Perinatal Outcomes in Early and Late Gestational Diabetes Mellitus After Treatment From 24-28 Weeks' Gestation: A TOBOGM Secondary Analysis.

OBJECTIVE: In most gestational diabetes mellitus (GDM) studies, cohorts have included women combined into study populations without regard to whether hyperglycemia was present earlier in pregnancy. In this study we sought to compare perinatal outcomes between groups: women with early GDM (EGDM group: diagnosis before 20 weeks but no treatment until 24-28 weeks if GDM still present), with late GDM (LGDM group: present only at 24-28 weeks), and with normoglycemia at 24-28 weeks (control subjects). RESEARCH DESIGN AND METHODS: This is a secondary analysis of a randomized controlled treatment trial where we studied, among women with risk factors, early (<20 weeks' gestation) GDM defined according to World Health Organization 2013 criteria. Those receiving early treatment for GDM treatment were excluded. GDM was treated if present at 24-28 weeks. The primary outcome was a composite of birth before 37 weeks' gestation, birth weight ≥4,500 g, birth trauma, neonatal respiratory distress, phototherapy, stillbirth/neonatal death, and shoulder dystocia. Comparisons included adjustment for age, ethnicity, BMI, site, smoking, primigravity, and education. RESULTS: Women with EGDM (n = 254) and LGDM (n = 467) had shorter pregnancy duration than control subjects (n = 2,339). BMI was lowest with LGDM. The composite was increased with EGDM (odds ratio [OR] 1.59, 95% CI 1.18-2.12)) but not LGDM (OR 1.19, 95% CI 0.94-1.50). Induction of labor was higher in both GDM groups. In comparisons with control subjects there were higher birth centile, higher preterm birth rate, and higher rate of neonatal jaundice for the EGDM group (but not the LGDM group). The greatest need for insulin and/or metformin was with EGDM. CONCLUSIONS: Adverse perinatal outcomes were increased with EGDM despite treatment from 24-28 weeks' gestation, suggesting the need to initiate treatment early, and more aggressively, to reduce the effects of exposure to the more severe maternal hyperglycemia from early pregnancy.

Role of sex and gender-related variables in development of metabolic syndrome: A prospective cohort study.

INTRODUCTION: The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate.  Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex. METHOD: Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003-2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex,  age and gender-related factors were also tested. RESULTS: Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41-0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated a decreased risk of MetS compared to males. Conversely smoking and unemployment were significant risk factors for MetS development among male adults. CONCLUSIONS: Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people.

The Interplay of Adipokines, Body Composition and Glucose Homeostasis in Pregnant Women with a History of RYGB Operation.

Roux-en-Y gastric bypass operations (RYGB-OP) and pregnancy alter glucose homeostasis and the adipokine profile. This study investigates the relationship between adipokines and glucose metabolism during pregnancy post-RYGB-OP. (1) Methods: This is a post hoc analysis of a prospective cohort study during pregnancy in 25 women with an RYGB-OP (RY), 19 women with obesity (OB), and 19 normal-weight (NW) controls. Bioimpedance analysis (BIA) was used for metabolic characterization. Plasma levels of adiponectin, leptin, fibroblast-growth-factor 21 (FGF21), adipocyte fatty acid binding protein (AFABP), afamin, and secretagogin were obtained. (2) Results: The phase angle (φ) was lower in RY compared to OB and NW. Compared to OB, RY, and NW had lower leptin and AFABP levels, and higher adiponectin levels. φ correlated positively with leptin in RY (R = 0.63, p < 0.05) and negatively with adiponectin in OB and NW (R = -0.69, R = -0.69, p < 0.05). In RY, the Matsuda index correlated positively with FGF21 (R = 0.55, p < 0.05) and negatively with leptin (R = -0.5, p < 0.05). In OB, FGF21 correlated negatively with the disposition index (R = -0.66, p < 0.05). (3) Conclusions: The leptin, adiponectin, and AFABP levels differ between RY, OB, and NW and correlate with glucose metabolism and body composition. Thus, adipokines might influence energy homeostasis and maintenance of cellular health during pregnancy.

[Gestational diabetes mellitus (Update 2023)]. / Gestationsdiabetes (GDM) (Update 2023).

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and the offspring. Women detected to have diabetes early in pregnancy receive the diagnosis of overt, non-gestational, diabetes (glucose: fasting ≥ 126 mg/dl, spontaneous ≥ 200 mg/dl or HbA1c ≥ 6.5% before 20 weeks of gestation). GDM is diagnosed by an oral glucose tolerance test (oGTT) or increased fasting glucose (≥ 92 mg/dl). Screening for undiagnosed type 2 diabetes at the first prenatal visit is recommended in women at increased risk (history of GDM/pre-diabetes; malformation, stillbirth, successive abortions or birth weight > 4500 g previously; obesity, metabolic syndrome, age > 35 years, vascular disease; clinical symptoms of diabetes (e.g. glucosuria) or ethnic origin with increased risk for GDM/T2DM (Arab, South- and Southeast Asian, Latin American)) using standard diagnostic criteria. Performance of the oGTT (120 min; 75 g glucose) may already be indicated in the first trimester in high-risk women but is mandatory between gestational week 24-28 in all pregnant women with previous non-pathological glucose metabolism. Following WHO recommendations, which are based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, GDM is defined, if fasting venous plasma glucose is ≥ 92 mg/dl or 1 h ≥ 180 mg/dl or 2 h ≥ 153 mg/dl after glucose loading (international consensus criteria). In case of one pathological value a strict metabolic control is mandatory. After bariatric surgery we do not recommend to perform an oGTT due to risk of postprandial hypoglycemia. All women with GDM should receive nutritional counseling, be instructed in blood glucose self-monitoring and motivated to increase physical activity to moderate intensity levels-if not contraindicated (Evidence level A). If blood glucose levels cannot be maintained in the therapeutic range (fasting < 95 mg/dl and 1 h after meals < 140 mg/dl, Evidence level B) insulin therapy should be initiated as first choice (Evidence level A). Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. Regular obstetric examinations including ultrasound examinations are recommended (Evidence level A). Neonatal care of GDM offspring at high risk for hypoglycaemia includes blood glucose measurements after birth and if necessary appropriate intervention. Monitoring the development of the children and recommendation of healthy lifestyle are important issues to be tackled for the whole family. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g oGTT (WHO criteria) 4-12 weeks postpartum. Assessment of glucose parameters (fasting glucose, random glucose, HbA1c or optimally oGTT) are recommended every 2-3 years in case of normal glucose tolerance. All women have to be instructed about their increased risk of type 2 diabetes and cardiovascular disease at follow-up. Possible preventive meassures, in particular lifestyle changes as weight management and maintenance/increase of physical activity should be discussed (evidence level A).

[Sex and gender-specific aspects in prediabetes and diabetes mellitus-clinical recommendations (Update 2023)]. / Geschlechtsspezifische Aspekte bei Prädiabetes und Diabetes mellitus ­ klinische Empfehlungen (Update 2023).

Metabolic diseases dramatically affect the life of men and women from infancy up to old age in different and manifold ways and are a major challenge for the healthcare system. The treating physicians are confronted with the different needs of women and men in the clinical routine. Gender-specific differences affect pathophysiology, screening, diagnostic and treatment strategies of diseases as well as the development of complications and mortality rates. Impairments in glucose and lipid metabolism, regulation of energy balance and body fat distribution and therefore the associated cardiovascular diseases, are greatly influenced by steroidal and sex hormones. Furthermore, education, income and psychosocial factors play an important role in the development of obesity and diabetes differently in men and women. Males appear to be at greater risk of diabetes at a younger age and at a lower body mass index (BMI) compared to women but women feature a dramatic increase in the risk of diabetes-associated cardiovascular diseases after the menopause. The estimated future years of life lost owing to diabetes is somewhat higher in women than men, with a higher increase in vascular complications in women but a higher increase of cancer deaths in men. In women prediabetes or diabetes are more distinctly associated with a higher number of vascular risk factors, such as inflammatory parameters, unfavourable changes in coagulation and higher blood pressure. Women with prediabetes and diabetes have a much higher relative risk for vascular diseases. Women are more often morbidly obese and less physically active but may have an even greater benefit in health and life expectation from increased physical activity than men. In weight loss studies men often showed a higher weight loss than women; however, diabetes prevention is similarly effective in men and women with prediabetes with a risk reduction of nearly 40%. Nevertheless, a long-term reduction in all cause and cardiovascular mortality was so far only observed in women. Men predominantly feature increased fasting blood glucose levels, women often show impaired glucose tolerance. A history of gestational diabetes or polycystic ovary syndrome (PCOS) as well as increased androgen levels and decreased estrogen levels in women and the presence of erectile dysfunction or decreased testosterone levels in men are important sex-specific risk factors for the development of diabetes. Many studies showed that women with diabetes reach their target values for HbA1c, blood pressure and low-density lipoprotein (LDL)-cholesterol less often than their male counterparts, although the reasons are unclear. Furthermore, sex differences in the effects, pharmacokinetics and side effects of pharmacological treatment should be taken more into consideration.

The Timing of Pregnancies After Bariatric Surgery has No Impact on Children's Health-a Nationwide Population-based Registry Analysis.

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.

Need for improving immunization status and preventive care in diabetes mellitus patients.

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.

Evaluation of a Bariatric Monitoring Pass for Primary Care Physicians.

INTRODUCTION: There are a growing number of patients undergoing bariatric surgery requiring lifelong follow-up. Therefore, follow-up care can no longer be covered by specialized outpatient clinics alone due to the sharp rise in the number of bariatric patients. Bariatric Patients in Primary Care: Postoperative Nutrition and Lifestyle Management (BagEL) is a survey to evaluate a newly developed structured disease management program including nutrition and lifestyle management in primary care. METHODS: The study is conceived as a randomized cohort study with a control group. An expert questionnaire for general practitioners (GPs) was developed to assess the usability of a structured postoperative care system regarding nutrition and lifestyle management for bariatric patients in primary care. A structured follow-up program in primary care with a so-called bariatric monitoring passport (BMP) was provided for patients in the intervention (INT) group and the existing information sheet "Metabolic surgery and perioperative care" for the control (CON) group. 124 patients, who met inclusion criteria and who underwent a bariatric procedure first time, served as ambassadors for delivery of the expert questionnaire and study documents to their individual GPs. RESULTS: A total of 39 (31.5%) different GPs from 124 ambassador patients responded. For the primary outcome "Does the aftercare-booklets support treatment of bariatric patients?" GPs of the INT group rated the new designed aftercare booklet (INT) significantly more helpful for treating bariatric patients than the one from the CON group (p = 0.041). DISCUSSION/CONCLUSION: These results suggest that GPs are welcoming supportive tools like our BMP to improve the care of long-term follow-up of bariatric patients and should actively participate in the development of lifelong disease management plans necessary to cope with the rapidly growing number of patients.

Cardiovascular health through a sex and gender lens in six South Asian countries: Findings from the WHO STEPS surveillance.

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. 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. 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" 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. Results: 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 (ß: 0.05, 95% confidence interval (CI) = 0.01-0.08, P < 0.05) was significantly associated with better CVH compared to males. Being married (ßmale = -0.30, 95% CI = -0.37, -0.23 vs ßfemale = -0.23, 95% CI = -0.29, -0.17; P < 0.001) and having a household size ≥5 (ßmale = -0.15, 95% CI = -0.24, -0.06 vs ßfemale = -0.11, 95% CI = -0.16, -0.04; P < 0.01) were associated with poorer CVH, more so in males. Being married was also associated with high risk of CVD (ORmale = 2.54, 95% CI = 1.68-3.86, P < 0.001 vs ORfemale = 1.19, 95% CI = 0.84-1.68, P = 0.31), significant in males. Conclusions: 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.

Sex-Specific Differences in Mortality of Patients with a History of Bariatric Surgery: a Nation-Wide Population-Based Study.

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.

Glypican-4 in pregnancy and its relation to glucose metabolism, insulin resistance and gestational diabetes mellitus status.

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.

The Effect of Cardiovascular Comorbidities on Women Compared to Men: Longitudinal Retrospective Analysis.

BACKGROUND: Although men are more prone to developing cardiovascular disease (CVD) than women, risk factors for CVD, such as nicotine abuse and diabetes mellitus, have been shown to be more detrimental in women than in men. OBJECTIVE: We developed a method to systematically investigate population-wide electronic health records for all possible associations between risk factors for CVD and other diagnoses. The developed structured approach allows an exploratory and comprehensive screening of all possible comorbidities of CVD, which are more connected to CVD in either men or women. METHODS: Based on a population-wide medical claims dataset comprising 44 million records of inpatient stays in Austria from 2003 to 2014, we determined comorbidities of acute myocardial infarction (AMI; International Classification of Diseases, Tenth Revision [ICD-10] code I21) and chronic ischemic heart disease (CHD; ICD-10 code I25) with a significantly different prevalence in men and women. We introduced a measure of sex difference as a measure of differences in logarithmic odds ratios (ORs) between male and female patients in units of pooled standard errors. RESULTS: Except for lipid metabolism disorders (OR for females [ORf]=6.68, 95% confidence interval [CI]=6.57-6.79, OR for males [ORm]=8.31, 95% CI=8.21-8.41), all identified comorbidities were more likely to be associated with AMI and CHD in females than in males: nicotine dependence (ORf=6.16, 95% CI=5.96-6.36, ORm=4.43, 95% CI=4.35-4.5), diabetes mellitus (ORf=3.52, 95% CI=3.45-3.59, ORm=3.13, 95% CI=3.07-3.19), obesity (ORf=3.64, 95% CI=3.56-3.72, ORm=3.33, 95% CI=3.27-3.39), renal disorders (ORf=4.27, 95% CI=4.11-4.44, ORm=3.74, 95% CI=3.67-3.81), asthma (ORf=2.09, 95% CI=1.96-2.23, ORm=1.59, 95% CI=1.5-1.68), and COPD (ORf=2.09, 95% CI 1.96-2.23, ORm=1.59, 95% CI 1.5-1.68). Similar results could be observed for AMI. CONCLUSIONS: Although AMI and CHD are more prevalent in men, women appear to be more affected by certain comorbidities of AMI and CHD in their risk for developing CVD.

Sex differences in brown adipose tissue activity and cold-induced thermogenesis.

INTRODUCTION: Brown adipose tissue (BAT) is suggested to exhibit a sexual dimorphism and thus contributes to the observed sex differences in cardiometabolic risk observed between women and men. Clinical data supporting this hypothesis are however scarce. The aim of this study was to investigate the relationship between BAT activity and sex using positron emission tomography (PET) - the current gold-standard for BAT quantification. METHODS: In this study, we included 95 subjects with a wide BMI range (20-55 kg/m2) aged from 18 to 50 years. Avoiding shivering, participants were cooled with a water-perfused vest to achieve adequate BAT activation. BAT activity was determined by 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT). Cold-induced thermogenesis (CIT) was quantified by indirect calorimetry. RESULTS: BAT was present in 44.6% of pre-menopausal women and in 35.9% of men (p = 0.394). CIT was significantly higher in women (p = 0.024). Estradiol levels were positively associated with CIT independent of age, sex, body fat and other sex hormones (b = 0.360, p = 0.016). In women, CIT decreased during the menstrual cycle, with lower levels in the luteal phase similar to median concentrations in men. CONCLUSION: The prevalence of cold-activated BAT is slightly but non-significantly higher in pre-menopausal women than men. CIT is increased in females and independently associated with estradiol, suggesting that sex hormones may play a role in different thermogenic responses between men and women.

Diagnostic Role of PET/CT Tracers in the Detection and Localization of Tumours Responsible for Ectopic Cushing's Syndrome.

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.

Risk of Typical Diabetes-Associated Complications in Different Clusters of Diabetic Patients: Analysis of Nine Risk Factors.

OBJECTIVES: Diabetic patients are often diagnosed with several comorbidities. The aim of the present study was to investigate the relationship between different combinations of risk factors and complications in diabetic patients. RESEARCH DESIGN AND METHODS: We used a longitudinal, population-wide dataset of patients with hospital diagnoses and identified all patients (n = 195,575) receiving a diagnosis of diabetes in the observation period from 2003-2014. We defined nine ICD-10-codes as risk factors and 16 ICD-10 codes as complications. Using a computational algorithm, cohort patients were assigned to clusters based on the risk factors they were diagnosed with. The clusters were defined so that the patients assigned to them developed similar complications. Complication risk was quantified in terms of relative risk (RR) compared with healthy control patients. RESULTS: We identified five clusters associated with an increased risk of complications. A combined diagnosis of arterial hypertension (aHTN) and dyslipidemia was shared by all clusters and expressed a baseline of increased risk. Additional diagnosis of (1) smoking, (2) depression, (3) liver disease, or (4) obesity made up the other four clusters and further increased the risk of complications. Cluster 9 (aHTN, dyslipidemia and depression) represented diabetic patients at high risk of angina pectoris "AP" (RR: 7.35, CI: 6.74-8.01), kidney disease (RR: 3.18, CI: 3.04-3.32), polyneuropathy (RR: 4.80, CI: 4.23-5.45), and stroke (RR: 4.32, CI: 3.95-4.71), whereas cluster 10 (aHTN, dyslipidemia and smoking) identified patients with the highest risk of AP (RR: 10.10, CI: 9.28-10.98), atherosclerosis (RR: 4.07, CI: 3.84-4.31), and loss of extremities (RR: 4.21, CI: 1.5-11.84) compared to the controls. CONCLUSIONS: A comorbidity of aHTN and dyslipidemia was shown to be associated with diabetic complications across all risk-clusters. This effect was amplified by a combination with either depression, smoking, obesity, or non-specific liver disease.

Iron Deficiency - Not Only a Premenopausal Topic After Bariatric Surgery?

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.

Sex, Gender, and Cardiovascular Health in Canadian and Austrian Populations.

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: ß = -1.33, 95% confidence interval [CI] -1.44 to -1.22; AT-HIS: ß = -1.08, 95% CI -1.26 to -0.89)) were associated with worse CVH, female sex (CCHS: ß = 0.35, 95% CI (0.33-0.37); AT-HIS: ß = 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.

Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality.

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.

Combined exenatide and dapagliflozin has no additive effects on reduction of hepatocellular lipids despite better glycaemic control in patients with type 2 diabetes mellitus treated with metformin: EXENDA, a 24-week, prospective, randomized, placebo-controlled pilot trial.

AIMS: To investigate the potential synergistic effects of combined exenatide (EXE) and dapagliflozin (DAPA) versus (PLAC) placebo and DAPA on hepatocellular lipid (HCL) reduction after 24 weeks of treatment. MATERIALS AND METHODS: Thirty patients with type 2 diabetes were randomized to weekly EXE and daily DAPA (n = 16) or weekly PLAC and daily DAPA (n = 14). Inclusion criteria were glycated haemoglobin (HbA1c) 48 to 97 mmol/mol (6.5-11%), age 18 to 75 years, body mass index (BMI) ≥25 kg/m2 and metformin ≥1000 mg. The primary endpoint, HCL levels, were measured at baseline and after 24 weeks of treatment using magnetic resonance spectroscopy. Between-group effects were analysed using general linear models, adjusted for baseline outcome variables, age, sex and BMI. Within-group differences were assessed using a paired t-test. RESULTS: After 24 weeks, HCLs were reduced in both treatment groups (absolute change from baseline: EXE + DAPA -4.4%, 95% confidence interval [CI] -8.2, -0.7, P < 0.05; PLAC + DAPA -3.9%, 95% CI -6.0, -1.7, P < 0.01; relative change: EXE + DAPA -35.6%, PLAC + DAPA -32.3%) with no difference between groups. Similar findings were observed for subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). HbA1c (EXE + DAPA -17.8 mmol/mol, [95% CI -24.8, -10.8], P <0.001; PLAC + DAPA -6.9 mmol/mol, [95% CI -10.5, -3.3], P = 0.001) and fasting glucose significantly decreased in both groups, although EXE + DAPA achieved better glycaemic control than PLAC + DAPA (adjusted difference: HbA1c -6.0 mmol/mol [95% CI -9.7, -2.2], P < 0.01). Body weight was reduced in both treatment groups (EXE + DAPA -7.3 kg, 95% CI -9.9, -4.8, P <0.001; PLAC + DAPA -4.6 kg, 95% CI -7.4, -1.8, P <0.01) with comparable results between groups. Changes in HCLs and weight, hip and waist circumference, VAT and SAT were positively associated. CONCLUSION: After 24 weeks, HCLs were significantly but comparably reduced in the EXE + DAPA and PLAC + DAPA groups, despite significantly better glycaemic control in the combined group EXE + DAPA. Changes in HCLs were associated with weight loss and reduction of visceral adiposity, but not with glucose control. Further studies are necessary to evaluate possible additional long-term effects of a combined treatment.