Publications by authors named "Dieplinger H"

Rationale & Objective: Afamin is a vitamin E-binding glycoprotein primarily expressed in liver and kidney. This study investigated whether serum afamin concentrations are associated with kidney function and incident kidney failure.

Study Design: Prospective cohort study with 6.

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Article Synopsis
  • Routine genetic testing for hypercholesterolemia identifies a causative monogenic variant in less than 50% of patients due to additional polygenic factors influencing cholesterol levels.
  • The study analyzed 1,020 individuals, including 252 with clinically diagnosed hypercholesterolemia, using advanced sequencing methods and genetic score calculations to identify 9 new variants in the LDLR gene.
  • Integrating genetic scores, particularly for lipoprotein(a) (Lp(a)), improved identification of clear disease causes to 68.8%, emphasizing the significance of Lp(a) in hypercholesterolemia and suggesting that better testing methods could lead to more tailored treatment strategies.
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Background And Aims: FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost effectiveness of screening for familial hypercholesterolemia (FH) and at providing an overview of the main characteristics and methodological approaches of applied decision-analytic models.

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Congenital disorders of lipid metabolism are characterised by LDL-C concentrations > 190 mg/dl (4.9 mM) and/or triglycerides > 200 mg/dl (2.3 mM) in young individuals after having excluded a secondary hyperlipoproteinemia.

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Objectives: In the general population, increased afamin concentrations are associated with the prevalence and incidence of metabolic syndrome as well as type 2 diabetes. Although metabolic syndrome is commonly associated with nonalcoholic fatty liver disease (NAFLD), there exist no information on afamin and NAFLD.

Methods: Afamin concentrations were cross-sectionally measured in 146 Austrian patients with NAFLD, in 45 patients without NAFLD, and in 292 age- and sex-matched healthy controls.

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Aim: Afamin is a liver-produced glycoprotein, a potential early marker of metabolic syndrome. Here we investigated regulation of afamin in a course of the metabolic disease development and in response to 3-month exercise intervention.

Methods: We measured whole-body insulin sensitivity (euglycemic hyperinsulinemic clamp), glucose tolerance, abdominal adiposity, hepatic lipid content (magnetic resonance imaging/spectroscopy), habitual physical activity (accelerometers) and serum afamin (enzyme-linked immunosorbent assay) in 71 middle-aged men with obesity, prediabetes and newly diagnosed type 2 diabetes.

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Article Synopsis
  • Familial hypercholesterolaemia (FH) is primarily caused by mutations in LDLR, APOB, or PCSK9 genes, with differences in LDL cholesterol levels observed based on the specific mutation present.
  • Data from 2866 children across eight European countries revealed that LDLR mutations are the most common in cases of FH, while the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly by country.
  • Children with LDLR mutations generally had higher LDL-C levels and a greater family history of coronary heart disease compared to those with APOB mutations.
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Background And Aims: For children with heterozygous familial hypercholesterolaemia (HeFH), European guidelines recommend consideration of statin therapy by age 8-10 years for those with a low density lipoprotein cholesterol (LDL-C) >3.5 mmol/l, and dietary and lifestyle advice. Here we compare the characteristics and lipid levels in HeFH children from Norway, UK, Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece.

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Background And Aims: Lipoprotein (a) [Lp(a)] is an established causal risk factor for cardiovascular disease (CVD), independently of low-density lipoproteins (LDL) and other risk factors. The recognition of Lp(a) as an atherogenic molecule has raised the demand for reliable quantification methods in the clinical laboratory. The aim of this work is to compare commercial immunochemical assays.

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Background: Patients suffering from polycystic ovary syndrome (PCOS) are often insulin resistant and at elevated risk for developing gestational diabetes mellitus (GDM). The aim of this study was to explore afamin, which can be determined preconceptionally to indicate patients who will subsequently develop GDM. Serum concentrations of afamin are altered in conditions of oxidative stress like insulin resistance (IR) and correlate with the gold standard of IR determination, the HOMA index.

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Purpose: Oxidative stress is involved in the pathogenesis of hypertensive disorders such as preeclampsia (PE) and associated with the human vitamin E-binding protein afamin. The aim of this study was, therefore, to analyse afamin in the first trimester of patients developing PE later in pregnancy and in control subjects without pregnancy complications.

Methods: In this retrospective study, 137 serum samples from the first trimester of pregnancy were analysed in a case-control study design.

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Article Synopsis
  • The study investigates afamin, a vitamin E-binding protein, as a potential early biomarker for predicting gestational diabetes mellitus (GDM), focusing on its role in insulin resistance and its increasing levels during pregnancy.
  • Researchers analyzed afamin concentrations in 59 GDM patients and 51 controls in the first trimester, and 105 women in mid-trimester, comparing the results with oral glucose tolerance test outcomes.
  • Findings revealed significantly higher afamin levels in women with GDM in both cohorts, with specific distinctions noted between those treated with insulin and dietary interventions, suggesting afamin's potential as an early predictor for GDM.
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Afamin is an 87 kDa glycoprotein with five predicted N-glycosylation sites. Afamin's glycan abundance contributes to conformational and chemical inhomogeneity presenting great challenges for molecular structure determination. For the purpose of studying the structure of afamin, various forms of recombinantly expressed human afamin (rhAFM) with different glycosylation patterns were thus created.

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Objective: Aim of the study was to assess the correlation of first trimester serum afamin levels with three-dimensional placental bed vascularization in pregnant women and its prognostic value for predicting pre-eclampsia and future fetal and maternal complications during pregnancy.

Methods: In this nested case-control study all pregnant women registered for delivery during a period of 3 years were routinely screened in the first trimester. Serum afamin levels were assessed in 764 women and correlated to 5 pregnancy outcome groups: gestational hypertension (n = 76), pre-eclampsia (n = 33), intrauterine growth restriction (n = 91), pre-term birth (n = 39), gestational diabetes mellitus (n = 170); In addition, measurements of first trimester myometrial vascularization index were performed and, in combination with afamin tested as a possible screening method to detect women at-risk for the development of adverse complications in low-risk pregnancies at the time of the first trimester.

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Objective: Aim of this study was to assess the prognostic capability of afamin to predict pregnancy complications.

Method: First-trimester screening was consecutively performed in 4948 pregnant women, of whom 474 women developed pregnancy complications [gestational hypertension (n=84), pre-eclampsia (n=30), intrauterine growth restriction (n=107), preterm birth (n=44), and gestational diabetes mellitus (n=209)]. To each woman with pregnancy complications an uncomplicated pregnancy was matched for body mass index.

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Afamin, a human plasma glycoprotein and putative transporter of hydrophobic molecules, has been shown to act as extracellular chaperone for poorly soluble, acylated Wnt proteins, forming a stable, soluble complex with functioning Wnt proteins. The 2.1-Å crystal structure of glycosylated human afamin reveals an almost exclusively hydrophobic binding cleft capable of harboring large hydrophobic moieties.

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Objective: The human vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in line with observations in transgenic mice. We thus investigated whether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR).

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Background: The potential for global collaborations to better inform public health policy regarding major non-communicable diseases has been successfully demonstrated by several large-scale international consortia. However, the true public health impact of familial hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide.

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The monoclonal antibody N14 is used as a detection antibody in ELISA kits for the human glycoprotein afamin, a member of the albumin family, which has recently gained interest in the capture and stabilization of Wnt signalling proteins, and for its role in metabolic syndrome and papillary thyroid carcinoma. As a rare occurrence, the N14 Fab is N-glycosylated at Asn26L at the onset of the V1 antigen-binding loop, with the α-1-6 core fucosylated complex glycan facing out of the L1 complementarity-determining region. The crystal structures of two non-apparent (pseudo) isomorphous crystals of the N14 Fab were analyzed, which differ significantly in the elbow angles, thereby cautioning against the overinterpretation of domain movements upon antigen binding.

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Background: High lipoprotein(a) [Lp(a)] concentrations and low molecular weight (LMW) apolipoprotein(a) [apo(a)] isoforms are associated with cardiovascular disease and mortality in the general population. We examined the association of both with all-cause mortality and cardiovascular endpoints in haemodialysis patients with diabetes mellitus.

Methods: This is a post hoc analysis of the prospective 4D Study (German Diabetes Dialysis Study) that evaluated atorvastatin compared with placebo in 1255 haemodialysis patients with type 2 diabetes mellitus (median follow-up 4 years).

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Decreasing low-density lipoprotein cholesterol (LDL-C) is one of the few established and proven principles for the prevention and treatment of atherosclerosis. The higher the individual cardiovascular risk, the higher the benefit of lipid-lowering pharmacotherapy. Therefore, treatment options are chosen based on a patient's total cardiovascular risk.

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In 2010, eight Austrian medical societies proposed a joint position statement on the management of metabolic lipid disorders for the prevention of vascular complications. An updated and extended version of these recommendations according to the current literature is presented, referring to the primary and secondary prevention of vascular complications in adults, taking into consideration the guidelines of other societies. The "Austrian Lipid Consensus - 2016 update" provides guidance for individualized risk stratification and respective therapeutic targets, and discusses the evidence for reducing vascular endpoints with available lipid-lowering therapies.

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The human glycoprotein afamin was discovered as the fourth member of the albumin gene family. Despite intense research over the last 20 years, our knowledge of afamin's physiological or pathophysiological functions is still very limited. Circulating afamin is primarily of hepatic origin and abundant concentrations are found in plasma, cerebrospinal, ovarian follicular and seminal fluids.

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