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Importance: A male predominance is reported in hospitalised patients with COVID-19 alongside a higher mortality rate in men compared to women. Objective: To assess if the reported sex bias in the COVID-19 pandemic is validated by analysis of a subset of patients with severe disease. Design: A nationwide retrospective cohort study was performed using the Austrian National COVID Database. We performed a sex-specific Lasso regression to select the covariates best explaining the outcomes of mechanical ventilation and death using variables known before ICU admission. We use logistic regression to construct a sex-specific "risk score" for the outcomes using these variables. Setting: We studied the characteristics and outcomes of patients admitted to intensive care units (ICUs) in Austria. Participants: 5118 patients admitted to the ICU in Austria with a COVID-19 diagnosis in 03/2020–03/2021. Exposures: Demographic and clinical characteristics, vital signs and laboratory tests, comorbidities, and management of patients admitted to ICUs were analysed for possible sex differences. Main outcomes and measures: The aim was to define risk scores for mechanical ventilation and mortality for each sex to provide better sex-sensitive management and outcomes in the future. Results: We found balanced accuracies between 55% and 65% to predict the outcomes. Regarding outcome death, we found that the risk score for pre-ICU variables increases with age, renal insufficiency (f: OR 1.7(2), m: 1.9(2)) and decreases with observance as admission cause (f: OR 0.33(5), m: 0.36(5)). Additionally, the risk score for females also includes respiratory insufficiency (OR 2.4(4)) while heart failure for males only (OR 1.5(1)). Conclusions and relevance: Better knowledge of how sex influences COVID-19 outcomes at ICUs will have important implications for the ongoing pandemic's clinical care and management strategies. Identifying sex-specific features in individuals with COVID-19 and fatal consequences might inform preventive strategies and public health services. [ABSTRACT FROM AUTHOR]

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 ca rdiovascular 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 a mong 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 biologica l 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 psy chosocial 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 diabet es. [ABSTRACT FROM AUTHOR]

Clinical guidelines for the management of type 2 diabetes recommend individual therapy considering age, duration of disease, presence of complication and risk of hypoglycaemia. However, at present, the patient's sex has no impact on clinical decisions. Yet, there is mounting data pointing at biological and psychosocial differences between men and women with great impact on progression of disease and complications. Moreover, choices and preferences of therapeutic strategies as well as adherence to lifestyle and pharmacological interventions differ in both sexes. In addition, drug therapy may have sex-specific side effects. Therefore, there is need of more research on biological differences and of evidence-based individualised targeted sex-sensitive therapeutic concepts. Clinical guidelines must consider relevant sex-differences. Development and implementation of sex-specific programs may help to improve adherence to therapy and to reduce progression of disease and development of complications. A more gender-sensitive clinical approach may improve quality of life and increase health and life expectancy in men and women with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population.Methods: Medical claims data of 1 847 051 patients with hospital stays during 2006-2007 were used to estimate age- and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins.Results: Patients treated with insulin or insulin secretagogues showed up to ninefold increased risks for cancers of the colon [males only (m)], liver (m), pancreas, lung (m) and brain (m), as well as a strongly decreased risk for prostate cancer (m). In patients taking statins, the risks were generally decreased, with a greater risk reduction in patients not receiving antihyperglycaemic therapies. The strongest effects were observed for use of insulin and pancreatic cancer [m: OR 4.5, 95% CI: 3.1-6.6; females (f): OR 4.2, 95% CI: 2.5-7.1], sulfonylureas (m: OR 2.8, 95% CI: 1.7-4.6; f: OR 3.0, 95% CI: 2.1-4.2) or glitazones and skin cancer (f: OR 0.54, 95% CI: 0.36-0.80), as well as metformin and cancer of the prostate (m: OR 0.82, 95% CI: 0.75-0.91) and corpus uteri (f: OR 1.7, 95% CI: 1.4-2.0) and non-Hodgkin's lymphoma (f: OR 0.76, 95% CI: 0.64-0.91).Conclusions: The use of statins offsets insulin-related cancer risks in patients with diabetes independently of sex and age. Overall, our data support the hyperglycaemia-cancer hypothesis. A reduction in endogenous or exogenous hyperinsulinaemia may be beneficial for cancer prevention. Therefore, insulin-sparing and insulin-sensitizing drugs should be the preferred treatment choices. [ABSTRACT FROM AUTHOR]

Evidence for the predictive value of IADPSG/WHO2013 diagnostic gestational diabetes mellitus criteria for long-term maternal and offspring outcomes is missing. Recently, William L Lowe Jr and colleagues report a high risk of maternal glycaemic disorders and childhood adiposity 10 to 14 years after untreated gestational diabetes mellitus in the HAPO Follow-up Study. [ABSTRACT FROM AUTHOR]

Aims To determine the impact of gender on glycaemic control and hypoglycaemia in insulin-naïve patients with type 2 diabetes ( T2DM). Methods Data were pooled from six randomized clinical trials of insulin glargine or NPH insulin in insulin-naïve, inadequately controlled patients. Female [n = 1251; mean glycated haemoglobin ( HbA1c) level 8.99%, age 56.91 years, diabetes duration 9.84 years] and male patients (n = 1349; mean HbA1c 8.9%, age 57.47 years, diabetes duration 10.13 years) were started on and treated with insulin glargine or NPH insulin for 24-36 weeks. HbA1c and fasting blood glucose levels, percent achieving HbA1c target of <7% and insulin dose change were recorded. Results For both men and women, HbA1c levels were significantly reduced over time (p < 0.001); a significantly greater HbA1c reduction was observed in men than in women (−1.36 vs. −1.22; p = 0.002). Significantly fewer women achieved target HbA1c of <7% (p < 0.001). At the study end, women had a significantly higher insulin dose/kg than men (0.47 vs. 0.42 U/kg; p < 0.001). The incidence rates of severe and severe nocturnal hypoglycaemia were significantly higher in women (3.28% vs. 1.85%; p < 0.05 and 2.24% vs. 0.59%; p < 0.001, respectively). Women were more likely to experience severe hypoglycaemia [odds ratio ( OR) 1.80; 95% confidence interval ( CI) 1.08, 3.00; p = 0.02] and severe nocturnal hypoglycaemia ( OR: 3.80; 95% CI 1.72, 8.42; p = 0.001). Conclusions These observations confirm studies that found a smaller improvement in HbA1c and greater hypoglycaemia in women during insulin treatment. Physicians should be aware of the need to determine and closely monitor dosing, particularly in women, to optimize the balance between glycaemic control and hypoglycaemia risk. [ABSTRACT FROM AUTHOR]

Despite substantial progress in the study of diabetes, important questions remain about its comorbidities and clinical heterogeneity. To explore these issues, we develop a framework allowing for the first time to quantify nation-wide risks and their age- and sex-dependence for each diabetic comorbidity, and whether the association may be consequential or causal, in a sample of almost two million patients. This study is equivalent to nearly 40,000 single clinical measurements. We confirm the highly controversial relation of increased risk for Parkinson’s disease in diabetics, using a 10 times larger cohort than previous studies on this relation. Detection of type 1 diabetes leads detection of depressions, whereas there is a strong comorbidity relation between type 2 diabetes and schizophrenia, suggesting similar pathogenic or medication-related mechanisms. We find significant sex differences in the progression of, for instance, sleep disorders and congestive heart failure in diabetic patients. Hypertension is a highly sex-sensitive comorbidity with females being at lower risk during fertile age, but at higher risk otherwise. These results may be useful to improve screening practices in the general population. Clinical management of diabetes must address age- and sex-dependence of multiple comorbid conditions. [ABSTRACT FROM AUTHOR]

BackgroundPlasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated. Materials and methodsFasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g). ResultsFasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 ± 2 ng mL-1, hypothyroid 10.2 ± 2 ng mL-1, euthyroid 12.7 ± 3 ng mL-1). In obese hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) than in lean hypothyroid patients, twofold higher (P < 0.005) than in obese hyperthyroid patients matched for fat mass and 30% increased (P < 0.01) compared with obese euthyroid subjects. There were no differences between fasting and post-prandial (OGTT) leptin concentrations in any group. Normalization of thyroid function did not affect plasma leptin, which remained elevated (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mass index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma leptin correlated with plasma insulin concentration only in hyperthyroid patients (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and... [ABSTRACT FROM AUTHOR]

Background: Little is known about the impact of sex-specific differences in the management of type 1 diabetes (T1DM). Thus, we evaluated the influence of gender on risk factors, complications, clinical care and adherence in patients with T1DM. Methods: In a cross-sectional study, sex-specific disparities in glycaemic control, cardiovascular risk factors, diabetic complications, concomitant medication use and adherence to treatment recommendations were evaluated in 225 consecutive patients (45.3% women) who were comparable with respect to age, diabetes duration, and body mass index. Results: Although women with T1DM had a higher total cholesterol than men, triglycerides were higher in obese men and males with HbA1c>7% than in their female counterparts. No sex differences were observed in glycaemic control and in micro- or macrovascular complications. However, the subgroup analysis showed that nephropathy was more common in obese men, hyperlipidaemic women and all hypertensive patients, whereas peripheral neuropathy was more common in hyperlipidaemic women. Retinopathy was found more frequently in women with HbA1c>7%, obese men and in both sexes with a long duration of diabetes. The multivariate analysis revealed that microvascular complications were associated with the duration of disease and BMI in both sexes and with hyperlipidaemia in males. The overall adherence to interventions according to the guidelines was higher in men than in women. This adherence was concerned particularly with co-medication in patients diagnosed with hypertension, aspirin prescription in elderly patients and the achievement of target lipid levels following the prescription of statins. Conclusions: Our data showed sex differences in lipids and overweight in patients with T1DM. Although glycaemic control and the frequency of diabetic complications were comparable between the sexes, the overall adherence to guidelines, particularly with respect to the prescription of statins and aspirin, was lower in women than in men. [ABSTRACT FROM AUTHOR]

Background Clinicians and health professionals are increasingly challenged to understand and consider the different health needs of women and men. The increase of gender awareness and the expanding science of gender medicine will affect more and more clinical practice. This review addresses gender-specific aspects in metabolic disorders and related complications, which represent an increasing burden of this century and a great challenge to public health. Design There is increasing evidence of gender-related differences in risk factors, clinical manifestation and sequelae of obesity and diabetes and increasing knowledge that prevention, detection and therapy of illness affect men and women differently. Results Some gender-specific aspects, especially regarding cardiovascular disease, have been studied in more detail, but for many complications sex-related analyses of the results of both clinical trials and basic science are still missing or disregarded. Impaired glucose and lipid metabolism as well as dysregulation of energy balance and body fat distribution have a great impact on overall health via neuroendocrine changes and inflammatory pathways and deteriorate the course of many diseases with particular harm for women. Metabolic diseases dramatically affect life of men and women from infancy up to old age and are a major challenge for women during pregnancy. Great impact is attached to the intrauterine period and the lifelong implications of fetal programming. Conclusions Initiation of prospective studies on the impact of gender as primary outcome and investigation of gender-related pathophysiological mechanisms of chronic diseases will help to improve patient care and to implement evidence-based gender-specific prevention programs and clinical recommendations in future. [ABSTRACT FROM AUTHOR]

Objective. Women with previous gestational diabetes mellitus (GDM) have a high risk for development of type 2 diabetes mellitus. The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) could be related to disorders of the glucose metabolism. To evaluate if ADMA predicts deterioration of glucose tolerance in women with previous GDM and to assess concentration changes we analysed ADMA in women with previous GDM after delivery and after a median follow-up of 2.75 years (interquartile range: 1.47–4.60). Design. Prospective cohort study. Subjects and methods. ADMA, symmetric dimethylarginine (SDMA) andl-arginine were determined in 77 women with previous GDM who underwent a 75-g oral glucose tolerance test 4 months after delivery and at follow-up. Results. Deterioration in glucose tolerance was observed in 36% of the women with ADMA above and 11% of those with ADMA below the median (0.56 μmol L−1; P = 0.008, log-rank test). ADMA correlated significantly with mean arterial blood pressure and nonsignificantly with body mass index ( P = 0.050) but not with insulin resistance, fasting glucose, lipids or glomerular filtration rate. The fully adjusted hazard ratio for a decline of glucose tolerance during follow-up was 3.94 (95% CI: 1.16–13.37; P = 0.028) for subjects with ADMA above the median. SDMA andl-arginine were not associated with changes in the glucose tolerance status. ADMA andl-arginine decreased significantly during follow-up. Conclusions. High serum ADMA after delivery is associated with deterioration in glucose tolerance in women with previous GDM and declines in the following years. [ABSTRACT FROM AUTHOR]

Aim: This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T). The association of these agents with several other factors related to glucose metabolism was also investigated, as well as the relation of insulin sensitivity and secretion with markers of endothelial function such as different adhesion molecules (cAMs), that is vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-Selectin. Methods: Twenty type 2 diabetic patients treated with diet only underwent a 3-h OGTT for measurement of plasma glucose, insulin, proinsulin, C-peptide and cAMs before and after administration of randomly given M (n = 9; 1700 mg/day) or T (n = 11; 600 mg/day). After 16 weeks of treatment, a second OGTT was performed. Insulin sensitivity was calculated with homeostasis model assessment and with oral glucose insulin sensitivity (OGIS), which quantifies dynamic glucose clearance per unit change of insulin. Insulin secretion was assessed by modelling technique. Differences in these parameters before and after treatment, as well as possible relationships with cAMs, were assessed. Results: Basal and stimulated plasma glucose decreased after therapy in both the groups by approximately 20%. Basal insulin resistance also decreased. Insulin sensitivity in dynamic conditions (OGIS: ml/min/m2) increased with M (289.3 ± 18.8 vs. 234.7 ± 18.1, p < 0.02) and tended to improve with T (323.5 ± 18.1 vs. 286.8 ± 22.1, p = 0.09). Total insulin secretion over the OGTT [TIS: nmol/l(3 h)] tended to decrease with M (17.1 ± 2.5 vs. 27.3 ± 0.3, p = 0.08) but not with T (23.6 ± 3.5 vs. 22.5 ± 2.7). Plasma concentrations of E-Selectin decreased in T (38.0 ± 2.3 vs. 51.2 ± 6.1 ng/ml, p < 0.05). No correlation was found between insulin sensitivity and cAMs. Conclusions: Model-based indices of insulin sensitivity and secretion during an OGTT can be able to detect changes observed in patients under treatment with pharmacological agents such as M or T. Both the drugs improved glucose control similarly. Decreased plasma E-Selectin concentrations were seen in patients on T therapy only. [ABSTRACT FROM AUTHOR]

Abstract: A frequently used index of beta-cell function from the OGTT is the insulinogenic index, IGI. However, there is still some controversy about its validity. In a group of 145 women with different degrees of glucose tolerance, we compared IGI to the corresponding index with C-peptide, ΔCP30/ΔG 30, which better describes beta-cell function. We also validated both indices with measurements of beta-cell function derived from IVGTT. IGI strongly correlated (R =0.82, P <0.0001) with ΔCP30/ΔG 30. Both IGI and ΔCP30/ΔG 30 correlated significantly with the corresponding index from IVGTT, though IGI correlation was stronger (IGI: R =0.67, P <0.0001; ΔCP30/ΔG 30: R =0.56, P <0.0001). Also indices derived from areas under the curve of insulin, glucose and C-peptide were analyzed. Finally, we compared IGI to similar indices with samples at 60, 90 and 120min, more often available than that at 30min. We conclude that IGI is an acceptable index of beta-cell function, as also mirrored by ΔCP30/ΔG 30. However, the weaker correlation of the C-peptide index with the more accurate index from the IVGTT suggests that it should be used with caution. The index at 60min can be used as surrogate of IGI, but not the indices at 90 and 120min. [Copyright &y& Elsevier]

OBJECTIVE: Fetal insulin concentrations reflect the intra-uterine glucose load given the fetus by the mother. In this study, we assessed the association between maternal glucose levels during oral glucose tolerance testing and fetal cord insulin. METHODS: Pregnant women with an oral glucose tolerance test (OGTT) result were included in this prospective study. The patients were divided into 3 groups according to their 1-hour OGTT glucose concentration: up to 160 mg/dL (control, group I), 160 -179 mg/dL (intermediate, group II), and gestational diabetes mellitus (GDM, group III). Patients with GDM were assigned to insulin therapy if blood glucose levels were not in the preferable range. RESULTS: Of the 930 patients who entered the study, 570 (61.3%) were assigned to group 1,76 (8.2%) to group II, and 284 (30.5%) to group III. The cord blood insulin value was significantly (P < .001, Mann-Whitney test) higher in group II (median, 12.8 μU/mL; range, 3-130 μU/mL) than in group I (median, 7.25 μU/mL; range, < 3-98 μU/mL). Cord blood insulin values were higher, albeit not significantly (P = .100, Mann-Whitney test), in group II than in group III (median, 9.9 μU/mL; range, <3-61 μU/mL). CONCLUSION: Children whose mothers had a 1-hour value between 160 and 179 mg/dL had significantly higher cord blood insulin values than offspring of women with a 1-hour value below 160 mg/dL. [ABSTRACT FROM AUTHOR]

Women with previous gestational diabetes (pGDM) are frequently insulin-resistant, which could relate to intramyocellular lipid content (IMCL). IMCL were measured with ¹H nuclear magnetic resonance spectroscopy in soleus (IMCL-S) and tibialis-anterior muscles (IMCL-T) of 39 pGDM (32 ± 2 years, waist-to-hip ratio 0.81 ± 0.01) and 22 women with normal glucose tolerance (NGT; 31 ± 1 years, 0.76 ± 0.02) at 4-6 months after delivery. Body fat mass (BFM) was assessed from bioimpedance analysis, insulin sensitivity index (S[sub I]), and glucose effectiveness (S[sub G]) from insulin-modified frequently sampled glucose tolerance tests, pGDM exhibited 45% increased BFM, 35% reduced S[sub I] and S[sub G] (P < 0.05), and 40% (P < 0.05) and 55% (P < 0.005) higher IMCL-S and IMCL-T, respectively. IMCL related to body fat (BFM P < 0.005, leptin P < 0.03), but only IMCL-T correlated (P < 0.03) with S[sub I] and glucose tolerance index independent of BMI. Insulin-resistant pGDM (n = 17) had higher IMCL-S (+66%) and IMCL-T (+86%) than NGT and insulin-sensitive pGDM (+28%). IMCL were also higher (P < 0.005, P = 0.05) in insulinsensitive pGDM requiring insulin treatment during pregnancy and inversely related to the gestational week of GDM diagnosis. Thus, IMCL-T reflects insulin sensitivity, whereas IMCL-S relates to obesity. IMCL could serve as an additional parameter of increased diabetes risk because it identifies insulin-resistant pGDM and those who were diagnosed earlier and/or required insulin during pregnancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE — The relationship between splanchnic glucose uptake (SGU) after oral glucose administration and metabolic control in type 1 diabetic patients is controversial. We estimated SGU as well as peripheral glucose uptake and the time required for glucose absorption by a validated method, the oral glucose (OG) clamp, in type 1 diabetic patients with different levels of long-term glycemic control. RESEARCH DESIGN AND METHODS — An OG clamp (which combines a hyperinsulinemic clamp [120 mU · m[sup -2] · min[sup -1]] with an OR load [75 g] during steady state glucose uptake) was performed in eight type 1 diabetic patients with good metabolic control (DG) (HbA[sub 1c] 6.1 ± 0.2%, BMI 23.1 ± 0.7 kg/m²), eight type 1 diabetic patients with poor metabolic control (DP) (HbA[sub 1c] 8.5 ± 0.3%, BMI 25.4 ± 1.4 kg/m²), and eight healthy matched control subjects (C) (HbA[sub 1c] 5.1 ± 0.1%, BMI 25 ± 1.3 kg/m²) to determine SGU, glucose uptake, and glucose absorption. RESULTS — Glucose uptake calculated from 120 to 180 min during the clamp was 9.13 ± 0.55mg·kg[sup -1] min[sup -1] in C, 8.18 ± 0.71 mg·kg[sup -1] · min[sup -1] in DG, and 7.42 ± 0.96 mg·kg [sup -1] ·min[sup -1] in DP (NS). Glucose absorption was 140 ± 6 min in C, 156 ± 4 min in DG, and 143 ± 7 min in DP (NS). The respective calculated SGU was 14.5 ± 5.6% in C, 17.8 ± 3.1% in DG, and 18.8 ± 4.2% in DP (NS) and did not correlate with HbA[sub 1c] values. CONCLUSIONS — Peripheral glucose uptake, SGU after oral glucose administration, and the glucose absorption time were not different in type 1 diabetic patients independent of glycemic control when compared with healthy subjects. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusions To identify factors associated with neonatal respiratory distress (NRD) in early Gestational diabetes mellitus (eGDM).Nested case–control analysis of the TOBOGM trial.Seventeen hospitals: Australia, Sweden, Austria and India.Pregnant women, <20 weeks' gestation, singleton, GDM risk factors.Women with GDM risk factors completed an oral glucose tolerance test (OGTT) before 20 weeks: those with eGDM (WHO‐2013 criteria) were randomised to immediate or deferred GDM treatment. Logistic regression compared pregnancies with/without NRD, and in pregnancies with NRD, those with/without high‐dependency nursery admission for ≤24 h with those admitted for >24 h. Comparisons were adjusted for age, pre‐pregnancy body mass index, ethnicity, smoking, primigravity, education and site. Adjusted odds ratios (95% CI) are reported.NRD definition: ≥4 h of respiratory support (supplemental oxygen or supported ventilation) postpartum. Respiratory distress syndrome (RDS): Supported ventilation and ≥24 h nursery stay.Ninety‐nine (12.5%) of 793 infants had NRD; incidence halved (0.50, 0.31–0.79) if GDM treatment was started early. NRD was associated with Caesarean section (2.31, 1.42–3.76), large for gestational age (LGA) (1.83, 1.09–3.08) and shorter gestation (0.95, 0.93–0.97 per day longer). Among NRD infants, >24 h nursery‐stay was associated with higher OGTT 1‐h glucose (1.38, 1.08–1.76 per mmol/L). Fifteen (2.0%) infants had RDS.Identifying and treating eGDM reduces NRD risk. NRD is more likely with Caesarean section, LGA and shorter gestation. Further studies are needed to understand the mechanisms behind this eGDM complication and any long‐term effects. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the guideline recommended diagnostic tools NT-proBNP and NYHA classification, with a focus on sex-specific differences. Background: Patients with Type 2 Diabetes (T2D) face a heart failure (HF) risk up to four times higher than those without T2D, particularly affecting women more than twice as much as men. Despite distinct pathophysiological differences between men and women, there are currently no sex-specific recommendations for the diagnostic algorithm of HF in diabetic patients. Methods: A total of 2083 patients with T2D were enrolled, and the primary endpoint was heart failure during hospitalization within a 5-year timeframe. The secondary endpoint was all-cause death. Results: In female patients, frequency of HF diagnosis prior to or during hospitalization and mortality did not differ significantly between NYHA II and III, in contrast to male patients. Additionally, there was no notable difference in mean NT-proBNP levels between NYHA stage II and III only in female patients. The multivariable regression analysis highlighted NYHA classification not to be a predictor of NT-proBNP levels in female but solely in male patients. On multivariable Cox regression NYHA score was also no significant risk factor for occurence of HF in female patients. Furthermore, there was no significant disparity in mortality between men with NT-proBNP levels between 125 and 400 pg/ml and those below 125 pg/ml, whereas in women mortality was significantly higher in the group with NT-proBNP levels between 125 and 400 pg/ml than below 125 pg/ml. Conclusion: These findings suggest that NYHA classification may not be the most suitable tool for assessing the diagnosis of HF in female patients with T2D. Moreover, the need for consideration of a more symptom-independent screening for HF in female patients with T2D and re-evaluation of current guidelines especially regarding sex-specific aspects is highlighted. [ABSTRACT FROM AUTHOR]

Our aim is to investigate if sex and gender influence the association of hypertension and their comorbidities. We investigated how gender differences in five socioeconomic factors impact the relation between hypertension and ten comorbidities including diabetes mellitus, renal disease, and chronic pulmonary disease in European countries grouped by their gender inequality index using representative survey data from the European Health Interview Survey. Using logistic regressions, we compute the ratio of odds ratios in females versus males. Therefore, an ORR > 1 is associated with a higher odds ratio for females than for males while an ORR < 1 means the opposite. To account for multiple hypothesis testing, we applied the Bonferroni correction. Hypertension in both sexes was associated with lower educational level, being unemployed, and lower income. In males, being divorced/widowed (OR1.12, p < 0.001) had an association to hypertension, whereas in females, being common-law/married (OR1.30, p < 0.001) and being divorced/widowed (OR1.17, p < 0.001) was associated with a higher risk for hypertension. Moreover, in hypertension, females who worked had an association with myocardial infarction (OR1.39, p < 0.001) and having post-secondary education had an association with arthrosis (OR 1.35, p < 0.001) compared to males. Our findings show that gender variables influence the association of hypertension and comorbidities, especially in females. These results can be used to inform targeted prevention measures taking gender-specific contextual factors into account. [ABSTRACT FROM AUTHOR]

Looks a mathematical model that described beta-cell secretion during an oral glucose tolerance test (OGTT). Aim of the model; Techniques used in experiment; Findings; References to insulin, C-peptide and islet amyloid polypeptide.

In this article, the authors discuss various articles on pathophysiology of lipid and glucose metabolism in women with prior history of gestational diabetes mellitus, risk of developing type 2 diabetes and cardiovascular complications published in this issue of the periodical.

Diabetes is associated with micro- and macrovascular complications. The aim of the study was to investigate microvascular parameters (glycocalyx dimensions, perfused and total capillary density) in vivo in patients with type 1 and type 2 diabetes mellitus. In vivo sublingual videomicroscopy using sidestream darkfield - derived imaging was performed in 36 patients with diabetes mellitus (type 1: n = 20, type 2: n = 16) and compared to a control group of 36 healthy volunteers. Patients with HbA1c levels ≥ 8% had a significantly higher perfused boundary region (PBR; signifying the loss of glycocalyx dimensions) compared to patients with HbA1c levels < 8%, which was more pronounced in type 1 diabetes (2.08 μm [1.95–2.16 μm] vs.1.9 μm [1.66–1.94 μm], p =.029). Capillary density did not differ significantly between patients with diabetes and healthy controls. PBR was inversely related to RBC filling percentage and perfused capillary density in diabetic patients (r = −0.754, p <.001 and r = −0.505, p =.002, respectively) as well as in healthy volunteers (r = −0.701, p <.001 and r = −0.150, p = n.s.) signifying the association between glycocalyx dimensions and microvessel perfusion. Renal parameters were associated with microvascular perfusion in patients with type 2 diabetes (correlation between eGFR and perfused capillary density: r = 0. 568, p =.027/RBC filling percentage: r = 0.657, p =.008). In addition, the ratio of perfused/total capillary density correlated with CRP levels in type 2 diabetes (r = 0.682, p =.021). In conclusion, diabetes is associated with loss of glycocalyx density. • Sublingual microcirculation was visualized in diabetic patients using sidestream darkfield - derived videomicroscopy. • Loss of glycocalyx was associated with HbA1c levels ≥ 8%. • Glycocalyx dimensions correlated with microvessel perfusion • Reduced microvessel perfusion was associated with impaired renal function in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and offspring. GDM is diagnosed by an oral glucose tolerance test (OGTT) or fasting glucose concentrations in the diabetic range. In case of a high risk for GDM/type 2 diabetes (history of GDM or prediabetes impaired fasting glucose or impaired glucose tolerance]; malformation, stillbirth, successive abortions or birth-weight > 4500 g in previous pregnancies) performance of the OGTT (120 min; 75 g glucose) is recommended already in the first trimester and -- if normal -- the OGTT should be repeated in the second/third trimester. In case of clinical symptoms of diabetes (glucosuria, macrosomia) the test has to be performed immediately. All other women should undergo a diagnostic test between 24 and 28 gestational weeks. If fasting plasma glucose exceeds 95 mg/dl, 1 h 180 mg/dl and 2 hrs 155 mg/dl after glucose loading (OGTT) the woman is classified as GDM (one pathological value is sufficient). In this case a strict metabolic control is mandatory. All women should receive nutritional counseling and be instructed in blood glucose self-monitoring. If blood glucose levels cannot be maintained in the normal range (fasting < 95 mg/dl and 1 h after meals < 130 mg/dl) insulin therapy should be initiated. Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g OGTT (WHO criteria). [ABSTRACT FROM AUTHOR]

Given the steady increase in the use of oral antidiabetic medication, better knowledge of their effects on neonatal outcomes in gestational diabetes mellitus is essential. Recently, Marie-Victoire Sénat and colleagues investigated the use of glyburide over standard insulin treatment in a noninferiority multicentre randomized trial, which found higher risk of perinatal complications under glyburide therapy. [ABSTRACT FROM AUTHOR]

Background: There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes. Methods: This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7–6.4% [40–47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof. Results: Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1–4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95–2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29–2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15–10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years. Conclusions: In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936. [ABSTRACT FROM AUTHOR]

Background: Following years of pandemic severe acute respiratory syndrome coronavirus 2 infections labelled Covid-19, long lasting impairment summarized as post-Covid syndrome (PCS) challenges worldwide healthcare. Patients benefit from rehabilitation programs, but sex specific aspects of improvement remain little understood. The aim of the study was to assess whether women and men differ in response to outpatient pulmonary rehabilitation for PCS. Methods: 263 (54.4% female) patients partaking in outpatient pulmonary rehabilitation (OPR) due to PCS between March 2020 and July 2022 were included in a prospective observational cohort study. Outcomes were assessed at baseline and before discharge from OPR and included six-minute walking distance (6MWD), 1-second forced expiratory volume (FEV1), diffusion capacity for carbon monoxide, maximal inspiratory pressure (MIP), dyspnea (medical research council scale), and post-Covid functional status scale (PCFS). Sexspecific changes in outcomes following OPR were assessed by linear mixed model and presented as mean differences (MD) with 95% confidence intervals. Linear regression was applied to test whether 6MWD correlates with PCFS and the minimal clinically important difference (MCID) in 6MWD regarding an improvement of at least one point in PCFS was computed with logistic regression. Results: Significant improvement throughout OPR was observed for all outcomes (all p < 0.0001). Despite less severe Covid-19 infections, PCFS scores remained higher in females after OPR (p = 0.004) and only 19.4% of women compared to 38.5% of men achieved remission of functional impairment. At baseline as well as after OPR, females showed higher symptom load compared to men in dyspnea (p = 0.0027) and scored lower in FEV1 (p = 0.009) and MIP (p = 0.0006) assessment. Performance in 6MWD was comparable between men and women. An increase of 35 m in 6MWD was computed as minimal clinically important difference to improve functional impairment. Conclusion: Both subjective symptoms such as fatigue and dyspnea and objective impairment in performance in pulmonary function were more frequently observed among women. Despite improvement throughout OPR in both women and men, the sex-gap in symptom load could not be closed as women less often achieved remission from functional impairment due to PCS. Intensified treatment of these symptoms should be considered in women undergoing rehabilitation for PCS. Plain english summary: While female sex is protective during the acute infection of Covid-19, women are at increased risk of developing post-Covid syndrome (PCS) even after only mild Covid-19 infections. Severity and frequency of symptoms such as fatigue and shortness of breath are known to be higher in women compared to men. Many different rehabilitation protocols are used for PCS, but a knowledge gap regarding sex related differences in rehabilitation success remains. Both female and male patients with PCS undergoing outpatient pulmonary rehabilitation improved in the maximum walking distance achieved within 6 min and selfrated impairment in everyday living. Although women less frequently required inpatient treatment for acute Covid-19 infection, female patients with PCS showed higher impairment in everyday living, lower capacity of physical exercise and more frequent shortness of breath, fatigue and breathing muscle weakness. Only 19.4% of women compared to 38.5% of men achieved complete remission of impairment in everyday living. Our results show that women treated for PCS retain greater symptom burden and are at risk of unsuccessful rehabilitation, calling for more targeted treatment in female patients after Covid-19 infection. Highlights: Six weeks of outpatient pulmonary rehabilitation successfully improved 6-minute walking distance, pulmonary function and Covid-19 related functional limitations in daily living. Women achieved remission of functional limitations less often than men (19.4% vs. 38.5%). Women reported more severe dyspnea and showed greater impairment of maximal inspiratory pressure and forced expiratory volume compared to men. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Metabolic syndrome is a major risk factor for cardiovascular diseases. • Sex, and gendered related variables are important consideration for development of MetS. • older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. • 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. • Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6–8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes. [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]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). In consideration of emerging evidence that there are clinically relevant sex-related differences in the course of T2DM and subsequent cardiovascular outcomes, it is unknown if SGLT2i therapy is sex-independently utilized in daily clinical practice. Methods: Patients with T2DM and HF admitted to a tertiary academic center between January 2014 and April 2020 were identified through a search of electronic health records. Data on antidiabetic therapy were acquired at discharge and were screened for SGLT2i prescription. Results: Overall, 812 patients (median age 70 years, 29.7% female) were included in the present analysis. Only 17.3% of the study population received an SGLT2i. In comparison between sexes, females show lower rates of SGLT2i prescription (11.2% vs. 19.8%, p = 0.003), despite comparable patient characteristics. Furthermore, male HF patients showed a significantly higher probability of SGLT2i prescription with an adjusted odds ratio of 2.59 (95% confidence interval 1.29–5.19; p = 0.008). Females who did not receive an SGLT2i showed higher rates of chronic kidney disease (25.2% vs. 7.4%, p = 0.039) and greater levels of N-terminal pro b-type natriuretic peptide (NT-proBNP; 2092 vs. 825 pg/mL, p = 0.011) as compared to female SGLT2i recipients, which did not explain the observed sex-related disparities. Conclusion: SGLT2i are potentially underutilized in female patients with HF and T2DM, despite an overall increasing prescription trend during the observation period. Reasons for withholding therapy could not be objectified. The present data indicate a major need to increase awareness of guideline-directed therapy, especially in female HF patients. [ABSTRACT FROM AUTHOR]

We aimed to investigate the effect of gender-affirming hormone therapy (GAHT) on cardiovascular disease risk factors focusing on glucose tolerance. This primarily translational study enrolled 16 transgender persons assigned female at birth (AFAB), 22 assigned male at birth (AMAB), and 33 age- and BMI-matched cisgender controls at the Medical University of Vienna from 2013 to 2020. A 3-Tesla MRI scan to measure intramyocardial, pancreatic, hepatic fat content and subcutaneous-to-visceral adipose tissue ratio (SAT/VAT-ratio), an oral glucose tolerance test (oGTT), bloodwork including brain natriuretic peptide (pro-BNP), sex hormones and two glucose-metabolism related biomarkers (adiponectin, betatrophin) were performed. Estrogen intake was associated with higher fasting insulin (p = 0.034) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p = 0.037), however, lower HbA1c levels (p = 0.031) in AMAB than cisgender males. Adiponectin (p = 0.001) and betatrophin (p = 0.034) levels were higher in AMAB than cisgender males, but similar to cisgender females. Compared to cisgender females, AFAB displayed no differences in glucose metabolism or SAT/VAT-ratio. AFAB had lower pro-BNP levels (p = 0.014), higher liver enzymes (AST: p = 0.011; ALT: p = 0.012) and lower HDL levels (p = 0.017) than cisgender females, but comparable levels to cisgender males. AMAB showed an increased heart rate (p < 0.001) and pro-BNP (p = 0.002) levels, but a more favorable SAT/VAT-ratio (p = 0.013) and lower creatine kinase (CK) (p = 0.001) than cisgender males. There were no relevant differences in organ fat content between transgender persons and their respective cisgender controls. In AMAB, most investigated parameters adapted to levels seen in cisgender females except for parameters related to fasted insulin resistance. AMAB should be monitored with respect to the development of insulin resistance. [ABSTRACT FROM AUTHOR]

Hyperglycemia contributes to morbidity and mortality in diabetic patients. Reaching treatment targets with regard to control of glycemia is thus a central goal in the treatment of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of oral antidiabetic drugs according to current scientific evidence. [ABSTRACT FROM AUTHOR]

Hyperglycemia contributes to morbidity and mortality in diabetic patients. Reaching treatment targets with regard to control of glycemia is thus a central goal in the treatment of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of insulin according to current scientific evidence. [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]

Brain aging is a naturally occurring process resulting in the decline of cognitive functions and increased vulnerability to develop age‐associated disorders. Fluctuation in lipid species is crucial for normal brain development and function. However, impaired lipid metabolism and changes in lipid composition in the brain have been increasingly recognized to play a crucial role in physiological aging, as well as in several neurodegenerative diseases. In the last decades, the role of sexual dimorphism in the vulnerability to develop age‐related neurodegeneration has increased. However, further studies are warranted for detailed assessment of how age, sex, and additional non‐biological factors may influence the lipid changes in brains. The aim of this work is to address the presence of sex differences in the brain lipid changes that occur along aging, and in the two most common age‐related neurodegenerative disorders (Alzheimer's and Parkinson's diseases). We included the studies that assessed lipid‐related alterations in the brain of both humans and experimental models. Additionally, we explored the influence of sex on lipid‐lowering therapies. We conclude that sex exerts a notable effect on lipid modifications occurring with age and neurodegeneration, and in lipid‐reducing interventions. Therefore, the application of sex as an experimental variable is strongly encouraged for future research in the field of precision medicine approach. [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]

Background: Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF. Methods: KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables. Results: Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010). Conclusions: In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF. Plain language summary: Chronic kidney disease (CKD) is a condition that affects the kidneys and increases the risk of heart problems. Males and females may experience CKD differently, and our study aimed to understand the differences in the development of calcification in the blood vessels of the heart (coronary artery calcification, or CAC) and the heart valves (aortic valve calcification, or AVC) between males and females with CKD. We analysed 214 males and 107 females with CKD who had undergone a heart scan (computer tomography, or CT) to measure CAC and AVC. We collected information on age, diabetes, cardiovascular disease, and markers of inflammation and oxidative stress. Our results showed that in both males and females CAC was associated with age. In males, CAC was associated with diabetes and cardiovascular disease, while in females, it was linked to markers of inflammation. In females, CAC was also associated with mortality regardless of age. Unfortunately, we had insufficient samples of females with AVC for analysis. However, in males AVC was associated with age and inflammation. Overall, our study indicates sex-specific differences in the development of calcification in the blood vessels and heart valves of CKD patients. In females, inflammation and oxidative stress are associated with CAC, while in males, oxidative stress and inflammation are associated with CAC and AVC, respectively. These findings underscore the importance of considering these differences when assessing cardiovascular complications in CKD patients. It may help in developing personalised treatment approaches for both males and females with CKD. Highlights: The gold standard technique of computer-tomography was used to measure coronary artery calcification (CAC) and aortic valve calcification (AVC) scores in males and females with kidney failure. In male kidney failure patients age and inflammatory burden was significantly associated with AVC. In addition, cardiovascular disease, diabetes, and oxidative stress were significantly associated with CAC score. In female kidney failure patients age, oxidative stress, and inflammation were significantly associated with CAC score. Cardiovascular calcification presents with a sex-specific biomarker signature that may affect cardiovascular complications in males and females with kidney failure. [ABSTRACT FROM AUTHOR]

Background: Accuracy of the FreeStyle Libre™ Flash Glucose Monitoring System has not been evaluated in pregnant women with diabetes. The aim of this study was to determine accuracy (compared to self-monitoring of blood glucose [SMBG]), clinical safety, and acceptability of the FreeStyle Libre System when used at home by this population.Materials and Methods: Seventy-four participants, with type 1 (T1D, n = 24), type 2 (T2D, n = 11), or gestational (n = 39) diabetes, were enrolled across 13 sites (9 in United Kingdom, 4 in Austria). Average gestation was 26.6 ± 6.8 weeks (mean ± standard deviation), age was 30.5 ± 5.1 years, diabetes duration was 13.1 ± 7.3 years for T1D and 3.2 ± 2.5 years for T2D, and 49/74 (66.2%) used insulin to manage their diabetes. Sensors were worn for up to 14 days. Sensor glucose values (masked) were compared with capillary SMBG values (made at least 4 times/day).Results: Clinical accuracy of sensor results versus SMBG results was demonstrated, with 88.1% and 99.8% of results within Zone A and Zones A and B of the Consensus Error Grid, respectively. Overall mean absolute relative difference was 11.8%. Sensor accuracy was unaffected by the type of diabetes, the stage of pregnancy, whether insulin was used, age or body mass index. User questionnaires indicated high levels of satisfaction with sensor wear, system use, and comparison to SMBG. There were no unanticipated device-related adverse events.Conclusions: Good agreement was demonstrated between the FreeStyle Libre System and SMBG. Accuracy of the system was unaffected by patient characteristics, indicating that the system is safe and accurate to use by pregnant women with diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the RESULTS of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of >4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9°/o). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 g in the immediate-treatment group and 2.91 g in the control group (adjusted mean difference, -0.04 g; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.). [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]

Simple Summary: Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important contributing factor. Preclinical models are crucial for exploring and understanding the physiology of the heart and age-related changes, as well as cardiac pathological aspects. In line with this, the Octodon degus (O. degus) is a diurnal rodent that has been claimed as an interesting model for aging research. However, several aspects of this experimental model are not fully characterized yet. In this work, we evaluated the cardiac electric activity by electrocardiogram recording in the aging process, considering differences between males and females. We provide the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. Our results demonstrate that both age and sex influence the cardiac function and the incidence of arrhythmias. Therefore, this research indicates that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex. Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the O. degus during the aging process in both females and males. Taking into account the age and sex, our study provides the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. We found that the QRS complex duration and QTc significantly increased with age, whereas the heart rate significantly decreased. On the other hand, the P wave, PR and QTc segments durations, S wave voltage and electrical axis were found to be significantly different between males and females. The heart rhythm was also altered in aged animals, resulting in an increased incidence of arrhythmias, especially in males. Based on these results, we suggest that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex. [ABSTRACT FROM AUTHOR]

Many cells adapt to hyperosmolal conditions by upregulation of organic osmolytes to maintain cell function and integrity. Glycerophosphocholine (GPC), a recognized osmolyte in renal medullary cells, is the major phosphodiester (PDE) in human skeletal muscle, wherefore we hypothesized muscular GPC to be associated with surrogate parameters of fluid status and osmolality in healthy humans. The objective of this study was to investigate the relationship of muscular GPC with surrogate parameters of body fluid status and osmolality. We analyzed data of 30 healthy volunteers who underwent noninvasive 31P-magnetic resonance spectroscopy of either calf (n = 17) or thigh (n = 13) muscle. Therefore, we conducted correlation analyses between phosphor metabolites, and blood values depicting body fluid status and osmolality. Relevant parameters were further implemented in a multivariable regression model to evaluate if GPC concentrations can depict variations in fluid and electrolyte balance. Uric acid (0.437, P = 0.018) and urea (0.387, P = 0.035) were significantly correlated with GPC, which in case of uric acid was independent of sex. Considering sex, following multivariable regression reported GPC as suitable parameter to predict uric acid (R² = 0.462, adjusted R² = 0.421; P < 0.001). Our data indicate a connection between muscular GPC concentrations and uric acid, which is a marker of body fluid status, in healthy human subjects, suggesting that skeletal muscle might regulate GPC content in adaptation to changes in fluid status. [ABSTRACT FROM AUTHOR]

Pre-existing type 2 diabetes at the time of planning pregnancy and in pregnancy In principle, type 2 diabetes mellitus is associated with the same fetal risks as type 1 diabetes mellitus. Lifestyle Accompanying drug therapy in type 2 diabetes and pregnancy, the lifestyle recommendations generally applicable to diabetes, as well as the general recommendations for weight gain in pregnancy dependent on pre-conceptional weight, should also be followed. The spectrum of malformations associated with maternal diabetes (type 1 diabetes/type 2 diabetes) includes, in particular, congenital heart defects (2.3-4%, approximately 4-fold increased compared to women without diabetes), neural tube defects (1.2-2.5%, 2- to 3-fold increased), skeletal anomalies, omphaloceles, malformations of the urinary tract, and biliary atresia with splenic anomalies [32][33][34][35]. Oral anti-diabetic agents for women with established diabetes/impaired glucose tolerance or previous gestational diabetes planning pregnancy, or pregnant women with pre-existing diabetes. [Extracted from the article]

If there are indications of GDM (polyhydramnios, macrosomia with abdominal circumference (AC)>head circumference (HC) or severe glucosuria), there is also an indication to retest for GDM with a diagnostic 75-g-oGTT in the third trimester in case of a negative screening in the 24 SP th sp -28 SP th sp weeks of gestation. The risk of conversion to manifest diabetes is increased in pre-conception obese women, Asian women, GDM diagnosis<24 SP th sp week of pregnancy, insulin therapy, oGTT value>=200 mg/dl (11.1 mmol/l) during pregnancy for 1 hour, HbA1c>=5.7% at the time of GDM diagnosis. Diagnostics of GDM after bariatric surgery GDM diagnosis via an oral glucose tolerance test is not possible (dumping phenomenon) after surgical procedures that influence resorption. An overview of conflicts of interest can be found at: https://www.awmf.org/fileadmin/user upload/Leitlinien/057 D Diabetes Ges/057-008i S3 Gestationsdiabetes-mellitus-GDM-Diagnostik-Therapie-Nachsorge 2018-03.pdf Notice of update The DDG practice recommendations are updated regularly during the second half of the calendar year. [Extracted from the article]

Objective: The COVID-19 pandemic influences mental health drastically. Therefore, our aim was to investigate whether biological sex and gender-related factors are associated with mental health during the COVID-19 pandemic. Materials and Methods: The International COVID-19 Awareness and Responses Evaluation Study is an international multiwave cross-sectional observational cohort study of public awareness, attitudes, and responses to public health policies (www.mbmc- cmcm.ca/covid19). The study is led by the Montreal Behavioural Medicine Centre in collaboration with 200 international collaborators from 42 countries. It has received research ethics board approval from the Comité d'éthique de recherche du CIUSSS-NIM (Centre intégré universitaire de santé et de services sociaux du Nord- de-l'île-de-Montréal), approval no.: 2020-2099/25-03-2020. Recruitment began on March 27, 2020, and the survey is available in 34 languages. The associations between biological sex, sociocultural gender, and mental health were assessed in multivariate logistic regression models only for the European population (n = 12,300). Results: Positive correlations were found between female sex and "feeling nervous, anxious or worried" (OR = 3.2, p < 0.001, 95% CI 1.87–5.63) and "feeling sad, depressed or hopeless" (OR 1.8, p = 0.031, CI 1.05–3.05). Male sex was related to more frequently "feeling irritable, frustrated, and angry" (OR = 1.8, p = 0.04, 95% CI 1.03–2.99). Concerning gender, a negative correlation between being employed and "feeling lonely or isolated" (OR = 0.26, p < 0.001, 95% CI 0.11–0.59) was observed in the female cohort. Conclusion: Sex and gender differences exist in the emotional responses during the COVID-19 pandemic. Especially, within the female cohort, unemployment is negatively associated with mental health. Therefore, this study suggests more targeted psychological and social support for females during the pandemic. [ABSTRACT FROM AUTHOR]

Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems. Physiologically reasonable population mean estimates were obtained for all estimated model parameters, including plasma volume, interstitial volume of the peripheral circulation (mainly skeletal muscle), uptake clearance into the interstitial space, hepatic and renal clearance, as well as total insulin delivery into plasma. The results indicate that, at a population level, the proposed physiologically based model provides a useful description of insulin disposition, which allows for the assessment of muscle insulin uptake. [ABSTRACT FROM AUTHOR]