Barbara Obermayer-pietsch - Academia.edu (original) (raw)

Papers by Barbara Obermayer-pietsch

PLOS ONE, 2015

We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exerci... more We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567.

Current opinion in clinical nutrition and metabolic care, 2015

Polycystic ovary syndrome (PCOS) is a very common endocrine disease in women all over the world. ... more Polycystic ovary syndrome (PCOS) is a very common endocrine disease in women all over the world. A variety of symptoms such as hirsutism and hyperandrogenism, irregular menstrual cycles and anovulatory infertility together with metabolic dysfunction, insulin resistance, and type 2 diabetes mellitus in lean and obese individuals and the development of consecutive diseases are key problems in this heterogeneous syndrome. Disease-modifying and potentially disease-causing candidate genes are described. A number of genetic associations have been investigated, whereby genes related to normal-weight insulin resistance and chronic inflammation are of central interest for PCOS pathomechanisms. New insights in the pharmacogenetics of PCOS might help to individualize therapeutic options. Enormous progress has been made in the genetics of insulin resistance in PCOS. However, because of the individual heterogeneity of PCOS and the lack of evident functional studies, the syndrome is only partly u...

Endocrinology, Diabetes & Metabolism Case Reports, 2015

Cushing's syndrome (CS) due to ectopic ACTH production accounts for about 10% of all type... more Cushing's syndrome (CS) due to ectopic ACTH production accounts for about 10% of all types of CS and is frequently associated with metabolic alkalosis. Treatment of CS involves surgical resection and/or medical therapy to control hypercortisolism. We present the case of an 80-year-old woman affected by CS due to an unknown cause. The patient had severe metabolic alkalosis with refractory hypokalemia. To treat the underlying CS, fluconazole was initiated due to unavailability of ketoconazole. In spite of markedly decreasing cortisol levels, metabolic alkalosis persisted. Treatment of metabolic alkalosis with acetazolamide was thus initiated and pH levels successfully lowered. This case report shows that hypercortisolism can be effectively treated with fluconazole in cases where ketoconazole is unavailable or not tolerated and that persistent severe metabolic alkalosis caused by glucocorticoid excess can be safely and successfully treated with acetazolamide. Hypercortisolism can be effectively treated with fluconazole where ketoconazole is unavailable or not tolerated.Glucocorticoid excess can cause severe metabolic alkalosis.Persistent severe metabolic alkalosis can be safely and successfully treated with acetazolamide.

Hypertension, 2015

Vitamin D deficiency is a risk factor for arterial hypertension, but randomized controlled trials... more Vitamin D deficiency is a risk factor for arterial hypertension, but randomized controlled trials showed mixed effects of vitamin D supplementation on blood pressure (BP). We aimed to evaluate whether vitamin D supplementation affects 24-hour systolic ambulatory BP monitoring values and cardiovascular risk factors. The Styrian Vitamin D Hypertension Trial is a single-center, double-blind, placebo-controlled study conducted from June 2011 to August 2014 at the endocrine outpatient clinic of the Medical University of Graz, Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxyvitamin D levels below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for 8 weeks. Primary outcome measure was 24-hour systolic BP. Secondary outcome measures were 24-hour diastolic BP, N-terminal-pro-B-type natriuretic peptide, QTc interval, renin, aldosterone, 24-hour urinary albumin excretion, homeostasis model assessment-insulin resistance, triglycerides, high-density lipoprotein cholesterol, and pulse wave velocity. A total of 188 participants (mean [SD] age, 60.1 [11.3] years; 47% women; 25-hydroxyvitamin D, 21.2 [5.6] ng/mL) completed the trial. The mean treatment effect (95% confidence interval) for 24-hour systolic BP was -0.4 (-2.8 to 1.9) mm Hg (P=0.712). Triglycerides increased significantly (mean change [95% confidence interval], 17 [1-33] mg/dL; P=0.013), but no further significant effects were observed for secondary outcomes. Vitamin D supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on BP and several cardiovascular risk factors, but it was associated with a significant increase in triglycerides.

Clinical pharmacology and therapeutics, 1992

In a randomized, double-blind, crossover study in 10 healthy volunteers the hemodynamic effects, ... more In a randomized, double-blind, crossover study in 10 healthy volunteers the hemodynamic effects, drug plasma concentrations, and thyroid hormone profiles were compared after oral administration for 1 week of 40 mg t.i.d. racemic (R,S)-propranolol versus 20 mg t.i.d. optically pure (S)-propranolol. During exercise, both substances decreased heart rate (-14%, p less than 0.01), as well as the overall rate pressure product (-19%, p less than 0.01) to the same extent, indicating similar beta-blocking effects. After oral application of (R,S)-propranolol the maximal plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) of (S)-propranolol were higher than those of (R)-propranolol (eudismic ratios (S)- over (R)-propranolol Cmax, 1.36 [p less than 0.01] and AUC, 1.42 [p less than 0.01]) despite dose-equivalence of both enantiomers in the administered racemic (R,S)-propranolol preparation indicating different pharmacokinetic properties. Mean values of Cmax a...

Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent second... more Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95 out of 297 patients with angiographically confirmed PAD stages II (pain in the calves and/or thighs only during exercise) or IV (history of, or presence of local ulcers) and compared them with 44 matched healthy controls regarding their medical history, bone density measurements of the femoral neck and calcaneal bone ultrasound. Bone pain, myalgias and mobility restriction as well as routine laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and analysed. 25(OH)D was significantly lower in PAD IV patients (9.6+/-4.6 ng/ml, P<0.0001) as compared to PAD II stages and controls (19.0+/-7.6 and 19.1+/-9.1 ng/ml), paralleled by lower serum calcium [2.24+/-0.02 mmol/l, P=0.0002 versus PAD II (2.36+/-0.02) and P<0.0001 versus controls (2.39+/-0.02)] and higher iPTH serum levels (66.3+/-3.6 pg/ml, P<0.0001) as compared to PAD II patients (45.3+/-3.5) and healthy controls (38.5+/-2.4). Alkaline phosphatase and serum crosslaps values were significantly higher and age-adjusted bone density and bone ultrasound measurements significantly lower in PAD IV patients, who were also twice as likely to have bone pain and myalgias as PAD II patients. Bone ultrasound measurements correlated significantly with both clinical severity and pain as well as serological parameters of bone metabolism. Underlying PAD has a significant impact on bone density and metabolism as well as on bone and muscular pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and should be regularly monitored and treated for their vitamin D deficiencies.

PLoS ONE, 2014

To evaluate the association between androstenedione, testosterone, and free testosterone and meta... more To evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome. We analyzed the association between androstenedione, testosterone, and free testosterone and metabolic parameters in a cross-sectional study including 706 polycystic ovary syndrome and 140 BMI-matched healthy women. Polycystic ovary syndrome women were categorized into 4 groups: normal androstenedione and normal free testosterone (NA/NFT), elevated androstenedione and normal free testosterone (HA/NFT), normal androstenedione and elevated free testosterone (NA/HFT), elevated androstenedione and free testosterone (HA/HFT). Polycystic ovary syndrome women with elevated free testosterone levels (HA/HFT and NA/HFT) have an adverse metabolic profile including 2 h glucose, HbA1c, fasting and 2 h insulin, area under the insulin response curve, insulin resistance, insulin sensitivity index (Matsuda), triglycerides, total and high density lipoprotein cholesterol levels compared to NA/NFT (p<0.05 for all age- and BMI-adjusted analyses). In binary logistic regression analysis adjusted for age and BMI, odds ratio for insulin resistance was 2.78 (1.34-5.75, p = 0.006) for polycystic ovary syndrome women with HA/HFT compared to NA/NFT. We found no significantly increased risk of metabolic disorders in polycystic ovary syndrome women with HA/NFT. In multiple linear regression analyses (age- and BMI-adjusted), we found a significant negative association between androstenedione/free testosterone-ratio and area under the insulin response curve, insulin resistance, and total cholesterol/high density lipoprotein cholesterol-ratio and a positive association with Matsuda-index, and high density lipoprotein cholesterol (p<0.05 for all). Polycystic ovary syndrome women with elevated free testosterone levels but not with isolated androstenedione elevation have an adverse metabolic phenotype. Further, a higher androstenedione/free testosterone-ratio was independently associated with a beneficial metabolic profile.

Journal of Voice, 2010

The objective was to describe influences of sex hormones on the male voice in an elderly cohort. ... more The objective was to describe influences of sex hormones on the male voice in an elderly cohort. Sixty-three elderly males were recruited to undergo assessment of voice parameters, stroboscopy, voice-related questionnaires, a blood draw, and an ultrasound examination of the laryngeal skeleton. The group was divided into men with normal hormonal status and men with lowered levels of sex hormones, called hypogonades. Depending on the level of androgens, voice parameters did not differ. In subjects with decreased levels of estrogens, a significant increase in mean fundamental frequency, as well as changes of highest and lowest frequency plus a shift of the frequency range could be detected. We could detect significant changes of voice parameters depending on status of estrogens in elderly males. Androgens appear to have no impact on the elderly male voice. To our knowledge, this is the first prospective study that correlates sex hormones with voice parameters in elderly men.

The Journal of Clinical Endocrinology & Metabolism, 2007

Absolute fracture risk in nursing home patients is the highest among the communities studied. Scr... more Absolute fracture risk in nursing home patients is the highest among the communities studied. Screening for high-risk patients in such an environment is usually difficult. The objective was to investigate whether quantitative bone ultrasound measurements and/or markers of bone turnover/metabolism help in predicting which patients will incur hip or nonvertebral fractures. In this prospective study, mobile teams enrolled 1664 female patients from 95 nursing homes in Austria. Calcaneal stiffness (n = 1117), radial speed of sound (SOS) (n = 1332), and phalangeal SOS (n = 1498) measurements were performed at baseline. Serum samples (n = 960) were analyzed for serum calcium and phosphate, 25 hydroxyvitamin D, PTH, osteocalcin, C-terminal telopeptide crosslinks, and osteoprotegerin (OPG). Patients were prospectively followed for hip and other nonvertebral fractures for 2 yr. A total of 117 hip fractures and 269 nonvertebral fractures developed during a mean observation period of 2 yr. Prevalence of vitamin D deficiency and secondary hyperparathyroidism was high. A history of a past fracture was significantly associated with a hazard ratio (HR) of 1.47 (95% confidence interval, 1.01-2.15) and 1.65 (1.26-2.16) for the development of hip and nonvertebral fractures, respectively. Cox regression analysis revealed a multivariate adjusted elevation in both hip [HR 1.30 (1.12-1.43)] and nonvertebral [HR 1.14 (1.02-1.25)] fracture risk for each sd decrease in calcaneal stiffness. Patients in the lowest quartile for calcaneal stiffness Z-score had 2.5 and 1.2 times higher rates of hip and nonvertebral fractures when compared with patients in the highest quartile. Fracture rates were not statistically associated with baseline radial or phalangeal SOS measurements or with serum osteocalcin, C-terminal telopeptide crosslinks, and OPG concentrations. When adjusted for bone mass, higher serum OPG levels were associated with fewer hip as well as nonvertebral fractures [HR 0.85 (0.73-0.99) and 0.89 (0.80-0.99) per increment of 1]. Higher serum phosphate levels indicated an increased hip [HR 1.54 (1.07-2.21)] and nonvertebral fracture risk [HR 1.40 (1.10-1.78) per increase of 1 mg/dl]. Body mass index was protective of hip fractures [HR 0.94 (0.90-0.98) per increase of 1] as well as medication with acetylsalicylic acid [HR 0.59 (0.36-0.95) for hip and 0.72 (0.52-0.99) for nonvertebral fractures]. In contrast, current use of glucocorticoids [HR 5.65 (1.77-18.0)] and opiates [HR 1.85 (1.18-2.92)] exerted a negative effect on prospective hip fracture risk. Calcaneal stiffness measurements proved to be useful in predicting hip fractures and to a lesser extent nonvertebral fractures in nursing home residents. Radial and phalangeal bone ultrasound measurements and baseline markers of bone turnover, however, were not indicative of future fracture risk in this population.

Journal of Bone and Mineral Research, 2000

Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases.... more Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases. In several conditions such as low calcium intake, an influence of vitamin D receptor (VDR) polymorphisms on BMD has been suggested. In the present study, we investigated the relationship of Bsm I and Fok I polymorphisms of the VDR gene and BMD in patients with hyperthyroidism, a disease that often results in low BMD. Bsm I and Fok I genotypes were determined in 76 postmenopausal hyperthyroid patients and 62 healthy postmenopausal women as controls. Patients and controls were matched for age, time since menopause, and lifestyle factors and were free of estrogen medication. BMD evaluation included axial dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (PQCT). Low BMD was defined as -2.5 STD below the young adult mean value. Biochemical parameters investigated were thyroid hormones, osteocalcin, and 25-(OH)-vitamin D3 as well as routine laboratory data. Low BMD was found in 61% of hyperthyroid patients and in only 23% of euthyroid controls. In the group of hyperthyroid patients with low bone density, the BB genotype (VDR Bsm I polymorphisms) was significantly more frequent (39%) than in controls (13%; p = 0.003) and hyperthyroid patients with normal BMD (6%; p = 0.013). The odds ratio (OR) for low BMD in patients with BB genotype was 5.7 (95% CI, 1.7-19.1; p < 0.005) as compared with the Bb and bb genotypes and 5.5 (95% CI, 2.3-13.2; p < 0.0001) for hyperthyroidism alone. The cumulative risk for low BMD in patients with hyperthyroidism and BB genotype was 31.4 (95% CI, 3.9-256; p < 0.0003). VDR Fok I genotypes showed no significant relationship with BMD or other general or bone-specific parameters. Thus, hyperthyroidism and the genetic background of a BB genotype may promote synergistically the development of low BMD in hyperthyroid patients. Screening for the BB genotype in these patients therefore could help to identify those with particularly high risk for the development of low BMD and allow early treatment.

Journal of Bone and Mineral Research, 2003

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium int... more Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis.

Journal of Bone and Mineral Research, 2008

Recent studies have indicated a link between bone metabolism and cardiovascular events in patient... more Recent studies have indicated a link between bone metabolism and cardiovascular events in patients with chronic kidney disease (CKD). CKD is a major health problem worldwide. This study evaluates the role of noninvasive markers of bone metabolism in predicting cardiovascular morbidity (coronary artery disease, peripheral vascular disease, stroke) and mortality in patients with mild to severe forms of CKD. In a prospective cohort study, 627 patients with CKD were screened. To focus on bone metabolism, traditional risk factors for cardiovascular events were excluded, and 135 patients with CKD stages 1-5 were followed for 4 yr. Glomerular filtration rate was calculated by the Modification of Diet in Renal Disease formula. PTH (measured by four different assays), vitamin D 25 and 1,25, bone-specific alkaline phosphatase (BSALP), TRACP-5b, osteocalcin, serum collagen cross-link molecules, RANKL, and osteoprotegerin were determined. Predictors of cardiovascular events were evaluated by multivariable logistic regression, Kaplan-Meier survival, and Cox regression analysis. There were a total of 45 cardiovascular events (33%). Event rates were 5.6%, 29.1%, 45.2%, and 45.0% in CKD stages 1-2, 3, 4, and 5, respectively. In logistic regression, cardiovascular events were predicted only by (1) CKD stage (independent of age or sex; p < 0.001); (2) BSALP (p ‫ס‬ 0.03); and TRACP-5b (p ‫ס‬ 0.04). Markers of bone formation (BSALP) and resorption (TRACP-5b) can serve as predictors of cardiovascular morbidity and mortality in CKD.

European Archives of Oto-Rhino-Laryngology, 2011

Considerable clinical and experimental data suggest that vitamin D plays a role in pathogenesis a... more Considerable clinical and experimental data suggest that vitamin D plays a role in pathogenesis and progression of cancer; nevertheless clinical data for head and neck squamous cell carcinoma (HNSCC) are not available. The aim of our study was to associate tumor and clinical characteristics with status of vitamin D [25-hydroxyvitamin D (25(OH)D)]. 88 patients with newly diagnosed squamous cell carcinoma of the head and neck were included in the study. A blood draw was taken at the time of diagnosis. The observation period lasted from 2006 until 2010. When compared to a cohort from an epidemiological study, serum levels of 25(OH)D were significantly reduced in patients with HNSCC. We furthermore found disease-free survival, as well as overall survival times to be significantly associated with 25(OH)D levels. In conclusion, results from our study suggest an influence of vitamin D status on cancer incidence, as well as on mortality of HNSCC.

Endocrine Practice, 2014

Osteocalcin (OC) might play a hormone-like role in energy metabolism and the regulatory circuit b... more Osteocalcin (OC) might play a hormone-like role in energy metabolism and the regulatory circuit between the pancreas and osteoblasts. Effects of a 75-g oral glucose tolerance test (OGTT) on total OC, undercarboxylated (ucOC), and carboxylated osteocalcin (cOC) in insulin-resistant (IR) and noninsulin-resistant (nIR) premenopausal women was evaluated, and the relationships of changes in OC, ucOC, and cOC with area under the curve (AUC) insulin and the Matsuda index were examined. In this cross-sectional study, 105 premenopausal women underwent OGTT; 18 were IR (homeostatic model assessment of insulin resistance [HOMA-IR] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 2.6; (2 with type 2 diabetes, 2 with impaired glucose tolerance), and 87 were nIR (3 with impaired glucose tolerance). Changes in total OC, ucOC, and cOC were evaluated 60 and 120 minutes after glucose loading. At baseline, IR subjects had significantly lower levels of total OC, cOC, and ucOC. In nIR women, total OC decreased by 19% from 18.0 ng/mL (14.5-24.7) at baseline to 14.6 ng/mL (10.9-17.8) after 120 minutes, ucOC decreased by 22% from 3.2 ng/mL (2.1-4.5) to 2.5 ng/mL (1.7-3.5), and cOC decreased by 26% from 14.9 ng/mL (12.1-20.4) to 11.1 ng/mL (9.0-14.5) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001, respectively). No significant decreases were noted in IR subjects. The declines in OC and cOC predicted AUCinsulin (ΔOC: β = 0.301, P = .001; ΔcOC: β = 0.315, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and the Matsuda index (ΔOC: β = -0.235, P = .003; ΔcOC: β = -0.245, P = .002). Glucose intake lowers levels of OC, ucOC, and cOC in nIR women, the extent of which predicts IR and insulin sensitivity in premenopausal women. OC parameters seem suppressed in IR women. There might be a differential osteoblast response to oral glucose in IR and nIR women, with OC reflecting this finding.

BMC Endocrine Disorders, 2009

Background: Primary aldosteronism (PA) affects approximately 5 to 10% of all patients with arteri... more Background: Primary aldosteronism (PA) affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH) study we aim to prospectively evaluate diagnostic procedures for PA.

Gene, 2014

Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility proble... more Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.2) with metabolic disturbances in PCOS and healthy control women. Genetic variants rs17468190 (G/T) of MEP1A gene were analyzed in 576 PCOS women and 206 controls by using the Taqman fluorogenic 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-exonuclease assay. This polymorphism was tested for association with anthropometric, metabolic, hormonal, and functional parameters of PCOS. There was a borderline significant difference in genotype distribution between PCOS and control women (p=0.046). In overweight/obese PCOS patients, the variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism. In a dominant model, the GG genotype of the MEP1A gene was more strongly associated with insulin metabolism in overweight/obese PCOS women (body mass index, BMI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;25 kg/m(2)), than in GT+TT genotypes. The MEP1A GG-carriers showed a significantly increased homeostatic model assessment - insulin resistance (HOMA-IR) (p=0.003), elevation of fasting insulin (p=0.004) and stimulated insulin (30 min, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001; 60 min, p=0.009; 120 min, p=0.009) as well as triglyceride (p=0.032) levels. MEP1A is a possible target gene for disease modification in PCOS. It might contribute to the abnormalities of glucose metabolism and insulin sensitivity and serve as a diagnostic or therapeutic target gene for PCOS.

Bone, 2003

Osteoprotegerin (OPG) is an antiresorptive cytokine and a key regulator of osteoclastogenesis and... more Osteoprotegerin (OPG) is an antiresorptive cytokine and a key regulator of osteoclastogenesis and activity. Since OPG is downregulated by glucocorticoids and cyclosporine A in vitro we examined whether immunosuppressive therapy would play a role in the development of transplantation osteoporosis. We enrolled 57 cardiac transplant recipients (median time since transplantation, 3.2 years (1.1–11.5 years)) in this cross-sectional study. Standardized spinal

PLOS ONE, 2015

We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exerci... more We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567.

Current opinion in clinical nutrition and metabolic care, 2015

Polycystic ovary syndrome (PCOS) is a very common endocrine disease in women all over the world. ... more Polycystic ovary syndrome (PCOS) is a very common endocrine disease in women all over the world. A variety of symptoms such as hirsutism and hyperandrogenism, irregular menstrual cycles and anovulatory infertility together with metabolic dysfunction, insulin resistance, and type 2 diabetes mellitus in lean and obese individuals and the development of consecutive diseases are key problems in this heterogeneous syndrome. Disease-modifying and potentially disease-causing candidate genes are described. A number of genetic associations have been investigated, whereby genes related to normal-weight insulin resistance and chronic inflammation are of central interest for PCOS pathomechanisms. New insights in the pharmacogenetics of PCOS might help to individualize therapeutic options. Enormous progress has been made in the genetics of insulin resistance in PCOS. However, because of the individual heterogeneity of PCOS and the lack of evident functional studies, the syndrome is only partly u...

Endocrinology, Diabetes & Metabolism Case Reports, 2015

Cushing&#39;s syndrome (CS) due to ectopic ACTH production accounts for about 10% of all type... more Cushing&#39;s syndrome (CS) due to ectopic ACTH production accounts for about 10% of all types of CS and is frequently associated with metabolic alkalosis. Treatment of CS involves surgical resection and/or medical therapy to control hypercortisolism. We present the case of an 80-year-old woman affected by CS due to an unknown cause. The patient had severe metabolic alkalosis with refractory hypokalemia. To treat the underlying CS, fluconazole was initiated due to unavailability of ketoconazole. In spite of markedly decreasing cortisol levels, metabolic alkalosis persisted. Treatment of metabolic alkalosis with acetazolamide was thus initiated and pH levels successfully lowered. This case report shows that hypercortisolism can be effectively treated with fluconazole in cases where ketoconazole is unavailable or not tolerated and that persistent severe metabolic alkalosis caused by glucocorticoid excess can be safely and successfully treated with acetazolamide. Hypercortisolism can be effectively treated with fluconazole where ketoconazole is unavailable or not tolerated.Glucocorticoid excess can cause severe metabolic alkalosis.Persistent severe metabolic alkalosis can be safely and successfully treated with acetazolamide.

Hypertension, 2015

Vitamin D deficiency is a risk factor for arterial hypertension, but randomized controlled trials... more Vitamin D deficiency is a risk factor for arterial hypertension, but randomized controlled trials showed mixed effects of vitamin D supplementation on blood pressure (BP). We aimed to evaluate whether vitamin D supplementation affects 24-hour systolic ambulatory BP monitoring values and cardiovascular risk factors. The Styrian Vitamin D Hypertension Trial is a single-center, double-blind, placebo-controlled study conducted from June 2011 to August 2014 at the endocrine outpatient clinic of the Medical University of Graz, Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxyvitamin D levels below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for 8 weeks. Primary outcome measure was 24-hour systolic BP. Secondary outcome measures were 24-hour diastolic BP, N-terminal-pro-B-type natriuretic peptide, QTc interval, renin, aldosterone, 24-hour urinary albumin excretion, homeostasis model assessment-insulin resistance, triglycerides, high-density lipoprotein cholesterol, and pulse wave velocity. A total of 188 participants (mean [SD] age, 60.1 [11.3] years; 47% women; 25-hydroxyvitamin D, 21.2 [5.6] ng/mL) completed the trial. The mean treatment effect (95% confidence interval) for 24-hour systolic BP was -0.4 (-2.8 to 1.9) mm Hg (P=0.712). Triglycerides increased significantly (mean change [95% confidence interval], 17 [1-33] mg/dL; P=0.013), but no further significant effects were observed for secondary outcomes. Vitamin D supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on BP and several cardiovascular risk factors, but it was associated with a significant increase in triglycerides.

Clinical pharmacology and therapeutics, 1992

In a randomized, double-blind, crossover study in 10 healthy volunteers the hemodynamic effects, ... more In a randomized, double-blind, crossover study in 10 healthy volunteers the hemodynamic effects, drug plasma concentrations, and thyroid hormone profiles were compared after oral administration for 1 week of 40 mg t.i.d. racemic (R,S)-propranolol versus 20 mg t.i.d. optically pure (S)-propranolol. During exercise, both substances decreased heart rate (-14%, p less than 0.01), as well as the overall rate pressure product (-19%, p less than 0.01) to the same extent, indicating similar beta-blocking effects. After oral application of (R,S)-propranolol the maximal plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) of (S)-propranolol were higher than those of (R)-propranolol (eudismic ratios (S)- over (R)-propranolol Cmax, 1.36 [p less than 0.01] and AUC, 1.42 [p less than 0.01]) despite dose-equivalence of both enantiomers in the administered racemic (R,S)-propranolol preparation indicating different pharmacokinetic properties. Mean values of Cmax a...

Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent second... more Hypovitaminosis D is common in patients with peripheral arterial disease (PAD). Subsequent secondary hyperparathyroidism and osteomalacia contribute to bone pain and myalgias, and so aggravate clinical symptoms of claudication. We evaluated 95 out of 297 patients with angiographically confirmed PAD stages II (pain in the calves and/or thighs only during exercise) or IV (history of, or presence of local ulcers) and compared them with 44 matched healthy controls regarding their medical history, bone density measurements of the femoral neck and calcaneal bone ultrasound. Bone pain, myalgias and mobility restriction as well as routine laboratory parameters, serum vitamin D [25(OH)D], crosslaps (CTX), parathyroid hormone (PTH), osteocalcin (OC) and alkaline phosphatase (AP) were recorded and analysed. 25(OH)D was significantly lower in PAD IV patients (9.6+/-4.6 ng/ml, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) as compared to PAD II stages and controls (19.0+/-7.6 and 19.1+/-9.1 ng/ml), paralleled by lower serum calcium [2.24+/-0.02 mmol/l, P=0.0002 versus PAD II (2.36+/-0.02) and P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001 versus controls (2.39+/-0.02)] and higher iPTH serum levels (66.3+/-3.6 pg/ml, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) as compared to PAD II patients (45.3+/-3.5) and healthy controls (38.5+/-2.4). Alkaline phosphatase and serum crosslaps values were significantly higher and age-adjusted bone density and bone ultrasound measurements significantly lower in PAD IV patients, who were also twice as likely to have bone pain and myalgias as PAD II patients. Bone ultrasound measurements correlated significantly with both clinical severity and pain as well as serological parameters of bone metabolism. Underlying PAD has a significant impact on bone density and metabolism as well as on bone and muscular pain. Patients with PAD are at high risk for osteoporosis and osteomalacia and should be regularly monitored and treated for their vitamin D deficiencies.

PLoS ONE, 2014

To evaluate the association between androstenedione, testosterone, and free testosterone and meta... more To evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome. We analyzed the association between androstenedione, testosterone, and free testosterone and metabolic parameters in a cross-sectional study including 706 polycystic ovary syndrome and 140 BMI-matched healthy women. Polycystic ovary syndrome women were categorized into 4 groups: normal androstenedione and normal free testosterone (NA/NFT), elevated androstenedione and normal free testosterone (HA/NFT), normal androstenedione and elevated free testosterone (NA/HFT), elevated androstenedione and free testosterone (HA/HFT). Polycystic ovary syndrome women with elevated free testosterone levels (HA/HFT and NA/HFT) have an adverse metabolic profile including 2 h glucose, HbA1c, fasting and 2 h insulin, area under the insulin response curve, insulin resistance, insulin sensitivity index (Matsuda), triglycerides, total and high density lipoprotein cholesterol levels compared to NA/NFT (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 for all age- and BMI-adjusted analyses). In binary logistic regression analysis adjusted for age and BMI, odds ratio for insulin resistance was 2.78 (1.34-5.75, p = 0.006) for polycystic ovary syndrome women with HA/HFT compared to NA/NFT. We found no significantly increased risk of metabolic disorders in polycystic ovary syndrome women with HA/NFT. In multiple linear regression analyses (age- and BMI-adjusted), we found a significant negative association between androstenedione/free testosterone-ratio and area under the insulin response curve, insulin resistance, and total cholesterol/high density lipoprotein cholesterol-ratio and a positive association with Matsuda-index, and high density lipoprotein cholesterol (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 for all). Polycystic ovary syndrome women with elevated free testosterone levels but not with isolated androstenedione elevation have an adverse metabolic phenotype. Further, a higher androstenedione/free testosterone-ratio was independently associated with a beneficial metabolic profile.

Journal of Voice, 2010

The objective was to describe influences of sex hormones on the male voice in an elderly cohort. ... more The objective was to describe influences of sex hormones on the male voice in an elderly cohort. Sixty-three elderly males were recruited to undergo assessment of voice parameters, stroboscopy, voice-related questionnaires, a blood draw, and an ultrasound examination of the laryngeal skeleton. The group was divided into men with normal hormonal status and men with lowered levels of sex hormones, called hypogonades. Depending on the level of androgens, voice parameters did not differ. In subjects with decreased levels of estrogens, a significant increase in mean fundamental frequency, as well as changes of highest and lowest frequency plus a shift of the frequency range could be detected. We could detect significant changes of voice parameters depending on status of estrogens in elderly males. Androgens appear to have no impact on the elderly male voice. To our knowledge, this is the first prospective study that correlates sex hormones with voice parameters in elderly men.

The Journal of Clinical Endocrinology & Metabolism, 2007

Absolute fracture risk in nursing home patients is the highest among the communities studied. Scr... more Absolute fracture risk in nursing home patients is the highest among the communities studied. Screening for high-risk patients in such an environment is usually difficult. The objective was to investigate whether quantitative bone ultrasound measurements and/or markers of bone turnover/metabolism help in predicting which patients will incur hip or nonvertebral fractures. In this prospective study, mobile teams enrolled 1664 female patients from 95 nursing homes in Austria. Calcaneal stiffness (n = 1117), radial speed of sound (SOS) (n = 1332), and phalangeal SOS (n = 1498) measurements were performed at baseline. Serum samples (n = 960) were analyzed for serum calcium and phosphate, 25 hydroxyvitamin D, PTH, osteocalcin, C-terminal telopeptide crosslinks, and osteoprotegerin (OPG). Patients were prospectively followed for hip and other nonvertebral fractures for 2 yr. A total of 117 hip fractures and 269 nonvertebral fractures developed during a mean observation period of 2 yr. Prevalence of vitamin D deficiency and secondary hyperparathyroidism was high. A history of a past fracture was significantly associated with a hazard ratio (HR) of 1.47 (95% confidence interval, 1.01-2.15) and 1.65 (1.26-2.16) for the development of hip and nonvertebral fractures, respectively. Cox regression analysis revealed a multivariate adjusted elevation in both hip [HR 1.30 (1.12-1.43)] and nonvertebral [HR 1.14 (1.02-1.25)] fracture risk for each sd decrease in calcaneal stiffness. Patients in the lowest quartile for calcaneal stiffness Z-score had 2.5 and 1.2 times higher rates of hip and nonvertebral fractures when compared with patients in the highest quartile. Fracture rates were not statistically associated with baseline radial or phalangeal SOS measurements or with serum osteocalcin, C-terminal telopeptide crosslinks, and OPG concentrations. When adjusted for bone mass, higher serum OPG levels were associated with fewer hip as well as nonvertebral fractures [HR 0.85 (0.73-0.99) and 0.89 (0.80-0.99) per increment of 1]. Higher serum phosphate levels indicated an increased hip [HR 1.54 (1.07-2.21)] and nonvertebral fracture risk [HR 1.40 (1.10-1.78) per increase of 1 mg/dl]. Body mass index was protective of hip fractures [HR 0.94 (0.90-0.98) per increase of 1] as well as medication with acetylsalicylic acid [HR 0.59 (0.36-0.95) for hip and 0.72 (0.52-0.99) for nonvertebral fractures]. In contrast, current use of glucocorticoids [HR 5.65 (1.77-18.0)] and opiates [HR 1.85 (1.18-2.92)] exerted a negative effect on prospective hip fracture risk. Calcaneal stiffness measurements proved to be useful in predicting hip fractures and to a lesser extent nonvertebral fractures in nursing home residents. Radial and phalangeal bone ultrasound measurements and baseline markers of bone turnover, however, were not indicative of future fracture risk in this population.

Journal of Bone and Mineral Research, 2000

Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases.... more Bone mineral density (BMD) is modulated by genetic and environmental factors or certain diseases. In several conditions such as low calcium intake, an influence of vitamin D receptor (VDR) polymorphisms on BMD has been suggested. In the present study, we investigated the relationship of Bsm I and Fok I polymorphisms of the VDR gene and BMD in patients with hyperthyroidism, a disease that often results in low BMD. Bsm I and Fok I genotypes were determined in 76 postmenopausal hyperthyroid patients and 62 healthy postmenopausal women as controls. Patients and controls were matched for age, time since menopause, and lifestyle factors and were free of estrogen medication. BMD evaluation included axial dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (PQCT). Low BMD was defined as -2.5 STD below the young adult mean value. Biochemical parameters investigated were thyroid hormones, osteocalcin, and 25-(OH)-vitamin D3 as well as routine laboratory data. Low BMD was found in 61% of hyperthyroid patients and in only 23% of euthyroid controls. In the group of hyperthyroid patients with low bone density, the BB genotype (VDR Bsm I polymorphisms) was significantly more frequent (39%) than in controls (13%; p = 0.003) and hyperthyroid patients with normal BMD (6%; p = 0.013). The odds ratio (OR) for low BMD in patients with BB genotype was 5.7 (95% CI, 1.7-19.1; p &lt; 0.005) as compared with the Bb and bb genotypes and 5.5 (95% CI, 2.3-13.2; p &lt; 0.0001) for hyperthyroidism alone. The cumulative risk for low BMD in patients with hyperthyroidism and BB genotype was 31.4 (95% CI, 3.9-256; p &lt; 0.0003). VDR Fok I genotypes showed no significant relationship with BMD or other general or bone-specific parameters. Thus, hyperthyroidism and the genetic background of a BB genotype may promote synergistically the development of low BMD in hyperthyroid patients. Screening for the BB genotype in these patients therefore could help to identify those with particularly high risk for the development of low BMD and allow early treatment.

Journal of Bone and Mineral Research, 2003

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium int... more Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis.

Journal of Bone and Mineral Research, 2008

Recent studies have indicated a link between bone metabolism and cardiovascular events in patient... more Recent studies have indicated a link between bone metabolism and cardiovascular events in patients with chronic kidney disease (CKD). CKD is a major health problem worldwide. This study evaluates the role of noninvasive markers of bone metabolism in predicting cardiovascular morbidity (coronary artery disease, peripheral vascular disease, stroke) and mortality in patients with mild to severe forms of CKD. In a prospective cohort study, 627 patients with CKD were screened. To focus on bone metabolism, traditional risk factors for cardiovascular events were excluded, and 135 patients with CKD stages 1-5 were followed for 4 yr. Glomerular filtration rate was calculated by the Modification of Diet in Renal Disease formula. PTH (measured by four different assays), vitamin D 25 and 1,25, bone-specific alkaline phosphatase (BSALP), TRACP-5b, osteocalcin, serum collagen cross-link molecules, RANKL, and osteoprotegerin were determined. Predictors of cardiovascular events were evaluated by multivariable logistic regression, Kaplan-Meier survival, and Cox regression analysis. There were a total of 45 cardiovascular events (33%). Event rates were 5.6%, 29.1%, 45.2%, and 45.0% in CKD stages 1-2, 3, 4, and 5, respectively. In logistic regression, cardiovascular events were predicted only by (1) CKD stage (independent of age or sex; p < 0.001); (2) BSALP (p ‫ס‬ 0.03); and TRACP-5b (p ‫ס‬ 0.04). Markers of bone formation (BSALP) and resorption (TRACP-5b) can serve as predictors of cardiovascular morbidity and mortality in CKD.

European Archives of Oto-Rhino-Laryngology, 2011

Considerable clinical and experimental data suggest that vitamin D plays a role in pathogenesis a... more Considerable clinical and experimental data suggest that vitamin D plays a role in pathogenesis and progression of cancer; nevertheless clinical data for head and neck squamous cell carcinoma (HNSCC) are not available. The aim of our study was to associate tumor and clinical characteristics with status of vitamin D [25-hydroxyvitamin D (25(OH)D)]. 88 patients with newly diagnosed squamous cell carcinoma of the head and neck were included in the study. A blood draw was taken at the time of diagnosis. The observation period lasted from 2006 until 2010. When compared to a cohort from an epidemiological study, serum levels of 25(OH)D were significantly reduced in patients with HNSCC. We furthermore found disease-free survival, as well as overall survival times to be significantly associated with 25(OH)D levels. In conclusion, results from our study suggest an influence of vitamin D status on cancer incidence, as well as on mortality of HNSCC.

Endocrine Practice, 2014

Osteocalcin (OC) might play a hormone-like role in energy metabolism and the regulatory circuit b... more Osteocalcin (OC) might play a hormone-like role in energy metabolism and the regulatory circuit between the pancreas and osteoblasts. Effects of a 75-g oral glucose tolerance test (OGTT) on total OC, undercarboxylated (ucOC), and carboxylated osteocalcin (cOC) in insulin-resistant (IR) and noninsulin-resistant (nIR) premenopausal women was evaluated, and the relationships of changes in OC, ucOC, and cOC with area under the curve (AUC) insulin and the Matsuda index were examined. In this cross-sectional study, 105 premenopausal women underwent OGTT; 18 were IR (homeostatic model assessment of insulin resistance [HOMA-IR] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 2.6; (2 with type 2 diabetes, 2 with impaired glucose tolerance), and 87 were nIR (3 with impaired glucose tolerance). Changes in total OC, ucOC, and cOC were evaluated 60 and 120 minutes after glucose loading. At baseline, IR subjects had significantly lower levels of total OC, cOC, and ucOC. In nIR women, total OC decreased by 19% from 18.0 ng/mL (14.5-24.7) at baseline to 14.6 ng/mL (10.9-17.8) after 120 minutes, ucOC decreased by 22% from 3.2 ng/mL (2.1-4.5) to 2.5 ng/mL (1.7-3.5), and cOC decreased by 26% from 14.9 ng/mL (12.1-20.4) to 11.1 ng/mL (9.0-14.5) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001, respectively). No significant decreases were noted in IR subjects. The declines in OC and cOC predicted AUCinsulin (ΔOC: β = 0.301, P = .001; ΔcOC: β = 0.315, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and the Matsuda index (ΔOC: β = -0.235, P = .003; ΔcOC: β = -0.245, P = .002). Glucose intake lowers levels of OC, ucOC, and cOC in nIR women, the extent of which predicts IR and insulin sensitivity in premenopausal women. OC parameters seem suppressed in IR women. There might be a differential osteoblast response to oral glucose in IR and nIR women, with OC reflecting this finding.

BMC Endocrine Disorders, 2009

Background: Primary aldosteronism (PA) affects approximately 5 to 10% of all patients with arteri... more Background: Primary aldosteronism (PA) affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH) study we aim to prospectively evaluate diagnostic procedures for PA.

Gene, 2014

Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility proble... more Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.2) with metabolic disturbances in PCOS and healthy control women. Genetic variants rs17468190 (G/T) of MEP1A gene were analyzed in 576 PCOS women and 206 controls by using the Taqman fluorogenic 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-exonuclease assay. This polymorphism was tested for association with anthropometric, metabolic, hormonal, and functional parameters of PCOS. There was a borderline significant difference in genotype distribution between PCOS and control women (p=0.046). In overweight/obese PCOS patients, the variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism. In a dominant model, the GG genotype of the MEP1A gene was more strongly associated with insulin metabolism in overweight/obese PCOS women (body mass index, BMI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;25 kg/m(2)), than in GT+TT genotypes. The MEP1A GG-carriers showed a significantly increased homeostatic model assessment - insulin resistance (HOMA-IR) (p=0.003), elevation of fasting insulin (p=0.004) and stimulated insulin (30 min, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001; 60 min, p=0.009; 120 min, p=0.009) as well as triglyceride (p=0.032) levels. MEP1A is a possible target gene for disease modification in PCOS. It might contribute to the abnormalities of glucose metabolism and insulin sensitivity and serve as a diagnostic or therapeutic target gene for PCOS.

Bone, 2003

Osteoprotegerin (OPG) is an antiresorptive cytokine and a key regulator of osteoclastogenesis and... more Osteoprotegerin (OPG) is an antiresorptive cytokine and a key regulator of osteoclastogenesis and activity. Since OPG is downregulated by glucocorticoids and cyclosporine A in vitro we examined whether immunosuppressive therapy would play a role in the development of transplantation osteoporosis. We enrolled 57 cardiac transplant recipients (median time since transplantation, 3.2 years (1.1–11.5 years)) in this cross-sectional study. Standardized spinal