Publications by authors named "Barbara Obermayer-Pietsch"

164 Publications

Adverse body composition and lipid parameters in patients with prolactinoma: a case-control study.

BMC Endocr Disord 2021 Apr 26;21(1):81. Epub 2021 Apr 26.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

Background: Hyperprolactinaemia might cause adverse metabolic effects. The aim of our study was to compare parameters of body composition, glucose and lipid metabolism between untreated patients with prolactinoma and controls and to assess changes after initiation of cabergoline.

Methods: Case-control study with a retrospectively analyzed follow-up in patients with prolactinoma after initiation of cabergoline therapy.

Results: 21 patients with prolactinoma (9 micro- and 12 macroprolactinomas; 7 females) and 30 controls were analyzed. Patients with prolactinoma had significantly higher BMI than controls; fat mass did not differ between groups. Only men - but not women - with prolactinoma had significantly higher fat mass at all six sites measured compared to controls. Levels of LDL (130 (107-147.5) vs. 94.5 (80-127.5) mg/dl, p < 0.001) were significantly higher, levels of HDL (56 ± 16.7 vs. 69.2 ± 14.6 mg/dl, p = 0.004) significantly lower than in controls. Fasting glucose, HOMA-IR, HbA1c, adiponectin, CRP, and homocysteine did not differ between groups. After a median of 10 weeks (IQR 7-18 weeks) after initiation of cabergoline, total (from 212.5 ± 36.2 to 196.9 ± 40.6 mg/dl, p = 0.018) and LDL cholesterol (130 (107-147.5) to 106.5 (94.3-148) mg/dl, p = 0.018) had significantly decreased. Analyzing men and women separately, this change occurred in men only.

Conclusions: Reasons for the association between prolactin and metabolic parameters include direct effects of prolactin on adipose tissue, hyperprolactinaemia-triggered hypogonadism and dopamine-agonist therapy per se. Altered lipid metabolism in patients with prolactinoma might imply an increased cardiovascular risk, highlighting the necessity to monitor metabolic parameters in these patients.
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http://dx.doi.org/10.1186/s12902-021-00733-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074459PMC
April 2021

Natural autoantibodies to the gonadotropin-releasing hormone receptor in polycystic ovarian syndrome.

PLoS One 2021 2;16(4):e0249639. Epub 2021 Apr 2.

Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Context: Polycystic ovarian syndrome (PCOS) is a complex disease with different subtypes and unclear etiology. Among the frequent comorbidities are autoimmune diseases, suggesting that autoantibodies (aAb) may be involved in PCOS pathogenesis.

Objective: As the gonadal axis often is dysregulated, we tested the hypothesis that aAb to the gonadotropin-releasing hormone receptor (GnRH-R) are of diagnostic value in PCOS.

Design: An in vitro assay for quantifying aAb to the GnRH-R (GnRH-R-aAb) was established by using a recombinant fusion protein of full-length human GnRH-R and firefly luciferase. A commercial rabbit antiserum to human GnRH-R was used for standardization. Serum samples of control subjects and different cohorts of European PCOS patients (n = 1051) were analyzed.

Results: The novel GnRH-R-aAb assay was sensitive, and signals were linear on dilution when tested with the commercial GnRH-R antiserum. Natural GnRH-R-aAb were detected in one control (0.25%) and two PCOS samples (0.31%), and 12 samples were slightly above the threshold of positivity. The identification of samples with positive GnRH-R-aAb was reproducible and the signals showed no matrix interferences.

Conclusion: Natural GnRH-R-aAb are present in a very small fraction of adult control and PCOS subjects of European decent. Our results do not support the hypothesis that the GnRH-R constitutes a relevant autoantigen in PCOS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249639PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018624PMC
April 2021

[Long-term treatment concepts for osteoporosis].

Internist (Berl) 2021 May 12;62(5):474-485. Epub 2021 Mar 12.

Klin. Abteilung Endokrinologie und Diabetologie, Univ. Klinik für Innere Medizin, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich.

The need for a long-term pharmacological treatment of osteoporosis, the problem of potential compliance issues and also potentially severe side effects during the treatment are of central interest not only for patients but also for medical guidelines and prescribers. This review summarizes the current knowledge about the pharmacological substances used and the current scientifically based guidelines and approaches for the long-term use as well as the monitoring and potential treatment changes with a special focus on future developments.
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http://dx.doi.org/10.1007/s00108-021-00993-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079292PMC
May 2021

Longitudinal Study of Pelvic Floor Characteristics Before, During, and After Pregnancy in Nulliparous Women.

J Ultrasound Med 2021 Mar 7. Epub 2021 Mar 7.

Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

Objectives: To investigate the changes in the pelvic floor before, during, and after pregnancy in the same collective of nulliparous women.

Methods: In a prospective observational pilot study between April 2015 and June 2019 in nulliparous women with planned pregnancy, we used the pelvic organ prolapse quantification (POP-Q) system; a 2-dimensional (2D) sonography to investigate the bladder neck, cervix, and anorectal junction positions; and a 3D/4D sonography to measure the hiatus of the levator ani muscle (LH area) during Valsalva maneuver. Five visits were planned: 1 before, 3 during, and 1 visit after pregnancy.

Results: Twenty-four women participated in the study. We achieved a minimum of 2 visit measurements from 10 women who became pregnant. The LH area decreased during the first trimester and then increased until the third trimester. Postpartum, the LH area reached the prepregnancy state. We observed changes in the bladder neck mobility, bladder neck position, cervix, and anorectal junction from the first trimester. Postpartum, the bladder neck mobility was higher, and the position of the bladder neck and anorectal junction was lower than before pregnancy. We observed no remarkable changes in the POP-Q state during pregnancy.

Conclusion: This was the first study to investigate pelvic floor characteristics in the same collective before, during, and after pregnancy. We observed pelvic floor changes from the prepregnancy state to the first trimester to postpartum. The study results need to be confirmed in a larger study.
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http://dx.doi.org/10.1002/jum.15689DOI Listing
March 2021

Risk of Insulin Resistance and Metabolic Syndrome in Women with Hyperandrogenemia: A Comparison between PCOS Phenotypes and Beyond.

J Clin Med 2021 Feb 18;10(4). Epub 2021 Feb 18.

Department of Internal Medicine, Division of Endocrinology and Diabetology, Endocrinology Lab Platform, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women, with a wide spectrum of possible phenotypes, symptoms and sequelae according to the current clinical definition. However, there are women who do not fulfill at least two out of the three commonly used "Rotterdam criteria" and their risk of developing type 2 diabetes or obesity later in life is not defined. Therefore, we addressed this important gap by conducting a retrospective analysis based on 750 women with and without PCOS. We compared four different PCOS phenotypes according to the Rotterdam criteria with women who exhibit only one Rotterdam criterion and with healthy controls. Hormone and metabolic differences were assessed by analysis of variance (ANOVA) as well as logistic regression analysis. We found that hyperandrogenic women have per se a higher risk of developing insulin resistance compared to phenotypes without hyperandrogenism and healthy controls. In addition, hyperandrogenemia is associated with developing insulin resistance also in women with no other Rotterdam criterion. Our study encourages further diagnostic and therapeutic approaches for PCOS phenotypes in order to account for varying risks of developing metabolic diseases. Finally, women with hyperandrogenism as the only symptom should also be screened for insulin resistance to avoid later metabolic risks.
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http://dx.doi.org/10.3390/jcm10040829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922675PMC
February 2021

Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial.

Nutrients 2021 Feb 7;13(2). Epub 2021 Feb 7.

Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, = 0.031) and LH/FSH ratio (mean treatment effect -0.335, 95% CI -0.621 to 0.050, = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.
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http://dx.doi.org/10.3390/nu13020547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914670PMC
February 2021

Vitamin D Concentrations at Term Do Not Differ in Newborns and Their Mothers with and without Polycystic Ovary Syndrome.

J Clin Med 2021 Feb 2;10(3). Epub 2021 Feb 2.

Division of Obstetrics and Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria.

Studies suggest that non-pregnant women with polycystic ovary syndrome (PCOS) may be at elevated risk of 25 hydroxyvitamin D (25(OH)D) deficiency. Furthermore, there is evidence suggesting that 25(OH)D may also play an important role during pregnancy. Data regarding 25(OH)D deficiency during pregnancy in PCOS patients and its association with perinatal outcome is scarce. The aim of the study was to investigate whether mothers with and without PCOS have different 25(OH)D levels at term, how maternal 25(OH)D levels are reflected in their offspring, and if 25(OH)D levels are associated with an adverse perinatal outcome. Therefore, we performed a cross-sectional observational study and included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS and an ongoing pregnancy ≥ 37 + 0 weeks of gestation who gave birth in our institution between March 2013 and December 2015. Maternal serum and cord blood 25(OH)D levels were analyzed at the day of delivery. Maternal 25(OH)D levels did not differ significantly in women with PCOS and without PCOS ( = 0.998), nor did the 25(OH)D levels of their respective offspring ( = 0.692). 25(OH)D deficiency (<20 ng/mL) was found in 26.9% and 22.5% of women with and without PCOS ( = 0.430). There was a strong positive correlation between maternal and neonatal 25(OH)D levels in both investigated groups (r ≥ 0.79, < 0.001). Linear regression estimates of cord blood 25(OH)D levels are about 77% of serum 25(OH)D concentrations of the mother. Compared to healthy controls, the risk for maternal complications was increased in PCOS women (48% vs. 65%; = 0.009), while there was no significant difference in neonatal complications (22% and 22%; = 1.0). However, 25(OH)D levels were similar between mothers and infants with and without perinatal complications. Although the share of women and infants with 25(OH)D deficiency was high in women with PCOS and without PCOS, it seems that the incidence of adverse perinatal outcome was not affected. The long-term consequences for mothers and infants with a 25(OH)D deficiency have to be investigated in future studies.
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http://dx.doi.org/10.3390/jcm10030537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867163PMC
February 2021

Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS.

J Clin Endocrinol Metab 2020 10 26. Epub 2020 Oct 26.

Medical Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark.

Context: Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients.

Methods: A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion.

Results: Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment.

Conclusions: A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.
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http://dx.doi.org/10.1210/clinem/dgaa756DOI Listing
October 2020

Activation of nuclear factor-kappa B subunits c-Rel, p65 and p50 by plasma lipids and fatty acids across the menstrual cycle.

Free Radic Biol Med 2020 11 23;160:488-500. Epub 2020 Aug 23.

Human Nutrition & Metabolism Research and Training Center, Institute of Molecular Biosciences, University of Graz, Graz, Austria. Electronic address:

This study focused on a comprehensive analysis of the canonical activation pathway of the redox-sensitive transcription factor nuclear factor-kappa B (NF-κB) in peripheral blood mononuclear cells, addressing c-Rel, p65 and p50 activation in 28 women at early (T1) and late follicular (T2) and mid (T3) and late luteal (T4) phase of the menstrual cycle, and possible relations with fasting plasma lipids and fatty acids. For the first time, strong inverse relations of c-Rel with apolipoprotein B were observed across the cycle, while those with LDL cholesterol, triglycerides as well as saturated (SFA), particularly C14-C22 SFA, monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) clustered at T2. In contrast, p65 was positively related to LDL cholesterol and total n-6 PUFA, while p50 did not show any relations. C-Rel was not directly associated with estradiol and progesterone, but data suggested an indirect C22:5n-3-mediated effect of progesterone. Strong positive relations between estradiol and individual SFA, MUFA and n-3 PUFA at T1 were confined to C18 fatty acids; C18:3n-3 was differentially associated with estradiol (positively) and progesterone (inversely). Given specific roles of c-Rel activation in immune tolerance, inhibition of c-Rel activation by higher plasma apolipoprotein B and individual fatty acid concentrations could have clinical implications for female fertility.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.08.012DOI Listing
November 2020

miRNA Mechanisms Underlying the Association of Beta Blocker Use and Bone Mineral Density.

J Bone Miner Res 2021 Jan 22;36(1):110-122. Epub 2020 Sep 22.

Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME, USA.

Osteoporosis is a debilitating and costly disease that causes fractures in 33% of women and 20% of men over the age of 50 years. Recent studies have shown that beta blocker (BB) users have higher bone mineral density (BMD) and decreased risk of fracture compared with non-users. The mechanism underlying this association is thought to be due to suppression of adrenergic signaling in osteoblasts, which leads to increased BMD in rodent models; however, the mechanism in humans is unknown. Also, several miRNAs are associated with adrenergic signaling and BMD in separate studies. To investigate potential miRNA mechanisms, we performed a cross-sectional analysis using clinical data, dual-energy X-ray absorptiometry (DXA) scans, and miRNA and mRNA profiling of whole blood from the Framingham Study's Offspring Cohort. We found nine miRNAs associated with BB use and increased BMD. In parallel network analyses, we discovered a subnetwork associated with BMD and BB use containing two of these nine miRNAs, miR-19a-3p and miR-186-5p. To strengthen this finding, we showed that these two miRNAs had significantly higher expression in individuals without incident fracture compared with those with fracture in an external data set. We also noted a similar trend in association between these miRNA and Z-score as calculated from heel ultrasound measures in two external cohorts (SOS-Hip and SHIP-TREND). Because miR-19a directly targets the ADRB1 mRNA transcript, we propose BB use may downregulate ADRB1 expression in osteoblasts through increased miR-19a-3p expression. We used enrichment analysis of miRNA targets to find potential indirect effects through insulin and parathyroid hormone signaling. This analysis provides a starting point for delineating the role of miRNA on the association between BB use and BMD. © 2020 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4160DOI Listing
January 2021

Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes.

Diabetes Metab Syndr Obes 2020 18;13:2069-2080. Epub 2020 Jun 18.

Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria.

Purpose: Organic cation transporters (Octs) use cations like endogenous compounds, toxins, and drugs, such as metformin, as substrates. Therefore, these proteins determine the pharmacokinetics and -dynamics of metformin and thus its efficacy. Of note, metformin is today the most commonly used pharmaceutical in the treatment of type 2 diabetes (T2DM) with nevertheless a great variability in clinical response, which attributes to genetic variances. The aim of this study was to determine the influence of intronic OCT1 SNPs on prevalence of all-cause and cardiovascular death.

Patients And Methods: Genotypes of 27 intronic SNPs in OCT1 were investigated in the LURIC study, a prospective cohort of 3316 participants scheduled for coronary angiography. We investigated whether these variants were associated with all-cause and cardiovascular death in 73 individuals with T2DM under metformin therapy, in individuals without diabetes, individuals with T2DM and individuals with T2DM without metformin therapy.

Results: In a multivariate Cox regression analysis adjusted for classical cardiovascular risk factors, 4 intronic OCT1 SNPs were significantly associated with all-cause and cardiovascular mortality in individuals with T2DM on metformin therapy.

Conclusion: According to their OCT1 genotype, some individuals with T2DM on metformin therapy might be prone to an increased risk of cardiovascular death.
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http://dx.doi.org/10.2147/DMSO.S235663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308180PMC
June 2020

Human Milk Oligosaccharides Modulate the Risk for Preterm Birth in a Microbiome-Dependent and -Independent Manner.

mSystems 2020 Jun 9;5(3). Epub 2020 Jun 9.

Interactive Microbiome Research, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Preterm birth (PTB) is one of the leading causes of neonatal mortality. The causes for spontaneous PTB are multifactorial and often remain unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with or without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood. We identified several microbial signatures, such as , , sp., and sp., associated with a short cervix, PTB, and/or preterm contractions. In addition, we observed associations between sialylated HMOs, in particular 3'-sialyllactose, with PTB, short cervix, and increased inflammation and confirmed an influence of HMOs on the microbiome profile. Since they identify serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome mediated and potentially associated with specific HMO signatures in urine. Our results support current efforts to improve diagnostics and therapeutic strategies in PTB. The causes for preterm birth (PTB) often remain elusive. We investigated whether circulating human milk oligosaccharides (HMOs) might be involved in modulating urinary and vaginal microbiome promoting or preventing PTB. We identified here HMOs and key microbial taxa associated with indicators of PTB. Based on our results, we propose two models for how HMOs might modulate risk for PTB: (i) by changes in HMOs associated with sterile inflammation (microbiome-independent) and (ii) by HMO-driven shifts in microbiome (microbiome-dependent). Our findings will guide current efforts to better predict the risk for PTB in seemingly healthy pregnant women and also provide appropriate preventive strategies.
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http://dx.doi.org/10.1128/mSystems.00334-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289590PMC
June 2020

Impact of Short-Term Isoflavone Intervention in Polycystic Ovary Syndrome (PCOS) Patients on Microbiota Composition and Metagenomics.

Nutrients 2020 Jun 1;12(6). Epub 2020 Jun 1.

Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, 8010 Graz, Austria.

Background: Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide and is associated with disorders of glucose metabolism. Hormone and metabolic signaling may be influenced by phytoestrogens, such as isoflavones. Their endocrine effects may modify symptom penetrance in PCOS. Equol is one of the most active isoflavone metabolites, produced by intestinal bacteria, and acts as a selective estrogen receptor modulator.

Method: In this interventional study of clinical and biochemical characterization, urine isoflavone levels were measured in PCOS and control women before and three days after a defined isoflavone intervention via soy milk. In this interventional study, bacterial equol production was evaluated using the log(equol: daidzein ratio) and microbiome, metabolic, and predicted metagenome analyses were performed.

Results: After isoflavone intervention, predicted stool metagenomic pathways, microbial alpha diversity, and glucose homeostasis in PCOS improved resembling the profile of the control group at baseline. In the whole cohort, larger equol production was associated with lower androgen as well as fertility markers.

Conclusion: The dynamics in our metabolic, microbiome, and predicted metagenomic profiles underline the importance of external phytohormones on PCOS characteristics and a potential therapeutic approach or prebiotic in the future.
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http://dx.doi.org/10.3390/nu12061622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656308PMC
June 2020

Identification of blood cell transcriptome-based biomarkers in adulthood predictive of increased risk to develop metabolic disorders using early life intervention rat models.

FASEB J 2020 07 31;34(7):9003-9017. Epub 2020 May 31.

Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics and Obesity), CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), University of the Balearic Islands, Palma de Mallorca, Spain.

Calorie restriction during gestation in rats has long-lasting adverse effects in the offspring. It induces metabolic syndrome-related alterations, which are partially reversed by leptin supplementation during lactation. We employed these conditions to identify transcript-based nutrient sensitive biomarkers in peripheral blood mononuclear cells (PBMCs) predictive of later adverse metabolic health. The best candidate was validated in humans. Transcriptome analysis of PBMCs from adult male Wistar rats of three experimental groups was performed: offspring of control dams (CON), and offspring of 20% calorie-restricted dams during gestation without (CR) and with leptin supplementation throughout lactation (CR-LEP). The expression of 401 genes was affected by gestational calorie restriction and reversed by leptin. The changes preceded metabolic syndrome-related phenotypic alterations. Of these genes, Npc1 mRNA levels were lower in CR vs CON, and normalized to CON in CR-LEP. In humans, NPC1 mRNA levels in peripheral blood cells (PBCs) were decreased in subjects with mildly impaired metabolic health compared to healthy subjects. Therefore, a set of potential transcript-based biomarkers indicative of a predisposition to metabolic syndrome-related alterations were identified, including NPC1, which was validated in humans. Low NPC1 transcript levels in PBCs are a candidate biomarker of increased risk for impaired metabolic health in humans.
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http://dx.doi.org/10.1096/fj.202000071RRDOI Listing
July 2020

Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF.

J Clin Endocrinol Metab 2020 08;105(8)

Service of Bone Diseases, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland.

Context: Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population.

Design: The European Calcified Tissue Society and the International Osteoporosis Foundation convened a working group to produce an updated review of literature published after 2017 on this topic.

Results: Fragility fractures in PW are rare and mostly due to secondary osteoporosis (ie, in presence of an underlying disease such as hormonal, inflammatory, or digestive disorders). In absence of another disorder, low bone mineral density (BMD) together with fragility fractures qualifies as idiopathic osteoporosis. In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities. BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-tumor necrosis factor alpha improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3%-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed.

Conclusion: The majority of PW with osteoporosis have an underlying disease. Specific therapy of these diseases, as well as antiresorptive and anabolic drugs, improve BMD, but without evidence of fracture reduction.
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http://dx.doi.org/10.1210/clinem/dgaa306DOI Listing
August 2020

Genetic Components of 25-Hydroxyvitamin D Increase in Three Randomized Controlled Trials.

J Clin Med 2020 Feb 19;9(2). Epub 2020 Feb 19.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

The 25-Hydroxyvitamin D (25[OH)D) serum concentration depends on vitamin D intake, endogenous vitamin D production and genetic factors. The latter have been demonstrated in large genome-wide association studies indicating that single nucleotide polymorphisms (SNPs) in genes related to the vitamin D metabolism are as important for serum 25(OH)D levels as the influence of season. The mechanism on how these SNPs influence serum 25(OH)D levels are still unclear. The aim of the present study was to investigate the genetic effects of ten selected SNPs related to vitamin D metabolism on 25-hydroxyvitamin D increase (∆25(OH)D) after vitamin D supplementation in three randomized controlled trials. Genotypes of SNPs related to vitamin D metabolism were determined in 411 participants with 25(OH)D concentrations < 75 nmol/l receiving 20,000 IU cholecalciferol per week for 8 or 12 weeks after study inclusion. For the vitamin D receptor (VDR) rs10783219 polymorphism, the minor A-allele was associated with lower ∆25(OH)D values in the entire study population ( = 0.022), which was not consistent in all three cohorts when analysed separately. VDR rs10783219 might therefore be a genetic modulator of increasing 25-hydroxyvitamin D concentrations. Considering the wide-spread use of vitamin D supplementation, future large and well-designed randomized controlled trials (RCTs) should investigate the clinical impact of this polymorphism.
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http://dx.doi.org/10.3390/jcm9020570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074051PMC
February 2020

Are soluble ST2 levels influenced by vitamin D and/or the seasons?

Endocr Connect 2019 06 1;8(6):691-700. Epub 2019 Jun 1.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

Objective: Cardiovascular disease manifestation and several associated surrogate markers, such as vitamin D, have shown substantial seasonal variation. A promising cardiovascular biomarker, soluble ST2 (sST2), has not been investigated in this regard – we therefore determined if systemic levels of sST2 are affected by seasonality and/or vitamin D in order to investigate their clinical interrelation and usability.

Design: sST2 levels were measured in two cohorts involving hypertensive patients at cardiovascular risk, the Styrian Vitamin D Hypertension Trial (study A; RCT design, 8 weeks 2800 IU cholecalciferol daily) and the Ludwigshafen Risk and Cardiovascular Health Study (LURIC; study B; cross-sectional design).

Methods: The effects of a vitamin D intervention on sST2 levels were determined in study A using ANCOVA, while seasonality of sST2 levels was determined in study B using ANOVA.

Results: The concentrations of sST2 remained unchanged by a vitamin D intervention in study A, with a mean treatment effect (95% confidence interval) of 0.1 (−0.6 to 0.8) ng/mL; P = 0.761), despite a rise in 25(OH)D (11.3 (9.2–13.5) ng/mL; P < 0.001) compared to placebo. In study B, seasonal variations were present in 25(OH)D levels in men and women with or without heart failure (P < 0.001 for all subgroups), while sST2 levels remained unaffected by the seasons in all subgroups.

Conclusions: Our study provides the first evidence that systemic sST2 levels are not interrelated with vitamin D levels or influenced by the seasons in subjects at cardiovascular risk.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528407PMC
June 2019

Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health.

Oxid Med Cell Longev 2019 19;2019:4851323. Epub 2019 Nov 19.

Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UK.

Glycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease. Related modified amino acids formed by proteolysis are excreted in urine. We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen. We recruited 200 human subjects with early-stage health decline and healthy controls. Urinary amino acid metabolites were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning was applied to optimise and validate algorithms to discriminate between study groups for potential diagnostic utility. Urinary analyte changes were as follows: impaired metabolic health-increased N -carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health-increased glucosepane; and impaired renal health-increased BCAAs and decreased N -(-glutamyl)lysine. Algorithms combining subject age, BMI, and BCAAs discriminated between healthy controls and impaired metabolic, vascular, and renal health study groups with accuracy of 84%, 72%, and 90%, respectively. In 2-step analysis, algorithms combining subject age, BMI, and urinary N -fructosyl-lysine and valine discriminated between healthy controls and impaired health (any type), accuracy of 78%, and then between types of health impairment with accuracy of 69%-78% ( random selection 33%). From likelihood ratios, this provided small, moderate, and conclusive evidence of early-stage cardiovascular, metabolic, and renal disease with diagnostic odds ratios of 6 - 7, 26 - 28, and 34 - 79, respectively. We conclude that measurement of urinary glycated, oxidized, crosslinked, and branched-chain amino acids provides the basis for a noninvasive health screen for early-stage health decline in metabolic, vascular, and renal health.
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http://dx.doi.org/10.1155/2019/4851323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885816PMC
April 2020

[Neuroendocrine tumors in daily gastroenterology and endoscopy - a practice manual].

Z Gastroenterol 2019 Dec 11;57(12):1493-1513. Epub 2019 Dec 11.

Klinische Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Wien, Austria.

Neuroendocrine tumors of the gastrointestinal tract (GI-NET) are rare tumors. Functional tumors with hormonal syndromes (e. g., insulinoma, gastrinoma) are less common than non-functional tumors, which usually have an indolent course. Therapy for GI-NET is multimodal, including endoscopic or surgical procedures aiming at complete removal of tumor tissue. Patients in later stages may benefit from interventional radiology or medical therapy. This article gives an overview regarding the key aspects of GI-NET therapy in daily gastroenterology practice with emphasis on endoscopic diagnosis and therapy.
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http://dx.doi.org/10.1055/a-1013-4279DOI Listing
December 2019

[Austrian Consensus on High Blood Pressure 2019].

Wien Klin Wochenschr 2019 Nov;131(Suppl 6):489-590

Universitätsklinik für Innere Medizin, Gemeinsame Einrichtung, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich.

Elevated blood pressure remains a major cause of cardiovascular disease, disability, and premature death in Austria, with suboptimal rates of detection, treatment and control also in recent years. Management of hypertension is a common challenge for physicians with different spezializations. In an attempt to standardize diagnostic and therapeutic strategies and, ultimately, to increase the rate of patients with controlled blood pressure and to decrease the burden of cardiovascular disease, 13 Austrian medical societies reviewed the evidence regarding prevention, detection, workup, treatment and consequences of high blood pressure in general and in various clinical scenarios. The result is presented as the first national consensus on blood pressure. The authors and societies involved are convinced that a joint national effort is needed to decrease hypertension-related morbidity and mortality in our country.
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http://dx.doi.org/10.1007/s00508-019-01565-0DOI Listing
November 2019

Androgen and Anti-Mullerian Hormone Concentrations at Term in Newborns and Their Mothers with and without Polycystic Ovary Syndrome.

J Clin Med 2019 Nov 1;8(11). Epub 2019 Nov 1.

Division of Obstetrics and Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria.

The aetiology of polycystic ovary syndrome (PCOS) is not particularly mapped; however, a complex interaction of various factors, such as genetic, environmental and intrauterine factors, can be assumed. Experimental animal studies and clinical observations support the hypothesis that developmental programming by excess intrauterine steroid is relevant. The aim of the study was to investigate whether mothers with and without PCOS exhibit different androgen and anti-Mullerian hormone (AMH) levels at the end of pregnancy and how maternal hormone levels are reflected in their offspring. Between March 2013 and December 2015, we performed a prospective cross-sectional study at the Medical University of Graz. We included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS, both with an ongoing pregnancy ≥37 + 0 weeks of gestation, who gave birth in our institution. Primary outcome parameters were the levels of maternal and neonatal androgens (testosterone, free testosterone, androstenedione) and AMH at delivery. Androgen levels in female offspring of PCOS and non-PCOS women at birth did not differ, while maternal hormone levels differed significantly. Androgen levels in PCOS boys were significantly higher when compared to levels in PCOS girls. Our findings do not support the hypothesis that maternal androgen excess contributes to elevated androgen concentrations in the female offspring. Nevertheless, the effects of the increased androgen concentrations in mothers on their offspring have to be investigated in future studies.
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http://dx.doi.org/10.3390/jcm8111817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912752PMC
November 2019

Evaluation and comparison of six noninvasive tests for prediction of significant or advanced fibrosis in nonalcoholic fatty liver disease.

United European Gastroenterol J 2019 10 12;7(8):1113-1123. Epub 2019 Jul 12.

Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Background: In nonalcoholic fatty liver disease (NAFLD), advanced fibrosis has been identified as an important prognostic factor with increased liver-related mortality and treatment need. Due to the high prevalence of NAFLD, noninvasive risk stratification is needed to select patients for liver biopsy and treatment.

Objective: To compare the diagnostic accuracy of several widely available noninvasive tests for assessment of fibrosis among patients with NAFLD with or without nonalcoholic steatohepatitis (NASH).

Methods: We enrolled consecutive patients with NAFLD admitted to two Austrian referral centers who underwent liver biopsy. Liver stiffness measurement (LSM) was obtained by vibration-controlled transient elastography (VCTE, FibroScan) and blood samples were collected for determination of enhanced liver fibrosis (ELF) test, FibroMeter, FibroMeter, NAFLD fibrosis score (NFS), and fibrosis-4 index (FIB-4).

Results: Our study cohort contained 186 patients with histologically confirmed NAFLD. On liver histology, NASH was present in 92 patients (50%), significant fibrosis (F ≥ 2) in 71 patients (38%), advanced fibrosis (F ≥ 3) in 49 patients (26%), and F ≥ 3 plus NASH in 35 patients (19%). For diagnosis of F ≥ 2, F ≥ 3, and F ≥ 3 plus NASH, respectively, receiver operating characteristic (ROC) analysis revealed superior diagnostic accuracy of ELF score (area under ROC curve (AUROC) 0.85, 0.90, 0.90), FibroMeter (AUROC 0.86, 0.88, 0.89), FibroMeter (AUROC 0.84, 0.88, 0.88), and LSM per protocol (AUROC 0.87, 0.95, 0.91) versus FIB-4 (AUROC 0.80, 0.82, 0.81) or NFS (AUROC 0.78, 0.80, 0.79).

Conclusion: Proprietary fibrosis panels and VCTE show superior diagnostic accuracy for noninvasive diagnosis of fibrosis stage in NAFLD as compared to FIB-4 and NFS.
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http://dx.doi.org/10.1177/2050640619865133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794685PMC
October 2019

Early renal dysfunction and fibroblast growth factor-23 in patients with small vessel disease-related stroke.

Sci Rep 2019 10 28;9(1):15410. Epub 2019 Oct 28.

Department of Neurology, Medical University of Graz, Graz, Austria.

Interactions between cerebral small vessel disease (CSVD) and renal dysfunction (RD) have been reported, but previous studies were mostly retrospective and limited to measurements of estimated glomerular filtration rate (eGFR). In this prospective, longitudinal study of patients with CSVD-related recent small subcortical infarcts (RSSI), we aimed at a comprehensive exploration of markers of early RD and their association with microvascular brain damage. We investigated 101 stroke patients (mean age: 60.2 ± 10.7 years) with an MRI-confirmed RSSI who underwent follow-up brain MRI 15 months post-stroke. Besides serum creatinine and eGFR, we assessed urinary Albumin-Creatinine Ratio and fibroblast growth factor-23 (FGF-23). RD was classified according to recent Kidney Disease: Improving Global Outcomes criteria. We identified 24 patients with RD, only six patients revealed an eGFR <60 mL/min/1.73 m². RSSI patients with RD more often had severe white matter hyperintensities (WMH, 58% vs. 36%, p = 0.04). CSVD progression was not dependent on RD. However, patients in the highest FGF-23 quartile more frequently had new microangiopathic lesions on follow-up MRI (50% vs. 21%, p = 0.03). Early RD was found in a quarter of RSSI patients and associated with WMH severity, but not CSVD progression. High FGF-23 indicates an increased risk for ongoing microvascular brain damage, warranting further studies.
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http://dx.doi.org/10.1038/s41598-019-51965-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817845PMC
October 2019

The Effect of Vitamin D Supplementation on its Metabolism and the Vitamin D Metabolite Ratio.

Nutrients 2019 Oct 21;11(10). Epub 2019 Oct 21.

Division of Endocrinology and Diabetology, Endocrinology Lab Platform, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

25-hydroxyvitamin D (25(OH)D) is commonly measured to assess vitamin D status. Other vitamin D metabolites such as 24,25-dihydroxyvitamin D (24,25(OH)D) provide additional insights into vitamin D status or metabolism. Earlier studies suggested that the vitamin D metabolite ratio (VMR), calculated as 24,25(OH)D/25(OH)D, could predict the 25(OH)D increase after vitamin D supplementation. However, the evidence for this additional value is inconclusive. Therefore, our aim was to assess whether the increase in 25(OH)D after supplementation was predicted by the VMR better than baseline 25(OH)D. Plasma samples of 106 individuals (25(OH)D < 75 nmol/L) with hypertension who completed the Styrian Vitamin D Hypertension Trial (NC.T.02136771) were analyzed. Participants received vitamin D (2800 IU daily) or placebo for 8 weeks. The treatment effect (ANCOVA) for 25(OH)D, 24,25(OH)D and the VMR was 32 nmol/L, 3.3 nmol/L and 0.015 (all < 0.001), respectively. Baseline 25(OH)D and 24,25(OH)D predicted the change in 25(OH)D with comparable strength and magnitude. Correlation and regression analysis showed that the VMR did not predict the change in 25(OH)D. Therefore, our data do not support routine measurement of 24,25(OH)D in order to individually optimize the dosage of vitamin D supplementation. Our data also suggest that activity of 24-hydroxylase increases after vitamin D supplementation.
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http://dx.doi.org/10.3390/nu11102539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836132PMC
October 2019

Diagnostic Accuracy of the Aldosterone-to-Active Renin Ratio for Detecting Primary Aldosteronism.

J Endocr Soc 2019 Sep 19;3(9):1748-1758. Epub 2019 Jul 19.

Bad Gleichenberg Clinic, Bad Gleichenberg, Austria.

Context: The aldosterone-to-active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but prospective study data on its sensitivity and specificity are sparse.

Objective: To investigate the diagnostic accuracy of the AARR for detecting PA.

Design: Prospective diagnostic accuracy study.

Setting: This study was conducted from February 2009 to August 2015 at the outpatient clinic of the Department of Endocrinology and Diabetology of the Medical University of Graz, Austria.

Participants: Four hundred patients with arterial hypertension who were referred to a tertiary care center for screening for endocrine hypertension.

Intervention: Participants had a determination of the AARR (index test) and a second AARR determination followed by a saline infusion test (SIT) after 2 to 6 weeks. PA was diagnosed in individuals with any AARR ≥3.7 ng/dL/µU/mL [including a plasma aldosterone concentration (PAC) of ≥9 ng/dL] who had a PAC ≥10 ng/dL after the SIT. We did not substantially alter antihypertensive drug intake.

Main Outcome Measures: Primary outcome was the receiver-operating characteristic (ROC) curve of the AARR in diagnosing PA.

Results: A total of 382 participants were eligible for analyses; PA was diagnosed in 18 (4.7%) patients. The area under the ROC curve of the AARR in detecting PA was 0.973 (95% CI, 0.956 to 0.990). Sensitivity and specificity for a positive AARR in diagnosing PA were 100% (95% CI, 81.5% to 100.0%) and 89.6% (95% CI, 86.0% to 92.5%), respectively.

Conclusions: The AARR has good diagnostic accuracy for detecting PA.
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http://dx.doi.org/10.1210/js.2019-00145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735732PMC
September 2019

Effect of Low-Dose Aspirin on Soluble FMS-Like Tyrosine Kinase 1/Placental Growth Factor (sFlt-1/PlGF Ratio) in Pregnancies at High Risk for the Development of Preeclampsia.

J Clin Med 2019 Sep 10;8(9). Epub 2019 Sep 10.

Department of Obstetrics and Gynecology, Division of Obstetrics, Medical University of Graz, A-8036 Graz, Austria.

Background: Soluble FMS-like Tyrosine Kinase 1 (sFlt-1) and placental growth factor (PlGF) have been reported to be highly predictive several weeks before the onset of preeclampsia.

Objective: To investigate longitudinal changes of serum levels sFlt-1 and PlGF in pregnant women at high risk for the development of preeclampsia and to reveal an impact of aspirin on maternal serum concentrations of sFlt-1 and PlGF.

Methods: This was a prospective longitudinal study in 394 women with various risk factors for the development of preeclampsia (chronic hypertension, antiphospholipid syndrome/APS or systemic lupus erythematosus/SLE, thrombophilia, women with a history of preeclampsia, pathologic first trimester screening for preeclampsia) and 68 healthy women. Serum levels of sFlt-1 and PlGF were measured prospectively at 4-week intervals (from gestational weeks 12 until postpartum).

Results: The sFlt-1/PlGF ratio was significantly higher in women with an adverse obstetric outcome compared to women with a normal pregnancy, starting between 20 and 24 weeks of gestation. There was no effect of aspirin on sFlt-1/PlGF ratio in women with chronic hypertension, APS/SLE, thrombophilia and controls. The use of aspirin showed a trend towards an improvement of the sFlt-1/PlGF ratio in women with preeclampsia in a previous pregnancy and a significant effect on the sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia.

Conclusions: Our findings reveal an impact of aspirin on sFlt-1/PlGF ratio in women with a pathologic first trimester screening for preeclampsia, strongly supporting its prophylactic use.
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http://dx.doi.org/10.3390/jcm8091429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780316PMC
September 2019

Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans.

Cell Metab 2019 09 27;30(3):462-476.e6. Epub 2019 Aug 27.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Austria; Center for Biomarker Research in Medicine (CBmed), Graz, Austria; HEALTH Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH, Neue Stiftingtalstraße 2, Graz, Austria.

Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
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http://dx.doi.org/10.1016/j.cmet.2019.07.016DOI Listing
September 2019

Effects of Vitamin D Supplementation on Body Composition and Metabolic Risk Factors in Men: A Randomized Controlled Trial.

Nutrients 2019 Aug 14;11(8). Epub 2019 Aug 14.

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

Vitamin D might play a role in metabolic processes and obesity. We therefore examined vitamin D effects on metabolic markers and obesity in a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial. We included 200 healthy men with serum 25-hydroxyvitamin D (25(OH) D) levels <75 nmol/L. Subjects received 20,000 IU of vitamin D3/week ( = 100) or placebo ( = 100) for 12 weeks. Outcome measures were metabolic markers, anthropometric measures, and body composition assessed by Dual-energy X-ray absorptiometry. One-hundred and ninety-two men completed the study. We found a significant treatment effect on fasting glucose/fasting insulin ratio (-5.3 (-10.4 to -0.2), = 0.040), whereas we observed no significant effect on the remaining outcome parameters. In subgroup analyses of men with baseline 25(OH)D levels <50 nmol/L ( = 80), we found a significant effect on waist circumference (1.6 (0.3 to 2.9) cm, = 0.012), waist-to-hip ratio (0.019 (0.002 to 0.036), = 0.031), total body fat (0.029 (0.004 to 0.055) %, = 0.026), and android fat (1.18 (0.11 to 2.26) %, = 0.010). In middle-aged healthy men, vitamin D treatment had a negative effect on insulin sensitivity. In vitamin D deficient men, vitamin D has an unfavorable effect on central obesity and body composition.
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http://dx.doi.org/10.3390/nu11081894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723889PMC
August 2019