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We aim to comprehensively identify typical life-spanning trajectories and critical events that impact patients' hospital utilization and mortality. We use a unique dataset containing 44 million records of almost all inpatient stays from 2003 to 2014 in Austria to investigate disease trajectories. We develop a new, multilayer disease network approach to quantitatively analyze how cooccurrences of two or more diagnoses form and evolve over the life course of patients. Nodes represent diagnoses in age groups of ten years; each age group makes up a layer of the comorbidity multilayer network. Inter-layer links encode a significant correlation between diagnoses (p < 0.001, relative risk > 1.5), while intra-layers links encode correlations between diagnoses across different age groups. We use an unsupervised clustering algorithm for detecting typical disease trajectories as overlapping clusters in the multilayer comorbidity network. We identify critical events in a patient's career as points where initially overlapping trajectories start to diverge towards different states. We identified 1260 distinct disease trajectories (618 for females, 642 for males) that on average contain 9 (IQR 2–6) different diagnoses that cover over up to 70 years (mean 23 years). We found 70 pairs of diverging trajectories that share some diagnoses at younger ages but develop into markedly different groups of diagnoses at older ages. The disease trajectory framework can help us to identify critical events as specific combinations of risk factors that put patients at high risk for different diagnoses decades later. Our findings enable a data-driven integration of personalized life-course perspectives into clinical decision-making. [ABSTRACT FROM AUTHOR]

Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T. [ABSTRACT FROM AUTHOR]

Introduction: Gremlin-1 is a peptide that functions as an antagonist to bone morphogenic proteins and is overexpressed in obesity and type 2 diabetes mellitus. Gremlin-1 has not yet been investigated in pregnancy, pregnancy-related insulin resistance or gestational diabetes mellitus (GDM). Patients and methods: Gremlin-1 levels were measured throughout the pregnancy of 58 women at high risk for GDM at the Medical University of Vienna. Furthermore, an oral glucose tolerance test, fasting insulin, fasting glucose, sex hormones, blood lipids, liver and renal parameters, and markers of bone development were evaluated at two points during pregnancy (< 20 weeks of gestation (GW), GW 24–28) and 12–14 weeks postpartum. Results: Gremlin-1 levels decreased from < 20 GW (mean = 9.2 pg/ml, SD = 8.4 pg/ml) to GW 24–28 (mean = 6.7 pg/ml, SD = 5.7 pg/ml, p = 0.033) and increased again postpartum, albeit not significantly (mean = 10.7 pg/ml, SD = 13.1 pg/ml, p = 0.339). During pregnancy, Gremlin-1 levels correlated negatively with osteocalcin and procollagen type I aminoterminal propeptide (P1NP), markers of bone health. Concerning glucose metabolism, Gremlin-1 levels were inversely related to the Insulinogenic Index at GW < 20. However, Gremlin-1 levels were not significantly different between women with normal glucose tolerance and GDM during pregnancy. Postpartum, Gremlin-1 was associated with the fatty liver index, osteocalcin levels, diastolic blood pressure and weight. Conclusion: Gremlin-1 levels decreased significantly during pregnancy. The biomarker is not related to GDM status, but correlates negatively with the Insulinogenic Index, an index related to beta cell function. Trial Registry Number ACTRN12616000924459. [ABSTRACT FROM AUTHOR]

Purpose: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) regulation, developed as treatment for patients with type 2 diabetes, can be imaged with the glucose analogue alpha-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me4FDG), a positron emission tomography (PET) tracer with a high affinity for SGLT1 and SGLT2 proteins. With regard to therapy effectiveness, we aimed to investigate whether clinical parameters or Me4FDG excretion could predict response to SGLT2i in patients with type 2 diabetes. Methods: In a longitudinal, prospective study, 19 patients with type 2 diabetes underwent Me4FDG combined PET and magnetic resonance imaging (PET/MRI) scans at baseline and 2 weeks after initiation of therapy with SGLT2i, accompanied by the collection of blood and urine samples. Me4FDG-excretion was determined from the Me4FDG uptake in the bladder. Long-term response was determined by HbA1c level after 3 months; a strong response to the therapy was defined as a reduction of HbA1c by at least 10% from baseline. Results: SGLT2i resulted in significantly increased Me4FDG excretion (4.8 vs. 45.0, P < 0.001) and urine glucose (56 vs. 2806 mg/dl, P < 0.001). Baseline urine glucose and baseline Me4FDG excretion correlated both with long-term decline in HbA1c with r = 0.55 (P < 0.05). However, only Me4FDG excretion was a predictor of a strong response to SGLT2i (P = 0.005, OR 1.9). Conclusions: Using Me4FDG-PET, we demonstrated for the first time renal SGLT2-related excretion before and after short-term SGLT2i treatment. In contrary to other clinical parameters, SGLT2-related excretion before treatment was a robust predictor of long-term HbA1c response in patients with type 2 diabetes, suggesting that therapy effectiveness is only dependent of endogenous SGLT2 processes. [ABSTRACT FROM AUTHOR]

Sharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns. [ABSTRACT FROM AUTHOR]

Summary: Background: The incidence and the comorbidities, such as infectious diseases (e.g. pneumonia or influenza) of diabetes mellitus are increasing. Therefore, the purpose of this study is to investigate immunization status and preventive care in diabetes mellitus patients. Methods: Two groups from the Austrian health interview survey 2014 were identified, a cohort of diabetes mellitus (DM) individuals (n = 678) and a non-diabetes mellitus (non-DM) cohort (n = 15,093). The frequencies of doctors' visits, preventive care and immunization status were compared. Furthermore, the study population was divided by age (> 50 years, < 50 years) and differences between > 50 years old DM with < 50 years old DM and the > 50 years old DM and > 50 years old Non-DM cohort were investigated. Results: In the DM cohort a higher frequency of influenza immunization (13.3% vs. 7.1%, p < 0.001), doctor visits (89.4% vs. 75.4%, p < 0.001), and preventive care, such as colonoscopy (11.2% vs. 6.8%, p < 0.001) and hemoccult tests (32.6% vs. 22.1%, p < 0.001) was observed. Even though older DM individuals have a higher risk for complications, the > 50 years DM cohort has similar frequencies of colonoscopy, hemoccult test and immunization against influenza and TBE (tick-borne encephalitis) compared to > 50 years Non-DM. Although the > 50 years old DM cohort had a higher frequency of doctors' visits, they still had lower frequencies of mammography and dentists' visits compared to > 50 years old Non-DM. In comparison to the < 50 years old DM cohort, the > 50 years DM cohort was related to lower intact immunization status of tetanus, diphtheria, Polio and TBE. Still a higher frequency of intact immunization of pneumococcus, influenza and doctors' visits in the > 50 years old DM cohort compared to the < 50 years old DM cohort can be reported. Conclusion: Preventive care and immunization status in the DM cohort just differ slightly from the general cohort but still should be improved. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes mellitus is increasing in both sexes, but men are usually diagnosed at a younger age and lower body fat mass than women. Worldwide, an estimated 17.7 million more men than women have diabetes mellitus. Women appear to bear a greater risk factor burden at the time of their type 2 diabetes diagnosis, especially obesity. Moreover, psychosocial stress might play a more prominent role in diabetes risk in women. Across their lifespan, women experience greater hormone fluctuations and body changes due to reproductive factors than men. Pregnancies can unmask pre-existing metabolic abnormalities, resulting in the diagnosis of gestational diabetes, which appears to be the most prominent risk factor for progression to type 2 diabetes in women. Additionally, menopause increases women's cardiometabolic risk profile. Due to the progressive rise in obesity, there is a global increase in women with pregestational type 2 diabetes, often with inadequate preconceptual care. There are differences between men and women regarding type 2 diabetes and other cardiovascular risk factors with respect to comorbidities, the manifestation of complications and the initiation of and adherence to therapy. Women with type 2 diabetes show greater relative risk of CVD and mortality than men. Moreover, young women with type 2 diabetes are currently less likely than men to receive the treatment and CVD risk reduction recommended by guidelines. Current medical recommendations do not provide information on sex-specific or gender-sensitive prevention strategies and management. Thus, more research on sex differences, including the underlying mechanisms, is necessary to increase the evidence in the future. Nonetheless, intensified efforts to screen for glucose metabolism disorders and other cardiovascular risk factors, as well as the early establishment of prophylactic measures and aggressive risk management strategies, are still required for both men and women at increased risk of type 2 diabetes. In this narrative review we aim to summarise sex-specific clinical features and differences between women and men with type 2 diabetes into risk factors, screening, diagnosis, complications and treatment. [ABSTRACT FROM AUTHOR]

This study aims to quantify whether age and sex groups in Austrian regions are equally affected by the rise of type 2 diabetes. Population-wide medical claims data was obtained for citizens in Austria aged above 50 year, who received antihyperglycemic treatments or underwent HbA1c monitoring between 2012 and 2017. Diabetes incidence was measured using an epidemiological diabetes progression model accounting for patients who discontinued antihyperglycemic therapy; the erratic group. Out of 746,184 patients, 268,680 (140,960 females) discontinued their treatment and/or monitoring for at least one year. Without adjusting for such erratic patients, incidence rates increase from 2013 to 2017 (females: from 0·5% to 1·1%, males: 0·5% to 1·2%), whereas they decrease in all groups after adjustments (females: − 0·3% to − 0·5%, males: − 0·4% to − 0·5%). Higher mortality was observed in the erratic group compared to patients on continued antihyperglycemic therapy (mean difference 12% and 14% for females and males, respectively). In summary, incidence strongly depends on age, sex and place of residency. One out of three patients with diabetes in Austria discontinued antihyperglycemic treatment or glycemic monitoring for at least one year. This newly identified subgroup raises concern regarding adherence and continuous monitoring of diabetes care and demands further evaluation. [ABSTRACT FROM AUTHOR]

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Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Wiener Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Bariatric surgery has a favorable effect on fertility in women. However, due to a lack of data regarding children's outcomes, the ideal time for conception following bariatric surgery is unknown. Current guidelines advise avoiding pregnancy during the initial weight loss phase (12–24 months after surgery) as there may be potential risks to offspring. Thus, we aimed to analyze health outcomes in children born to mothers who had undergone bariatric surgery. The surgery-to-delivery interval was studied. Materials and Methods: A nationwide registry belonging to the Austrian health insurance funds and containing health-related data claims was searched. Data for all women who had bariatric surgery in Austria between 01/2010 and 12/2018 were analyzed. A total of 1057 women gave birth to 1369 children. The offspring's data were analyzed for medical health claims based on International Classification of Diseases (ICD) codes and number of days hospitalized. Three different surgery-to-delivery intervals were assessed: 12, 18, and 24 months. Results: Overall, 421 deliveries (31%) were observed in the first 2 years after surgery. Of these, 70 births (5%) occurred within 12 months after surgery. The median time from surgery to delivery was 34 months. Overall, there were no differences noted in frequency of hospitalization and diagnoses leading to hospitalization in the first year of life, regardless of the surgery-to-delivery interval. Conclusion: Pregnancies in the first 24 months after bariatric surgery were common. Importantly, the surgery-to-delivery interval had no significant impact on the health outcome of the children. [ABSTRACT FROM AUTHOR]

COVID-19 research has relied heavily on convenience-based samples, which—though often necessary—are susceptible to important sampling biases. We begin with a theoretical overview and introduction to the dynamics that underlie sampling bias. We then empirically examine sampling bias in online COVID-19 surveys and evaluate the degree to which common statistical adjustments for demographic covariates successfully attenuate such bias. This registered study analysed responses to identical questions from three convenience and three largely representative samples (total N = 13,731) collected online in Canada within the International COVID-19 Awareness and Responses Evaluation Study (www.icarestudy.com). We compared samples on 11 behavioural and psychological outcomes (e.g., adherence to COVID-19 prevention measures, vaccine intentions) across three time points and employed multiverse-style analyses to examine how 512 combinations of demographic covariates (e.g., sex, age, education, income, ethnicity) impacted sampling discrepancies on these outcomes. Significant discrepancies emerged between samples on 73% of outcomes. Participants in the convenience samples held more positive thoughts towards and engaged in more COVID-19 prevention behaviours. Covariates attenuated sampling differences in only 55% of cases and increased differences in 45%. No covariate performed reliably well. Our results suggest that online convenience samples may display more positive dispositions towards COVID-19 prevention behaviours being studied than would samples drawn using more representative means. Adjusting results for demographic covariates frequently increased rather than decreased bias, suggesting that researchers should be cautious when interpreting adjusted findings. Using multiverse-style analyses as extended sensitivity analyses is recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients do not access physicians at random but rather via naturally emerging networks of patient flows between them. As mass quarantines, absences due to sickness, or other shocks thin out these networks, the system might be pushed to a tipping point where it loses its ability to deliver care. Here, we propose a data-driven framework to quantify regional resilience to such shocks via an agent-based model. For each region and medical specialty we construct patient-sharing networks and stress-test these by removing physicians. This allows us to measure regional resilience indicators describing how many physicians can be removed before patients will not be treated anymore. Our model could therefore enable health authorities to rapidly identify bottlenecks in access to care. Here, we show that regions and medical specialties differ substantially in their resilience and that these systemic differences can be related to indicators for individual physicians by quantifying their risk and benefit to the system. As mass quarantines, absences due to sickness, or other shocks thin out patient-physician networks, the system might be pushed to a tipping point where it loses its ability to deliver care. Here, the authors propose a data-driven framework to quantify regional resilience to such shocks via an agent-based model. [ABSTRACT FROM AUTHOR]

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 < 0.01), 2‑h stimulated glucose levels during the OGTT (ρ = −0.18, p < 0.01), HbA1c levels (ρ = −0.13, p < 0.05), FLI and BMI in prediabetic males; however, no relationship between testosterone and metabolic parameters could be found in prediabetic females. 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. [ABSTRACT FROM AUTHOR]

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 < 0.001(Chi-squared)). Moreover, the 30-day mortality was 0.19% and sixfold higher in men compared to women (0.48 vs. 0.08%; p < 0.001). CV (82%) and PSY (55%) were the most common comorbidities in deceased patients with no sex-specific differences. Diabetes (38%) was more common in men (43 vs. 33%; 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. [ABSTRACT FROM AUTHOR]

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 < 21st week of gestation (GW), and at GW 35–37. GPC-4 levels increased from < 21 GW (mean = 2.38 pg/ml, SD = 0.68 pg/ml) to GW 35–37 (mean = 2.96 pg/ml, SD = 0.77 pg/ml, p < 0.001). At the same time, GPC-4 levels correlated negatively with estimated glomerular filtration rate (eGFR), serum protein and serum albumin levels and were positively related to creatinine and uric acid levels at GW 35–37. Concerning glucose metabolism, GPC-4 levels were inversely related to ISSI-2, fasting insulin and HOMA-IR, however, not significantly different between women with normal glucose tolerance (NGT) and GDM (p = 0.239). In conclusion, GPC-4 levels rose significantly during pregnancy, correlated negatively with fasting insulin and HOMA-IR but might not be related to gestational diabetes mellitus status. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Background: Assessing the quality of life (QOL) for patients with type 2 diabetes is an essential part of diabetes management, especially for the evaluation of new antidiabetic treatments and glucose monitoring technologies. Accordingly, the aim of this study was to assess QOL according to treatment types. Methods: This cross-sectional study included 170 patients with type 2 diabetes from the region of Melk in Lower Austria. Of the patients 61 used only oral antidiabetic agents (OAD) and 109 patients were treated with insulin (with or without OAD). The QOL was assessed in patients using sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors). Among the 170 patients with type 2 diabetes 95 used SGLT2 inhibitors. The World Health Organization Quality of Life BREF (WHOQOL-BREF) assessment was used to assess QOL among these patients. The Mann–Whitney U-test was utilized in this study and a P value <0.05 was considered statistically significant. Results: Regarding the 170 participants, most were male (58.82%) and the mean glycated hemoglobin (HbA1c) level was 55.46 ± 12.30 mmol/mol (7.2%). The WHOQOL-BREF scores among type 2 diabetes patients were relatively high, which reflect a good QOL and the mean physical, psychological, social and environmental domain scores were 64.53 ± 20.15, 71.29 ± 18.08, 70.10 ± 20.08, and 84.419 ± 11.22 SD, respectively. There were no statistically significant differences in WHOQOL scores of the domains between the insulin-treated group and OAD group and between the group treated with SGLT2 inhibitors and the group not treated with SGLT2 inhibitors. Conclusion: This study showed no QOL distinctions between treatment groups in patients with type 2 diabetes; however, a large cohort study is needed to examine these groups further. [ABSTRACT FROM AUTHOR]

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. RANK promotes the hormone-mediated development of thymic regulatory T cells during pregnancy; loss of RANK is associated with impaired maturation of maternal regulatory T cells, leading to fetal loss and the development of gestational diabetes. [ABSTRACT FROM AUTHOR]

Purpose Of Review: This narrative review makes the case for greater efforts to reduce cardiovascular disease (CVD) risk in women with diabetes.Recent Findings: In 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. The 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context: A substantial number of patients undergoing bariatric surgery are prescribed psychopharmacological medication. However, the impact of concomitant psychopharmacological medication on the frequency of relevant vitamin deficiencies in postoperative follow-up is not known. Methods: Five hundred twenty-four patients with obesity who underwent bariatric surgery (January 2004 to September 2018) with follow-up of at least 12 months, were included in retrospective analysis. Postoperative follow-up visits between January 2015 and September 2019 were analyzed. Anthropometric and laboratory data were analyzed at the first documented follow-up visit after on average 39.5 ± 37.3 months and at every following visit during the observation period. Patients with prescribed psychopharmacological drugs (PD) were compared with patients without (control group, CON). Results: Psychopharmacological medication was documented in 25% (132) of patients. In 59 patients documented prescription of more than one psychiatric drug was found, whereas psychopharmacological monotherapy was found in 73 patients. Frequencies of vitamin deficiencies were comparable between PD and CON (vitamin A: p = 0.852; vitamin D: p = 0.622; vitamin E: p = 0.901; folic acid: p = 0.941). Prevalence of vitamin B12 deficiency was rare (6% CON, 1% PD) but was significantly higher in CON (p = 0.023). A comparison of CON and POLY also showed no significant differences between the groups concerning prevalence of vitamin deficiencies. Conclusions: Intake of psychopharmacological medication is highly prevalent in patients after bariatric surgery. Patients with psychopharmacological medication, who participate in structured follow-up care after bariatric surgery, are not at higher risk for vitamin deficiencies compared with controls. [ABSTRACT FROM AUTHOR]

Summary: Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

While there is considerable evidence about sex-related differences between men and women in drug metabolism, efficacy and safety of frequently prescribed drugs such as analgesics, tranquillizers, statins and beta-blockers, clinicians' awareness of the implications on dosing and adverse event monitoring in routine practice is inadequate. Some drugs are more effective in men than women (e.g. ibuprofen) or vice versa (e.g. opioids, benzodiazepine), typically owing to pharmacodynamic causes. The 5-hydroxytryptamine (5-HT) receptor 3 antagonist alosetron is approved for women only since it largely lacks efficacy in men. For statins, equal efficacy was demonstrated in secondary prevention of cardiovascular events, but primary prevention is still under debate. For some drugs (e.g. paracetamol, metoprolol), women are at significantly higher risk of adverse effects. Therefore, considering sex-specific features in clinical trials and therapeutic guidelines is warranted to ensure efficacy and safety of medicines. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The DALI (vitamin D and lifestyle intervention in the prevention of gestational diabetes mellitus (GDM)) study aimed to prevent GDM with lifestyle interventions or Vitamin D supplementation (1600 IU/day). This review summarizes the learnings from the DALI studies among pregnant women with a BMI ≥ 29 kg/m2.Recent Findings: Women diagnosed with GDM earlier in pregnancy had a worse metabolic profile than those diagnosed later. A combined physical activity (PA) and healthy eating (HE) lifestyle intervention improved both behaviours, limited gestational weight gain (GWG) and was cost-effective. Although GDM risk was unchanged, neonatal adiposity was reduced due to less sedentary time. Neither PA nor HE alone limited GWG or GDM risk. Fasting glucose was higher with HE only intervention, and lower with Vitamin D supplementation. Our combined intervention did not prevent GDM, but was cost-effective, limited GWG and reduced neonatal adiposity. [ABSTRACT FROM AUTHOR]

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Background: Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, primary adrenal insufficiency (AI) is associated with an increased mortality, mainly due to cardiovascular disease. The role of MC replacement is not known. Therefore, we assessed whether renin concentrations during routine GC and MC substitution therapy are associated with heart function and morphology. Methods: Thirty two patients with primary AI were included in a cross-sectional case–control study. In total, 17 patients and 34 healthy controls (age: 48 ± 12 vs. 46 ± 18 years; BMI: 23 ± 3 vs. 24 ± 3 kg/m2) underwent magnetic resonance spectroscopy and imaging measurements to assess cardiac function, morphology, ectopic lipids, and visceral/subcutaneous fat mass. Patients were divided according to their actual plasma renin concentration at the study visit (Actual-Reninlow vs. Actual-Reninhigh) and their median plasma renin concentration of previous visits (Median-Reninlow vs. Median-Reninhigh). Results: Ejection fraction was higher (67 ± 5 vs. 55 ± 3%; p = 0.001) and left ventricular mass was lower (60 ± 9 vs. 73 ± 10 g/m2; p = 0.025) in Actual-Reninhigh. Median-Reninhigh was associated with lower cardiac mass (64 ± 9 vs. 76 ± 11 g/m2; p = 0.029). Blood pressure, glucose, and lipid metabolism, as well as ectopic lipid content, pericardial fat mass, and visceral/subcutaneous fat were not different between the groups. Compared with controls, ejection fraction was significantly lower in patients with AI (56 ± 4 vs. 63 ± 8%; p = 0.019). No differences were found in patients with ≤20 mg compared with >20 mg of hydrocortisone per day. Conclusions: Higher renin concentrations are associated with more favorable cardiac function and morphology in patients with primary AI. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Offspring of obese women are at increased risk of features of the metabolic syndrome, including obesity and diabetes. Lifestyle intervention in pregnancy might reduce adverse effects of maternal obesity on neonatal adiposity. Methods: In the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention (DALI) lifestyle trial, 436 women with a BMI ≥29 kg/m2 were randomly assigned to counselling on healthy eating (HE), physical activity (PA) or HE&PA, or to usual care (UC). In secondary analyses of the lifestyle trial, intervention effects on neonatal outcomes (head, abdominal, arm and leg circumferences and skinfold thicknesses, estimated fat mass, fat percentage, fat-free mass and cord blood leptin) were assessed using multilevel regression analyses. Mediation of intervention effects by lifestyle and gestational weight gain was assessed. Results: Outcomes were available from 334 neonates. A reduction in sum of skinfolds (−1.8 mm; 95% CI −3.5, −0.2; p = 0.03), fat mass (−63 g; 95% CI −124, −2; p = 0.04), fat percentage (−1.2%; 95% CI −2.4%, −0.04%; p = 0.04) and leptin (−3.80 μg/l; 95% CI −7.15, −0.45; p = 0.03) was found in the HE&PA group, and reduced leptin in female neonates in the PA group (−5.79 μg/l; 95% CI −11.43, −0.14; p = 0.05) compared with UC. Reduced sedentary time, but not gestational weight gain, mediated intervention effects on leptin in both the HE&PA and PA groups. Conclusions/interpretation: The HE&PA intervention resulted in reduced adiposity in neonates. Reduced sedentary time seemed to drive the intervention effect on cord blood leptin. Implications for future adiposity and diabetes risk of the offspring need to be elucidated. Trial registration: ISRCTN70595832. [ABSTRACT FROM AUTHOR]