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    Lipoprotein(a)-activated immunity, insulin resistance and new-onset diabetes
    (Taylor & Francis Ltd, 2017) Kaya, Aysem; Onat, Altan; Yuksel, Husniye; Can, Gunay; Yuksel, Murat; Ademoglu, Evin
    Objectives: Some evidence suggests that serum lipoprotein[Lp](a) may be inversely linked to type-2 diabetes. We aimed to determine in nondiabetic people the relationship of serum [Lp](a) with insulin resistance and new-onset diabetes (NOD). Materials and methods: Population-based middle-aged adults (n = 1685) were categorized by fasting glucose and stratified to gender, having excluded prevalent diabetic subjects. NOD (n = 90) occurred over a median 5 years' follow-up. Results: Subjects that subsequently developed NOD, derived both from the normoglycemia and impaired fasting glucose (IFG) groups,were distinguished, among others, primarily by significantly elevated serum gamma glutamyltransferase, reduced Lp(a) (by 31%) and, compared to IFG, by low total cholesterol levels. Partial correlation of Lp(a) with homeostatic model assessment (HOMA) was inverse in normoglycemic men; such correlation, neutral in normoglycemic women, proved inverse in IFG (r = -0.17). Circulating Lp(a) in individuals with paired measures increased significantly (1.55-fold) in the period from baseline up to NOD. Multivariable-adjusted logistic regression analysis for NOD in combined sexes indicated independent and additive prediction by serum Lp(a), albeit inverse in direction (RR 0.84, [95%CI 0.72; 0.97]). Conclusion: Lp(a) is significantly reduced in the period preceding NOD and is inversely associated with HOMA index, observations consistent with underlying autoimmune activation.
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    Low acylation stimulating protein levels are associated with cardiometabolic disorders-secondary to autoimmune activation?
    (Turkish Soc Cardiology, 2017) Onat, Altan; Altay, Servet; Yuksel, Murat; Karadeniz, Yusuf; Can, Gunay; Yuksel, Husniye; Ademoglu, Evin
    Objective: We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation. Methods: Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as healthy. Results: ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in healthy men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values =22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF Conclusion: Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for reduced values and increased likelihood of cardiometabolic disorders.
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    Serum total and high-density lipoprotein phospholipids: Independent predictive value for cardiometabolic risk
    (Churchill Livingstone, 2014) Onat, Altan; Cakmak, H. Altug; Can, Gunay; Yuksel, Murat; Koroglu, Bayram; Yuksel, Husniye
    Objective: Given that serum phospholipids (PL) may serve as inflammation mediators, we studied whether they predicted metabolic syndrome (MetS), type-2 diabetes or coronary heart disease (CHD) risk in people prone to enhanced low-grade inflammation. Methods: We analyzed unselected middle-aged Turkish adults with available serum total (n = 852) and HDL-PL (n = 428) measurements and follow-up (mean 6.6 years) by Cox or logistic regression, after exclusion of prevalent cases of outcome disorder. The enzymatic method used measured total content of phosphatidylcholine, sphingomyelin and lyso-phosphatidylcholine. Results: Most lipid and non-lipid variables were significantly different in the upper two compared with the lowest total PL tertile, whereby apolipoprotein (apo)A-I and HDL-cholesterol were higher (not lower). ApoA-I. HDL-cholesterol and uric acid were uniformly positive independent linear covariates of total and HDL PI, apoA-I even in participants without MetS. After adjustment for sex, age, waist circumference. HDL-cholesterol and systolic blood pressure, logistic regression for incident MetS disclosed a 3-fold risk (RR [95% CI 1.28; 6.81]) in the upper HDL-pl tertile. In Cox regression models, while the combined two higher HDL-pl tertiles significantly protected against CHD risk in males (HR 0.29 [95% CI 0.10; 0.89]), they weakly tended to impart risk in females: upper two total PL tertiles tended to increased risk of diabetes and CHD. Conclusion: Excess total PL may mediate inflammatory properties to apoA-I. HDL and uric acid. Excess HDL-pl independently predict risk for MetS in each gender, but are protective against CHD risk in men, possibly because oxidized PL content mediated by total PL is sex-dependent, as reviewed elsewhere. (C) 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.