Publications by authors named "Verena Theiler-Schwetz"

35 Publications

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature.

Nutrients 2022 Jun 17;14(12). Epub 2022 Jun 17.

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

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.
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http://dx.doi.org/10.3390/nu14122518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229801PMC
June 2022

Mathematical Modeling of Free Thyroxine Concentrations During Methimazole Treatment for Graves' Disease: Development and Validation of a Computer-Aided Thyroid Treatment Method.

Front Endocrinol (Lausanne) 2022 31;13:841888. Epub 2022 May 31.

Institute of Automation and Control, Graz University of Technology, Graz, Austria.

Background: Methimazole (MMI) is the first-line treatment for patients with Graves' disease (GD). While there are empirical recommendations for initial MMI doses, there is no clear guidance for subsequent MMI dose titrations. We aimed to (a) develop a mathematical model capturing the dynamics of free thyroxine (FT4) during MMI treatment (b), validate this model by use of numerical simulation in comparison with real-life patient data (c), develop the software application Digital Thyroid (DigiThy) serving either as a practice tool for treating virtual patients or as a decision support system with dosing recommendations for MMI, and (d) validate this software framework by comparing the efficacy of its MMI dosing recommendations with that from clinical endocrinologists.

Methods: Based on concepts of automatic control and by use of optimization techniques, we developed two first order ordinary differential equations for modeling FT4 dynamics during MMI treatment. Clinical data from patients with GD derived from the outpatient clinic of Endocrinology at the Medical University of Graz, Austria, were used to develop and validate this model. It was subsequently used to create the web-based software application DigiThy as a simulation environment for treating virtual patients and an autonomous computer-aided thyroid treatment (CATT) method providing MMI dosing recommendations.

Results: Based on MMI doses, concentrations of FT4, thyroid-stimulating hormone (TSH), and TSH-receptor antibodies (TRAb), a mathematical model with 8 patient-specific constants was developed. Predicted FT4 concentrations were not significantly different compared to the available consecutively measured FT4 concentrations in 9 patients with GD (52 data pairs, p=0.607). Treatment success of MMI dosing recommendations in 41 virtually generated patients defined by achieved target FT4 concentrations preferably with low required MMI doses was similar between CATT and usual care. Statistically, CATT was significantly superior (p<0.001).

Conclusions: Our mathematical model produced valid FT4 predictions during MMI treatment in GD and provided the basis for the DigiThy application already serving as a training tool for treating virtual patients. Clinical trial data are required to evaluate whether DigiThy can be approved as a decision support system with automatically generated MMI dosing recommendations.
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http://dx.doi.org/10.3389/fendo.2022.841888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205409PMC
June 2022

Effects of Vitamin D Supplementation on 24-Hour Blood Pressure in Patients with Low 25-Hydroxyvitamin D Levels: A Randomized Controlled Trial.

Nutrients 2022 Mar 24;14(7). Epub 2022 Mar 24.

Center on Aging and Mobility, University Hospital Zurich, City Hospital Waid&Triemli and University of Zurich, 8006 Zurich, Switzerland.

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011-2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all -values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (-0.196 per ng/mL 25(OH)D, 95% CI (-0.325 to -0.067); = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.
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http://dx.doi.org/10.3390/nu14071360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003372PMC
March 2022

[Emergency card, emergency medication, and information leaflet for the prevention and treatment of adrenal crisis (Addison crisis): an Austrian consensus document].

J Klin Endokrinol Stoffwechs 2022 2;15(1):5-27. Epub 2022 Mar 2.

St. Anna Kinderspital, Universitätsklinik für Kinder- und Jugendheilkunde, Medizinische Universität Wien, Wien, Österreich.

A central goal of the adrenal insufficiency management is the prevention of acute adrenal insufficiency (also known as adrenal crisis or Addison crisis). This consensus document was generated in order to achieve better implementation and harmonization of measures for the prevention and treatment of acute adrenal insufficiency in Austria. The following measures are generally recommended for all patients with adrenal insufficiency and are outlined in this manuscript: (1) Provision of a "steroid emergency card" and possibly also a medical alert bracelet or necklace (or similar identification). (2) Provision of a hydrocortisone injection kit (or alternative glucocorticoid preparations) for emergency use plus sufficient oral glucocorticoid doses for stress situations/illness. (3) Education of patients and relatives on glucocorticoid stress dosing and "sick day rules" as well as on self-injection of hydrocortisone. (4) Provision of a treatment guideline (information leaflet) for the prevention and therapy of the adrenal crisis, which should also be shown to healthcare staff if necessary. (5) Provision of an emergency phone number (contact details) of the responsible endocrine specialist team or other trained staff. (6) Reinforcement of patient education on a regular basis (preferably yearly). This consensus document also includes recommendations for glucocorticoid dosing in the perioperative setting as well as in various other stress situations.
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http://dx.doi.org/10.1007/s41969-022-00155-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889064PMC
March 2022

Expression Profiles of miR-22-5p and miR-142-3p Indicate Hashimoto's Disease and Are related to Thyroid Antibodies.

Genes (Basel) 2022 01 19;13(2). Epub 2022 Jan 19.

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

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder of the thyroid (AITD) and characterized by the presence of circulating autoantibodies evoked by a, to date, not fully understood dysregulation of the immune system. Autoreactive lymphocytes and inflammatory processes in the thyroid gland can impair or enhance thyroid hormone secretion. MicroRNAs (miRNAs) are small noncoding RNAs, which can play a pivotal role in immune functions and the development of autoimmunity. The aim of the present study was to evaluate whether the expression of 9 selected miRNAs related to immunological functions differ in patients with HT compared to healthy controls. MiRNA profiles were analysed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 24 patients with HT and 17 healthy controls. Systemic expressions of miR-21-5p, miR-22-3p, miR-22-5p, miR-142-3p, miR-146a-5p, miR-301-3p and miR-451 were significantly upregulated in patients with HT ( ≤ 0.01) and were suitable to discriminate between HT and healthy controls in AUC analysis. Altered expressions of miR-22-5p and miR-142-3p were associated with higher levels of thyroid antibodies, suggesting their contribution to the pathogenesis of HT.
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http://dx.doi.org/10.3390/genes13020171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8871926PMC
January 2022

SARS-CoV-2 reinfections: Overview of efficacy and duration of natural and hybrid immunity.

Environ Res 2022 06 8;209:112911. Epub 2022 Feb 8.

Departments of Medicine, Epidemiology and Population Health, Biomedical Data Science, and Statistics, Stanford University, Stanford, CA, 94305, USA. Electronic address:

Seroprevalence surveys suggest that more than a third and possibly more than half of the global population has been infected with SARS-CoV-2 by early 2022. As large numbers of people continue to be infected, the efficacy and duration of natural immunity in terms of protection against SARS-CoV-2 reinfections and severe disease is of crucial significance for the future. This narrative review provides an overview on epidemiological studies addressing this issue. National surveys covering 2020-2021 documented that a previous SARS-CoV-2 infection is associated with a significantly reduced risk of reinfections with efficacy lasting for at least one year and only relatively moderate waning immunity. Importantly, natural immunity showed roughly similar effect sizes regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant for which data are just emerging before final conclusions can be drawn. Risk of hospitalizations and deaths was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections compared to individuals receiving two doses of an mRNA vaccine, but data are not fully consistent. The combination of a previous SARS-CoV-2 infection and a respective vaccination, termed hybrid immunity, seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue. Natural immunity should be considered for public health policy regarding SARS-CoV-2.
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http://dx.doi.org/10.1016/j.envres.2022.112911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824301PMC
June 2022

Critical Appraisal of Large Vitamin D Randomized Controlled Trials.

Nutrients 2022 Jan 12;14(2). Epub 2022 Jan 12.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.

As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.
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http://dx.doi.org/10.3390/nu14020303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778517PMC
January 2022

Hypercortisolism in patients with cholestasis is associated with disease severity.

BMC Gastroenterol 2021 Dec 7;21(1):460. Epub 2021 Dec 7.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, University Hospital Graz, Graz, Austria.

Background: Cholestasis might lead to an impairment of adrenal function as suggested by in vitro and in vivo data as well as by clinical findings. Bile acid and adrenal steroid metabolism not only share the receptors farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), but supraphysiological bile acid levels were found to stimulate steroidogenesis independent of FXR and TGR5. Our previous experimental findings revealed that mice fed bile acids or subjected to common bile duct ligation develop hypercortisolemia. We thus aimed to assess adrenal gland function in patients with cholestasis.

Methods: Adrenal gland function was assessed in 36 patients with cholestasis and in 32 patients without cholestasis by measuring total serum cortisol, adrenocorticotropic hormone (ACTH), as well as the increase of cortisol 20 and 30 min after administration of 1 µg of ACTH. Bile acid levels and bile acid pool composition were determined by high-resolution mass spectrometry.

Results: Patients with cholestasis per definition had markedly elevated levels of alkaline phosphatase (AP), bilirubin and serum bile acids. Baseline cortisol and maximum cortisol after ACTH stimulation were significantly higher in patients with cholestasis compared to controls. Increase of cortisol after ACTH stimulation and ACTH did not differ. In the cholestasis group, baseline cortisol correlated with bilirubin but not with AP, total serum bile acids and levels of conjugated and unconjugated bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels.

Conclusions: We find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance.
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http://dx.doi.org/10.1186/s12876-021-02045-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650422PMC
December 2021

Acute suppurative thyroiditis due to leading to sepsis and acute respiratory distress syndrome: a case report.

Arch Endocrinol Metab 2021 Nov 11;65(6):846-851. Epub 2021 Nov 11.

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

Acute suppurative thyroiditis (AST) is a rare but potentially life-threatening thyroid disease with a high mortality if left untreated. Thus, differentiation from other thyroid disorders is highly important in clinical practice. A 22-year-old male patient was admitted to a tertiary care hospital with cervical pain, palpitations, thyrotoxicosis, and an inhomogeneously enlarged right thyroid lobe. In view of the clinical findings, subacute thyroiditis (SAT) was suspected and treatment with glucocorticoids was started. After initial amelioration, the patient developed cervical erythema, fever, and recurrent pain. A CT scan showed extensive phlegmonous inflammation and abscess formation, suggestive of AST. We started immediate empiric antibiotic therapy and performed surgical drainage of the abscess formations. Subsequently, the patient developed hypoxic respiratory failure, leading to ICU admission and intermittent need for non-invasive ventilation. Blood and abscess cultures were positive for . If left untreated, AST represents a potentially life-threatening disease. Thus, in clinically doubtful cases, liberal further assessment by means of cervical CT scans or fine needle aspiration biopsy are strongly advised.
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http://dx.doi.org/10.20945/2359-3997000000420DOI Listing
November 2021

Randomized trial of vitamin D versus placebo supplementation on markers of systemic inflammation in hypertensive patients.

Nutr Metab Cardiovasc Dis 2021 10 18;31(11):3202-3209. Epub 2021 Aug 18.

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

Background And Aims: Animal and cell models indicated that vitamin D modulates inflammatory activity, which is considered relevant in the pathogenesis of arterial hypertension and cardiovascular diseases. We therefore aimed to investigate the effect of vitamin D supplementation on systemic markers of inflammation in a cohort of hypertensive patients.

Methods And Results: The Styrian Vitamin D Hypertension Trial is a single-centre, double-blind, placebo-controlled study conducted from 2011 to 2014 in Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxy-vitamin-D (25(OH)D) concentration below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D per day or placebo for 8 weeks. The present investigation is a post-hoc analysis using analysis of co-variance (ANCOVA). Outcome measures were biomarkers of inflammation including CRP, leukocytes including subtypes and leukocyte-to-lymphocyte ratio, leucine and kynurenic acid. A total of 187 participants (mean age 60.1 ± 11.3years; 47% women; mean baseline 25(OH)D 21.1 ± 5.6 ng/mL) completed the trial. ANCOVA revealed a mean treatment effect for none of the respective outcomes and no significant results were detected in various subgroup analyses.

Conclusion: Vitamin D supplementation in hypertensive patients with insufficient 25(OH)D concentrations has no significant effect on lowering markers of systemic inflammation. Further studies investigating the effect of vitamin D on other inflammatory pathways and in populations with severe vitamin D deficiency and a significant inflammatory burden are required.

Registration: ClinicalTrials.gov Identifier: NCT02136771; EudraCT No. 2009-018,125-70. Start Date: 2011-04-06.
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http://dx.doi.org/10.1016/j.numecd.2021.07.028DOI Listing
October 2021

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

Associations of Serum Cortisol with Cardiovascular Risk and Mortality in Patients Referred to Coronary Angiography.

J Endocr Soc 2021 May 10;5(5):bvab017. Epub 2021 Feb 10.

Department of Internal Medicine, Division of Nephrology, Medical University of Graz, 8036 Graz, Austria.

Context: Serum cortisol may be associated with cardiovascular risk factors and mortality in patients undergoing coronary angiography, but previous data on this topic are limited and controversial.

Objective: We evaluated whether morning serum cortisol is associated with cardiovascular risk factors, lymphocyte subtypes, and mortality.

Methods: This is a prospective cohort study performed at a tertiary care centre in south-west Germany between 1997 and 2000. We included 3052 study participants who underwent coronary angiography. The primary outcome measures were cardiovascular risk factors, lymphocyte subtypes, and all-cause and cardiovascular mortality.

Results: Serum cortisol was associated with an adverse cardiovascular risk profile, but there was no significant association with coronary artery disease or acute coronary syndrome. In a subsample of 2107 participants, serum cortisol was positively associated with certain lymphocyte subsets, including CD16+CD56+ (natural killer) cells ( < 0.001). Comparing the fourth versus the first serum cortisol quartile, the crude Cox proportional hazard ratios (with 95% CIs) were 1.22 (1.00-1.47) for all-cause and 1.32 (1.04-1.67) for cardiovascular mortality, respectively. After adjustments for various cardiovascular risk factors, these associations were attenuated to 0.93 (0.76-1.14) for all-cause, and 0.97 (0.76-1.25) for cardiovascular mortality, respectively.

Conclusions: Despite significant associations with classic cardiovascular risk factors and natural killer cells, serum cortisol was not a significant and independent predictor of mortality in patients referred to coronary angiography. These findings might reflect that adverse cardiovascular effects of cortisol could be counterbalanced by some cardiovascular protective actions.
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http://dx.doi.org/10.1210/jendso/bvab017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041336PMC
May 2021

Vitamin D and Cardiovascular Disease: An Updated Narrative Review.

Int J Mol Sci 2021 Mar 12;22(6). Epub 2021 Mar 12.

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

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.
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http://dx.doi.org/10.3390/ijms22062896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998446PMC
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

SARS-CoV-2 re-infection risk in Austria.

Eur J Clin Invest 2021 Apr 21;51(4):e13520. Epub 2021 Feb 21.

Austrian Agency for Health and Food Safety (AGES), Vienna, Austria.

Background: A key question concerning coronavirus disease 2019 (COVID-19) is how effective and long lasting immunity against this disease is in individuals who were previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the risk of SARS-CoV-2 re-infections in the general population in Austria.

Methods: This is a retrospective observational study using national SARS-CoV-2 infection data from the Austrian epidemiological reporting system. As the primary outcome, we aim to compare the odds of SARS-CoV-2 re-infections of COVID-19 survivors of the first wave (February to April 30, 2020) versus the odds of first infections in the remainder general population by tracking polymerase chain reaction (PCR)-confirmed infections of both groups during the second wave from September 1 to November 30, 2020. Re-infection counts are tentative, since it cannot be excluded that the positive PCR in the first and/or second wave might have been a false positive.

Results: We recorded 40 tentative re-infections in 14 840 COVID-19 survivors of the first wave (0.27%) and 253 581 infections in 8 885 640 individuals of the remaining general population (2.85%) translating into an odds ratio (95% confidence interval) of 0.09 (0.07 to 0.13).

Conclusions: We observed a relatively low re-infection rate of SARS-CoV-2 in Austria. Protection against SARS-CoV-2 after natural infection is comparable with the highest available estimates on vaccine efficacies. Further well-designed research on this issue is urgently needed for improving evidence-based decisions on public health measures and vaccination strategies.
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http://dx.doi.org/10.1111/eci.13520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988582PMC
April 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

Development of a visual tool to assess six dimensions of health and its validation in patients with endocrine disorders.

Wien Klin Wochenschr 2021 Feb 4. Epub 2021 Feb 4.

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

Background: Psychosocial factors significantly influence patient care in many fields of medicine, among these in the field of endocrinology. Easily applicable validated assessment tools for such psychosocial factors are lacking. Visual instruments may facilitate doctor-patient communication. This study describes the development and validation of a multidimensional visual tool for the self-assessment of health.

Methods: An expert panel performed the multistep development of the psychosomatic assessment health disc (PAHD). Assessment of face validity was performed by means of a focus group of medical doctors (n = 6) and patient interviews (n = 24). For determining test-retest reliability, internal consistency and construct validity, patients of an endocrine outpatient clinic in Graz, Austria, completed the PAHD and the following questionnaires: short-form 36 health survey, work ability index, Pittsburgh sleep quality index and the social life scales of the life satisfaction questionnaire.

Results: A numeric six-item analogue scale was developed in the form of a disc. It addresses the following aspects of health: physical well-being, social life, sexuality, mental well-being, sleep, working ability/performance. For the validation process, 177 patients (57.1% females) participated in the study. Correlation coefficients of the six items with other questionnaires ranged between r = 0.51 (social life) and r = 0.72 (sleep). Test-retest reliability was assessed among 98 patients and was ≥ 0.74 for all 6 items, while Cronbach's alpha was 0.78.

Conclusion: The psychometric properties of the PAHD support its use in clinical encounters with patients suffering from endocrine disorders. Further validation studies may be required to extend its application to other fields of medicine.
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http://dx.doi.org/10.1007/s00508-021-01809-yDOI Listing
February 2021

NO Synthesis Markers are Not Significantly Associated with Blood Pressure and Endothelial Dysfunction in Patients with Arterial Hypertension: A Cross-Sectional Study.

J Clin Med 2020 Nov 30;9(12). Epub 2020 Nov 30.

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

Nitric oxide (NO) synthesis markers, comprising L-homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are significantly associated with cardiovascular events and mortality. Being involved in NO pathways, they may be of high importance regulating vascular tone and arterial hypertension, but data on this topic are sparse and controversial. In this study, we evaluated whether these NO synthesis markers are associated with blood pressure values and pulse wave velocity (PWV). This analysis was based on the data of the Styrian Vitamin D Hypertension Trial, which included adults with arterial hypertension. We analyzed correlations of NO synthesis markers with 24 h ambulatory blood pressure values and PWV (primary outcomes), as well as with anthropometric and laboratory data. A total of 509 patients were included in the present analysis. The mean age was 61.2 ± 10.5 years, mean PWV was 8.6 ± 2.4 m/s, mean 24 h systolic blood pressure was 127.5 ± 13.8 mmHg and mean 24 h diastolic blood pressure was 76.4 ± 9.5 mmHg. In bivariate analyses, there was a significant positive correlation between homoarginine and 24 h diastolic blood pressure (r = 0.1; 0.02), which was revealed to be no longer significant after adjustment for age, gender and glomerular filtration rate (GFR) in multivariate regression analysis. No other significant correlations of any NO synthesis markers with blood pressure or PWV were observed. In line with previous studies, there were inverse associations between homoarginine and age and between ADMA or SDMA and GFR ( < 0.05 for all). This study did not reveal a significant association between homoarginine, ADMA or SDMA and blood pressure or PWV in hypertensive adults. These results suggested that the associations of these parameters with adverse outcome may not be mediated by hypertension and/or endothelial dysfunction.
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http://dx.doi.org/10.3390/jcm9123895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760204PMC
November 2020

The Unrecognized Prevalence of Primary Aldosteronism.

Ann Intern Med 2020 10;173(8):681-682

Medical University of Graz, Graz, Austria (S.P., M.R.G., V.T., O.M., C.T.).

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http://dx.doi.org/10.7326/L20-1094DOI Listing
October 2020

Associations of Thyroid Hormones and Resting Heart Rate in Patients Referred to Coronary Angiography.

Horm Metab Res 2020 Dec 4;52(12):850-855. Epub 2020 Sep 4.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

Resting heart rate (RHR) is associated with increased risk of cardiovascular morbidity and mortality. Thyroid hormones exert several effects on the cardiovascular system, but the relation between thyroid function and RHR remains to be further established. We evaluated whether measures of thyroid hormone status are associated with RHR in patients referred to coronary angiography. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxin (FT4), and RHR were determined in 2795 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Median (25th to 75th percentile) serum concentrations were 1.25 (0.76-1.92) mU/l for TSH, 4.8 (4.2-5.3) pmol/l for FT3 and 17.1 (15.4-19.0) pmol/l for FT4, and mean (±standard deviation) RHR was 68.8 (±11.7) beats/min. Comparing the highest versus the lowest quartile, RHR (beats/min) was significantly higher in the fourth FT4 quartile [3.48, 95% confidence interval (CI): 2.23-4.73; p <0.001] and in the fourth FT3 quartile (2.30, 95% CI: 1.06-3.55; p <0.001), but there was no significant difference for TSH quartiles. In multiple linear regression analyses adjusting for various potential confounders, FT3 and FT4 were significant predictors of RHR (p <0.001 for both). In subgroups restricted to TSH, FT3, and FT4 values within the reference range, both FT3 and FT4 remained significant predictors of RHR (p <0.001 for all). In conclusion, in patients referred to coronary angiography, FT3 and FT4 but not TSH were positively associated with RHR. The relationship between free thyroid hormones and RHR warrants further investigations regarding its diagnostic and therapeutic implications.
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http://dx.doi.org/10.1055/a-1232-7292DOI Listing
December 2020

Accuracy and stability of an arterial sensor for glucose monitoring in a porcine model using glucose clamp technique.

Sci Rep 2020 04 20;10(1):6604. Epub 2020 Apr 20.

Medical University of Graz, Core Facility Experimental Biomodels, Division of Biomedical Research, Graz, Austria.

Intravascular glucose sensors have the potential to improve and facilitate glycemic control in critically ill patients and might overcome measurement delay and accuracy issues. This study investigated the accuracy and stability of a biosensor for arterial glucose monitoring tested in a hypo- and hyperglycemic clamp experiment in pigs. 12 sensors were tested over 5 consecutive days in 6 different pigs. Samples of sensor and reference measurement pairs were obtained every 15 minutes. 1337 pairs of glucose values (range 37-458 mg/dl) were available for analysis. The systems met ISO 15197:2013 criteria in 99.2% in total, 100% for glucose <100 mg/dl (n = 414) and 98.8% for glucose ≥100 mg/dl (n = 923). The mean absolute relative difference (MARD) during the entire glycemic range of all sensors was 4.3%. The MARDs within the hypoglycemic (<70 mg/dl), euglycemic (≥70-180 mg/dl) and hyperglycemic glucose ranges (≥180 mg/dl) were 6.1%, 3.6% and 4.7%, respectively. Sensors indicated comparable performance on all days investigated (day 1, 3 and 5). None of the systems showed premature failures. In a porcine model, the performance of the biosensor revealed a promising performance. The transfer of these results into a human setting is the logical next step.
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http://dx.doi.org/10.1038/s41598-020-63659-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170864PMC
April 2020

Secondary Hyperthyroidism due to an Ectopic Thyrotropin-Secreting Neuroendocrine Pituitary Tumor: A Case Report.

Eur Thyroid J 2020 Feb 21;9(2):106-112. Epub 2020 Jan 21.

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

Introduction: The main differential diagnoses of secondary hyperthyroidism include thyrotropin-secreting neuroendocrine pituitary tumors (TSH-PitNETs) and resistance to thyroid hormone. As a rare cause of secondary hyperthyroidism, ectopic thyrotropin-producing neuroendocrine pituitary tumors must also be considered.

Case Presentation: A 48-year-old female patient with overt hyperthyroidism and elevated thyrotropin was admitted to the endocrine outpatient clinic of a secondary care hospital in March 2018. The patient had an inconspicuous pituitary MRI and F18-F-DOPA PET-CT, but showed a tumor mass located at the pharyngeal roof. Most biochemical tests and an increased tracer uptake of the pharyngeal mass in a Ga68-DOTANOC PET-CT argued for the presence of an ectopic TSH-PitNET. After treatment with octreotide over 5 days and a consecutive normalization of free thyroxine and free triiodothyronine, the tumor was endoscopically resected. Histologically, the mass consisted of small partially spindle, partially polygonal monomorphic to mildly pleomorphic cells with immunoreactivity for thyrotropin and luteinizing hormone. Postoperatively, the patient required intermittent levothyroxine therapy.

Discussion And Conclusions: Ectopic TSH-PitNETs represent an extremely rare cause for secondary hyperthyroidism. While the diagnostic process may be complicated by negative imaging studies of the pituitary gland, family history, biochemical tests, and functional imaging using gallium-labelled somatostatin analogues may be helpful in establishing the diagnosis.
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http://dx.doi.org/10.1159/000505020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109380PMC
February 2020

Letter by Pilz et al Regarding Article, "Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment-Elevation Myocardial Infarction Care in Hong Kong, China".

Circ Cardiovasc Qual Outcomes 2020 05 3;13(5):e006734. Epub 2020 Apr 3.

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

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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006734DOI Listing
May 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

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

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

Feasibility of Blood Glucose Management Using Intra-Arterial Glucose Monitoring in Combination with an Automated Insulin Titration Algorithm in Critically Ill Patients.

Diabetes Technol Ther 2019 10;21(10):581-588

Department of Anesthesiology and Intensive Care Medicine, Karl Landsteiner Privatuniversität (KPU), Universitätsklinikum St. Pölten, St Pölten, Austria.

This two-center pilot study combined for the first time an intra-arterial glucose sensor with a decision support system for insulin dosing (SGCplus system) in critically ill patients with hyperglycemia. Twenty-two patients who were equipped with an arterial line and required iv insulin therapy were managed by the SGCplus system during their medical treatment at the intensive care unit. Time to target was 111 ± 195 min (80-150 mg/dL) and 135 ± 267 min (100-160 mg/dL) in the lower and higher glucose target group. Mean blood glucose (BG) was 142 ± 32 mg/dL with seven BG values <70 mg/dL. Mean daily insulin dose was 62 ± 38 U and mean daily carbohydrate intake 148 ± 50 g/day (enteral nutrition) and 102 ± 58 g/day (parenteral nutrition). Acceptance of SGCplus suggestions was high (93%). The SGCplus system can be safely applied in critically ill patients with hyperglycemia and enables good glycemic control.
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http://dx.doi.org/10.1089/dia.2019.0082DOI Listing
October 2019

Effects of vitamin D supplementation on metabolic and endocrine parameters in healthy premenopausal women: A randomized controlled trial.

Clin Nutr 2020 03 20;39(3):718-726. Epub 2019 Mar 20.

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

Background & Aims: Vitamin D supplementation may affect glycemic as well as hormonal regulation. Thus, the aim of the current study was to investigate whether vitamin D supplementation has any significant effects on metabolic and endocrine parameters in healthy premenopausal women. Primary outcome measure was the plasma glucose area under the curve (AUCgluc).

Methods: The current study was a single-center, double-blind, randomized placebo-controlled trial that was conducted at the Medical University of Graz, Austria, between March 2013 and October 2017. One-hundred and fifty healthy premenopausal women with 25-hydroxyvitamin D [25(OH)D] concentrations <75 nmol/L once weekly received either 20,000 IU of cholecalciferol or placebo (2:1 ratio) over a total of 24 weeks.

Results: In total, 127 women [age 36.2 ± 8.7 years; BMI 25.3 ± 5.6 kg/m; baseline 25(OH)D 55.8 ± 19.7 nmol/L] completed the study. Vitamin D supplementation had no significant effect on AUCgluc (mean treatment effect 11.70; p = 0.069), while it had a significant treatment effect on homeostatic model assessment-insulin resistance (HOMA-IR; mean treatment effect 0.31; p = 0.019) and quantitative insulin-sensitivity check index (QUICKI; mean treatment effect -0.019; p = 0.013). There was no significant effect on the remaining secondary outcome parameters.

Conclusions: In this randomized-controlled trial in healthy premenopausal women, there was a significant treatment effect of vitamin D supplementation on HOMA-IR and QUICKI, while there was no significant treatment effect on AUCgluc.
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http://dx.doi.org/10.1016/j.clnu.2019.03.007DOI Listing
March 2020
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