Rudolfstiftung Hospital Vienna

Vienna, Austria

Rudolfstiftung Hospital Vienna

Vienna, Austria

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Bannister C.A.,University of Cardiff | Holden S.E.,University of Cardiff | Jenkins-Jones S.,Global Epidemiology | Morgan C.L.,Global Epidemiology | And 4 more authors.
Diabetes, Obesity and Metabolism | Year: 2014

Aims: Clinical and observational studies have shown an increased risk of cardiovascular events and death associated with sulphonylureas versus metformin. However, it has never been determined whether this was due to the beneficial effects of metformin or detrimental effects of sulphonylureas. The objective of this study was therefore to compare all-cause mortality in diabetic patients treated first-line with either sulphonylurea or metformin monotherapy with that in matched individuals without diabetes. Methods: We used retrospective observational data from the UK Clinical Practice Research Datalink (CPRD) from 2000. Subjects with type 2 diabetes who progressed to first-line treatment with metformin or sulphonylurea monotherapy were selected and matched to people without diabetes. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables. Results: We identified 78241 subjects treated with metformin, 12222 treated with sulphonylurea, and 90463 matched subjects without diabetes. This resulted in a total, censored follow-up period of 503384years. There were 7498 deaths in total, representing unadjusted mortality rates of 14.4 and 15.2, and 50.9 and 28.7 deaths per 1000 person-years for metformin monotherapy and their matched controls, and sulphonylurea monotherapy and their matched controls, respectively. With reference to observed survival in diabetic patients initiated with metformin monotherapy [survival time ratio (STR)=1.0], adjusted median survival time was 15% lower (STR=0.85, 95% CI 0.81-0.90) in matched individuals without diabetes and 38% lower (0.62, 0.58-0.66) in diabetic patients treated with sulphonylurea monotherapy. Conclusions: Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first-line therapy and implies that metformin may confer benefit in non-diabetes. Sulphonylurea remains a concern. © 2014 John Wiley & Sons Ltd.


Schernthaner G.,Rudolfstiftung Hospital Vienna | Gross J.L.,Federal University of Rio Grande do Sul | Rosenstock J.,Dallas Diabetes and Endocrine Center at Medical City | Guarisco M.,Stanocola Medical Clinic | And 5 more authors.
Diabetes Care | Year: 2013

OBJECTIVE-To evaluate the efficacy and safety of canagliflozin, a sodium glucose cotransporter 2 inhibitor, compared with sitagliptin in subjects with type 2 diabetes inadequately controlled with metformin plus sulfonylurea. RESEARCH DESIGN AND METHODS-In this 52-week, randomized, double-blind, active-controlled, phase 3 study, subjects using stable metformin plus sulfonylurea (N = 755) received canagliflozin 300 mg or sitagliptin 100 mg daily. Primary end point was change from baseline in A1C at 52 weeks. Secondary end points included change in fasting plasma glucose (FPG) and systolic blood pressure (BP), and percent change in body weight, triglycerides, and HDL cholesterol. Safety was assessed based on adverse event (AE) reports. RESULTS-At 52 weeks, canagliflozin 300mg demonstrated noninferiority and, in a subsequent assessment, showed superiority to sitagliptin 100 mgin reducing A1C(-1.03%[-11.3mmol/mol] and -0.66% [-7.2 mmol/mol], respectively; least squares mean difference between groups, -0.37% [95% CI, -0.50 to -0.25] or -4.0 mmol/mol [-5.5 to -2.7]). Greater reductions in FPG, body weight, and systolic BP were observed with canagliflozin versus sitagliptin (P < 0.001). Overall AE rates were similar with canagliflozin (76.7%) and sitagliptin (77.5%); incidence of serious AEs and AE-related discontinuations was low for both groups. Higher incidences of genital mycotic infections and osmotic diuresis-related AEs were observed with canagliflozin, which led to one discontinuation. Hypoglycemia rates were similar in both groups. CONCLUSIONS-Findings suggest that canagliflozinmay be a new therapeutic tool providing better improvement in glycemic control and body weight reduction than sitagliptin, but with increased genital infections in subjects with type 2 diabetes using metformin plus sulfonylurea. © 2013 by the American Diabetes Association.


Holden S.E.,University of Cardiff | Jenkins-Jones S.,Global Epidemiology | Morgan C.L.,Global Epidemiology | Schernthaner G.,Rudolfstiftung Hospital Vienna | Currie C.J.,University of Cardiff
Diabetes, Obesity and Metabolism | Year: 2015

Aims: To evaluate the association between insulin exposure and all-cause mortality, incident major adverse cardiovascular events (MACE) and incident cancer in people with type 2 diabetes treated with insulin monotherapy. Methods: For this retrospective study, people with type 2 diabetes who progressed to insulin monotherapy from the year 2000 were identified from the UK Clinical Practice Research Datalink. The risks of progression to serious adverse outcomes were compared using Cox proportional hazards models. In the main analysis, insulin exposure was introduced into the model as prescribed international units per kilogram per day, as a cumulative, continuous, annually updated, time-dependent covariable. Results: A total of 6484 subjects with type 2 diabetes who progressed to treatment with insulin monotherapy from the year 2000 onwards were followed for a mean of 3.3years. The event numbers were as follows: deaths, n=1110; incident MACE, n=342; incident cancers, n=382. Unadjusted event rates were 61.3 deaths per 1000person-years, 26.4 incident MACE per 1000person-years and 24.6 incident cancers per 1000person-years. The adjusted hazard ratios in relation to 1-unit increases in insulin dose were 1.54 [95% confidence interval (CI) 1.32-1.78] for all-cause mortality, 1.37 (95% CI 1.05-1.81) for MACE and 1.35 (95% CI 1.04-1.75) for cancer. Conclusions: There was an association between increasing exogenous insulin dose and increased risk of all-cause mortality, MACE and cancer in people with type 2 diabetes. The limitations of observational studies mean that this should be further investigated using an interventional study design. © 2014 John Wiley & Sons Ltd.


Ay L.,Rudolfstiftung Hospital Vienna | Kopp H.-P.,Rudolfstiftung Hospital Vienna | Brix J.-M.,Rudolfstiftung Hospital Vienna | Ay C.,Medical University of Vienna | And 4 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010

Background: Patients with morbid obesity (MO; body mass index > 40 kg m-2) suffer from an increased risk of cardiovascular disease, stroke, venous thromboembolism and all-cause mortality. Objectives: Because weight loss by bariatric surgery reduces cardiovascular and all-cause mortality, we hypothesized that the plasmatic clotting system might be involved in cardiovascular risk. Patients/Methods: Thirty-six MO patients [mean age 42 (±13) years; 29 female) were investigated before and 2 years after bariatric surgery. Thrombin generation was measured with a commercially available assay (Technothrombin-TGA,Technoclone). Metabolic parameters and parameters of the hemostatic system, such as tissue factor (TF), TF pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1) and prothrombinfragment 1.2 (F1.2), were determined. To investigate associations of changing parameters, deltas were calculated. Results: Metabolic parameters improved with a mean weight loss of 41 (±19) kg. Postoperatively, the lag phase was significantly extended compared with preoperative values [median (25th-75th percentile), 7 (4-12) vs. 12 (7-19) min, P = 0.005]. Peak thrombin decreased after weight loss from 345 (232-455) to 282 (111-388) nm (P = 0.015) and the area under the curve from 3962 (3432-5023) to 3227 (2202-4030) nm thrombin (P < 0.001). TF, PAI-1 and F1.2 significantly decreased after weight loss. Analyses of the deltas showed a significant correlation between peak thrombin and total cholesterol (r = 0.50), triglycerides (r = 0.46) and HbA1c (r = 0.55). Moreover, an inverse correlation was found between insulin resistance and the lag phase (r = -0.46). Conclusion: Thrombin generation, a marker of the overall coagulation potential, decreased significantly with weight reduction. This might, at least in part, explain the decreased risk of cardiovascular disease after bariatric surgery. © 2010 International Society on Thrombosis and Haemostasis.


Ay L.,Rudolfstiftung Hospital Vienna | Hoellerl F.,Rudolfstiftung Hospital Vienna | Ay C.,Medical University of Vienna | Brix J.-M.,Rudolfstiftung Hospital Vienna | And 4 more authors.
European Journal of Clinical Investigation | Year: 2012

Background Albuminuria is an indicator of cardiovascular morbidity and mortality in patients with type 2 diabetic mellitus (T2DM). Materials and methods In our cross-sectional study, we measured thrombin generation (TG), a key process in haemostasis and a tool to detect an individual's coagulation potential, in normo-, micro- and macroalbuminuria in T2DM with and without macrovascular disease (MVD). The TG-assay was performed, and the TG-curve [including the lag phase, peak thrombin and area under the curve (AUC)] was analysed. Results A total of 160 patients (62 women; mean age±SD: 67±11years) with T2DM and normo-, micro- or macroalbuminuria were investigated. Of those, 90 (56%) patients had normoalbuminuria, 40 (25%) microalbuminuria and 30 (19%) macroalbuminuria. The AUC between the groups of patients with normo-, micro- and macroalbuminuria was statistically significantly different [3297 (2785; 3764) vs. 3222 (2381; 3678) vs. 3726 (3153; 4235) nM Thrombin; P=0Æ019]. T2DM patients with MVD (n=121) had a significantly shorter lag phase [12 (9; 16) vs. 20 (15; 25) min; P<0Æ001], a significantly higher peak thrombin [233 (130; 339) vs. 133 (82; 187)nM; P<0Æ001] and a significantly higher AUC [3464 (2969; 3868) vs. 3091 (2384; 3619)nM Thrombin; P=0Æ01] than T2DM patients without MVD (n=39), indicating an earlier and higher thrombin generation. Conclusion Our results support the hypothesis that TG may be involved in the pathogenesis of MVD in diabetic nephropathy as for the first time, we could show that patients with T2DM in different stages of diabetic nephropathy had disturbances in thrombin generation. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.


Hortenhuber T.,Medical University of Vienna | Rami-Mehar B.,Medical University of Vienna | Satler M.,Medical University of Vienna | Nagl K.,Medical University of Vienna | And 7 more authors.
Diabetes Care | Year: 2013

OBJECTIVE - The risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality in patients without diabetes. We hypothesized that EPCs are modified in children with T1DM and are related to characteristics of T1DM such as glycemic control. RESEARCH DESIGN AND METHODS - Children (n = 190; 156 T1DM subjects and 34 control subjects) were included in an observational cohort study and matched for age and sex. EPCs were enumerated by flow cytometry at the beginning (cross-sectional) and 1 year later (longitudinal). To analyze changes of variables during the observation, Δ values were calculated. RESULTS - EPCs were significantly reduced in T1DM children versus control subjects (609 ± 359 vs. 1,165 ± 484, P < 0.001). Multivariate regression modeling revealed that glycated hemoglobin A1c (HbA1c) was the strongest independent predictor of EPCs (β = -0.355, P < 0.001). Overall glycemic control at the beginning and end of study did not differ (7.8 ± 1.2 vs. 7.8 ± 1.2 relative %, P = NS), but we observed individual HbA1c changes of -4.30/+3.10 relative %. The strongest EPC increase was observed in the patients with the most favorable HbA1c lowering during the 1-year follow-up. Accordingly, the strongest EPC decrease was demonstrated in the patients with the strongest HbA1c worsening during the time period. CONCLUSIONS - This is the first prospective study demonstrating diminished EPCs in children with T1DM. The association of better glycemic control with an increase in EPC numbers within 1 year suggests that a reduction of the high cardiovascular disease burden might be mediated likewise. © 2013 by the American Diabetes Association.


Brix J.-M.,Rudolfstiftung Hospital Vienna | Hollerl F.,Medical University of Vienna | Koppensteiner R.,Medical University of Vienna | Schernthaner G.,Rudolfstiftung Hospital Vienna | Schernthaner G.-H.,Medical University of Vienna
European Journal of Clinical Investigation | Year: 2011

Background Type 2 diabetic patients with albuminuria have an increased risk for vascular complications. Albuminuria is related to endothelial dysfunction and plaque instability. YKL-40 is also associated with both and elevated in nondiabetic vascular patients. We investigated YKL-40 and its association with vascular disease in type 2 diabetic patients with albuminuria. Material and methods Two hundred and four patients with type 2 diabetes were included in a cross-sectional study: One hundred and six normo- (No-A), 64 micro- (Mi-A) and 34 macroalbuminuric (Ma-A) patients that did not differ for age, diabetes duration, HbA1c, body-mass-index, blood pressure, lipids and creatinine. YKL-40 was measured in serum samples and determined by ELISA. Results YKL-40 was significantly different in No-A: 87±57 vs. Mi-A 119±68 vs. Ma-A 157±75ngmL-1; P<0·001. Patients with macrovascular disease showed higher YKL-40 than those without: 115±72 vs. 87±49ngmL-1, P=0·003. In correlation analysis, YKL-40 was associated with urinary albumin excretion rate (AER), plasma creatinine, creatinine clearance (CC) and age. Two multivariate regression analyses were conducted: in the first one, AER and CC remained associated with YKL-40 and in the second one AER and age. Conclusions This is the first report of a significant elevation of YKL-40 in type 2 diabetic patients with albuminuria. In addition, we observed a significant association with macrovascular disease. Because we detected an association between YKL-40 with renal, micro- and macrovascular disease, this protein could play an important for the increased risk of type 2 diabetic patients with albuminuria for the development of cardiovascular disease. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.


Wimpissinger F.,Rudolfstiftung Hospital Vienna | Springer C.,Rudolfstiftung Hospital Vienna | Stackl W.,Rudolfstiftung Hospital Vienna
BJU International | Year: 2013

What's known on the subject? and What does the study add? Genital secretions during female orgasm (female ejaculation) have been a matter of controversy for centuries. Scientific work on this essential part of female sexual function has been able to differentiate between female ejaculation, urinary incontinence and vaginal transudate. According to earlier studies, less than 50% of women actually do ejaculate during sexual stimulation. Few affected women discuss female ejaculation with their physician - partly because of its physiological nature, partly through embarrassment. To gain knowledge on the characteristics of female ejaculation and its impact on women's sexual lives, an online questionnaire has been designed and published internationally. In this way, data from 320 women who perceive ejaculation could be acquired. Most women and their partners perceive female ejaculation as an enrichment of their sexual lives. Objective To study characteristics of female ejaculation as perceived by healthy women. To evaluate whether fluid emission during sexual activity has an impact on women's or their partners' sexual lives. Materials and Methods An online questionnaire consisting of 23 questions addressing the participants' characteristics, aspects of perceived female ejaculation, and its impact on women's and their partners' lives was published internationally on various online platforms. Results Over a period of 18 months, 320 women from all over the world were included in the study (excluding women below the age of 18 years and double entries). The women's mean age was 34.1 years (±11.1) and their mean age at first ejaculation was 25.4 years. Most women ejaculate a few times a week. The volume of ejaculation is approximately 2 oz (29.1%), and the fluid is usually clear as water (83.1%). For most women (78.8%) and their partners (90.0%), female ejaculation is an enrichment of their sexual lives, whereas 14 women (4.4%) stated that their partners were unaware of their potential ejaculation. Conclusions Perceived female ejaculation - and its onset - occurs in women of all ages. Most women who ejaculate do so on a regular basis. Female ejaculation is an enrichment of the sexual lives of women as well as their partners. © 2013 BJU International.


Type 2 diabetes is a rather complex metabolic disorder still associated with a 2-fold increased cardiovascular (CV) mortality despite a dramatic improvement in CV risk reduction by multifactorial intervention strategies. Intensive glucose control can also reduce CV morbidity, but this effect seems to be limited to younger patients with shorter duration of disease and no CV disease. Intensive glucose control - in particular when complex insulin strategies are used - is associated with a 5-fold increased risk for severe hypoglycemia, which could induce harm in some patients. In contrast to blood pressure and lipid-lowering interventions a reduction of CV mortality cannot be seen before 10-20 years after the start of the glucose-lowering intervention (metabolic memory, legacy effect). Future ongoing outcome studies in more than 50,000 patients will clarify whether new antidiabetic drugs - not inducing hypoglycemia or weight gain - will further improve the prognosis of T2DM patients. © 2010 Springer-Verlag.


Wimpissinger F.,Rudolfstiftung Hospital Vienna | Springer C.,Rudolfstiftung Hospital Vienna | Kurtaran A.,Rudolfstiftung Hospital Vienna | Stackl W.,Rudolfstiftung Hospital Vienna | Turk C.,Rudolfstiftung Hospital Vienna
BMC Urology | Year: 2014

Background: To investigate functional aspects of silent ureteral stones with special focus on obstruction and its relationship to renal anatomy. The present study is the first investigation of renal excretory function in patients with silent ureteral stones. Methods. Patients with primarily asymptomatic ureteral stones underwent a mercapto-acetyltriglycine (MAG-3) renal scintigraphy prior to treatment, in addition to anatomic evaluation of renal units and serum creatinine levels. The primary outcome measure was the presence or absence of obstruction. Secondary outcome measures were kidney anatomy, grade of hydronephrosis, location of stones, stone size, and serum creatinine levels. Results: During a ten-year period, 14 patients (median age 52.6 years; range 37.3 to 80.7 years) were included in the study. The relative frequency of primarily asymptomatic ureteral stones among all patients treated for ureteral stones in the study period was 0.7%. Eleven renal units showed some degree of hydronephrosis while 3 kidneys were not dilated. On the MAG-3 scan, 7 patients had an obstruction of the ureter, 5 had no obstruction, and 2 had dysfunction of the kidney. A statistically significant correlation was established between the grade of obstruction and stone size (p = 0.02). Conclusions: At the time of presentation, only 64.3% of the patients revealed an obstruction in the stone-bearing renal unit. The degree of hydronephrosis and renal function were very diverse in this subgroup of patients with ureteral stones. The onset of ureterolithiasis and the chronological sequence of obstruction remain unclear in patients who have never experienced symptoms due to their stones. © 2014 Wimpissinger et al.; licensee BioMed Central Ltd.

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