256 results on '"Kautzky-Willer A"'
Search Results
2. Mediators of lifestyle intervention effects on neonatal adiposity
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Lima, Rodrigo Antunes, Desoye, Gernot, Simmons, David, van Poppel, Mireille Nicoline Maria, Devlieger, Roland, Galjaard, Sander, Corcoy, Rosa, Adelantado, Juan M., Dunne, Fidelma, Harreiter, Jürgen, Kautzky-Willer, Alexandra, Damm, Peter, Mathiesen, Elisabeth R., Jensen, Dorte M., Andersen, Lise Lotte, Tanvig, Mette, Lapolla, Annunziata, Dalfra, Maria Grazia, Bertolotto, Alessandra, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Hill, David J., Snoek, Frank J., Jelsma, Judith G.M., Obstetrics & Gynecology, Medical psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), Public and occupational health, and Medical Psychology
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Leptin ,Physiology ,Fatty Acids, Nonesterified ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,NEFA ,Randomized controlled trial ,SDG 3 - Good Health and Well-being ,law ,Pregnancy ,030225 pediatrics ,Lifestyle intervention ,Medicine ,Humans ,Obesity ,Life Style ,Adiposity ,business.industry ,Infant, Newborn ,medicine.disease ,Cord blood ,Pediatrics, Perinatology and Child Health ,Gestation ,Female ,business ,Body mass index ,030217 neurology & neurosurgery - Abstract
We evaluated possible mediators underlying lifestyle intervention effects on neonatal adiposity, assessed with sum of skinfolds and cord blood leptin. This is a secondary analysis of the DALI study, a randomised controlled trial in nine European countries. Pregnant women with a pre-pregnancy body mass index of ≥29 kg/m2 were randomly assigned to counselling for healthy eating (HE), physical activity (PA), HE&PA combined, or to usual care. We considered five maternal metabolic factors at 24–28 and 35–37 weeks of gestation, and four cord blood factors as possible mediators of the effect of combined HE&PA counselling on neonatal adiposity. From all potential mediators, the intervention only affected cord blood non-esterified fatty acids (NEFA), which was higher in the HE&PA group compared to UC (0.068 (mmol/L), 95% CI: 0.004 to 0.133). Cord blood NEFA did not mediate the HE&PA intervention effects on neonatal sum of skinfolds or cord blood leptin, based on an indirect effect on skinfolds of 0.018 (mm), 95% CI: −0.217 to 0.253 and an indirect effect on leptin of −0.143 (μg/l), 95% CI: −0.560 to 0.273. The Dali study observed reductions in neonatal adiposity in pregnant women with obesity, but we were not able to identify the underlying metabolic pathway.
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- 2022
3. Sex-Specific Differences in Mortality of Patients with a History of Bariatric Surgery: a Nation-Wide Population-Based Study
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Eric Mörth, Jürgen Harreiter, Jakob Eichelter, Paul Fellinger, Michael Krebs, Tanja Stamm, Alexandra Kautzky-Willer, Peter Wolf, Miriam Hufgard-Leitner, Hannes Beiglböck, Alexander Kautzky, Gerhard Prager, Berthold Reichardt, and Bianca K. Itariu
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Original Contributions ,Population ,Disease ,Malignancy ,Comorbidities ,Healthcare research ,Diabetes mellitus ,Sex differences ,Health insurance ,Diabetes Mellitus ,Medicine ,Humans ,Obesity ,Mortality ,education ,Bariatric surgery ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Mortality rate ,Population-based registry analysis ,medicine.disease ,Sex specific ,Surgery ,Obesity, Morbid ,Population based study ,Cardiovascular Diseases ,Female ,business - Abstract
Purpose Bariatric surgery reduces mortality in patients with severe obesity and is predominantly performed in women. Therefore, an analysis of sex-specific differences after bariatric surgery in a population-based dataset from Austria was performed. The focus was on deceased patients after bariatric surgery. Materials and Methods The Austrian health insurance funds cover about 98% of the Austrian population. Medical health claims data of all Austrians who underwent bariatric surgery from 01/2010 to 12/2018 were analyzed. In total, 19,901 patients with 107,806 observed years postoperative were eligible for this analysis. Comorbidities based on International Classification of Diseases (ICD)-codes and drug intake documented by Anatomical Therapeutical Chemical (ATC)-codes were analyzed in patients deceased and grouped according to clinically relevant obesity-associated comorbidities: diabetes mellitus (DM), cardiovascular disease (CV), psychiatric disorder (PSY), and malignancy (M). Results In total, 367 deaths were observed (1.8%) within the observation period from 01/2010 to 04/2020. The overall mortality rate was 0.34% per year of observation and significantly higher in men compared to women (0.64 vs. 0.24%; p p p = 0.034), whereas malignant diseases (36%) were more frequent in women (30 vs. 41%; p = 0.025). Conclusion After bariatric surgery, short-term mortality as well as long-term mortality was higher in men compared to women. In deceased patients, diabetes was more common in men, whereas malignant diseases were more common in women. Graphical abstract
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- 2021
4. Sex and Gender Impact Mental and Emotional Well-Being During COVID-19 Pandemic: A European Countries Experience
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Teresa, Gisinger, Rubee, Dev, Alexander, Kautzky, Jürgen, Harreiter, Valeria, Raparelli, Karolina, Kublickiene, Maria, Trinidad Herrero, Colleen M, Norris, Kim L, Lavoie, Louise, Pilote, and Alexandra, Kautzky-Willer
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Male ,Cross-Sectional Studies ,Mental Health ,Humans ,COVID-19 ,Female ,Anxiety ,Pandemics - Published
- 2022
5. Sex, rurality and socioeconomical status in Spanish centennial population (2017)
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Louise Pilote, Alexandra Kautzky-Willer, Maria Herrero, Pedro Simón Cayuela Fuentes, Lorena Cuenca-Bermejo, Sandra Amador, Colleen M. Norris, Valeria Raparelli, Ana Maria Lucas-Ochoa, Karolina Kublickiene, and Emiliano Fernández-Villalba
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Adult ,Male ,Rural Population ,Aging ,Adolescent ,Urban Population ,Gross Domestic Product ,centenarians ,GDP per capita ,longevity ,rurality ,sex ,media_common.quotation_subject ,Population ,Gross domestic product ,NO ,Young Adult ,Life Expectancy ,Rurality ,Centennial ,Per capita ,Humans ,Child ,education ,Socioeconomic status ,Aged ,media_common ,Aged, 80 and over ,education.field_of_study ,Descriptive statistics ,Longevity ,Infant ,Cell Biology ,Middle Aged ,Geography ,Social Class ,Spain ,Child, Preschool ,Female ,Research Paper ,Demography - Abstract
World's population is exponentially aging as people reaching 100 years old has increased. The number of areas with the highest centennial population rates (Blue Zones), are significantly higher. Are there any determinant factors that favor this situation in Spain? The goal of this study was to determine the possible influence of sex, rurality and socioeconomic factors (Gross Domestic Product (GDP)) on the prevalence of the centennial population of the Spanish society. The Spanish register of inhabitants was published in 2017 by the National Statistics Institute. The analysis was carried out both by Autonomous Communities and by provinces in phases: a first descriptive analysis, followed by an inferential analysis, based on statistical tests (independent T- Student test, Pearson correlation and ANOVA). There were significant interactions between: i) sex and longevity (in favor of the female population); ii) female and rural housing and iii) female, GDP and urban areas. Feminization was proven in the longevity revolution, but, in general, GDP per Capita was not a significant survival factor on its own. This study was the first step of further analysis related to extreme longevity in Spain, which will include other dependent variables such as state of health and well-being as well as social factors.
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- 2021
6. Does diabetes mellitus mitigate the gender gap in COVID-19 mortality?
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Alexandra Kautzky-Willer
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Adult ,Male ,medicine.medical_specialty ,COVID-19 Vaccines ,Endocrinology, Diabetes and Metabolism ,Disease ,Type 2 diabetes ,Diabetes Complications ,Endocrinology ,Insulin resistance ,Sex Factors ,Pregnancy ,Diabetes mellitus ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,business.industry ,Mortality rate ,COVID-19 ,General Medicine ,Middle Aged ,medicine.disease ,Obesity ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Commentary ,Female ,Insulin Resistance ,business ,Psychosocial - Abstract
In this SARS-COV2-pandemic, diabetes mellitus (DM) soon emerged as one of the most prominent risk factors for a severe course of corona virus disease-2019 (COVID-19) and increased mortality due to hyperglycemia/insulin resistance, obesity, inflammation, altered immune status, and cardiovascular complications. In general, men are at a higher risk of severe or fatal COVID-19 disease irrespective of age, region and despite comparable infection rates in both sexes. In COVID-19, there is also a male predominance among hospitalized patients with diabetes, however, overall, data among patients with diabetes are ambiguous so far. Of note, similar to cardiovascular complications, women with type 2 diabetes (DM2) appear to lose their biological female advantage resulting in comparable death rates to those of men. The complex interplay of biological and behavioral factors, which may put men at greater risk of a severe or fatal course of COVID-19, and gender-related psychosocial factors, which may cause disadvantage to women concerning the infection rates, might explain why sex-disaggregated data among infected patients with diabetes are conflicting. Better knowledge on biological factors leading to functionally different immune responses and of gender-sensitive sociocultural determinants of COVID-19 infection rates may help to optimize prevention and management in the high-risk groups of men and women with diabetes.
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- 2021
7. Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality
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Claudia Tucci, Liam J. Ward, Leah Hernandez, Giulia Tosti, Peter Stenvinkel, Colleen M. Norris, Maria Herrero, Torkel B. Brismar, Magnus Söderberg, Louise Pilote, Valeria Raparelli, Karolina Kublickiene, Agne Laucyte-Cibulskiene, Jonaz Ripsweden, Thomas Ebert, and Alexandra Kautzky-Willer
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Male ,medicine.medical_specialty ,Growth Differentiation Factor 15 ,Physiology ,medicine.medical_treatment ,Biomarkers ,Calcification ,Cardiovascular disease ,Chronic kidney disease ,End stage kidney disease ,TMAO ,Uraemia ,Context (language use) ,030204 cardiovascular system & hematology ,Systemic inflammation ,Gastroenterology ,NO ,Gender Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Medicine ,Humans ,QP1-981 ,Renal replacement therapy ,Chitinase-3-Like Protein 1 ,Prospective Studies ,030304 developmental biology ,0303 health sciences ,business.industry ,Research ,Arteriosclerosis ,medicine.disease ,Comorbidity ,3. Good health ,Matrix Metalloproteinase 9 ,embryonic structures ,Biomarker (medicine) ,Kidney Failure, Chronic ,Female ,medicine.symptom ,business ,Kidney disease - Abstract
Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p p = 0.02). Conclusions In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.
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- 2021
8. Vitamin D3 Supplementation in Overweight/Obese Pregnant Women
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Jürgen, Harreiter, Lilian C, Mendoza, David, Simmons, Gernot, Desoye, Roland, Devlieger, Sander, Galjaard, Peter, Damm, Elisabeth R, Mathiesen, Dorte M, Jensen, Lise Lotte T, Andersen, Fidelma, Dunne, Annunziata, Lapolla, Maria G, Dalfra, Alessandra, Bertolotto, Ewa, Wender-Ozegowska, Agnieszka, Zawiejska, David, Hill, Judith G M, Jelsma, Frank J, Snoek, Christof, Worda, Dagmar, Bancher-Todesca, Mireille N M, van Poppel, Rosa, Corcoy, Alexandra, Kautzky-Willer, On Behalf Of The Dali Core Investigator Group, Public and occupational health, APH - Health Behaviors & Chronic Diseases, APH - Quality of Care, Medical psychology, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), Obstetrics & Gynecology, and Medical Psychology
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Leptin ,pregnancy outcomes ,INDEXES ,body fat distribution ,vitamin D ,Ketone Bodies ,Fatty Acids, Nonesterified ,skinfolds ,lipids ,D DEFICIENCY ,MELLITUS ,SDG 3 - Good Health and Well-being ,Pregnancy ,Humans ,overweight ,Obesity ,Life Style ,triglycerides ,METAANALYSIS ,Cholecalciferol ,obesity pregnancy ,RISK ,INSULIN-RESISTANCE ,Science & Technology ,Nutrition and Dietetics ,Nutrition & Dietetics ,Infant, Newborn ,Pregnancy Outcome ,birth outcomes ,cholesterol ,free fatty acids ,Cholesterol, LDL ,Vitamins ,Vitamin D Deficiency ,WEIGHT-GAIN ,Diabetes, Gestational ,cord blood ,OBESITY ,Dietary Supplements ,ADIPOSITY ,Female ,Pregnant Women ,Life Sciences & Biomedicine ,Food Science - Abstract
Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women
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- 2022
9. Sex and Gender Influence on Cardiovascular Health in Sub-Saharan Africa: Findings from Ghana, Gambia, Mali, Guinea, and Botswana
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Dev, Rubee, Ofili, Divine-Favour, Raparelli, Valeria, Behlouli, Hassan, Azizi, Zahra, Kublickiene, Karolina, Kautzky-Willer, Alexandra, Herrero, Maria Trinidad, Pilote, Louise, Norris, Colleen M., and GOING-FWD Consortium, on behalf of the
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Community and Home Care ,Adult ,Male ,Botswana ,Epidemiology ,Health Status ,Cardiovascular health ,Cardiovascular diseases ,sub-Saharan Africa ,Sex ,Gender ,Overweight ,Mali ,Ghana ,Cardiovascular Diseases ,Risk Factors ,Hypertension ,Humans ,Female ,Gambia ,Guinea ,Obesity ,Cardiology and Cardiovascular Medicine - Abstract
Background Sex and gender-based differences in cardiovascular health (CVH) has been explored in the context of high-income countries. However, these relationships have not been examined in low- and middle-income countries. There is an upsurge of cardiovascular diseases (CVDs) in sub-Saharan Africa (SSA). Irrespective of biological sex, gender-related factors could be the precursor of these conditions. Purpose To examine the associations between biological sex, gender-related variables, and CVH risk factors in SSA countries. Methods We conducted a retrospective analysis of the World Health Organization's “STEPwise approach to surveillance of risk factors for non-communicable disease” or “STEPS” survey, conducted in adults aged 18–69 years from Ghana, Gambia, Mali, Guinea, and Botswana. The surveys were conducted between 2006 and 2014. The main outcome was CVH, as measured by a composite measure of STEPS-HEART health index (smoking, hypertension, diabetes, obesity/overweight, and daily consumption of fruits and vegetables), values ranging from 0 (worst) to 5 (best or ideal). Multivariable logistic regression was applied to determine the gender-related factors related to poorer CVH (index less than 4). Two-way interaction between the sex and gender-related factors were tested by including an interaction term in bivariate models. Results Data included 15,356 adults (61.4% females, mean age 36.9 years). The prevalence of hypertension (21.6% vs. 13.8%) and overweight/obesity (48.3% vs. 27.5%) was higher among females as compared to males. Females were more likely to be unemployed (17.3% vs. 9.7%) or reported unpaid work (36.8% vs. 15.2%). Overall, females showed worse CVH than males (OR female = 0.95, 95% CI: 0.91–0.99). Being married was associated with better CVH compared with being single, more so for males (OR male = 1.09, 95% CI: 0.96–1.24, p interaction Conclusion This study highlights an alarmingly high prevalence of CVD risk factors, mainly overweight/obesity and hypertension among females in SSA population. Being female was associated with poorer CVH given the disproportionate burden of hypertension and overweight/obesity. Gender-related factors such as marital status and unpaid work were associated with better CVH in males compared to females. With the rising prevalence of CVDs in SSA, it will be important to consider the gender-related factors while implementing preventive programs and creating effective health policies. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The GENDER– NET Plus ERA-NET Initiative (project ref. number: GNP-78): The Canadian Institutes of Health Research (GNP-161904)
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- 2022
10. Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing’s Syndrome
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Michael Weber, Marcus Hacker, Barbara Fueger, Bianca K. Itariu, Lucia Zisser, Sazan Rasul, Georgios Karanikas, Alexandra Kautzky-Willer, Peter R. Mazal, Verena Pichler, Chrysoula Vraka, and Oana C. Kulterer
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Male ,Cancer Research ,PET-CT ,S syndrome ,medicine.diagnostic_test ,business.industry ,Contrast Media ,Cancer ,Gadolinium ,Computed tomography ,General Medicine ,Middle Aged ,medicine.disease ,18f fdopa ,Oncology ,Positron emission tomography ,Positron Emission Tomography Computed Tomography ,Humans ,Medicine ,Female ,business ,Nuclear medicine ,Cushing Syndrome ,Aged - Abstract
Background/aim Positron emission tomography/computed tomography (PET/CT) plays an important role in cancer localization in ectopic Cushing's syndrome (ECS). However, the choice of the optimal tracer for investigation of this disease is still unclear. We aimed to evaluate the diagnostic feasibility of [18F]fluoro-2-deoxyglucose ([18F]FDG), [18F]fluoro-L-dihydroxyphenylalanine ([18F] FDOPA), and [68Ga]-DOTA-1-Nal3-octreotide ([68Ga]-DOTANOC) in ECS. Patients and methods All PET/CT scans of patients admitted to our department for suspected ECS between 2010 and 2020 were retrospectively analysed. Results Collectively, 30 PET/CT examinations, 11 with [18F]FDOPA, 11 with [18F]FDG and 8 with [68Ga]GaDOTANOC were conducted for 18 patients eligible for analysis. [18F]FDG detected the tumour in 3/6 of the cases, [18F]FDOPA in 3/4, and [68Ga]GaDOTANOC in 3/3. [18F]FDOPA was the only tracer without false positive results. Conclusion [68Ga]GaDOTANOC and [18F]FDOPA showed superior results compared to [18F]FDG, although the sensitivity of the tracers might be influenced by the aetiology of the tumour underlying the ECS.
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- 2021
11. Iron Deficiency – Not Only a Premenopausal Topic After Bariatric Surgery?
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Ines Kunst, Alexandra Kautzky-Willer, Bettina Dreschl, Tamara Ranzenberger-Haider, Michael Krebs, Gerhard Prager, and Elias L. Meyer
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Male ,medicine.medical_specialty ,Dose ,Endocrinology, Diabetes and Metabolism ,Original Contributions ,Iron ,medicine.disease_cause ,medicine ,Humans ,Iron supplementation ,Retrospective Studies ,Bariatric surgery ,Nutrition and Dietetics ,Postmenopausal women ,Anemia, Iron-Deficiency ,business.industry ,Gastric bypass surgery ,Follow-up ,Iron deficiency ,Retrospective cohort study ,medicine.disease ,Surgery ,Obesity, Morbid ,Menopause ,Dietary Supplements ,Female ,business ,Multivitamin - Abstract
Purpose In our centre, specialized high dose multivitamin supplementation designed to meet the needs of patients after gastric bypass surgery is routinely recommended in the early postoperative period. The aim of the present study was to analyse whether iron supplementation prescribed in clinical practice is sufficient in both sexes and whether multivitamin supplementation standardized for women might potentially lead to iron overload in men. Materials/Methods This was a retrospective study covering the period up to 36 months after bariatric surgery. Three groups were compared (men, premenopausal and postmenopausal women). The iron status was evaluated employing serum ferritin concentrations. Results A total of 283 patients who had at least one follow-up visit between January 2015 and April 2018 at a specialized academic outpatient centre were included (71 men, 130 premenopausal women, 82 postmenopausal women). Thirty-six months after surgery, 33.3%, 68.4% and 54.5% of the men, pre- and postmenopausal women, respectively, were iron deficient. The preoperative prevalence of excess ferritin levels was 13.7% in premenopausal, 3.0% in postmenopausal women, 5.7% in men and declined in the following months. Conclusion Iron deficiency is very common after gastric bypass surgery, and even high dosages of multivitamin and mineral supplements might not be sufficient to prevent the development of iron deficiency. Men, pre- and postmenopausal women differ in their prevalence of iron deficiency which demands adapted iron dosage regimens based on the sex and the age. Iron overload is rare in all observed groups and highest in premenopausal women. Graphical abstract
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- 2021
12. Cortical Gyrification Morphology in ASD and ADHD: Implication for Further Similarities or Disorder-Specific Features?
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Gharehgazlou, Avideh, Vandewouw, Marlee, Ziolkowski, Justine, Wong, Jimmy, Crosbie, Jennifer, Schachar, Russell, Nicolson, Rob, Georgiades, Stelios, Dunne, Elizabeth, Harreiter, Jürgen, Kautzky-Willer, Alexandra, Damm, Peter, Mathiesen, Elisabeth R., Jensen, Dorte M., Andersen, Lise Lotte, Tanvig, Mette, Lapolla, Annunziata, Dalfra, Maria G., Bertolotto, Alessandra, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Hill, David, Snoek, Frank J., Jelsma, Judith G.M., and Desoye, Gernot
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Male ,lGI ,Attention Deficit Hyperactivity Disorder ,Adolescent ,Autism Spectrum Disorder ,Cognitive Neuroscience ,050105 experimental psychology ,Adaptive functioning ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cognition ,cortical gyrification ,mental disorders ,medicine ,Genetic predisposition ,Attention deficit hyperactivity disorder ,Humans ,0501 psychology and cognitive sciences ,10. No inequality ,Child ,Gyrification ,High rate ,Social communication ,Communication ,05 social sciences ,medicine.disease ,Comorbidity ,Autism spectrum disorder ,Attention Deficit Disorder with Hyperactivity ,Linear Models ,cerebral cortex ,Female ,Psychology ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Shared etiological pathways are suggested in ASD and ADHD given high rates of comorbidity, phenotypic overlap and shared genetic susceptibility. Given the peak of cortical gyrification expansion and emergence of ASD and ADHD symptomology in early development, we investigated gyrification morphology in 539 children and adolescents (6–17 years of age) with ASD (n=197) and ADHD (n=96) compared to typically developing controls (n=246) using the local Gyrification Index (lGI) to provide insight into contributing etiopathological factors in these two disorders. We also examined IQ effects and functional implications of gyrification by exploring the relation between lGI and ASD and ADHD symptomatology beyond diagnosis. General Linear Models yielded no group differences in lGI, and across groups, we identified an age-related decrease of lGI and greater lGI in females compared to males. No diagnosis-by-age interactions were found. Accounting for IQ variability in the model (n=484) yielded similar results. No significant associations were found between lGI and social communication deficits, repetitive and restricted behaviours, inattention or adaptive functioning. By examining both disorders and controls using shared methodology, we found no evidence of atypicality in gyrification as measured by the lGI in these conditions.
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- 2022
13. Biomarkers Predictive for In-Hospital Mortality in Patients with Diabetes Mellitus and Prediabetes Hospitalized for COVID-19 in Austria: An Analysis of COVID-19 in Diabetes Registry
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Faisal, Aziz, Hannah, Stöcher, Alexander, Bräuer, Christian, Ciardi, Martin, Clodi, Peter, Fasching, Mario, Karolyi, Alexandra, Kautzky-Willer, Carmen, Klammer, Oliver, Malle, Felix, Aberer, Erich, Pawelka, Slobodan, Peric, Claudia, Ress, Caren, Sourij, Lars, Stechemesser, Harald, Stingl, Thomas, Stulnig, Norbert, Tripolt, Michael, Wagner, Peter, Wolf, Andreas, Zitterl, Othmar, Moser, Christian, Schelkshorn, Susanne, Kaser, Harald, Sourij, and For The Covid-In Diabetes In Austria
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Aged, 80 and over ,Male ,COVID-19 ,SARS-CoV-2 ,diabetes mellitus ,biomarker ,Middle Aged ,Cohort Studies ,Prediabetic State ,Infectious Diseases ,Diabetes Mellitus, Type 2 ,Troponin T ,Risk Factors ,Virology ,Austria ,Humans ,Female ,Hospital Mortality ,Registries ,Biomarkers ,Aged - Abstract
Background: This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. Methods: This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or prediabetes hospitalized for COVID-19 in 11 hospitals in Austria. The primary outcome of this study was in-hospital mortality. The predictor variables included demographic characteristics, clinical parameters, comorbidities, use of medication, disease severity, and laboratory measurements of biomarkers. The association between biomarkers and in-hospital mortality was assessed using simple and multiple logistic regression analyses. The predictive performance of biomarkers was assessed using discrimination and calibration. Results: In our analysis, 70.8% had type 2 diabetes mellitus, 5.8% had type 1 diabetes mellitus, 14.9% had prediabetes, and 8.6% had other types of diabetes mellitus. The mean age was 70.3 ± 13.3 years, and 69.3% of patients were men. A total of 19.0% of patients died in the hospital. In multiple logistic regression analysis, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. The discrimination of NT-proBNP was 74%, and that of Troponin T was 81%. The calibration of NT-proBNP was adequate (p = 0.302), while it was inadequate for Troponin T (p = 0.010). Conclusion: Troponin T showed excellent predictive performance, while NT-proBNP showed good predictive performance for assessing in-hospital mortality in patients with diabetes mellitus hospitalized with COVID-19. Therefore, these cardiac biomarkers may be used for prognostication of COVID-19 patients.
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- 2022
14. Sex- and Gender-Based Pharmacological Response to Drugs
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Ilaria Campesi, Mark L. Heiman, Heiner K. Berthold, Vera Regitz-Zagrosek, Anne Z. Murphy, Santosh Dakal, Ioanna Gouni-Berthold, Franck Mauvais-Jarvis, Karen Reue, Flavia Franconi, Juan Jesus Carrero, Joshua B. Rubin, Sabra L. Klein, and Alexandra Kautzky-Willer
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Male ,0301 basic medicine ,Pharmacology ,Sex Characteristics ,business.industry ,MEDLINE ,Bioinformatics ,Precision medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Pharmaceutical Preparations ,Pharmacokinetics ,Humans ,Molecular Medicine ,Medicine ,Female ,Epigenetics ,Precision Medicine ,business ,030217 neurology & neurosurgery ,Organ system - Abstract
In humans, the combination of all sex-specific genetic, epigenetic, and hormonal influences of biologic sex produces different in vivo environments for male and female cells. We dissect how these influences of sex modify the pharmacokinetics and pharmacodynamics of multiple drugs and provide examples for common drugs acting on specific organ systems. We also discuss how gender of physicians and patients may influence the therapeutic response to drugs. We aim to highlight sex as a genetic modifier of the pharmacological response to drugs, which should be considered as a necessary step toward precision medicine that will benefit men and women. SIGNIFICANCE STATEMENT: This study discusses the influences of biologic sex on the pharmacokinetics and pharmacodynamics of drugs and provides examples for common drugs acting on specific organ systems. This study also discusses how gender of physicians and patients influence the therapeutic response to drugs.
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- 2021
15. Less sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women—a secondary analysis of the DALI study
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Frank J. Snoek, Fidelma Dunne, Sander Galjaard, Annunziata Lapolla, David Simmons, Mette Tanvig, Roland Devlieger, David J. Hill, Judith G. M. Jelsma, Erwin Stolz, Lise Lotte Torvin Andersen, Elisabeth R. Mathiesen, Maria Grazia Dalfrà, Peter Damm, Gernot Desoye, Rosa Corcoy, Juan M. Adelantado, Agnieszka Zawiejska, Alessandra Bertolotto, Jürgen Harreiter, Dorte Møller Jensen, Alexandra Kautzky-Willer, Ewa Wender-Ozegowska, Anna M. Dieberger, Mireille N M van Poppel, Obstetrics & Gynecology, Medical psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), Public and occupational health, APH - Quality of Care, and Medical Psychology
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Blood Glucose ,Lifestyle modification ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Medicine (miscellaneous) ,Body Mass Index ,0302 clinical medicine ,Pregnancy ,Insulin ,Longitudinal Studies ,030212 general & internal medicine ,Gestational diabetes ,RISK ,education.field_of_study ,Nutrition and Dietetics ,Obstetrics ,Gestational age ,GESTATIONAL DIABETES-MELLITUS ,Europe ,Gestation ,Female ,Life Sciences & Biomedicine ,Adult ,medicine.medical_specialty ,Population ,EXERCISE ,030209 endocrinology & metabolism ,Article ,Endocrinology & Metabolism ,03 medical and health sciences ,Insulin resistance ,SDG 3 - Good Health and Well-being ,HYPERGLYCEMIA ,medicine ,Vitamin D and neurology ,Humans ,Obesity ,education ,Exercise ,Life Style ,METAANALYSIS ,Science & Technology ,Nutrition & Dietetics ,business.industry ,Glucose Tolerance Test ,medicine.disease ,Pregnancy Complications ,Diabetes, Gestational ,PHYSICAL-ACTIVITY ,Insulin Resistance ,Sedentary Behavior ,business ,Body mass index - Abstract
Background/objectives Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women. Subjects/methods In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, 2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24–28 weeks and 35–37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness. Results 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (−0.137; −0.210, −0.064 and −0.133; −0.202, −0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011). Conclusions As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.
- Published
- 2021
16. Oral Contraceptive Intake and Iodine Status in Young Women
- Author
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Rodrig Marculescu, Doris Deischinger, Irina Gessl, Lana Kosi-Trebotic, Michael Krebs, Carola Deischinger, and Alexandra Kautzky-Willer
- Subjects
medicine.medical_specialty ,Adolescent ,Population ,Nutritional Status ,Medicine (miscellaneous) ,chemistry.chemical_element ,Pilot Projects ,Iodine ,Young Adult ,Pregnancy ,Prevalence ,medicine ,Humans ,education ,Iodine intake ,education.field_of_study ,Nutrition and Dietetics ,Obstetrics ,business.industry ,medicine.disease ,Urine Creatinine ,Iodine deficiency ,Iodine supplementation ,Cross-Sectional Studies ,chemistry ,Austria ,Creatinine ,Who guidelines ,Female ,Deficiency Diseases ,Urine sample ,business ,Contraceptives, Oral - Abstract
Objective: Similar to pregnant women, women taking an oral contraceptive (OC) might have elevated iodine requirements due to the altered hormonal state. This is the first study aimed at investigating the prevalence of iodine deficiency and possible influences of OC intake on urine creatinine and iodine levels in young women. Methods: One hundred fifty-five women between the age of 18 and 35 years (62 taking an OC and 93 controls) participated in a cross-sectional pilot study at the Medical University of Vienna, which included a 1-spot urine sample and a questionnaire on OC intake as well as a food questionnaire. Results: The median urinary iodine concentration (UIC) in this study was 68 μg/L (41, 111 μg/L) suggesting an inadequate iodine status in the women according to the WHO guidelines. Median UIC (OC: 89 μg/L, IQR 55–120; control: 59 μg/L, IQR 39–91, p = 0.010) and urine creatinine (OC: median = 99.0 μg/L, IQR 74.9–175.5; control: 77.0 μg/L, IQR 49.6–147.2, p = 0.030) levels were significantly higher in OC women than in the control group. UIC corrected for urine creatinine was comparable between both groups. Conclusion: With similar creatinine-corrected UICs in both groups, OC intake might not have a significant impact on iodine status. However, the low median UIC in a vulnerable group of young women potentially conceiving in the following years points at the necessity of optimizing the iodine intake in the Austrian population and reiterates the insufficiency of the current iodine supplementation measures.
- Published
- 2021
17. CTRP-1 levels are related to insulin resistance in pregnancy and gestational diabetes mellitus
- Author
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Dagmar Bancher-Todesca, Jürgen Harreiter, Sabina Baumgartner-Parzer, Carola Deischinger, Alexandra Kautzky-Willer, and Karoline Leitner
- Subjects
Adult ,Blood Glucose ,0301 basic medicine ,medicine.medical_specialty ,Waist ,endocrine system diseases ,Reproductive disorders ,medicine.medical_treatment ,Population ,lcsh:Medicine ,030209 endocrinology & metabolism ,Type 2 diabetes ,Article ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,Insulin resistance ,Pregnancy ,Internal medicine ,Glucose Intolerance ,medicine ,Humans ,Insulin ,education ,lcsh:Science ,education.field_of_study ,Multidisciplinary ,business.industry ,Postpartum Period ,lcsh:R ,Proteins ,nutritional and metabolic diseases ,Glucose Tolerance Test ,Translational research ,medicine.disease ,Gestational diabetes ,Diabetes, Gestational ,030104 developmental biology ,Gestation ,Female ,lcsh:Q ,Insulin Resistance ,business ,Biomarkers - Abstract
Recent studies have shown higher levels of CTRP-1 (C1QTNF-related protein) in patients with type 2 diabetes compared to controls. We aimed at investigating CTRP-1 in gestational diabetes mellitus (GDM). CTRP-1 levels were investigated in 167 women (93 with normal glucose tolerance (NGT), 74 GDM) of a high-risk population for GDM. GDM was further divided into GDM subtypes depending on a predominant insulin sensitivity issue (GDM-IR) or secretion deficit (GDM-IS). Glucose tolerance was assessed with indices [Matsuda index, Stumvoll first phase index, insulin-secretion-sensitivity-index 2 (ISSI-2), area-under-the-curve (AUC) insulin, AUC glucose] derived from an oral glucose tolerance test (oGTT) performed at
- Published
- 2020
18. Brown Adipose Tissue Prevalence Is Lower in Obesity but Its Metabolic Activity Is Intact
- Author
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Oana C. Kulterer, Carsten T. Herz, Marlene Prager, Christoph Schmöltzer, Felix B. Langer, Gerhard Prager, Rodrig Marculescu, Alexandra Kautzky-Willer, Marcus Hacker, Alexander R. Haug, and Florian W. Kiefer
- Subjects
Male ,Adipose Tissue, Brown ,Thinness ,Fluorodeoxyglucose F18 ,Positron-Emission Tomography ,Endocrinology, Diabetes and Metabolism ,Prevalence ,Humans ,Female ,Obesity - Abstract
Due to its high metabolic activity, brown adipose tissue (BAT) has become a promising target for the development of novel treatment concepts for metabolic disease. Despite several reports of a negative association between the presence of active BAT and obesity, very little is known about the quantitative and qualitative differences of BAT in lean and obese individuals. Systematic studies directly comparing cold-induced BAT activity in leanness and obesity are currently lacking. Here we studied BAT mass and function in 31 lean and 64 obese men and women. After a standardized cooling protocol using a water-perfused vest, 18F-FDG-positron emission tomography/computed tomography scans were performed, and BAT was delineated using lean body-mass adjusted standardized uptake value (SUV) thresholds in anatomic regions with fat radiodensity. Cold-induced thermogenesis (CIT), a functional readout of BAT activity, was quantified by indirect calorimetry. Active BAT was present in a significantly higher proportion of lean than obese individuals (58% vs. 33%, p=0.019). In these participants with active BAT, however, BAT volume and activity did not differ between leanness and obesity. Accordingly, CIT was similar in both weight groups. BAT metrics were not related to adiposity or total fat mass per se. However, in obese participants a strong negative correlation existed between visceral adipose tissue and BAT volume, 18F-FDG uptake and CIT. In summary, despite a significantly lower prevalence of BAT, the metabolic activity and thermogenic capacity of BAT appears to be still intact in obesity and is inversely associated with visceral fat mass.
- Published
- 2022
19. Lifetime risk, life expectancy, and years of life lost to type 2 diabetes in 23 high-income jurisdictions: a multinational, population-based study
- Author
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Dunya Tomic, Jedidiah I Morton, Lei Chen, Agus Salim, Edward W Gregg, Meda E Pavkov, Martti Arffman, Ran Balicer, Marta Baviera, Elise Boersma-van Dam, Ralph Brinks, Bendix Carstensen, Juliana C N Chan, Yiling J Cheng, Sandrine Fosse-Edorh, Sonsoles Fuentes, Hélène Gardiner, Hanne L Gulseth, Romualdas Gurevicius, Kyoung Hwa Ha, Annika Hoyer, György Jermendy, Alexandra Kautzky-Willer, Ilmo Keskimäki, Dae Jung Kim, Zoltán Kiss, Peter Klimek, Maya Leventer-Roberts, Chun-Yi Lin, Paz Lopez-Doriga Ruiz, Andrea O Y Luk, Stefan Ma, Manel Mata-Cases, Dídac Mauricio, Stuart McGurnaghan, Tomoaki Imamura, Sanjoy K Paul, Anna Peeters, Santa Pildava, Avi Porath, Cynthia Robitaille, Maria Carla Roncaglioni, Takehiro Sugiyama, Kang-Ling Wang, Sarah H Wild, Naama Yekutiel, Jonathan E Shaw, and Dianna J Magliano
- Subjects
Male ,Adult ,Young Adult ,Life Expectancy ,Endocrinology ,Diabetes Mellitus, Type 2 ,Incidence ,Endocrinology, Diabetes and Metabolism ,Australia ,Income ,Internal Medicine ,Humans ,Female - Abstract
BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting.; METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping.; FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1577234194), there were 5119585 incident cases of type 2 diabetes, 4007064 deaths in those with type 2 diabetes, and 11854043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years).; INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes.; FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia. Copyright © 2022 Elsevier Ltd. All rights reserved.
- Published
- 2022
20. Cardiovascular health through a sex and gender lens in six South Asian countries: Findings from the WHO STEPS surveillance
- Author
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Dev, Rubee, Raparelli, Valeria, Pilote, Louise, Azizi, Zahra, Kublickiene, Karolina, Kautzky-Willer, Alexandra, Herrero, Maria Trinidad, and Norris, Colleen M
- Subjects
Male ,Cross-Sectional Studies ,Cardiovascular Diseases ,Risk Factors ,Health Status ,Health Policy ,Public Health, Environmental and Occupational Health ,Humans ,Socio-culturale ,Female ,World Health Organization ,Retrospective Studies - Abstract
Sex and gender-based differences in cardiovascular health (CVH) has been explored in the context of high-income countries. However, these relationships have not been examined in low- and middle-income countries. The main aim of this study was to examine how sex and gender-related factors are associated with cardiovascular risk factors of people in South Asian countries.We conducted a retrospective analysis of the World Health Organization's "STEPwise approach to surveillance of risk factors for non-communicable disease" or "STEPS" from six South Asian countries, surveys conducted between 2014-2019. The main outcomes were CVH as measured by a composite measure of STEPS-HEART health index (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes and hypertension), values ranging from 0 (worst) to 6 (best or ideal) and self-reported occurrence of cardiovascular disease (ie, heart attack and stroke). Multivariate linear and logistic regression models were performed. Multiple imputation with chained equations was performed.The final analytic sample consisted of 33 106 participants (57.5% females). The mean STEPS-HEART index score in the South Asian population was 3.43 [SD: 0.92]. Female sex (β: 0.05, 95% confidence interval (CI) = 0.01-0.08,Among the South Asian population, being female may be advantageous in having an ideal CVH. However, gender-related factors such as marital status and large household size were associated with poorer CVH and greater risk of CVD, regardless of sex.
- Published
- 2022
21. Muscle‐Specific Relation of Acetylcarnitine and Intramyocellular Lipids to Chronic Hyperglycemia: A Pilot 3‐T 1 H MRS Study
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Michael Weber, Martin Krššák, Magdalena Bastian, Siegfried Trattnig, Michael Krebs, Michael Leutner, Radka Klepochová, and Alexandra Kautzky-Willer
- Subjects
Male ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Pilot Projects ,030209 endocrinology & metabolism ,Type 2 diabetes ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Tibialis anterior muscle ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,Clinical Trials and Investigations ,Intramyocellular lipids ,Muscle, Skeletal ,Acetylcarnitine ,Soleus muscle ,Nutrition and Dietetics ,business.industry ,Type 2 Diabetes Mellitus ,Skeletal muscle ,Lipid metabolism ,Original Articles ,Middle Aged ,Lipid Metabolism ,medicine.disease ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Original Article ,Female ,business ,medicine.drug - Abstract
Objective Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to intramyocellular lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (1H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control. Methods Acetylcarnitine and intramyocellular lipid concentrations were measured in 35 individuals stratified into three groups according to glucose tolerance and/or manifestation of type 2 diabetes mellitus. All MRS measurements were performed on a 3-T MR system. Results The differences in patient phenotype were mirrored by increased intramyocellular lipids in the tibialis anterior and decreased acetylcarnitine concentrations in the soleus muscle of type 2 diabetes patients when compared with normal glucose-tolerant individuals. Results suggest that intramyocellular lipids mirror whole-body glucose tolerance better in the tibialis anterior muscle, whereas acetylcarnitine is a better discriminator in the soleus muscle. Conclusions This muscle-specific behavior of metabolites could represent different fiber compositions in the examined muscles and should be considered when planning future metabolic studies.
- Published
- 2020
22. Pre-operative Obesity-Associated Hyperandrogenemia in Women and Hypogonadism in Men Have No Impact on Weight Loss Following Bariatric Surgery
- Author
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Gerhard Prager, Michael Krebs, Tamara Ranzenberger-Haider, Paul Fellinger, Alexandra Kautzky-Willer, Hannes Beiglböck, Bianca K. Itariu, and Peter Wolf
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Original Contributions ,Bariatric Surgery ,030209 endocrinology & metabolism ,Androgen Excess ,Androgen excess ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Weight loss ,Weight Loss ,Medicine ,Testosterone deficiency ,Humans ,Testosterone ,Obesity ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,Nutrition and Dietetics ,business.industry ,Hypogonadism ,Lipid metabolism ,Anthropometry ,Androgen ,medicine.disease ,Surgery ,Obesity, Morbid ,Functional hypogonadism ,Female ,medicine.symptom ,business ,Body mass index ,Hormone - Abstract
Background In severe obesity, hypogonadism in men and androgen excess in women are frequently observed. Sex hormones play an important role in body composition and glucose and lipid metabolism. However, whether pre-operative gonadal dysfunction impacts weight loss after bariatric surgery is not fully known. Methods A total of 49 men and 104 women were included in a retrospective analysis. Anthropometric characteristics, glucose and lipid metabolism, and androgen concentrations were assessed pre-operatively and 17.9 ± 11 or 19.3 ± 12 months post-operatively in men and women. Men with (HYPOmale) and without (controls: CONmale) pre-operative hypogonadism, as well as women with (HYPERfemale) and without (controls: CONfemale) pre-operative hyperandrogenemia, were compared. Results In men, pre-operative hypogonadism was present in 55% and linked to a higher body mass index (BMI): HYPOmale 50 ± 6 kg/m2 vs. CONmale 44 ± 5 kg/m2, p = 0.001. Bariatric surgery results in comparable changes in BMI in HYPOmale and CONmale − 16 ± 6 kg/m2 vs. − 14 ± 5 kg/m2, p = 0.30. Weight loss reversed hypogonadism in 93%. In women, androgen excess was present in 22%, independent of pre-operative BMI: CONfemale 44 ± 7 kg/m2 vs. HYPERfemale 45 ± 7 kg/m2, p = 0.57. Changes in BMI were comparable in HYPERfemale and CONfemale after bariatric surgery − 15 ± 6 kg/m2 vs. − 15 ± 5 kg/m2, p = 0.88. Hyperandrogenemia was reversed in 61%. Conclusions Besides being frequently observed, hypogonadism in men and androgen excess in women have no impact on post-surgical improvements in body weight and glucose and lipid metabolism. Weight loss resulted in reversal of hypogonadism in almost all men and of hyperandrogenemia in the majority of women.
- Published
- 2020
23. Micro- and macrovascular function in patients suffering from primary adrenal insufficiency: a cross-sectional case–control study
- Author
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Markus Müller, Renate Koppensteiner, Andrea Willfort-Ehringer, Anton Luger, Oliver Schlager, Peter Wolf, Michael Krebs, Paul Fellinger, Yvonne Winhofer, Alexandra Kautzky-Willer, Hannes Beiglböck, and Michael E. Gschwandtner
- Subjects
Adult ,Male ,medicine.medical_specialty ,Addison’s disease ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Carotid Intima-Media Thickness ,Plasma renin activity ,Renin–angiotensin–aldosterone system ,Primary Adrenal Insufficiency ,03 medical and health sciences ,Vascular Stiffness ,0302 clinical medicine ,Endocrinology ,Addison Disease ,Risk Factors ,Mineralocorticoid replacement therapy ,Internal medicine ,medicine ,Humans ,Reactive hyperemia ,Pulse wave velocity ,Aged ,business.industry ,Microcirculation ,Middle Aged ,Prognosis ,medicine.disease ,Glucocorticoid replacement therapy ,Cross-Sectional Studies ,Intima-media thickness ,Cardiovascular Diseases ,Austria ,Case-Control Studies ,Addison's disease ,Cardiology ,Arterial stiffness ,Original Article ,Female ,business ,Perfusion ,Follow-Up Studies - Abstract
Background Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, patients suffering from primary adrenal insufficiency (AI) have an increased mortality, mainly due to cardiovascular diseases. Only little knowledge exists on the contribution of MC substitution to the cardiovascular risk. Therefore, this study investigates the impact of plasma renin concentration on parameters of micro- and macrovascular function. Methods 26 patients with primary AI [female = 18, age: 51 (28; 78) years; BMI: 24 (18; 40) kg/m2; disease duration: 18 (5; 36) years] were included in this cross-sectional analysis. Intima media thickness (IMT) and pulse wave velocity (PWV) were investigated to assess macrovascular remodeling and arterial stiffness. Microvascular function was estimated by post-occlusive reactive hyperemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded. Patients were grouped according to their median plasma renin concentration of previous visits (Reninhigh vs Reninlow) and were compared to a group of healthy women [age: 44 (43; 46) years; BMI: 24.2 (21.8; 27.5)]. Results PWV was significantly higher in AI patients compared to controls [9.9 (5; 18.5) vs 7.3 (6.8; 7.7) m/s; p low time to peak perfusion was significantly longer [6.0 (3; 15) vs 3.5 (1.5; 11) s; p high and Reninlow. No impact of GC dose was observed. Conclusions Microvascular function is not impaired in patients with primary AI under adequate replacement therapy, although higher renin concentrations are associated with subclinical improvements. No relation between RAAS activity and macrovascular function is observed, while arterial stiffness might be increased in primary AI.
- Published
- 2020
24. Bariatric Surgery Impacts Levels of Serum Lipids during Pregnancy
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Christian S. Göbl, Michael Leutner, Wolfgang Eppel, Latife Bozkurt, and Alexandra Kautzky-Willer
- Subjects
0301 basic medicine ,Adult ,medicine.medical_specialty ,Health (social science) ,Offspring ,Birth weight ,Blood lipids ,Bariatric Surgery ,Mothers ,030209 endocrinology & metabolism ,lcsh:TX341-641 ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Physiology (medical) ,Hyperlipidemia ,medicine ,Humans ,hyperlipidemia ,gastric bypass ,triglycerides ,lcsh:RC620-627 ,Pregnancy ,030109 nutrition & dietetics ,medicine.diagnostic_test ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Lipids ,Surgery ,Obesity, Morbid ,Pregnancy Complications ,lcsh:Nutritional diseases. Deficiency diseases ,Case-Control Studies ,Gestation ,Female ,lipids (amino acids, peptides, and proteins) ,pregnancy ,Lipid profile ,business ,lcsh:Nutrition. Foods and food supply ,Lipoprotein ,Research Article - Abstract
Introduction: Bariatric surgery confers a high risk for nutritional deficiencies that could affect physiologic adaptation of lipids during pregnancy. We aimed to evaluate differences in serum lipids in pregnant women after bariatric surgery compared to obese and lean mothers. Methods: 25 women with a history of Roux-en-Y gastric bypass (RYGB), 19 obese and 19 normal-weight controls were included at the 24th–28th gestational week for determination of fasting lipids with follow-up in a subgroup after delivery. Data on neonatal biometry were additionally assessed. Results: Women after RYGB showed lower total-cholesterol (TC), low-density lipoprotein C (LDL-C), non-high-density lipoprotein C (non-HDL-C) and triglycerides (TG) compared to obese mothers. Despite their higher BMI, women after RYGB showed lower TC, LDL-C and non-HDL-C than normal-weight mothers. Ultrasensitive C-reactive protein was lower in RYGB mothers than in obese ones, reaching values of lean controls. Differences remained unchanged in BMI-matched comparison. Birth weight percentiles of RYGB offspring were associated with maternal TC (r = 0.59, p = 0.021), LDL-C (r = 0.71, p = 0.003), non-HDL (r = 0.59, p = 0.021) but not HDL-C or TG. After delivery, lipids decreased in all women; however, TC and LDL-C showed more attenuated decline in mothers after RYGB than control women. Conclusion: Pregnancies after RYGB show alterations of physiologic patterns in lipid profile. Further studies are required to evaluate whether imbalances in maternal lipids constitute a risk for abnormal fetal growth in this special cohort.
- Published
- 2020
25. Relationship between psychological stress and metabolism in morbidly obese individuals
- Author
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Hannah M. Münch, Friedrich Riffer, Elmar Kaiser, Manuel Sprung, Kathrin Heneis, Lore Streibl, and Alexandra Kautzky-Willer
- Subjects
Adult ,Male ,Adolescent ,media_common.quotation_subject ,030204 cardiovascular system & hematology ,Morbidly obese ,Anger ,medicine.disease_cause ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Weight loss ,Surveys and Questionnaires ,Humans ,Medicine ,Psychological stress ,030212 general & internal medicine ,Child ,media_common ,business.industry ,Psychological distress ,Lipid metabolism ,Feeding Behavior ,General Medicine ,medicine.disease ,Obesity ,Obesity, Morbid ,Quality of Life ,Female ,medicine.symptom ,Energy Metabolism ,business ,Body mass index ,Stress, Psychological ,Clinical psychology - Abstract
Despite evidence for a bidirectional relationship between obesity and stress-related mental disorders, the general relationship between psychological stress and metabolism is still controversial. Only few studies have addressed this relationship in morbidly obese individuals. The present study investigated the relationship between psychological distress, health-related quality of life (HRQL), eating behavior, negative emotions and body mass index (BMI), body composition and biomedical parameters of metabolism in an adult sample of 123 (94 females) morbidly obese individuals. No significant relationship was found between psychological distress and BMI, body composition or any of the parameters of metabolism; however, there was a strong and robust association between HRQL in the physical domain and BMI, body composition and several biomedical parameters of sugar and fat metabolism. The results also showed an interesting dissociation in the relationship between BMI and HRQL in the physical and psychology domains. Only little evidence was found for a relationship between eating behavior (e.g. restraint) or negative emotions (e.g. anger) and BMI, body composition and parameters of metabolism. There was, however, a significant gender difference in restraint eating. Other commonly reported gender differences in BMI, body composition, fat metabolism and liver values were also observed in this sample of morbidly obese individuals. Results from the present study highlight the relationship between HRQL in the physical domain and metabolism. Implications of these findings for weight loss treatment are discussed, emphasizing HRQL as an important treatment goal and the need for long-term psychological monitoring.
- Published
- 2019
26. Glypican-4 in pregnancy and its relation to glucose metabolism, insulin resistance and gestational diabetes mellitus status
- Author
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Carola Deischinger, Jürgen Harreiter, Karoline Leitner, Luna Wattar, Sabina Baumgartner-Parzer, and Alexandra Kautzky-Willer
- Subjects
Adult ,Blood Glucose ,Multidisciplinary ,Estradiol ,Science ,Kidney ,Article ,Diabetes, Gestational ,Glypicans ,Liver ,Pregnancy ,Medicine ,Humans ,Female ,Insulin Resistance ,Biomarkers ,Gestational diabetes ,Glycoproteins ,Glomerular Filtration Rate - Abstract
Glypican-4 (GPC-4) is an adipokine that enhances insulin receptor signaling. Plasma concentrations were found to be elevated in patients with prediabetes but reduced in type 2 diabetes mellitus. No study on Glypican-4 in pregnancy and pregnancy-related insulin resistance has been published yet. GPC-4 levels were investigated in 59 overweight women throughout their pregnancy at the Medical University of Vienna. GPC-4 levels, fasting insulin, fasting glucose, estradiol, liver and renal parameters, and markers of bone development were assessed before the
- Published
- 2021
27. Cross-Diagnosis Structural Correlates of Autistic-Like Social Communication Differences
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Kushki, Azadeh, Cardy, Robyn E., Panahandeh, Sina, Malihi, Mahan, Hammill, Christopher, Brian, Jessica, Iaboni, Alana, Taylor, Margot J., Dunne, Russell, Desoye, Gernot, Harreiter, Jürgen, Kautzky-Willer, Alexandra, Damm, Peter, Mathiesen, Elisabeth R., Jensen, Dorte M., Andersen, Liselotte L., Lapolla, Annunziata, Dalfra, Maria G., Bertolotto, Alessandra, Wender-Ozegowska, Ewa, Zawiejska, Agnieszka, Hill, David, Snoek, Frank J., Jelsma, Judith G.M., Bosmans, Judith E., and van Poppel, Mireille N.M.
- Subjects
Male ,Obsessive-Compulsive Disorder ,Autism Spectrum Disorder ,Cognitive Neuroscience ,autism spectrum disorder ,attention-deficit/hyperactivity disorder ,behavioral disciplines and activities ,Cellular and Molecular Neuroscience ,Typically developing ,obsessive–compulsive disorder ,mental disorders ,medicine ,Humans ,Attention deficit hyperactivity disorder ,Autistic Disorder ,AcademicSubjects/MED00385 ,Child ,Association (psychology) ,Language ,Social communication ,AcademicSubjects/SCI01870 ,Executive functions ,medicine.disease ,obsessive-compulsive disorder ,Attention Deficit Disorder with Hyperactivity ,Autism spectrum disorder ,Female ,Original Article ,AcademicSubjects/MED00310 ,Psychology ,Clinical psychology ,Social behavior - Abstract
Social communication differences are seen in autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive–compulsive disorder (OCD), but the brain mechanisms contributing to these differences remain largely unknown. To address this gap, we used a data-driven and diagnosis-agnostic approach to discover brain correlates of social communication differences in ASD, ADHD, and OCD, and subgroups of individuals who share similar patterns of brain-behavior associations. A machine learning pipeline (regression clustering) was used to discover the pattern of association between structural brain measures (volume, surface area, and cortical thickness) and social communication abilities. Participants (n = 416) included children with a diagnosis of ASD (n = 192, age = 12.0[5.6], 19% female), ADHD (n = 109, age = 11.1[4.1], 18% female), or OCD (n = 50, age = 12.3[4.2], 42% female), and typically developing controls (n = 65, age = 11.6[7.1], 48% female). The analyses revealed (1) associations with social communication abilities in distributed cortical and subcortical networks implicated in social behaviors, language, attention, memory, and executive functions, and (2) three data-driven, diagnosis-agnostic subgroups based on the patterns of association in the above networks. Our results suggest that different brain networks may contribute to social communication differences in subgroups that are not diagnosis-specific.
- Published
- 2021
28. Model-Based Assessment of Hepatic and Extrahepatic Insulin Clearance from Short Insulin-Modified IVGTT in Women with a History of Gestational Diabetes
- Author
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Agnese Piersanti, Noor Hasliza Binti Abdul Rahman, Christian Gobl, Laura Burattini, Alexandra Kautzky-Willer, Giovanni Pacini, Andrea Tura, and Micaela Morettini
- Subjects
Blood Glucose ,Diabetes, Gestational ,Diabetes Mellitus, Type 2 ,Pregnancy ,Humans ,Insulin ,Reproducibility of Results ,Female ,Insulin Resistance - Abstract
Insulin clearance is an integral component of insulin metabolism. Yet, little is known about separate contribution of hepatic and extrahepatic insulin clearance in type 2 diabetes and in high-risk populations, such as women who experienced gestational diabetes mellitus (pGDM). A model-based method was recently proposed to assess both contributions from 3-hour insulin-modified intravenous glucose tolerance test (IM-IVGTT); the aim of this study was to assess the reliability of short (1 hour) IM-IVGTT in the application of such model-based method and to evaluate the role of the two contributions in determining insulin clearance in pGDM. A total of 115 pGDM women and 41 who remained healthy during pregnancy (CNT) were analyzed early postpartum and underwent a 3-hour IMIVGTT. Peripheral insulin clearance (CL
- Published
- 2021
29. Awareness of sex and gender dimensions among physicians: the European federation of internal medicine assessment of gender differences in Europe (EFIM-IMAGINE) survey
- Author
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Ewelina, Biskup, Alberto M, Marra, Immacolata, Ambrosino, Elena, Barbagelata, Stefania, Basili, Jacqueline, de Graaf, Asunción, Gonzalvez-Gasch, Risto, Kaaja, Eleni, Karlafti, Dor, Lotan, Alexandra, Kautzky-Willer, Maria, Perticone, Cecilia, Politi, Karin, Schenck-Gustafsson, Andreia, Vilas-Boas, Jeanine, Roeters van Lennep, Emma A, Gans, Vera, Regitz-Zagrosek, Louise, Pilote, Marco, Proietti, Valeria, Raparelli, and Rijk, Gans
- Subjects
Europe ,Male ,Sex Factors ,Physicians ,Surveys and Questionnaires ,Internal Medicine ,Humans ,Female ,Middle Aged - Abstract
Sociocultural gender is a complex construct encompassing different aspects of individuals' life, whereas sex refers to biological factors. These terms are often misused, although they impact differently on individuals' health. Recognizing the role of sex and gender on health status is fundamental in the pursuit of a personalized medicine. Aim of the current study was to investigate the awareness in approaching clinical and research questions on the impact of sex and gender on health among European internists. Clinicians affiliated with the European Federation of Internal Medicine from 33 countries participated to the study on a voluntary basis between January 1st, 2018 and July 31st, 2019. Internists' awareness and knowledge on sex and gender issues in clinical medicine were measured by an online anonymized 7-item survey. A total of 1323 European internists responded to the survey of which 57% were women, mostly young or middle-aged (78%), and practicing in public general medicine services (74.5%). The majority (79%) recognized that sex and gender are not interchangeable terms, though a wide discrepancy exists on what clinicians think sex and gender concepts incorporate. Biological sex and sociocultural gender were recognized as determinants of health mainly in cardiovascular and autoimmune/rheumatic diseases. Up to 80% of respondents acknowledged the low participation of female individuals in trials and more than 60% the lack of sex-specific clinical guidelines. Internists also express the willingness of getting more knowledge on the impact of sex and gender in cerebrovascular/cognitive and inflammatory bowel diseases. Biological sex and sociocultural gender are factors influencing health and disease. Although awareness and knowledge remain suboptimal across European internists, most acknowledge the underrepresentation of female subjects in trials, the lack of sex-specific guidelines and the need of being more informed on sex and gender-based differences in diseases.
- Published
- 2021
30. Diabetes mellitus is associated with a higher relative risk for venous thromboembolism in females than in males
- Author
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Carola Deischinger, Elma Dervic, Stephan Nopp, Michaela Kaleta, Peter Klimek, and Alexandra Kautzky-Willer
- Subjects
Male ,Cohort Studies ,Endocrinology ,Risk Factors ,Endocrinology, Diabetes and Metabolism ,Diabetes Mellitus ,Internal Medicine ,Humans ,Infant ,Female ,Venous Thromboembolism ,General Medicine ,Retrospective Studies - Abstract
The risk for developing venous thromboembolism (VTE) is about equal in both sexes. Research suggests diabetes mellitus (DM) is a risk factor for pulmonary embolism and deep vein thrombosis, both forms of VTE. We aimed at investigating the sex-specific impact of DM on VTE risk.Medical claims data were analyzed in a retrospective, population-level cohort study in Austria between 1997 and 2014. 180,034 patients with DM were extracted and compared to 540,102 sex and age-matched controls without DM in terms of VTE risk and whether specific DM medications might modulate VTE risk.The risk to develop VTE was 1.4 times higher amongst patients with DM than controls (95% CI 1.36-1.43, p 0.001). The association of DM with newly diagnosed VTE was significantly greater in females (OR = 1.52, 95% CI 1.46-1.58, p 0.001) resulting in a relative risk increase of 1.17 (95% CI 1.11-1.23) across all age groups with a peak of 1.65 (95% CI 1.43-1.89) between 50 and 59 years. Dipeptidyl peptidase 4 inhibitors were associated with a higher risk for VTE amongst female DM patients (OR = 2.3, 95% CI 1.3-4.3, p = 0.0096).Amongst DM patients, females appear to be associated with a higher relative risk increase in VTE than males, especially during perimenopause.
- Published
- 2022
31. The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity: An Exploratory Sub-Analysis of the DALI Study
- Author
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Lilian Cristina Mendoza, Jürgen Harreiter, Gernot Desoye, David Simmons, Juan M. Adelantado, Alexandra Kautzky-Willer, Agnieszka Zawiejska, Ewa Wender-Ozegowska, Annunziata Lapolla, Maria G. Dalfra, Alessandra Bertolotto, Roland Devlieger, Fidelma Dunne, Elisabeth R. Mathiesen, Peter Damm, Lisse Lotte Andersen, Dorte Moller Jensen, David Hill, Mireille Nicoline Maria van Poppel, Rosa Corcoy, and Public and occupational health
- Subjects
EXPRESSION ,Blood Glucose ,obesity ,D SUPPLEMENTATION ,1,25-DIHYDROXYVITAMIN-D3 ,vitamin D compounds ,25OHD2 ,25OHD3 ,C3-epimer ,glucose homeostasis ,pregnancy ,D DEFICIENCY ,Calcifediol ,Cross-Sectional Studies ,Female ,Homeostasis ,Humans ,Insulin ,Obesity ,Pregnancy ,Pregnant Women ,Vitamin D ,Vitamins ,Diabetes, Gestational ,Insulin Resistance ,Insulin-Secreting Cells ,BETA-CELL FUNCTION ,RISK ,Science & Technology ,Nutrition and Dietetics ,Nutrition & Dietetics ,Diabetes ,GESTATIONAL DIABETES-MELLITUS ,Gestational ,ASSESSING INSULIN SENSITIVITY ,TOLERANCE TEST ,Life Sciences & Biomedicine ,RESISTANCE ,Food Science - Abstract
Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria
- Published
- 2022
32. Interaction between rs10830962 polymorphism in MTNR1B and lifestyle intervention on maternal and neonatal outcomes: secondary analyses of the DALI lifestyle randomized controlled trial
- Author
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Van Poppel, M. N. M., Corcoy, R., Hill, D., Simmons, D., Mendizabal, L., Zulueta, M., Simon, L., Desoye, G., Adelantado Perez, J. M., Kautzky-Willer, A., Harreiter, J., Damm, P., Mathiesen, E., Jensen, D. M., Andersen, L. L. T., Dunne, F., Lapolla, A., Dalfra, M. G., Bertolotto, A., Van Poppel, M., Jelsma, J. G. M., Snoek, F. J., Galjaard, S., Wender-Ozegowska, E., Zawiejska, A., Devlieger, R., Public and occupational health, Medical psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), APH - Quality of Care, and Medical Psychology
- Subjects
Lifestyle intervention ,Blood Glucose ,Leptin ,medicine.medical_treatment ,Medicine (miscellaneous) ,law.invention ,Randomized controlled trial ,law ,Pregnancy ,Insulin ,Gestational diabetes ,Melatonin ,Nutrition and Dietetics ,C-Peptide ,Diabetes ,Pregnancy Outcome ,Prenatal Care ,Insulin sensitivity ,Fetal Blood ,Gestational Weight Gain ,Cord blood ,Gestational ,Female ,medicine.symptom ,Diet, Healthy ,Receptor ,Adult ,medicine.medical_specialty ,Genotype ,Melatonin receptor 1B ,Polymorphism ,Alleles ,Diabetes, Gestational ,Exercise ,Humans ,Infant, Newborn ,Insulin Resistance ,Receptor, Melatonin, MT2 ,Life Style ,Polymorphism, Genetic ,Insulin resistance ,Genetic ,Internal medicine ,medicine ,Healthy ,business.industry ,MT2 ,Infant ,medicine.disease ,Newborn ,Diet ,business ,Weight gain - Abstract
Background: Interactions between polymorphisms of the melatonin receptor 1B (MTNR1B) gene and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or the healthy eating intervention is unknown. Objectives: The aim was to assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy. Methods: Women with a BMI (in kg/m2) of ≥29 (n = 436) received counseling on healthy eating (HE), physical activity (PA), or both. The control group received usual care. This secondary analysis had a factorial design with comparison of HE compared with no HE and PA compared with no PA. Maternal outcomes at 24-28 wk were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA-IR), disposition index, and development of GDM. Neonatal outcomes were cord blood leptin and C-peptide and estimated neonatal fat percentage. The interaction between receiving either the HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis. Results: GDM risk was increased in women homozygous for the G allele of rs10830962 (OR: 2.60; 95% CI: 1.34, 5.06) or rs10830963 (OR: 2.83; 95% CI: 1.24, 6.47). Significant interactions between rs10830962 and interventions were found: in women homozygous for the G allele but not in the other genotypes, the PA intervention reduced maternal fasting insulin (β: -0.16; 95% CI: -0.33, 0.02; P = 0.08) and HOMA-IR (β: -0.17; 95% CI: -0.35, 0.01; P = 0.06), and reduced cord blood leptin (β: -0.84; 95% CI: -1.42, -0.25; P = 0.01) and C-peptide (β: -0.62; 95% CI: -1.07, -0.17; P = 0.01). In heterozygous women, the HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (β: -1.6 kg; 95% CI: -2.4, -0.8 kg). No interactions were found. Conclusions: In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance, cord blood C-peptide, and cord blood leptin.
- Published
- 2021
33. Influence of Genotype and Hyperandrogenism on Sexual Function in Women With Congenital Adrenal Hyperplasia
- Author
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Sabina Baumgartner-Parzer, Hans Christian Egarter, Alexandra Kautzky-Willer, Kathrin Kirchheiner, Marie Helene Schernthaner-Reiter, Michaela Bayerle-Eder, Anton Luger, and Michael Krebs
- Subjects
Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,Genotype ,endocrine system diseases ,Sexual Behavior ,Urology ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,030232 urology & nephrology ,Physiology ,Context (language use) ,Orgasm ,urologic and male genital diseases ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Dehydroepiandrosterone sulfate ,medicine ,Humans ,Congenital adrenal hyperplasia ,Marriage ,hirsutism ,media_common ,030219 obstetrics & reproductive medicine ,Adrenal Hyperplasia, Congenital ,Dehydroepiandrosterone Sulfate ,business.industry ,Virilization ,Hyperandrogenism ,Gender Identity ,medicine.disease ,Psychiatry and Mental health ,Cross-Sectional Studies ,Phenotype ,Reproductive Medicine ,chemistry ,Female ,Steroid 21-Hydroxylase ,medicine.symptom ,Sexual function ,business - Abstract
Background Depending on CYP21A2 genotype, congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to biochemical alterations (including hyperandrogenism, hypocortisolism, and hypoaldosteronism) and a wide spectrum of phenotypic disease manifestation. The latter include life-threatening salt-wasting crises, prenatal virilization of genitalia in women (classic CAH [C-CAH]) as well as milder forms of the disease exclusively presenting with hirsutism, acne or reduced fertility (nonclassic CAH [NC-CAH]), and could influence sexual function and identity. Aim The present study evaluated sexual function, gender identification, and partner preference in women with C-CAH and NC-CAH. Methods In a cross-sectional cohort analysis, 35 female patients with CAH were divided into 2 groups: C-CAH (salt-wasting/simple virilizing; n = 17) and NC-CAH (n = 18) according to genotype and phenotype. Sexual function and sexual distress were assessed using established questionnaires, including the Female Sexual Function Index. Phenotype (defined by signs of hyperandrogenism) was assessed clinically (Ferriman-Gallwey score) and with the ovulatory function index. CYP21A2 genotype was determined by Sanger sequencing and multiplex ligation-dependent probe amplification. Sexual function was also separately analyzed in the context of clinical signs of androgenization in women with (n = 13) and without acne (n = 22). Outcomes The study outcomes were sexual function and sexual distress in relation to genotype, clinical signs of androgenization, and biochemical parameters. Results Women with NC-CAH had significantly lower orgasm scores, a trend toward lower sexual function with higher sexual distress, as well as biochemical evidence of hyperandrogenism (higher dehydroepiandrosterone sulfate and lower SHBG) and a trend toward more clinical signs of hyperandrogenism (hirsutism). Indicators of in utero and childhood androgen excess as well as the presence of acne in all patients were related to lower sexual function and higher sexual distress. Clinical signs of hyperandrogenism correlated well with cardiovascular and metabolic risk factors. Clinical Translation Women with NC-CAH and women with clinical signs of hyperandrogenism demonstrated higher distress compared to women with C-CAH and women without clinical signs of hyperandrogenism, respectively, regarding different aspects of sexual function. Conclusions These data underline the importance of early diagnosis and therapy initiation, especially in patients with NC-CAH.
- Published
- 2019
34. Glucagon-like peptide 1 (GLP-1) drives postprandial hyperinsulinemic hypoglycemia in pregnant women with a history of Roux-en-Y gastric bypass operation
- Author
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Christian S. Göbl, Wolfgang Eppel, Peter Klimek, Sabina Baumgartner-Parzer, Michael Leutner, Peter Husslein, Latife Bozkurt, Alexandra Kautzky-Willer, Stefan Thurner, Giovanni Pacini, and Jürgen Harreiter
- Subjects
Adult ,Blood Glucose ,0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Incretin ,030209 endocrinology & metabolism ,Carbohydrate metabolism ,medicine.disease_cause ,Incretins ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Glucagon-Like Peptide 1 ,Pregnancy ,Hyperinsulinism ,Insulin-Secreting Cells ,Internal medicine ,Humans ,Medicine ,Obesity ,Hyperinsulinemic hypoglycemia ,business.industry ,nutritional and metabolic diseases ,Anastomosis, Roux-en-Y ,Glucose Tolerance Test ,Lipid Metabolism ,medicine.disease ,Lipids ,Glucagon-like peptide-1 ,Diabetes, Gestational ,030104 developmental biology ,Postprandial ,Hyperglycemia ,Female ,Insulin Resistance ,business ,Postprandial Hypoglycemia ,Hormone - Abstract
The influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB.In this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed usingRYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ± 1.1% vs. 0.1 ± 0.2% in the OB and vs. 0.8 ± 0.6% in the NW groups, p 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ± 5.22% vs.5.68 ± 4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group.GLP-1 is mainly involved in the regulation of postprandial glucose metabolism and therefore especially in the development of postprandial hypoglycemia in pregnant RYGB patients, who are characterized by major alterations in glucose profiles, and thus in long-term regulation, multiple organ-related mechanisms, such as the lipid content in the liver, must be involved.
- Published
- 2019
35. Sex- and age-related differences of metabolic parameters in impaired glucose metabolism and type 2 diabetes compared to normal glucose tolerance
- Author
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Jana Vrbikova, Giovanni Pacini, Běla Bendlová, Andrea Tura, Alexandra Kautzky-Willer, and Ermanno Moro
- Subjects
Male ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Carbohydrate metabolism ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,Age related ,Glucose Intolerance ,Internal Medicine ,Humans ,Insulin ,Medicine ,Prediabetes ,Normal glucose tolerance ,business.industry ,Age Factors ,nutritional and metabolic diseases ,General Medicine ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Glucose ,Diabetes Mellitus, Type 2 ,Female ,Insulin Resistance ,business - Abstract
Aims This study analysed potential sex differences in glucose metabolism of European subjects with different degrees of glucose tolerance impairment. Methods Subjects with impaired glucose metabolism, IGM (n = 735), or type 2 diabetes, T2DM (n = 415), were compared to subjects with normal glucose tolerance, NGT (n = 422), with similar BMI. For both males (M) and females (F), 50 years threshold was used for estimation of menopausal/andropausal state. Subjects underwent 75-g OGTT for measurements of insulin sensitivity (OGIS), beta-cell function (insulinogenic index, IGIC), and overall metabolic condition, disposition index (DI). Results In IGM, OGIS did not change with age in both sexes, whereas marked reduction of IGIC was seen in F (p = 0.0003). In T2DM, again OGIS did not change with age, but M ≥ 50 yrs had reduced IGIC and DI (p Conclusions IGM did not reveal relevant changes of insulin resistance with age, but early phase insulin release deteriorated, with higher change in women. T2DM men featured age-related deterioration of glucose metabolism. In women, sex advantage seen in NGT vanished in T2DM, since glucose metabolism was overall not different than in men, both young and elderly.
- Published
- 2018
36. Project 'Backtoclinic I': An overview on the state of care of adult PKU patients in Austria
- Author
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Dorothea Möslinger, Sabine Scholl-Bürgi, Felix J. Resch, Daniela Karall, Miriam Hufgard-Leitner, Vassiliki Konstantopoulou, Thomas Scherer, Alexandra Kautzky-Willer, Marianna Beghini, Michaela Brunner-Krainz, Barbara Plecko, and Johannes Spenger
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Endocrinology, Diabetes and Metabolism ,030105 genetics & heredity ,Biochemistry ,Ambulatory Care Facilities ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Neonatal Screening ,Sex Factors ,Phenylketonurias ,Epidemiology ,Genetics ,medicine ,Humans ,Young adult ,Lost to follow-up ,Molecular Biology ,High rate ,Newborn screening ,Adult patients ,business.industry ,Age Factors ,Infant, Newborn ,nutritional and metabolic diseases ,Disease Management ,Middle Aged ,Austria ,Population study ,Female ,Lost to Follow-Up ,Gender gap ,business ,030217 neurology & neurosurgery - Abstract
Background High rates of lost to follow-up (LTFU) adult patients are a major concern in the long-term management of phenylketonuria (PKU). To address this issue, we designed the project “Backtoclinic” with the purpose of identifying LTFU adult PKU patients in Austria as a first step to reestablish appropriate treatment. Subjects and methods Individuals born between 1966 and 1999 and diagnosed with PKU through the National Austrian Newborn Screening Program (NANSP) were identified using the NANSP's database. Follow-up data were collected in the Austrian metabolic centers (Medical University of Vienna, Graz, Innsbruck and Salzburg). Patients with no contact to any of these centers within the previous two years were classified as LTFU. Epidemiological characteristics of the whole study population as well as of LTFU- and currently in follow-up patients were analyzed. Results Between 1966 and 1999, 281 individuals were diagnosed with PKU through the NANSP. Two patients died in their first year of life and were excluded from the analysis. Of the remaining 279 patients (mean age ± SD: 36.7 ± 9.1 y, 42.7% females), 177 (63.4%) are currently LTFU. The rate of LTFU patients is higher in men than in women (68.1% vs 57.5%), and markedly increases with age in both sexes. The gender gap is greatest in young adults (52.6% vs. 25.0% in the age range 20.0–24.9 y) and declines with age (94.4% vs. 80.0% in the age range > 45.0 y). Conclusions We found an alarming rate of 63.4% of LTFU adult PKU patients in Austria, and observed a gender gap in the PKU state of care. Our findings illustrate the urgent need for the metabolic community to identify LTFU adult PKU patients and to develop strategies to reestablish appropriate treatment for men and women with PKU.
- Published
- 2021
37. Diabetes Mellitus is Associated with a Higher Relative Risk for Parkinson's Disease in Women than in Men
- Author
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Peter Klimek, Elma Dervic, Carola Deischinger, Alexandra Kautzky-Willer, and Michaela Kaleta
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Parkinson's disease ,Population ,Disease ,Newly diagnosed ,Diabetes Complications ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Risk Factors ,Diabetes mellitus ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,Risk factor ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Parkinson Disease ,Odds ratio ,Middle Aged ,medicine.disease ,030104 developmental biology ,Cross-Sectional Studies ,Relative risk ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background: In general, the risk to develop Parkinson’s disease (PD) is higher in men compared to women. Besides male sex and genetics, research suggests diabetes mellitus (DM) is a risk factor for PD as well. Objective: In this population-level study, we aimed at investigating the sex-specific impact of DM on the risk of developing PD. Methods: Medical claims data were analyzed in a cross-sectional study in the Austrian population between 1997 and 2014. In the age group of 40–79 and 80+, 235,268 patients (46.6%females, 53.4%males) with DM were extracted and compared to 1,938,173 non-diabetic controls (51.9%females, 48.1%males) in terms of risk of developing PD. Results: Men with DM had a 1.46 times increased odds ratio (OR) to be diagnosed with PD compared to non-diabetic men (95%CI 1.38–1.54, p
- Published
- 2021
38. Diabetes and Pregnancy
- Author
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B. Pawlowski, Thierry Somville, Christoph Bührer, M. Sorger, Helmut Kleinwechter, Ute Schäfer-Graf, K. Schunck, Franz Kainer, Irene Hoesli, and Alexandra Kautzky-Willer
- Subjects
medicine.medical_specialty ,Pregnancy ,Obstetrics ,business.industry ,Endocrinology, Diabetes and Metabolism ,Pregnancy, High-Risk ,MEDLINE ,Infant, Newborn ,Pregnancy in Diabetics ,General Medicine ,medicine.disease ,Diabetes Mellitus, Type 1 ,Endocrinology ,Diabetes Mellitus, Type 2 ,Diabetes mellitus ,Germany ,Internal Medicine ,medicine ,Humans ,Female ,Neonatology ,business - Published
- 2021
39. Determinants of perceived health and unmet healthcare needs in universal healthcare systems with high gender equality
- Author
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Louise Pilote, Karolina Kublickiene, Teresa Gisinger, Alexandra Kautzky-Willer, Maria Herrero, Colleen M. Norris, Christina P. Tadiri, and Valeria Raparelli
- Subjects
Gender Equity ,Male ,medicine.medical_specialty ,Canada ,media_common.quotation_subject ,Health Status ,Immigration ,Socio-culturale ,Country/cultural determinants of health ,Health Services Accessibility ,03 medical and health sciences ,Social determinants of health ,0302 clinical medicine ,5. Gender equality ,Epidemiology ,Health care ,medicine ,Humans ,030212 general & internal medicine ,10. No inequality ,media_common ,Health Services Needs and Demand ,Public health ,030505 public health ,Patient-reported outcomes ,business.industry ,Public Health, Environmental and Occupational Health ,3. Good health ,Socioeconomic Factors ,Scale (social sciences) ,Austria ,Marital status ,Universal Health Care ,Female ,Biostatistics ,Public aspects of medicine ,RA1-1270 ,0305 other medical science ,business ,Delivery of Health Care ,Demography ,Research Article - Abstract
Background Patient attitudes about health and healthcare have emerged as important outcomes to assess in clinical studies. Gender is increasingly recognized as an intersectional social construct that may influence health. Our objective was to determine potential sex differences in self-reported overall health and access to healthcare and whether those differences are influenced by individual social factors in two relatively similar countries. Methods Two public health surveys from countries with high gender equality (measured by UN GII) and universal healthcare systems, Canada (CCHS2014, n = 57,041) and Austria (AT-HIS2014, n = 15,212), were analysed. Perceived health was assessed on a scale of 1 (very bad) to 4 (very good) and perceived unmet healthcare needs was reported as a dichotomous variable (yes/no). Interactions between sex and social determinants (i.e. employment, education level, immigration and marital status) on outcomes were analysed. Results Individuals in both countries reported high perceived health (Scoring > 2, 85.0% in Canada, 79.9% in Austria) and a low percentage reported unmet healthcare needs (4.6% in Canada, 10.7% in Austria). In both countries, sex and several social factors were associated with high perceived health, and a sex-by-marital status interaction was observed, with a greater negative impact of divorce for men. Female sex was positively associated with unmet care needs in both countries, and sex-by-social factors interactions were only detected in Canada. Conclusions The intersection of sex and social factors in influencing patient-relevant outcomes varies even among countries with similar healthcare and high gender equality.
- Published
- 2021
40. Sex, Gender, and Cardiovascular Health in Canadian and Austrian Populations
- Author
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Karolina Kublickiene, Louise Pilote, Zahra Azizi, Teresa Gisinger, Valeria Raparelli, Carola Deischinger, Alexandra Kautzky-Willer, Khaled El Emam, Maria Herrero, Uri Bender, and Colleen M. Norris
- Subjects
Male ,Canada ,Heart disease ,Cardiovascular health ,Health Status ,Socio-culturale ,Overweight ,Interquartile range ,Diabetes mellitus ,Surveys and Questionnaires ,Vegetables ,Diabetes Mellitus ,Medicine ,Humans ,Sex Distribution ,LS4_7 ,business.industry ,Smoking ,Middle Aged ,medicine.disease ,Obesity ,Confidence interval ,Diet ,Cross-Sectional Studies ,Cardiovascular Diseases ,Austria ,Fruit ,Community health ,Hypertension ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Demography - Abstract
Background Evidence differentiating the effect of biological sex from psychosociocultural factors (gender) in different societies and its relation to cardiovascular diseases is scarce. We explored the association between sex, gender, and cardiovascular health (CVH) among Canadian (CAN) and Austrian (AT) populations. Methods The Canadian Community Health Survey (CCHS) (n = 63,522; 55% female) and Austrian Health Interview Survey (AT-HIS) (n = 15,771; 56% female) were analyzed in a cross-sectional survey design. The CANHEART/ATHEART index, a measure of ideal CVH composed of 6 cardiometabolic risk factors (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes, and hypertension; range 0-6; higher scores reflecting better CVH) was calculated for both databases. A composite measure of psychosociocultural gender was computed for each country (range 0-1, higher score identifying characteristics traditionally ascribed to women). Results Median CANHEART 4 (interquartile range 3-5) and CAN gender scores 0.55 (0.49-0.60) were similar to median ATHEART 4 (3-5) and AT gender scores 0.55 (0.46-0.64). Although higher gender scores (CCHS: β = −1.33, 95% confidence interval [CI] −1.44 to −1.22; AT-HIS: β = −1.08, 95% CI −1.26 to −0.89)) were associated with worse CVH, female sex (CCHS: β = 0.35, 95% CI (0.33-0.37); AT-HIS: β = 0.60, 95% CI (0.55-0.64)) was associated with better CVH in both populations. In addition, higher gender scores were associated with increased prevalence of heart disease compared with female sex. The magnitude of this risk was higher in Austrians. Conclusions These results demonstrate that individuals with characteristics typically ascribed to women reported poorer cardiovascular health and higher risk of heart disease, independently from biological sex and baseline CV risk factors, in both countries. Female sex exhibited better CV health and a lower prevalence of heart disease than male in both populations. However, gender factors and magnitude of gender impact varied by country.
- Published
- 2021
41. RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy
- Author
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Shane J. F. Cronin, Dagmar Bancher-Todesca, Magdalena Paolino, Jürgen Harreiter, Josef M. Penninger, Verena Sigl, Andrea J. White, Iris Uribesalgo, Georg A. Holländer, Lukas Kenner, Alexandra Kautzky-Willer, Esther Rauscher, Michael Schuster, Christoph Bock, Rubina Koglgruber, Thomas Penz, Blanka Pranjic, Juan Pablo Fededa, Maria Novatchkova, Graham Anderson, and Sabine Dekan
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Placenta ,Adipose tissue ,030209 endocrinology & metabolism ,Thymus Gland ,Biology ,Intra-Abdominal Fat ,T-Lymphocytes, Regulatory ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Fetus ,Pregnancy ,Internal medicine ,Glucose Intolerance ,medicine ,Fetal macrosomia ,Adipocytes ,Glucose homeostasis ,Animals ,Humans ,Fetal Death ,Cell Proliferation ,Thymic involution ,Mice, Inbred BALB C ,Multidisciplinary ,Receptor Activator of Nuclear Factor-kappa B ,Epithelial Cells ,medicine.disease ,Transplantation ,Gestational diabetes ,Mice, Inbred C57BL ,Diabetes, Gestational ,030104 developmental biology ,Endocrinology ,Glucose ,Female ,Transcription Factors - Abstract
Successful pregnancies rely on adaptations within the mother1, including marked changes within the immune system2. It has long been known that the thymus, the central lymphoid organ, changes markedly during pregnancy3. However, the molecular basis and importance of this process remain largely obscure. Here we show that the osteoclast differentiation receptor RANK4,5 couples female sex hormones to the rewiring of the thymus during pregnancy. Genetic deletion of Rank (also known as Tnfrsf11a) in thymic epithelial cells results in impaired thymic involution and blunted expansion of natural regulatory T (Treg) cells in pregnant female mice. Sex hormones, in particular progesterone, drive the development of thymic Treg cells through RANK in a manner that depends on AIRE+ medullary thymic epithelial cells. The depletion of Rank in the mouse thymic epithelium results in reduced accumulation of natural Treg cells in the placenta, and an increase in the number of miscarriages. Thymic deletion of Rank also results in impaired accumulation of Treg cells in visceral adipose tissue, and is associated with enlarged adipocyte size, tissue inflammation, enhanced maternal glucose intolerance, fetal macrosomia, and a long-lasting transgenerational alteration in glucose homeostasis, which are all key hallmarks of gestational diabetes. Transplantation of Treg cells rescued fetal loss, maternal glucose intolerance and fetal macrosomia. In human pregnancies, we found that gestational diabetes also correlates with a reduced number of Treg cells in the placenta. Our findings show that RANK promotes the hormone-mediated development of thymic Treg cells during pregnancy, and expand the functional role of maternal Treg cells to the development of gestational diabetes and the transgenerational metabolic rewiring of glucose homeostasis.
- Published
- 2020
42. COVID‐19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission
- Author
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Caren Sourij, Christian Ciardi, Erich Pawelka, Alexander Bräuer, Peter Wolf, Susanne Kaser, Norbert J. Tripolt, Claudia Ress, Carmen Klammer, Harald Stingl, Martin Clodi, Thomas M. Stulnig, Faisal Aziz, Abderrahim Oulhaj, Slobodan Peric, Harald Sourij, Peter Fasching, Alexandra Kautzky-Willer, Andreas Zitterl, Lars Stechemesser, Mario Karolyi, Michael Wagner, and Oliver Malle
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Logistic regression ,Risk Assessment ,Prediabetic State ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Patient Admission ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Internal Medicine ,Health Status Indicators ,Humans ,Prediabetes ,Hospital Mortality ,Prospective Studies ,Aged ,Retrospective Studies ,Type 1 diabetes ,Framingham Risk Score ,business.industry ,SARS-CoV-2 ,Mortality rate ,coronavirus infection, diabetes, prediabetic state ,COVID-19 ,Original Articles ,Length of Stay ,Middle Aged ,medicine.disease ,Hospitals ,Diabetes Mellitus, Type 2 ,Austria ,Original Article ,Female ,business ,Cohort study - Abstract
Aim To assess predictors of in‐hospital mortality in people with prediabetes and diabetes hospitalized for COVID‐19 infection and to develop a risk score for identifying those at the greatest risk of a fatal outcome. Materials and Methods A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID‐19. The primary outcome was in‐hospital mortality and the predictor variables upon admission included clinical data, co‐morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in‐hospital mortality. Results The mean age of people hospitalized (n = 238) for COVID‐19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance (P = .128). A score including age, arterial occlusive disease, C‐reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in‐hospital mortality with a C‐statistic of 0.889 (95% CI: 0.837‐0.941) and calibration of 1.000 (P = .909). Conclusions The in‐hospital mortality for COVID‐19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in‐hospital mortality.
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- 2020
43. HbA1c during early pregnancy reflects beta-cell dysfunction in women developing GDM
- Author
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Giovanni Pacini, Karoline Leitner, Latife Bozkurt, Alexandra Kautzky-Willer, and Christian S. Göbl
- Subjects
Research design ,medicine.medical_specialty ,Cardiovascular and Metabolic Risk ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Prediabetic State ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Pregnancy ,Diabetes mellitus ,insulin resistance ,Glucose Intolerance ,Medicine ,Humans ,Glycated Hemoglobin ,030219 obstetrics & reproductive medicine ,lcsh:RC648-665 ,diabetes ,business.industry ,Obstetrics ,Insulin ,nutritional and metabolic diseases ,Glucose Tolerance Test ,medicine.disease ,Gestational diabetes ,Diabetes, Gestational ,glycated hemoglobin A ,Gestation ,Female ,Hemoglobin ,business ,gestational - Abstract
IntroductionIt is of current interest to assess eligibility of hemoglobin A1c (HbA1c) as a screening tool for earlier identification of women with risk for more severe hyperglycemia in pregnancy but data regarding accuracy are controversial. We aimed to evaluate if HbA1c mirrors pathophysiological precursors of glucose intolerance in early pregnancy that characterize women who develop gestational diabetes mellitus (GDM).Research design and methods220 pregnant women underwent an HbA1c measurement as well as an oral glucose tolerance test (OGTT) with multiple measurements of glucose, insulin and C-peptide for evaluation of insulin sensitivity and beta-cell function at 16th gestational week (IQR: 14–18). Clinical follow-ups were performed until end of pregnancy.ResultsIncreased maternal HbA1c ≥5.7% (39 mmol/mol) corresponding to pre-diabetes outside of pregnancy was associated with altered glucose dynamics during the OGTT. Pregnancies with early HbA1c ≥5.7% showed higher fasting (90.4±13.2 vs 79.7±7.2 mg/dL, pConclusionsHbA1c measured before recommended routine screening period reflects early pathophysiological derangements in beta-cell function and glucose disposal that are characteristic of GDM development and may be useful in early risk stratification.
- Published
- 2020
44. Biological and Psychological Stress Correlates Are Linked to Glucose Metabolism, Obesity, and Gender Roles in Women
- Author
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Karin Stengg, Alexander Kautzky, Alexandra Kautzky-Willer, Sabine Fröhlich, and Kathrin Heneis
- Subjects
Adult ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Perceived Stress Scale ,030209 endocrinology & metabolism ,Overweight ,Gender Role ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Internal medicine ,Medicine ,Humans ,Obesity ,Aged ,Glucose Metabolism Disorders ,Endocrine and Autonomic Systems ,business.industry ,Middle Aged ,medicine.disease ,Bem Sex-Role Inventory ,Cardiovascular Diseases ,Lean body mass ,Female ,medicine.symptom ,business ,Psychosocial ,Body mass index ,Stress, Psychological ,Clinical psychology ,Research Article - Abstract
Objectives: Psychological stress affects central as well as peripheral metabolism and hormone trafficking via the hypothalamic-pituitary-adrenal axis. Stress thereby plays a decisive role in the etiology and progression of overweight and obesity, leading to several chronic diseases, such as diabetes, and mental health disorders. The interplay of biological and psychometric correlates of stress, anthropometric, immunological, and metabolic parameters and psychosocial factors such as gender roles, however, remains poorly understood. Methods: In this exploratory study, 43 healthy women were assessed for glucose metabolism by an oral glucose tolerance test and computation of functional parameters for insulin secretion, sensitivity, and resistance. Further, the fatty liver index (FLI) and anthropometric parameters body mass index (BMI), waist-to-hip ratio, body fat, and lean mass were assessed. Psychological stress assessment included the “Brief Symptom Inventory” (BSI), the “Burnout Dimensions Inventory” (BODI), and Perceived Stress Scale (PSS). Biological stress response was evaluated with heart rate variability and cortisol levels. Finally, gender role self-identification was assessed with the “Bem Sex-Role Inventory” (BSRI). Generalized linear models were computed for exploratory association with psychometric outcome. Uncorrected p values are reported. Results: Burnout and PSS scores were associated with insulin secretion, sputum cortisol, thyroid-stimulating hormone, anthropometric measures, and gender role. BSI ratings for psychiatric symptom dimensions were associated with insulin resistance, sex hormones, anthropometric measures, and gender role. Female self-identification was associated with higher BMI as well as body fat and a higher FLI. Conclusions: Considering the increased risk of unfavorable metabolic, cardiovascular, and also mental health outcome in obese women, a higher BMI in women with predominant female gender self-identification may be relevant for clinical risk assessment. The broad range of interacting biological, psychological, and gender-related parameters calls for an integrative management of both mental and endocrinological health. However, the exploratory nature of the study requires replication in larger samples before definite conclusion can be drawn.
- Published
- 2020
45. Do Women with Diabetes Need More Intensive Action for Cardiovascular Reduction than Men with Diabetes?
- Author
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Helena Fadl, David Simmons, Juergen Harreiter, and Alexandra Kautzky-Willer
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,Macrovascular Complications in Diabetes (VR Aroda and L-S Chang, Section Editors) ,030209 endocrinology & metabolism ,Type 2 diabetes ,Disease ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Diabetes mellitus ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Diabetes management ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Mass Screening ,Sex hormones ,education ,Gestational diabetes ,CVD risk factors ,education.field_of_study ,business.industry ,Prevention ,Absolute risk reduction ,Gender ,Cardiovascular disease ,medicine.disease ,Lipids ,Diabetes, Gestational ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Relative risk ,Female ,Sex ,business - Abstract
Purpose of ReviewThis narrative review makes the case for greater efforts to reduce cardiovascular disease (CVD) risk in women with diabetes.Recent FindingsIn a recent meta-analysis including five CVOTs of diabetes medications with 46,606 subjects, women (vs men) with type 2 diabetes had a higher relative risk for stroke (RR 1.28; 95% CI 1.09, 1.50) and heart failure (1.30; 1.21, 1.40). Prior studies found higher “within-gender” RR for CVD mortality in women with diabetes although men have an absolute higher risk. Women with prior gestational diabetes mellitus (GDM) have a 2-fold higher CVD risk than the background population. Worse CVD and CVD risk factor management in women, as well as lower female therapy adherence, contribute further to these disparities.SummaryThe mechanism behind this excess risk includes biological, hormonal, socioeconomic, clinical, and behavioral factors that still require further investigation. The need for more intensive CVD reduction in women now includes more attention to screening for both incident diabetes and CVD risk factors among high-risk women.
- Published
- 2020
46. Increase in testosterone levels is related to a lower risk of conversion of prediabetes to manifest diabetes in prediabetic males
- Author
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Sonja Nistler, Luise Bellach, Peter Klimek, Caspar Matzhold, Robert Winker, Georg Endler, Stefan Thurner, Alexandra Kautzky-Willer, Michael Leutner, and Evelyne Wohlschläger-Krenn
- Subjects
0301 basic medicine ,Blood Glucose ,Male ,medicine.medical_specialty ,030209 endocrinology & metabolism ,Carbohydrate metabolism ,Lower risk ,Prediabetic State ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,Medicine ,Humans ,Testosterone ,Prediabetes ,business.industry ,Fatty liver ,Testosterone (patch) ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,Endocrinology ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Homeostatic model assessment ,Female ,Insulin Resistance ,business - Abstract
Summary Background Testosterone plays an important role in the regulation of glucose metabolism. While earlier studies have shown that it has a protective effect in males, unfavorable effects of testosterone on glucose metabolism have been reported in females; however, whether there is a sex-specific relationship between testosterone and glucose metabolism in patients with prediabetes has not been investigated in detail hitherto. Methods This cross-sectional analysis investigated 423 males and 287 females with diagnosed prediabetes. Detailed assessment of their metabolic profiles was performed, including a 2‑h oral glucose tolerance test (OGTT), HbA1c levels, calculation of insulin resistance with homeostatic model assessment for insulin resistance (HOMA-IR), assessment of lipid metabolism, anthropometric parameters and the fatty liver index (FLI). By using Spearman’s correlation test, we investigated the sex-specific relationship between testosterone and metabolism in the prediabetic individuals. Results In the present study, prediabetic females (mean age 58.6 years, confidence interval [CI: 57.6 y; 59.5 y]) were characterized by lower fasting plasma glucose levels (104.2 mg/dl [CI: 103.0 mg/dl; 105.4 mg/dl] vs. 106.9 mg/dl [CI: 106.0 mg/dl; 107.8 mg/dl]) and a lower FLI (49.5 [CI: 45.7; 53.2] vs. 58.8 [CI: 55.8; 61.8]), but presented with a higher risk of developing manifest type 2 diabetes in the next 10 years (FINDRISK score: 17.6 [CI: 17.1; 18.1] vs. 16.1 [CI: 15.7; 16.5]) when compared to prediabetic males (mean age: 58.04 years [CI: 57.0 y; 59.1 y]). Testosterone was negatively related to insulin resistance (HOMA-IR: Spearman’s ρ: −0.33, p p p Conclusion The increase of testosterone levels in males was related to a more favorable glucose metabolism, including lower HbA1c, lower stimulated glucose levels and higher insulin sensitivity; however, in prediabetic females, testosterone was not related to glucose metabolism.
- Published
- 2020
47. Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality
- Author
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Engelbert Knosp, Greisa Vila, Alexandra Kautzky-Willer, Christian Zauner, Christian Scheuba, Stefan Wolfsberger, Alexander Micko, Christina Siess, Marie Helene Schernthaner-Reiter, Philipp Riss, and Anton Luger
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multivariate analysis ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Context (language use) ,Hypokalemia ,Disease ,030204 cardiovascular system & hematology ,Malignancy ,Infections ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Cushing syndrome ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Neoplasms ,Thromboembolism ,medicine ,Prevalence ,Humans ,Cushing Syndrome ,Retrospective Studies ,business.industry ,Biochemistry (medical) ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Prognosis ,Survival Rate ,chemistry ,Austria ,Female ,Glycated hemoglobin ,medicine.symptom ,business ,Follow-Up Studies - Abstract
Context Cushing syndrome (CS) results in significant morbidity and mortality. Objective To study acute and life-threatening complications in patients with active CS. Methods We performed a retrospective cohort study using inpatient and outpatient records of patients with CS in a tertiary center. A total of 242 patients with CS were included, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. We collected acute complications necessitating hospitalization, from appearance of first symptoms of hypercortisolism until 1 year after biochemical remission. Mortality data were obtained from the national registry. Baseline factors relating to and predicting acute complications were tested using uni- and multivariate analysis. Results The prevalence of acute complications was 62% in patients with benign pituitary CS, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Complications observed in patients with benign CS included infections (25%), thromboembolic events (17%), hypokalemia (13%), hypertensive crises (9%), cardiac arrhythmias (5%), and acute coronary events (3%). Among these patients, 23% had already been hospitalized for acute complications before CS was suspected, and half of complications occurred after the first surgery. Glycated hemoglobin (HbA1c) and 24-hour urinary free cortisol positively correlated with the number of acute complications per patient. Patients with malignant disease had significantly higher rates of acute complications. Mortality during the observation period was 2.8% and 59% in benign and malignant CS, respectively. Conclusions This analysis highlights the whole spectrum of acute and life-threatening complications in CS, and their high prevalence even before disease diagnosis and after successful surgery.
- Published
- 2020
48. Sex-specific trends in smoking prevalence over seven years in different Austrian populations: results of a time-series cross-sectional analysis
- Author
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Thomas Dorner, Alexandra Kautzky-Willer, and Helmut Brath
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Cross-sectional study ,Population ,Logistic regression ,preventive medicine ,Risk Factors ,general medicine (see internal medicine) ,Diabetes mellitus ,Epidemiology ,medicine ,Prevalence ,Humans ,education ,Preventive healthcare ,education.field_of_study ,business.industry ,Public health ,general diabetes ,Smoking ,public health ,health policy ,General Medicine ,Middle Aged ,medicine.disease ,Obesity ,Cross-Sectional Studies ,Austria ,Medicine ,Female ,epidemiology ,business ,Demography - Abstract
ObjectivesAim of this study was to examine trends over time in smoking status in men and women, and in subgroups, in Austria, a country with poor smoking regulation policies.Design and participantsTwo cross-sectional surveys (Austrian Health Interview Surveys for 2007 and 2014), each with more than 15 000 participants from the general population, aged ≥15 years.Outcome measuresPrevalence of self-reported daily smoking. ORs for daily smoking in subgroups, presented as results of logistic regression models, adjusted for sociodemographic variables and presence of chronic diseases.ResultsPrevalence of daily cigarette smoking was 26.0% for men in both years, and increased from 19.1% to 22.0% (pConclusionsThere has been a remarkable increase in smoking prevalence over the 7-year period in women in Austria, especially for those with chronic diseases, higher age, lower education and a migration background. Better political and clinical efforts are needed to reduce the high tobacco use in Austria.
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- 2020
49. Diabetes mellitus is associated with a higher risk for major depressive disorder in women than in men
- Author
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Michael Leutner, Lana Kosi-Trebotic, Peter Klimek, Alexander Kautzky, Elma Dervic, Carola Deischinger, and Alexandra Kautzky-Willer
- Subjects
Adult ,Male ,medicine.medical_specialty ,obesity ,Endocrinology, Diabetes and Metabolism ,Population ,Overweight ,Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Prevalence ,Medicine ,Humans ,Risk factor ,education ,Depression (differential diagnoses) ,Aged ,education.field_of_study ,Depressive Disorder, Major ,business.industry ,Middle Aged ,medicine.disease ,RC648-665 ,Obesity ,030227 psychiatry ,Cross-Sectional Studies ,type 2 ,Cohort ,diabetes mellitus ,depression ,Major depressive disorder ,Epidemiology/Health services research ,Female ,medicine.symptom ,sex characteristics ,business ,030217 neurology & neurosurgery - Abstract
IntroductionBoth diabetes mellitus and being female significantly increase the risk of being diagnosed with major depressive disorder (MDD). The diagnosis of MDD, combined with diabetes mellitus, can be detrimental in terms of mortality and morbidity. We aimed at investigating the impact of diabetes mellitus on the gender gap in MDD over the course of a human lifetime.Research design and methodsIn a cross-sectional study over the course of 17 years, medical claims data of the general Austrian population (n=8 996 916) between 1997 and 2014 was analyzed. Of these, 123 232 patients with diabetes mellitus were extracted and compared with non-diabetic controls.ResultsIn a cohort of 123 232 patients with diabetes mellitus and 1 933 218 controls (52% females, 48% males), women with diabetes had 2.55 times increased ORs to be diagnosed with MDD compared with women without diabetes (95% CI 2.48 to 2.62, pConclusionsDiabetes mellitus is a stronger risk factor for MDD in women than in men, with the greatest width of the gender gap between 40 and 49 years. High-risk patients for MDD, such as overweight female patients with diabetes, should be more carefully assessed and monitored.
- Published
- 2020
50. Betatrophin is downregulated in pregnant women with a history of RYGB operation and a high risk of postprandial hypoglycaemia
- Author
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Peter Klimek, Caspar Matzhold, Michael Leutner, Stefan Thurner, Luise Bellach, Carola Deischinger, and Alexandra Kautzky-Willer
- Subjects
Adult ,0301 basic medicine ,medicine.medical_specialty ,Betatrophin ,Peptide Hormones ,Gastric Bypass ,lcsh:Medicine ,Adipose tissue ,Article ,Obesity, Maternal ,03 medical and health sciences ,0302 clinical medicine ,Angiopoietin-Like Protein 8 ,Pregnancy ,Risk Factors ,Internal medicine ,medicine ,Humans ,Obesity ,Prospective Studies ,lcsh:Science ,Prospective cohort study ,Gestational diabetes ,Multidisciplinary ,business.industry ,lcsh:R ,nutritional and metabolic diseases ,medicine.disease ,Hypoglycemia ,Angiopoietin-like Proteins ,030104 developmental biology ,Postprandial ,Endocrinology ,Basal (medicine) ,Cohort ,Female ,lcsh:Q ,business ,030217 neurology & neurosurgery - Abstract
Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. So far, no data exist about the role of betatrophin in pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation with a high risk of postprandial hypoglycaemia. In this prospective clinical study, an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed between the 24th and 28th week of pregnancy and 3–6 months post-partum in a cohort of obese and normal-weight pregnant women, as well as in women with a history of RYGB operation. In the cohort of pregnant women with RYGB and exaggerated risk of postprandial hypoglycaemic events, basal and dynamic betatrophin levels during the OGTT were lower than in the obese or normal-weight pregnant women (basal levels: 13.66 ± 5.88 vs. 19.03 ± 4.15 vs. 15.68 ± 6.48, p = 0.016; OGTT 60′: 13.33 ± 5.40 vs. 17.37 ± 3.16 vs. 15.84 ± 4.99, p = 0.030). During the OGTT, basal and dynamic betatrophin levels at 60′ were positively associated with glucose levels at 60 min (r = 0.55, p = 0.01 and r = 0.45, p = 0.039). This positive association was followed by significant hypoglycaemic events in the RYGB group. It was only in the RYGB group that betatrophin was negatively related to the disposition index (rho = -0.53, p = 0.014). After pregnancy there was a decrease in basal and stimulated betatrophin levels during the OGTT in all three patient groups. In comparison to normal-weight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort.
- Published
- 2020
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