency in male patients who developed MetS (30.2%) whereas in females, frequency was higher than in males (69.3%). Finally, a BMI≥ 25 kg/m2 had intermediate sensitivity and specificity regardless of gender. WC showed the highest odds ratio (2.62, 95%CI: 1.18–5.78) for the prediction of CV occurrence. Conclusion: The present study confirms WHtR as an excellent screening tool in identifying MetS carriers, but, different from reports in other countries, it shows a lower specificity in our population. [ABSTRACT FROM AUTHOR]

Objective: To compare choroidal thickness between patients with type 2 diabetes (T2D) and healthy controls measured using swept-source optical coherence tomography (SS-OCT). Methods: The sample comprised 157 eyes of 94 T2D patients, 48 eyes of which had diabetic macular edema (DME), and 71 normal eyes of 38 healthy patients. Subfoveal (SF) choroidal thickness, and choroidal thickness at 500-μm intervals up to 2500 μm nasal and temporal from the fovea were measured using the SS-OCT. Choroidal thicknesses were compared between groups using Student’s t-test. Additionally, Pearson correlations were calculated between diabetes duration, glycosylated hemoglobin (HbA1c) levels, and choroidal thickness. Results: Mean diabetes duration was 16.6±9.5 years, while mean glycosylated hemoglobin was 7.7±1.3%. Overall, the choroid was significantly thinner in T2D patients. Individuals with DME had reduced choroidal thickness in all measurements, except at 2000 and 2500-μm nasal positions, compared to healthy controls. There was a moderate correlation between choroidal thickness and HbA1c levels in DME patients (SF: r = 0.342; p = 0.017). Diabetes duration did not correlate significantly with choroidal thickness. Conclusion: SS-OCT measurements revealed that the choroid was significantly thinner in T2D patients, moderate non-proliferative diabetic retinopathy patients, and DME patients than in healthy individuals. Further studies are needed to clarify the effect of diabetes on this layer and the relationship between choroidal thickness and DME. [ABSTRACT FROM AUTHOR]

Background: The last decades have seen great advances in the understanding, treatment, and prevention of cardiovascular disease (CVD). Although mortality rates due to CVD have declined significantly in the last decades, the burden of CVD is still high, particularly in older adults. This raises the question whether contemporary populations of older adults are experiencing better or worse objective as well as subjective health than earlier-born cohorts. The aim of this study was to examine differences in modifiable indicators of cardiovascular health (CVH), comparing data obtained 20 years apart in the Berlin Aging Study (BASE, 1990–93) and the Berlin Aging Study II (BASE-II, 2009–2014). Methods: Serial cross-sectional analysis of 242 propensity-score-matched participants of BASE (born 1907–1922) and BASE-II (born 1925–1942). Body mass index (BMI), blood pressure, total cholesterol, glycated hemoglobin (HbA1c), diet, smoking and physical activity were operationalized according to the “Life’s simple 7“(LS7) criteria of the American Heart Association. Results: 121 matched pairs were identified based on age, sex, and education. In the later-born BASE-II sample, the mean LS7 score was significantly higher than in the earlier-born sample (7.8±1.8 vs. 6.4±2.1, p<0.001), indicating better CVH. In detail, diet, physical activity, smoking, cholesterol, and HbA1c were more favorable, whereas blood pressure was significantly higher in individuals from the later-born cohort. BMI did not differ significantly between the two matched samples. Notably, despite better CVH, later-born individuals (BASE-II) reported lower self-rated health, presumably because of higher health expectations. Conclusions: Overall, cardiovascular health was significantly better in the later-born cohort, but several notable exceptions exist. [ABSTRACT FROM AUTHOR]

Objective: Several studies have indicated that elevated levels of circulating ferritin are associated with disturbances in energy metabolism. But none of this gave a clearly pathologic mechanism. We aimed to explore the independent relationship between serum ferritin levels and dyslipidemia. Methods: We performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for dyslipidemia, lipid parameters, the homeostasis model assessment of insulin resistance (HOMA-IR) and the risk of diabetes, according to sex-specific quartiles of serum ferritin by using the data of China Health and Nutrition Survey (2009 CHNS). We used three models to estimate the strength of the correlation. The basic model (Model 1) is without adjustment and the Model 2 and Model 3 are adjusted for demographic, anthropometric, and lifestyle confounding factors. Results: In both genders, the ORs for high TG level, TC level and LDL-C level increased progressively and for HDL-C decreased across the ferritin quartiles (P<0.001 for trend). After adjustment for confounding factors in different logistic regression models, the results remained unchanged. The ORs for the risk of diabetes and high HOMA-IR level in the highest quartile group of serum ferritin levels were significantly increased in Model 1, but after adjustment for lipid parameters, the ORs for the risk of diabetes was decreased from 1.91 (95% CI: 1.37–2.67; P<0.001 for trend) to 1.48 (95% CI: 1.03–2.12; P = 0.036 for trend) in men, and from 5.40 (95% CI: 3.38–8.63; P<0.001 for trend) to 1.43 (95% CI: 0.83–2.43; P = 0.498 for trend) in women, and the ORs for IR was decreased from 1.86 (95% CI: 1.57–2.20; P<0.001 for trend) to 1.25 (95% CI: 1.05–1.50; P = 0.114 for trend) in men, and from 1.93 (95% CI: 1.63–2.28; P<0.001 for trend) to 1.24 (95% CI: 1.01–1.51; P = 0.012 for trend) in women. Conclusion: Our results provide evidence that serum ferritin levels are significantly associated with lipid parameters, independent of glucose metabolism disorders and components of metabolic syndrome (MetS). Thus, serum ferritin plays a key role in energy metabolism disorders and may affect glucose metabolism through lipid metabolism. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT) (n = 821) and participants with type 2 diabetes (T2D) (n = 861) recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES). A validated food frequency questionnaire (FFQ) was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors)]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day) (Pinteraction = 0.0001) on high-density lipoprotein cholesterol (HDL-C), where the ‘T’ allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008) and those in the highest tertile (P = 0.017) had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day) (Pinteraction<0.0001) on HDL-C, where the minor allele carriers had higher HDL-C in the lowest PUFA tertile (P = 0.024) and those in the highest PUFA tertile had lower HDL-C (P = 0.028) than GG homozygotes. In addition, a significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre intake (g/day) on HDL-C (Pinteraction<0.0001). None of the other interactions between the SNPs and lifestyle factors were statistically significant after correction for multiple testing. Our findings indicate that the association between TCF7L2 SNP rs12255372 and HDL-C may be modified by dietary fat intake in this Asian Indian population. [ABSTRACT FROM AUTHOR]

Metabolic diseases such as type 2 diabetes mellitus (T2DM) and metabolic syndromes (MetS) have been recognized as the important risk factors for asymptomatic intracranial vertebrobasilar stenosis (IVBS). Although fatty liver index (FLI) is significantly related with these diseases, the association between FLI and IVBS remains unclear. In the present study, 2368 participants (30–75 years) were recruited from a Chinese prospective cohort study of PMMJS. Amongst them, 2281 individuals who did not have IVBS at baseline were enrolled in the 6-year following-up study. In cross-sectional analysis based on the baseline characteristics, the results showed that FLI was positively related with IVBS prevalence. Compared to the participants with FLI < 30, the adjusted OR (95% CI) of IVBS was 2.07 (1.18, 3.62) and 2.85 (1.39, 5.18) in the groups of 30 ≤ FLI < 60 and FLI ≥ 60, respectively. In longitudinal analysis, the results showed that the participants with FLI ≥ 60 had an increased risk of asymptomatic IVBS compared to those with FLI < 30 [adjusted HR (95%CI): 1.65 (1.05, 2.60)]. Moreover, exclusion of persons with hypertension, T2DM and MetS did not alter the associations between FLI and asymptomatic IVBS. Therefore, our results suggest that elevated FLI is an independent risk factor for asymptomatic IVBS in Chinese adults. [ABSTRACT FROM AUTHOR]

Background: High serum phosphate is associated with coronary artery disease in patients with normal and impaired renal function. We asked: Does the serum phosphate range provide prediction of primary cardiac events? We extracted coded primary care data for over 100,000 patients from a database of 135 primary medical practices. Patients aged between 18 and 90 years without pre-existing cardiovascular diagnoses were included from a potential sample of over 1·2 million individuals. Methods and findings: Binary logistic regression models were used to evaluate the contribution of QRISK factors and electrolytes, including serum phosphate, to cardiac outcomes at five and nine years following an initial phosphate measurement. At five-year review (n = 113,993), low serum phosphate (OR 1·75, 95%CI 1·36–2·23, p<0·001), high-normal (OR 1·50, 95%CI 1·29–1·74, p<0·001), and high serum phosphate (OR 1·74, 95%CI 1·06–2·70, p = 0·02) were long-term risk factors for primary cardiac disease events after adjusting for confounding variables. A similar pattern was seen at our nine-year review. Conclusions: The extremes of serum phosphate may confer cardiac event risk with a U-shaped trend. In particular, we raise new cardiac concerns for low serum phosphate in the general population. Also, the normal range for phosphate may require redefinition among healthy adults. [ABSTRACT FROM AUTHOR]

Lipid and lipoprotein subclasses are associated with metabolic and cardiovascular diseases, yet the genetic contributions to variability in subclass traits are not fully understood. We conducted single-variant and gene-based association tests between 15.1M variants from genome-wide and exome array and imputed genotypes and 72 lipid and lipoprotein traits in 8,372 Finns. After accounting for 885 variants at 157 previously identified lipid loci, we identified five novel signals near established loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG. Four of the signals were identified with a low-frequency (0.005

Objective: Microvascular dysfunction is an important underlying mechanism of microvascular diseases. Determinants (age, sex, hypertension, dyslipidemia, hyperglycemia, obesity, and smoking) of macrovascular diseases affect large-artery endothelial function. These risk factors also associate with microvascular diseases. We hypothesized that they are also determinants of microvascular (endothelial) function. Methods: In The Maastricht Study, a type 2 diabetes-enriched population-based cohort study (n = 1991, 51% men, aged 59.7±8.2 years), we determined microvascular function as flicker light-induced retinal arteriolar %-dilation and heat-induced skin %-hyperemia. Multiple linear regression analyses were used to assess the associations of cardiovascular risk factors (age, sex, waist circumference, total-to-high-density lipoprotein (HDL) cholesterol ratio, fasting plasma glucose (FPG), 24-h systolic blood pressure, and cigarette smoking) with retinal and skin microvascular function. Results: In multivariate analyses, age and FPG were inversely associated with retinal and skin microvascular function (regression coefficients per standard deviation (SD) were -0.11SD (95%CI: -0.15;-0.06) and -0.12SD (-0.17;-0.07) for retinal arteriolar %-dilation and -0.10SD (-0.16;-0.05) and -0.11SD (-0.17;-0.06) for skin %-hyperemia, respectively. Men and current smokers had -0.43SD (-0.58;-0.27) and -0.32SD (-0.49;-0.15) lower skin %-hyperemia, respectively. 24-h systolic blood pressure, waist circumference, and total-to-HDL cholesterol ratio were not statistically significantly associated with these microvascular functions. Conclusions: Associations between cardiovascular risk factors and retinal and skin microvascular function show a pattern that is partly similar to the associations between cardiovascular risk factors and macrovascular function. Impairment of microvascular function may constitute a pathway through which an adverse cardiovascular risk factor pattern may increase risk of diseases that are partly or wholly of microvascular origin. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a primary driver for chronic cardiovascular conditions and there is no comprehensive literature about its management in South Africa. The objective of this study was to assess the prevalence, awareness, treatment, and control of dyslipidemia in rural South Africa and how they are impacted by different behaviors and non-modifiable factors. To fulfill this objective we recruited for this cohort study adults aged ≥40 years residing in the Agincourt sub-district of Mpumalanga Province. Data collection included socioeconomic and clinical data, anthropometric measures, blood pressure (BP), HIV-status, point-of-care glucose and lipid levels. Framingham CVD Risk Score was ascribed to patients based upon categories for 10 year cardiovascular risk of low (<3%), moderate (≥3% and <15%), high (≥15% and <30%), and very high (≥30%).LDL cholesterol control by risk category was defined according to South African Guidelines. Multivariable logistic regression models were built to identify factors that were significantly associated with dyslipidemia and awareness of dyslipidemia From 5,059 respondents a total of 4247 subjects (83.9%) had their cholesterol levels measured and were included in our analysis. Overall, 67.3% (2860) of these met criteria for dyslipidemia, only 30 (1.05%) were aware of their condition, and only 21 subjects (0.73%) were on treatment. The majority have abnormalities in triglycerides (59.3%). As cardiovascular risk increased the rates of lipid control according to LDL level dropped. Multivariate logistic regression analyses showed that being overweight was predictive of dyslipidemia (OR 1.76; 95%CI 1.51–2.05, p<0.001) and dyslipidemia awareness (OR 2.58; 95%CI 1.19–5.58; p = 0.017). In conclusion, the very low awareness and treatment of dyslipidemia in this cohort indicate a greater need for systematic screening and education within the population and demonstrate that there are multiple opportunities to allay this burden. [ABSTRACT FROM AUTHOR]

Background: Little information is available regarding which type of dialyzer membrane results in good prognosis in patients on chronic hemodialysis. Therefore, we conducted a cohort study from a nationwide registry of hemodialysis patients in Japan to establish the association between different dialyzer membranes and mortality rates. Methods: We followed 142,412 patients on maintenance hemodialysis (female, 39.1%; mean age, 64.8 ± 12.3 years; median dialysis duration, 7 [4–12] years) for a year from 2008 to 2009. We included patients treated with seven types of high-flux dialyzer membranes at baseline, including cellulose triacetate (CTA), ethylene vinyl alcohol (EVAL), polyacrylonitrile (PAN), polyester polymer alloy (PEPA), polyethersulfone (PES), polymethylmethacrylate (PMMA), and polysulfone (PS). Cox regression was used to estimate the association between baseline dialyzers and all-cause mortality as hazard ratios (HRs) and 95% confidence intervals for 1-year mortality adjusting for potential confounders, and propensity score matching analysis was performed. Results: The distribution of patients treated with each membrane was as follows: PS (56.0%), CTA (17.3%), PES (12.0%), PEPA (7.5%), PMMA (4.9%), PAN (1.2%), and EVAL (1.1%). When data were adjusted using basic factors, with PS as a reference group, the mortality rate was significantly higher in all groups except for the PES group. When data were further adjusted for dialysis-related factors, HRs were significantly higher for the CTA, EVAL, and PEPA groups. When the data were further adjusted for nutrition-and inflammation-related factors, HRs were significantly lower for the PMMA and PES groups compared with the PS group. After propensity score matching, HRs were significantly lower for the PMMA group than for the PS group. Conclusion: The results suggest that the use of different membrane types may affect mortality in hemodialysis patients. However, further long-term prospective studies are needed to clarify these findings, including whether the use of the PMMA membrane can improve prognosis. [ABSTRACT FROM AUTHOR]

Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins can alter lipid density, packing and interactions, and are considered an important factor that affects fluidity variation in membranes. Red blood cells (RBC) membrane physical state, showing pronounced alterations in Type 1 diabetes mellitus (T1DM), could be the ideal candidate for monitoring the disease progression and the effects of therapies. On these grounds, the measurement of RBC membrane fluidity alterations can furnish a more sensitive index in T1DM diagnosis and disease progression than Glycosylated hemoglobin (HbA1c), which reflects only the information related to glycosylation processes. Here, through a functional two-photon microscopy approach we retrieved fluidity maps at submicrometric scale in RBC of T1DM patients with and without complications, detecting an altered membrane equilibrium. We found that a phase separation between fluid and rigid domains occurs, triggered by systemic effects on membranes fluidity of glycation and oxidation. The phase separation patterns are different among healthy, T1DM and T1DM with complications patients. Blood cholesterol and LDL content are positively correlated with the extent of the phase separation patterns. To quantify this extent a machine learning approach is employed to develop a Decision-Support-System (DSS) able to recognize different fluidity patterns in RBC. Preliminary analysis shows significant differences(p<0.001) among healthy, T1DM and T1DM with complications patients. The development of an assay based on Phase separation of the plasma membrane of the Red Blood cells is a potential tool for diagnosis and progression monitoring of type 1 diabetes mellitus, and could allow customization and the selection of medical treatments in T1DM in clinical settings, and enable the early detection of complications. [ABSTRACT FROM AUTHOR]

Objective: We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. Methods: HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. Results: HAE was significantly reduced in MetSyn patients (49.0 ± 10.9% vs. 61.2 ± 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6% vs. 12.3 ± 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. Conclusions: MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-mediated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk. [ABSTRACT FROM AUTHOR]