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Background: Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy. Objective: To explore the relationships between self‐reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy. Methods: Cross‐sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks' gestation to evaluate sleep. BMI <25 kg/m2 served as the reference group in multivariable logistic regression. Results: Among the 2865 women included, the prevalence of overweight and obesity classes I‐III was 28%, 19%, 11% and 12%, respectively. There was no relationship between sleep duration and BMI. The risk of insufficient sleep >5 days/month was higher in class II and class III obesity (1.38 (1.03–1.85) and 1.34 (1.01–1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25–2.02), 2.68 (2.07–3.48), 4.35 (3.21–5.88) to 4.96 (3.65–6.74), respectively)). Conclusions: Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI. [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]

Background: Individuals with chronic kidney disease are affected by acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) due to multiple comorbidities and altered immune system. The first step of the infection process is the binding of SARS‐CoV‐2 with angiotensin‐converting enzyme 2 (ACE2) receptor, followed by its priming by transmembrane protease serine 2 (TMPRSS2). We hypothesized that circulating soluble ACE2 levels, as well as the expressions of ACE2 and TMPRSS2 in the microvasculature, are increased in patients with end‐stage kidney disease (ESKD). Methods: A total of 210 participants were enrolled, representing 80 ESKD patients and 73 non‐CKD controls for soluble ACE2, and 31 ESKD and 26 non‐CKD controls for vasculature and fat tissue bioassays. We have assessed ACE2 expression in blood using ELISA and in tissue using immunofluorescence. Results: Soluble ACE2 levels were higher in ESKD patients compared to controls; however, there is no sex difference observed. In ESKD and controls, soluble ACE2 positively correlated with Interleukin 6 (IL‐6) and C‐reactive protein (CRP), respectively. Similarly, ACE2 tissue expression in the vasculature was higher in ESKD patients; moreover, this higher ACE2 expression was observed only in male ESKD patients. In addition, TMPRSS2 expression was observed in vessels from males and females but showed no sex difference. The expression of ACE2 receptor was higher in ESKD patients on ACE‐inhibitor/angiotensin blocker treatment. Conclusion: ESKD is associated with increased ACE2 levels in the circulation and pronounced in male vasculature; however, further studies are warranted to assess possible sex differences on specific treatment regime(s) for different comorbidities present in ESKD. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. Design: Multicentre randomised controlled trial. Setting: Hospitals in nine European countries. Population: A cohort of 112 pregnant women with placental tissue. Methods: Both ST and moderate‐to‐vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. Main outcome measures: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR‐γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. Results: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin–glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR‐γ on neonatal sum of skinfolds (P < 0.05). Conclusions: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese. Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese. [ABSTRACT FROM AUTHOR]

Objective: Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to intramyocellular lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (1H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control.Methods: Acetylcarnitine and intramyocellular lipid concentrations were measured in 35 individuals stratified into three groups according to glucose tolerance and/or manifestation of type 2 diabetes mellitus. All MRS measurements were performed on a 3-T MR system.Results: The differences in patient phenotype were mirrored by increased intramyocellular lipids in the tibialis anterior and decreased acetylcarnitine concentrations in the soleus muscle of type 2 diabetes patients when compared with normal glucose-tolerant individuals. Results suggest that intramyocellular lipids mirror whole-body glucose tolerance better in the tibialis anterior muscle, whereas acetylcarnitine is a better discriminator in the soleus muscle.Conclusions: This muscle-specific behavior of metabolites could represent different fiber compositions in the examined muscles and should be considered when planning future metabolic studies. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) and anxiety disorders are both common and especially challenging during pregnancy. Considering possible risks of intrauterine drug exposure of the child, the role of psychopharmacological treatment is ambiguous and various negative obstetric outcomes were inconsistently associated with medication. Consequently, a critical examination of peri‐ and postnatal phenomena associated with intrauterine exposure to antidepressants based on serotonin reuptake inhibition (SRI) and subsumed under the term "poor neonatal adaptation syndrome" (PNAS) is urgently called for. Methods: A comprehensive literature search was conducted, revealing a total number of 33 relevant studies and 69 individual outcomes among 3025 screened studies. Seventeen outcomes allowed meta‐analytic evaluation (random effects model). Measures for heterogeneity (I2) and contour‐enhanced funnel plots were generated. Results: Single studies showed increased risks for deficits in neurological functioning and autonomous adaptation in SRI exposed infants. Meta‐analytical evaluation showed increased symptom occurrence or severity in exposed neonates for low APGAR scores, birth weight, size for gestational age, preterm delivery, neuromuscular and autonomous regulation, and higher rates of admission to specialized care. Mostly, increased risk after SRI exposure was supported by comparison to unexposed infants born to mothers diagnosed with depression. Conclusion: Whereas statistically significant evidence for various effects of intrauterine exposure to SRI was found, the clinical relevance remains unresolved because of inherently low data quality in this research domain and insufficiently defined samples and outcomes. More systematic research under ethical considerations is required to improve multiprofessional counseling in the many women dealing with MDD during pregnancy and the peripartum. [ABSTRACT FROM AUTHOR]

Summary: Recent human and animal studies have found associations between gut microbiota composition and serum levels of sex hormones, indicating that they could be an important factor in shaping the microbiota. However, little is known about the effect of regular hormonal fluctuations over the menstrual cycle or CHC‐related changes of hormone levels on gut microbiota structure, diversity and dynamics. The aim of this study was to investigate the effect of CHCs on human gut microbiota composition. The effect of CHC pill intake on gut microbiota composition was studied in a group of seven healthy pre‐menopausal women using the CHC pill, compared to the control group of nine age‐matched healthy women that have not used hormonal contraceptives in the 6 months prior to the start of the study. By analysing the gut microbiota composition in both groups during one menstrual cycle, we found that CHC usage is associated with a minor decrease in gut microbiota diversity and differences in the abundance of several bacterial taxa. These results call for further investigation of the mechanisms underlying hormonal and hormonal contraceptive‐related changes of the gut microbiota and the potential implications of these changes for women's health. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. Methods: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012–2014). In women with a BMI ≥29 kg/m2, insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first‐phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM‐R (above‐median insulin resistance alone), GDM‐S (below‐median insulin secretion alone), and GDM‐B (combination of both) and the few remaining women were excluded. Results: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM‐R group (n = 143) had higher fasting and post‐load glucose values and insulin levels, with a greater risk of having large‐for‐gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50–7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20–4.40)]. Women in the GDM‐S (n = 37) and GDM‐B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. Conclusions: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both. [ABSTRACT FROM AUTHOR]

Aim: To assess predictors of in‐hospital mortality in people with prediabetes and diabetes hospitalized for COVID‐19 infection and to develop a risk score for identifying those at the greatest risk of a fatal outcome. Materials and Methods: A combined prospective and retrospective, multicentre, cohort study was conducted at 10 sites in Austria in 247 people with diabetes or newly diagnosed prediabetes who were hospitalized with COVID‐19. The primary outcome was in‐hospital mortality and the predictor variables upon admission included clinical data, co‐morbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and to develop a risk score for in‐hospital mortality. Results: The mean age of people hospitalized (n = 238) for COVID‐19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy and 24.4% died in the hospital. The mortality rate in people with diabetes was numerically higher (26.7%) compared with those with prediabetes (14.9%) but without statistical significance (P =.128). A score including age, arterial occlusive disease, C‐reactive protein, estimated glomerular filtration rate and aspartate aminotransferase levels at admission predicted in‐hospital mortality with a C‐statistic of 0.889 (95% CI: 0.837‐0.941) and calibration of 1.000 (P =.909). Conclusions: The in‐hospital mortality for COVID‐19 was high in people with diabetes but not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient variables showed excellent predictive performance for assessing in‐hospital mortality. [ABSTRACT FROM AUTHOR]

Objectives: Predictors for unfavorable treatment outcome in major depressive disorder (MDD) applicable for treatment selection are still lacking. The database of a longitudinal multicenter study on 1079 acutely depressed patients, performed by the German research network on depression (GRND), allows supervised and unsupervised learning to further elucidate the interplay of clinical and psycho‐sociodemographic variables and their predictive impact on treatment outcome phenotypes. Experimental Procedures: Treatment response was defined by a change of HAM‐D 17‐item baseline score ≥50% and remission by the established threshold of ≤7, respectively, after up to eight weeks of inpatient treatment. After hierarchical symptom clustering and stratification by treatment subtypes (serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotic, and lithium augmentation), prediction models for different outcome phenotypes were computed with random forest in a cross‐center validation design. In total, 88 predictors were implemented. Results: Clustering revealed four distinct HAM‐D subscores related to emotional, anxious, sleep, and appetite symptoms, respectively. After feature selection, classification models reached moderate to high accuracies up to 0.85. Highest accuracies were observed for the SSRI and TCA subgroups and for sleep and appetite symptoms, while anxious symptoms showed poor predictability. Conclusion: Our results support a decisive role for machine learning in the management of antidepressant treatment. Treatment‐ and symptom‐specific algorithms may increase accuracies by reducing heterogeneity. Especially, predictors related to duration of illness, baseline depression severity, anxiety and somatic symptoms, and personality traits moderate treatment success. However, prospectives application of machine learning models will be necessary to prove their value for the clinic. [ABSTRACT FROM AUTHOR]

Background: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity.Objectives: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed.Methods: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest.Results: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at <20 weeks was directly associated with neonatal adiposity (β = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (β = 0.26 mm, 95% CI 0.08, 0.44).Conclusions: The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes. [ABSTRACT FROM AUTHOR]

The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second‐line treatment after metformin and are often ranked at the same level as newer glucose‐lowering medications. Strong evidence now shows that sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT‐2is and GLP‐1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT‐2is and/or GLP‐1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second‐line agents continues to be acceptable in resource‐constrained settings. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To investigate the importance of time in pregnancy and neonatal sex on the association between maternal metabolic parameters and neonatal sum of skinfolds. Methods: This was a longitudinal, secondary analysis of the vitamin D and lifestyle intervention for gestational diabetes mellitus study, conducted in nine European countries during 2012 to 2015. Pregnant women with a pre‐pregnancy body mass index (BMI) of ≥29 kg/m2 were invited to participate. We measured 14 maternal metabolic parameters at three times during pregnancy: <20 weeks, 24 to 28 weeks, and 35 to 37 weeks of gestation. The sum of four skinfolds assessed within 2 days after birth was the measure of neonatal adiposity. Results: In total, 458 mother‐infant pairs (50.2% female infants) were included. Insulin resistance (fasting insulin and HOMA‐index of insulin resistance) in early pregnancy was an important predictor for boys' sum of skinfolds, in addition to fasting glucose and maternal adiposity (leptin, BMI and neck circumference) throughout pregnancy. In girls, maternal lipids (triglycerides and fatty acids) in the first half of pregnancy were important predictors of sum of skinfolds, as well as fasting glucose in the second half of pregnancy. Conclusions: Associations between maternal metabolic parameters and neonatal adiposity vary between different periods during pregnancy. This time‐dependency is different between sexes, suggesting different growth strategies. [ABSTRACT FROM AUTHOR]

Aims: To investigate the mechanism of action of 55P0251, a novel multiflorine‐derived substituted quinazolidine that augments insulin release and lowers blood glucose in rodents, but does not act via mechanisms addressed by any antidiabetic agent in clinical use. Materials and Methods: Using male mice, we determined the effects of 55P0251 on glucose tolerance, insulin secretion from isolated islets and blood oxygen saturation, including head‐to‐head comparison of 55P0251 to its inverted enantiomer 55P0250, as well as to other anti‐hyperglycaemic multiflorine derivatives discovered in our programme. Results: 55P0251 was clearly superior to its inverted enantiomer in the glucose tolerance test (area under the curve: 11.3 mg/kg 55P0251, 1.19 ± 0.04 min*mol/L vs 55P0250, 1.80 ± 0.04 min*mol/L; P <.0001). For insulin release in vitro, this superiority became visible only under concomitant adrenergic background stimulation (glucose‐stimulated insulin release, fmol*islet−1*30 min−1: without α2‐adrenoceptor agonist: 500 μmol/L 55P0251, 390 ± 34, vs 55P0250, 459 ± 40, nonsignificant; with α2‐adrenoceptor agonist: 250 μmol/L 55P0251, 138 ± 9, vs 55P0250, 21 ± 6; P <.0001). Since receptor binding assays suggested antagonism at α2A‐adrenoceptors as a potential mechanism of action, we measured oxygen saturation in capillary blood from the tail as a surrogate of vasoconstriction, which supported α2‐antagonistic action in vivo (90 mg/kg 55P0251, 83 ± 3%, vs 55P0250, 57 ± 3%; P <.0001). Lack of association between glucose‐lowering activities and α2A‐adrenoceptor binding affinity arising from comparison of multiflorine derivatives was attributed to differences in their pharmacokinetic properties. Conclusions: Our findings suggest that 55P0251 and related multiflorine derivatives are to be categorized as α2‐adrenoceptor antagonists with potential to lower blood glucose by blocking α2A‐adrenoceptors on pancreatic β cells. [ABSTRACT FROM AUTHOR]

Background: Based on biological and behavioural diversity sex and gender may affect comorbidities associated with prediabetes and diabetes. Besides evaluating the prevalence of prediabetes and diabetes (using fasting plasma glucose and HbA1c levels), the primary aim of the study is to investigate sex and gender differences in the prevalence of comorbidities in subjects with prediabetes and diabetes and to identify possible risk factors associated with prediabetes and diabetes. Design: This observational, population‐based cohort study included 11.014 subjects aged 6‐80 years. Examinations included blood samples, ankle‐brachial index, ECG, dual‐energy X‐ray absorptiometry scan and an interviewer‐administered questionnaire. Results: Across all ages, prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%), and 5.4% for diabetes (male 7.3%; female 3.7%). The prevalence of prediabetes ranged from 4.4% (6‐<10 years) up to 40.4% (70+ years) in men and from 4.8% up to 42.3% in women. Comorbidity profile was markedly different between male and female, particularly in those with prediabetes: women more often suffered from arrhythmia, noncoronary artery disease, osteoporosis, increased systemic inflammatory biomarkers and depression, while men with prediabetes more often showed angina pectoris, myocardial infarction and media sclerosis. Conclusions: The unexpected 4.6% prevalence of prediabetes in children aged 6‐10 underscores the need for population‐based studies across all ages and the onset of prevention of diabetes at a young age. Marked differences have been found in comorbidities as men with prediabetes and diabetes more often suffer from cardiovascular disease, while women more often show arrhythmia, noncoronary artery disease, increased systemic inflammatory biomarkers and depression. [ABSTRACT FROM AUTHOR]

Objectives: Clinical variables were investigated in the 'treatment resistant depression (TRD)‐ III' sample to replicate earlier findings by the European research consortium 'Group for the Study of Resistant Depression' (GSRD) and enable cross‐sample prediction of treatment outcome in TRD. Experimental procedures: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. Results: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD‐I. Conclusion: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD‐III enabled robust prediction of treatment outcome in TRD‐I. [ABSTRACT FROM AUTHOR]

Introduction: According to the European Agency for Safety and Health at Work (EU‐OSHA), hospitals represent a work environment with high job strain. Prolonged perceived occupational stress may result in symptoms of burnout, such as emotional exhaustion (EE), depersonalisation (DP) and reduced personal accomplishment (PA). Understanding which factors may reduce vulnerability for burnout is an important requirement for well‐targeted occupational stress prevention in mental hospital staff. Objective: To identify the influence of gender, age, working field, family structure, education, voluntarily occupational training during holidays and length of stay on job on occupational stress perception. Methods: In a cross‐sectional design, 491 employees (311 female, 180 male) of an Austrian mental health centre participated in the study. The extent of perceived occupational stress was assessed by the Maslach Burnout Inventory (MBI) with the scales for emotional exhaustion, depersonalisation and personal accomplishment. Participants were divided according to their working field in those working with/without patients. Findings: Prevalence of emotional exhaustion was higher in women working with patients compared to men working with patients (25% vs. 18%, p = 0.003). Age above 45 years was significantly associated with decreased vulnerability for burnout in men (EE p = 0.040, DP p = 0.010, PA p = 0.007), but not in women. A lower level of education had a significant impact on depersonalisation in both sexes (p = 0.001 for men, p = 0.048 for women). Length of stay on job showed a significant influence on emotional exhaustion. No significant relationship was found between family structure and vulnerability for burnout. Conclusion: Gender had a differential effect on perceived occupational stress indicating a need for gender‐tailored preventive strategies. Age, working field, education, voluntarily occupational training during holidays and length of stay on job affect vulnerability for burnout in mental hospital staff. [ABSTRACT FROM AUTHOR]

Aims To analyse the effects of patient characteristics and different oral antidiabetes drug (OAD) use on standardised clinical outcomes in type 2 diabetes patients initiating insulin glargine 100 U/mL ( Gla-100). Materials and methods Patient-level data from 16 randomized, treat-to-target clinical trials that added Gla-100 to existing metformin ( MET), sulfonylurea ( SU) or metformin plus sulfonylurea ( MET+ SU) treatment in insulin-naïve patients inadequately controlled by oral therapy were analysed and patients were followed for ≥24 weeks. Change in glycated haemoglobin A1c ( HbA1c) from baseline to week 24, other glycaemic endpoints and incidence of hypoglycaemia (overall, nocturnal, and severe) were analysed by age (<65 vs ≥65 years), gender (male vs female), body mass index ( BMI; <25 vs ≥25 to <30 vs >30 kg/m2) and concomitant OAD ( MET vs SU vs MET+ SU). Results At baseline, the overall population ( N = 3188) had a mean age of 57.7 years, BMI of 30.5 kg/m2, HbA1c of 8.7%, fasting plasma glucose of 192 mg/dL, and 52.7% were male. Younger and older patients had similar HbA1c reductions with Gla-100 and a similar risk of hypoglycaemia. Females and patients with BMI <25 kg/m2 were less likely to achieve HbA1c targets and more likely to experience hypoglycaemia, regardless of concomitant OAD. Adding Gla-100 to SU therapy (alone or in combination with MET) increased hypoglycaemia risk across all analyses. Conclusions Our data suggest that female patients with type 2 diabetes and normal-weight patients treated with Gla-100 and MET ± SU are less likely to achieve glycaemic targets and, therefore, may require more clinical attention. Addition of Gla-100 to SU regimens may increase hypoglycaemia risk irrespective of age, gender, or BMI. [ABSTRACT FROM AUTHOR]

Background Increased hepatic fat and cardiac fat are common in patients with type 2 diabetes mellitus (T2 DM) and are associated with a greater risk of liver fibrosis and cardiovascular ( CV) events. Sex-specific differences of dipeptidyl peptidase-four ( DPP-4) inhibitor effects on hepatic ( HCL) and myocardial fat content ( MYCL) have not yet been evaluated. Method Forty-one T2 DM patients (20 male, 21 female) received a gliptin add-on therapy if HbA1c goals were not reached under metformin monotherapy. They underwent cardiac and liver magnetic resonance tomography and spectroscopy before and 6 months after therapy initiation. Plasma samples were analysed for the growth differentiation factor 15 ( GDF-15), a novel marker for cardiovascular risk. Results Thirty-eight patients on gliptin therapy completed the study. We observed a positive correlation between MYCL and HCL before therapy ( R = 0·41, P = 0·05). After 6 months of therapy, we noticed a significant weight reduction in women only ( P = 0·02) whereas waist circumference decreased similarly in both sexes. HbA1c sunk significantly in both sexes ( P = 0·002). HCL decreased significantly ( P = 0·0004), with women featuring higher basal HCL ( P < 0·05). MYCL decreased in women only ( P = 0·01) and GDF-15 comparably in both sexes ( P < 0·05). Conclusions 6 months of DPP-4-therapy led to a significant overall decrease in HCL and body weight such as a reduction of MYCL only in women. This preliminary data set could implicate that gliptin may be a feasible therapy option in fatty liver patients with diabetes potentially including positive effects on cardiovascular function particularly in women. [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]

Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BPND) in patients with ADHD and to assess associations of SERT BPND between the brain regions. 25 medication-free patients with ADHD (age ± SD; 32.39 ± 10.15; 10 females) without any psychiatric comorbidity and 25 age and sex matched healthy control subjects (33.74 ± 10.20) were measured once with PET and the highly selective and specific radioligand [11C]DASB. SERT BPND maps in nine a priori defined ROIs exhibiting high SERT binding were compared between groups by means of a linear mixed model. Finally, adopted from structural and functional connectivity analyses, we performed correlational analyses using regional SERT binding potentials to examine molecular interregional associations between all selected ROIs. We observed significant differences in the interregional correlations between the precuneus and the hippocampus in patients with ADHD compared to healthy controls, using SERT BPND of the investigated ROIs ( P < 0.05; Bonferroni corrected). When correlating SERT BPND and age in the ADHD and the healthy control group, we confirmed an age-related decline in brain SERT binding in the thalamus and insula ( R2 = 0.284, R2 = 0.167, Ps < 0.05; Bonferroni corrected). The results show significantly different interregional molecular associations of the SERT expression for the precuneus with hippocampus in patients with ADHD, indicating presumably altered functional coupling. Altered interregional coupling between brain regions might be a sensitive approach to demonstrate functional and molecular alterations in psychiatric conditions. Hum Brain Mapp 38:792-802, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disorder with a strong genetic component. The norepinephrine transporter (NET) is a key target for ADHD treatment and the NET gene has been of high interest as a possible modulator of ADHD pathophysiology. Therefore, we conducted an imaging genetics study to examine possible effects of single nucleotide polymorphisms (SNPs) within the NET gene on NET nondisplaceable binding potential (BPND) in patients with ADHD and healthy controls (HCs). Twenty adult patients with ADHD and 20 HCs underwent ( S,S) -[18F]FMeNER-D2 positron emission tomography (PET) and were genotyped on a MassARRAY MALDI-TOF platform using the Sequenom iPLEX assay. Linear mixed models analyses revealed a genotype-dependent difference in NET BPND between groups in the thalamus and cerebellum. In the thalamus, a functional promoter SNP (−3081 A/T) and a 5′-untranslated region (5′UTR) SNP (−182 T/C), showed higher binding in ADHD patients compared to HCs depending on the major allele. Furthermore, we detected an effect of genotype in HCs, with major allele carriers having lower binding. In contrast, for two 3′UTR SNPs (*269 T/C, *417 A/T), ADHD subjects had lower binding in the cerebellum compared to HCs depending on the major allele. Additionally, symptoms of hyperactivity and impulsivity correlated with NET BPND in the cerebellum depending on genotype. Symptoms correlated positively with cerebellar NET BPND for the major allele, while symptoms correlated negatively to NET BPND in minor allele carriers. Our findings support the role of genetic influence of the NE system on NET binding to be pertubated in ADHD. Hum Brain Mapp 37:884-895, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies. [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]

Background Tissue-specific dipeptidyl-peptidase 4 ( DPP4) dysregulation has been described in adults with diabetes mellitus. The DPP4 -incretin system has not been studied in foetal life. In this study, DPP4 activity and glucagon-like peptide-1 ( GLP-1) levels were assessed in cord blood of neonates born to women with gestational diabetes mellitus ( GDM) and nondiabetic controls. Material and methods This study has been conducted in two Hungarian and one Austrian centres. Patients: A total of 568 pregnant women were enrolled in the study after their OGTT between the 24th and 28th gestational week. Cord blood samplings with DPP4 activity and GLP-1 level measurements were possible in 270 ( DPP4: 159 control, 111 GDM) and 112 ( GLP-1: 72 control, 40 GDM) cases. OGTT (24-28th gestational week) and cord blood sampling at delivery were performed. Cord serum DPP4 activity was determined in a continuous monitoring microplate-based kinetic assay, and cord plasma GLP-1 was measured using a fluorescence ELISA method. Results Cord serum DPP4 activity was lower in GDM [mean (95% CI): 28·07 U/L (26·32-29·82 U/L)] than in controls [31·61 U/L (29·93-33·29 U/L), MWU P = 0·0015]. Cord plasma active GLP-1 levels were close to the lower detection limit and were not altered in GDM (control: mean = 3·43 pM, 95% CI: 3·04-3·82 pM, GDM: mean = 3·61 pM, 95% CI: 2·96-4·28 pM - MWU test P = 0·6). Conclusions Decreased cord serum DPP4 activity in gestational diabetes mellitus might be the result of an adaptive foetal response or an early dysregulation in the entero-insular axis with consequences beyond the incretin system. Cord plasma GLP-1 levels may reflect the missing oral intake with a limited glucose sensing of L cells via the circulation in foetal life. [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]

Objective To assess the association between diabetes mellitus ( DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer ( NMIBC), Patients and Methods We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007., Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality., Results Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin., Within a median (interquartile range) follow-up of 64 (22-106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes., In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [ HR]: 1.45, 95% confidence interval [ CI] 1.09-1.94, P = 0.01) and progression ( HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM., DM with metformin use was independently associated with a lower risk of disease recurrence ( HR: 0.50, 95% CI 0.27-0.94, P = 0.03)., Conclusion Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence., The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation. [ABSTRACT FROM AUTHOR]

Background Pentraxin 3 ( PTX3) is a cytokine-inducible molecule expressed in different tissues, the levels of which increase in a response to a variety of inflammatory conditions. Recently, it has been linked to the serum glucose levels and some comorbidities in type 2 diabetes. Materials and methods Here, we aimed to investigate the role of PTX3 in gestational diabetes mellitus ( GDM), which is considered a forerunner of type 2 diabetes. Fasting PTX3 serum levels were measured in 90 women [45 GDM, 45 normal glucose tolerance ( NGT)] during pregnancy. In addition, PTX3 was measured during a 2 h, 75 g oral glucose tolerance test ( OGTT) in 20 women (10 GDM, 10 NGT) at 24-28 weeks of gestation and in 16 of them after delivery (10 GDM, 6 NGT). Results A continuous increase in PTX3 levels was observed during the OGTT and reached in the GDM group a significant difference after 120 min compared with baseline ( P < 0·05). Additionally, a rise in the PTX3 concentration was significantly higher in the GDM- compared with the NGT group, 120 min after glucose challenge ( P < 0·01). During pregnancy, serum glucose and C-peptide were positively correlated with the PTX3 levels in the whole study group, whereas a negative association was found with the insulin sensitivity parameters QUICKI and OGIS. Conclusions Dependence of PTX3 on serum glucose levels was more pronounced in women with GDM than in the NGT group. This notion together with its inverse relation to the parameters of insulin sensitivity, suggests a potential involvement of PTX3 in GDM pathology. [ABSTRACT FROM AUTHOR]

Objective The development of overt diabetes in women with prior gestational diabetes mellitus (prior GDM) has been linked to several risk factors including age, obesity and insulin therapy during pregnancy; the role of recurrent GDM as a further risk factor remains unclear. As studies examining detailed metabolic consequences of recurrent GDM are missing and the role of recurrent GDM on cardiovascular risk is unknown, our aim was to investigate the impact of recurrent GDM (within 5 years after an index pregnancy) on metabolic and cardiovascular parameters. Methods Oral and intravenous glucose tolerance tests as well as assessment of cardiovascular risk factors were performed at baseline (6 months after index pregnancy) and 5 years thereafter in 21 prior GDM with recurrent GDM (rec GDM), 41 prior GDM with no additional pregnancy (nonrec GDM) and 10 healthy controls [ CON]. Results Despite weight gain in rec GDM (2·3 ± 5·1 vs. −1·3 ± 6·7 kg, P < 0·04), glucose tolerance, insulin sensitivity and secretion did not differ compared with nonrec GDM at baseline and follow-up. Furthermore, rec GDM did not exhibit increased cardiovascular risk factors. Metabolic deterioration in (19% of) the total prior GDM group was associated with decreased insulin sensitivity ( OGIS:367·4 ± 89·6 vs. 436·4 ± 75·5 mL/min*m², P = 0·01), hyperinsulinaemia ( TIS:37·9 ± 9·7 vs. 28·0 ± 10·2 nM, P < 0·006) and postchallenge hyperglycaemia at 5 years postpartum. Conclusions Recurrence of gestational diabetes was not associated with deterioration of glucose metabolism, insulin sensitivity and secretion nor with increased cardiovascular risk. Consequently, prior GDM should not be recommended to refrain from subsequent pregnancies, but be encouraged to regain and maintain normal body weight after delivery and regularly undergo OGTTs to early detect metabolic deterioration. [ABSTRACT FROM AUTHOR]

The impact of sex and age on glucose metabolism in the development of overweight/obesity is a matter of debate. We hypothesized that insulin sensitivity (IS) and β-cell function (BF) in a normal white population will differ between males and females and aimed to evaluate the possible effects of BMI and age on metabolic parameters of both sexes. This study is a cross-sectional analysis of the general community. IS was measured with quantitative insulin sensitivity check index (QUICKI) and oral glucose insulin sensitivity (OGIS) and BF with the insulinogenic index during 75-g 2-h oral glucose-tolerance tests (OGTTs). We studied 611 females and 361 males with normal glycemia according to both fasting and 2-h glucose (85 ± 0.3 mg/dl (means ± SE) in females and 89 ± 0.4 in males (P < 0.0001), and 93 ± 1 in females and 89 ± 1 in males (P = 0.005), respectively). Females were younger (37 ± 1 years) than males (40 ± 1, P < 0.0001), but no difference was found in mean BMI (BMI = 25.8 ± 0.2 kg/m2 in both). Student's two-sample t-test was used for simple comparison between and within genders, multiple linear regressions to account for covariates. During the OGTT, females had lower glucose (area under the curve (AUC) 133 ± 1 mg/ml·2 h vs. 148 ± 2; P < 0.00001), while insulinemia was comparable (AUC 5.3 ± 0.1 mU/ml·2 h vs. 5.7 ± 0.2, P = 0.15). IS remained higher in females (473 ± 3 ml/min/m2 vs. 454 ± 3, P < 0.0001) also after having accounted for age and BMI (P = 0.015). No difference was observed in fasting insulin or BF. However, BF increased by 46% with BMI and when accounting for age and BMI, BF of females was significantly higher (P < 0.0001). Because IS and BF are higher in females than in males, sex should be considered in metabolic studies and overweight/obese populations. [ABSTRACT FROM AUTHOR]

Summary Objective To evaluate the relationship of plasma fetuin-A levels with markers of bone turnover in male and female type 2 diabetic subjects. Background Fetuin-A, which is a serum protein produced by the liver and promotes bone mineralization, is an independent risk factor for type 2 diabetes, whilst type 2 diabetes is associated with an increased incidence of osteoporosis or fractures. It is not known how fetuin-A levels relate to parameters of bone metabolism in type 2 diabetes. Design and patients Eighty patients with type 2 diabetes [40 men and 40 women matched for age, body mass index (BMI) and time since diagnosis of diabetes] were studied. Fetuin-A together with metabolic parameters and levels of serum carboxy-terminal telopeptide of type 1 collagen (C-telopeptide), osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), bone alkaline phosphatase (ALP) and sex hormones was determined in all participants. Results Fetuin-A levels did not differ significantly between male and female diabetic subjects. In a model adjusted for age, BMI, fatty liver index (FLI), time since diagnosis of diabetes, HbA 1c, antidiabetic and lipid-lowering drug therapies, smoking, total serum protein, creatinine, gamma glutamyl-transferase, parathyroid hormone, C-reactive protein, glomerular filtration rate, and presence of micro-, cardio-, and peripheral vascular diabetic complications, fetuin-A showed a significant positive association with levels of bone ALP ( r = 0·71, P = 0·006) in men. In women, fetuin-A was significantly negatively associated with C-telopeptide ( r = −0·60, P = 0·03) levels. Conclusions Results suggest an independent association of fetuin-A levels with markers of bone turnover in male and female patients with type 2 diabetes. More studies are needed to determine whether fetuin-A could serve as a new marker for fracture risk or osteoporosis in type 2 diabetes and to explore its potential sexually dimorphic effects. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 351-358 (2012) Abstract Aims Women with former gestational diabetes are at increased risk of Type 2 diabetes, which likely relates to hyperlipidaemia and ectopic lipid storage, mainly in the liver. Here, we examined the response of non-esterified fatty acid dynamics to oral glucose loading (oral glucose tolerance test). Methods We studied women with former gestational diabetes with normal glucose tolerance ( n = 60) or impaired glucose metabolism ( n = 12) and compared them with healthy women after normal pregnancy (control subjects, n = 15). During a 3-h oral glucose tolerance test, glucose, insulin and non-esterified fatty acid were frequently measured to compute the area under the non-esterified fatty acid curve and parameters of β-cell function and insulin sensitivity. Through mathematical modelling, we assessed insulin sensitivity of lipolysis inhibition and the fractional non-esterified fatty acid turnover rate. We also measured some serum liver enzymes. Results Women with former gestational diabetes were slightly older and had greater body mass than control subjects. Subjects with impaired glucose metabolism had lower oral glucose insulin sensitivity, but higher fasting insulin and area under the non-esterified fatty acid curve, which inversely related to oral glucose insulin sensitivity and independently determined mean glycaemia. Model-derived non-esterified fatty acid parameters were lower in subjects with impaired glucose metabolism than in control subjects, particularly sensitivity of non-esterified fatty acid inhibition to insulin (2.50 ± 0.52 vs. 1.06 ± 0.20·10−2 ml/μU). Also, subjects with impaired glucose metabolism had higher liver transaminases. However, all non-esterified fatty acid parameters showed only modest inverse correlation with liver transaminases. Conclusions Despite greater insulinaemia, circulating non-esterified fatty acids are higher in women with former gestational diabetes than in control subjects, which likely results from reduced sensitivity of lipolysis inhibition to insulin. This parameter may serve as indicator of an early metabolic derangement in this population at risk for diabetes. [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 To evaluate β-cell function and insulin sensitivity in subjects with overt (OH) and subclinical hypothyroidism (SH) before and after T4 replacement therapy. Background Disturbances in glucose metabolism have been observed in hypothyroid states. However, the clinical significance and potential reversibility of these alterations by T4 replacement therapy remain to be elucidated especially in patients with SH. Design and patients Parameters of glucose metabolism have been investigated in subjects with OH ( n = 12) and SH ( n = 11). Insulin sensitivity has been assessed by the euglycaemic–hyperinsulinaemic clamp technique and β-cell function by mathematical modelling of data derived from an oral glucose tolerance test. Results Fasting and dynamic glycaemia as assessed by the AUCGlucose remained unaltered following substitution therapy ( P > 0·05). Insulin sensitivity significantly improved only in subjects with OH ( P < 0·05). Fasting insulin and proinsulin concentrations increased proportionally in both groups ( P < 0·05) with the proinsulin : insulin ratio remaining unchanged ( P > 0·05). Total insulin secretion was higher in OH before initiation of therapy ( P < 0·05). In both groups, dynamic parameters including total insulin secretion, hepatic insulin extraction and the adaptation index were significantly attenuated ( P < 0·05) after restoration of thyroid function, whereas the disposition index and the basal insulin secretion rate remained unaltered ( P > 0·05). Conclusion In summary, SH and OH are characterized by attenuated basal plasma insulin levels and increased glucose-induced insulin secretion. T4 replacement therapy partially ameliorates the insulin secretion profile and reduces the demand on pancreatic β-cells after glucose challenge to an extent that exceeds any effect attributable to the improvement in insulin sensitivity. [ABSTRACT FROM AUTHOR]

Objective Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. Design and patients A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Results Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4·2 ± 0·3 vs. 5·4 ± 0·4 10-4 min-1 (µU/ml)-1; OGTT: 440 ± 7 vs. 472 ± 9 ml min-1 m-2). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 ± 5 vs. 124 ± 7 pmol min-1 m-2 mm-1, P = 0·0407) and insulin secretion at 5 mm glucose (168 ± 9 vs. 206 ± 10 pmol min-1 m-2, P = 0·003). Conclusions Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis. [ABSTRACT FROM AUTHOR]

Aims Acute insulin release (AIR) in response to intravenous glucose injection (IVGTT) can be abolished in diabetic subjects when their response to oral glucose is maintained. To elucidate this phenomenon, we examined the relationships between fasting plasma glucose (FPG) and the secretory responses to an IVGTT and an oral glucose test (OGTT). Methods We measured AIR and secretion after a 75-g OGTT in 221 subjects [age 37 ± 11 years, body mass index (BMI) 28 ± 5 kg/m2; mean ± sd] with normal glucose tolerance (NGT, n = 147), impaired FPG/impaired glucose tolerance (IFG/IGT, n = 28) and Type 2 diabetes ( n = 46). Insulin secretion was calculated by C-peptide deconvolution; pancreatic B-cell glucose sensitivity was obtained by OGTT modelling. Results Both AIR [186 (185), 142 (164) and 10 (16) pmol/l, median (interquartile range)] and B-cell glucose sensitivity [98 (64), 66 (53) and 16 (20) pmol min−1 m−2 l mmol−1] decreased across glucose tolerance category ( P < 0.0001). However, AIR became ~0 at ~7 mmol/l FPG, whereas B-cell glucose sensitivity declined gradually throughout the FPG range. In addition, for FPG > 7 mmol/l, AIR was no longer related to FPG, whereas a strong relationship between FPG and B-cell glucose sensitivity was preserved (ρ = −0.71, P < 0.0001). In a multivariate regression model, adjusting for sex, age and BMI, glucose sensitivity [standardized regression coefficient (std.r.) = −0.67, P < 0.0001], but not AIR (std.r. = 0.03, P = 0.55), was an independent predictor of FPG. Conclusions AIR vanishes at fasting or 2-h glucose levels, at which levels some B-cell glucose sensitivity is retained; therefore, AIR has a limited ability to quantify B-cell function in hyperglycaemic states. [ABSTRACT FROM AUTHOR]

Ghrelin is reduced in various states of insulin resistance. The aim of this study was to examine the relationship between ghrelin and glucose metabolism during pregnancy – a natural insulin-resistant state – in women with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or gestational diabetes mellitus (GDM) and potential changes 3 months after delivery. A total of 54 women, 37 pregnant and with various degrees of insulin resistance and 24 postpartum (PP, seven of them also studied during pregnancy) were studied. Ghrelin plasma concentrations at fasting and 60′ following glucose loading (75 g-2 h-oral glucose tolerance test), area under the curve of plasma glucose (G-AUCOGTT) and insulin sensitivity [homeostatic model assessment (HOMA) and oral glucose sensitivity index (OGIS) indices, respectively] were determined. Both baseline and 60′ ghrelin concentrations were to a comparable degree (∼ by 65%) suppressed in NGT, IGT and GDM as compared to the PP group (the latter being indistinguishable from NGT regarding glucose tolerance and insulin sensitivity). In all women studied both during and after pregnancy, ghrelin levels rose from pregnancy to PP (mean increase 313.8%; P < 0.03). There was no correlation between baseline ghrelin and insulin sensitivity as estimated from both baseline (HOMA) and dynamic (OGTT:OGIS) glucose and insulin data. Ghrelin is substantially decreased during pregnancy, but glucose-induced ghrelin suppression is preserved at a lower level. There is apparently no relation to the degree of insulin resistance. [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]

Background Cardiac autonomic neuropathy is a common dysfunction in manifest diabetes mellitus and is associated with duration of diabetes and/or an inadequate glycaemic control. Heart rate variability (HRV) reflects autonomic heart function. The aim of the present study was to investigate whether in women with prior gestational diabetes (GD; pre-type 2 diabetes) alterations of cardiac autonomic function can be observed after delivery in relation to insulin sensitivity and glycaemic control. Materials and methods Forty-eight healthy women with prior GD were consecutively admitted to the study. HRV was analysed by both time, as well as frequency, domain methods using 24-h Holter monitoring. In addition, 20 women with normal glucose tolerance during and after pregnancy were investigated as control subjects. All women underwent a frequently sampled intravenous glucose tolerance test (FSIGT) for measurement of insulin sensitivity. Results Time domain analysis (standard deviation of normal RR intervals; SDNN) showed a reduced HRV in 25 out of the 48 (52%) women with prior GD. Frequency domain analysis revealed that in these 25 subjects both low and high frequency components of power spectral density (reflecting mainly sympathetic respectively parasympathetic activity) were reduced, indicating that sympathetic as well as parasympathetic functional impairment may be assumed. However, a relative predominance of the sympathetic over parasympathetic cardiac function was observed. The impairment of cardiac autonomic function (reduced SDNN) was correlated with HbA1c values and the 2-h blood glucose concentration (oral glucose tolerance test) but not with insulin sensitivity. Conclusion The present results demonstrate that in 52% of the women examined who had prior GD, an impairment of cardiac sympathetic as well as parasympathetic function was present, which related to glycaemic control, but not to insulin sensitivity. This infers that functional autonomic changes could be an early prognostic indicator in pre-type 2 diabetes. [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]

Background Women with a history of gestational diabetes (p-GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease. Materials and methods Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control. All women underwent an oral (OGTT) as well as an intravenous glucose tolerance test (FSIGT). Mathematical model analysis disclosed that 50% ( n = 37 each) of the p-GDM subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of interest were determined using commercially available test systems. Results Women with p-GDM and IIS had significantly increased body fat mass (BFM) ( P ≤ 0·001) compared with women with p-GDM and NIS and controls, whereas the waist to hip ratio (WHR) was similar in both p-GDM groups but was higher compared with the controls ( P ≤ 0·001). Mean PAI-1 and t-PA as well as fasting and stimulated plasma concentrations of proinsulin, C-peptide and insulin were elevated, whereas the disposition index was lower in women with p-GDM and IIS compared with women with p-GDM and NIS and the controls ( P < 0·001). Plasma levels of fibrinogen and vWF did not differ between the groups. Obese women with IIS had higher PAI-1 levels than lean women with IIS ( P ≤ 0·001). PAI-1 inversely correlated with the insulin sensitivity index (SI) but only in women with IIS ( P < 0·0001). On regression analysis, only fasting proinsulin and WHR remained significant independent predictors of PAI-1 elevation in IIS ( P ≤ 0·0001 and P ≤ 0·001). The PAI-1/SI ratio was elevated in women with IIS independently of their glucose tolerance status ( P < 0·001 vs. NIS and controls). Conclusions Plasminogen activator inhibitor type 1 is elevated in p-GDM women with IIS and depends on plasma proinsulin and abdominal obesity. An increase of the PAI-1/SI ratio further characterizes obese insulin-resistant p-GDM women who may be at risk for diabetes and angiopathy. [ABSTRACT FROM AUTHOR]

Background Former gestational diabetes (fGDM) constitutes a risk condition for the development of Type 2 diabetes. Former gestational diabetes is often characterized by obesity and hyperglycaemia, which may be concomitant and independent risk factors. Materials and methods To assess insulin sensitivity and β-cell function in fGDM uncomplicated by obesity and hyperglycaemia, we studied 24 lean fGDM women and 23 control women matched for age (30·7 ± 0·7 years, whole cohort), body mass index (22·2 ± 0·3 kg m−2), and indistinguishable for plasma glucose both at fasting and at 120 min. Several insulin sensitivity and β-cell function indices were computed: homeostasis model assessment insulin resistance index (HOMA-R), insulin sensitivity index derived from an oral glucose tolerance test (OGIS), insulinogenic index, other empirical indices of insulin secretion and β-cell function, and indices obtained using a β-cell model. Results Though the majority of indices, and in particular insulin sensitivity (HOMA-R: 1·35 ± 0·13 vs. 1·65 ± 0·14; OGIS: 492·7 ± 6·3 vs. 496·4 ± 9·4 mL min−1 m−2), were not significantly different in the two groups, the β-cell glucose sensitivity obtained by modelling analysis was lower in fGDM (108 ± 14 vs. 165 ± 22 pmol min−1 m−2 mM−1, P = 0·031). Conclusions Impairment of β-cell glucose sensitivity may be an intrinsic risk factor in fGDM independently of obesity and hyperglycaemia. Furthermore, we have shown that modelling analysis, in contrast to the empirical parameters, may be able to detect early β-cell alterations in fGDM women. [ABSTRACT FROM AUTHOR]

Objective Serum C-reactive protein (CRP) concentrations were measured longitudinally throughout pregnancy to test the hypothesis that CRP could relate more closely to glucose tolerance than to adiposity. Methods The CRP concentrations in pregnant women with normal glucose tolerance (NGT) and those with gestational diabetes mellitus (GDM) were measured at the same time as the oral glucose tolerance test (OGTT), at the 24th and 28th weeks of gestation and between the 37th and 38th weeks of gestation. Results At the end of the third trimester, women with GDM had significantly higher CRP levels than women with NGT [median (interquartile range), 9·7 mg L−1 (5·4–16·0) and 5·7 mg L−1 (5·1–7·2); P < 0·001, respectively], but at the time of the diagnostic OGTT no significant difference between the two groups was observed. This was owing to a significant increase of CRP in women with GDM between the time of the OGTT and the 37th−38th gestational weeks [median (interquartile range), 1·9 mg L−1 (−2·2, 6·7); P = 0·01]; whereas, no change in CRP was found in women with NGT [median (interquartile range), −0·1 mg L−1 (−2·4, 3·1); P = 0·76]. Multiple linear regression analysis showed only a significant independent influence of GDM ( P < 0·001) on maternal CRP concentrations in the 37th−38th gestational weeks and a significant influence of body mass index ( P < 0·007), but no influence of GDM at the time of the OGTT. Conclusion These data suggest that in women with gestational diabetes the CRP concentration is primarily related to the degree of adiposity until the second trimester and that thereafter impaired glucose metabolism appears to be the predominant predictor of changes in CRP. [ABSTRACT FROM AUTHOR]

BackgroundGrowth hormone deficiency is associated with increased morbidity and mortality from cardiovascular diseases, which might be related to changes in glucose and lipid metabolism. DesignTo assess the influence of long-term growth hormone replacement therapy (GHRT) on glucose metabolism we examined eight growth hormone-deficient (GHD) adults (seven female/one male; age, 46 ± 3 years; body mass index, 31 ± 2 kg m-2) over a period of 18 months in comparison to an adequate control group consisting of eight obese subjects matched for age, sex, and body mass index. We performed frequently sampled intravenous glucose tolerance tests (FSIGT) with minimal model analysis before the study, and after 12 and 18 months. ResultsFollowing GHRT, insulin-like growth factor-1 (IGF-1) increased significantly from a basal level of 75.9 ± 18.9 to 200.8 ± 31.0 μg L-1 after 12 months of therapy and remained stable, thereafter. GHRT did not affect fasting blood glucose, basal insulin, cholesterol, blood pressure and body weight. However, at 12 months, HbA1c (6.0 ± 0.1 vs. 5.6 ± 0.1% at basal, P < 0.05) and triglyceride (2.3 ± 0.4 vs. 1.4 ± 0.3 mmol L-1) significantly increased but returned to pretreatment values at 18 months. Insulin sensitivity was higher in GHD (8.2 ± 3.1) compared to controls (3.6 ± 0.53 × 10-4 min-1/(μU mL-1), P = 0.06) and decreased significantly after 18 months of GHRT to 5.1 ± 2.6, P < 0.05. Basal insulin secretion was similar to that in the control group and increased significantly after 12 and 18 months, total insulin secretion only after 12 months. SG (glucose effectiveness)was lower in GHD patients (0.0095 ± 0.001 min-1) compared to controls (0.020 ± 0.003 min-1, P < 0.05) and increased significantly after 12 and 18 months of GHRT (0.016 ± 0.002, and 0.015 ± 0.001... [ABSTRACT FROM AUTHOR]

Background The degree of bacterial contamination in the wound bed plays a key role in determining the level of "take" of keratinocyte grafts in burn patients. This study was done to evaluate the best suited antimicrobial agent for topical application in relation to antimicrobial activity and cytotoxic effect on graft cells. Objective The cytotoxicity of 7 antibacterial agents (gentamicin sulphate, ciprofloxacin hydrochloride. bacitracin, polymyxin B sulphate, diethanolamin salt of fusidic acid, teicoplanin, vancomycin hydrochloride), one antifungal substance (amphotericin B sodium deoxycholate) and one antiseptic agent (povidone iodine) on cultured human keratinocytes, HaCaT keratinocytes and fibroblasts was investigated. Material and methods The effects of these agents were tested using two separate assays - the neutral red assay and the Bradford protein assay. In order to assess toxicity of the agent, the obtained midpoint cytotoxicity (MC50) was compared to the respective minimal inhibitory concentration (MIC) for receiving the cytotoxic potential in microbiologically effective doses. Results Antibiotics effective against Staphylococcus aureus with a small potential of toxicity are Bacitracin, Fusidic acid, Vancomycin and Teicoplanin. Gentamicin and Ciprofloxacin are effective against both Staphylococcus aureus and Pseudomonas aeruginosa with a low potential of toxicity. Conclusion The use of antimicrobial agents with a midpoint cytotoxicity (MC50) higher than the minimal inhibitory concentration (MIC) by at least a factor of 100 might reduce the risk of toxic injury to graft cells. [ABSTRACT FROM AUTHOR]

Objective: The degree of reproducibility and precision of the mechanical direct profilometry and the intra- and interindividual fluctuations of 7 surface parameters were investigated. Material and methods: Negative replicas were sampled from defined areas of the skin of 31 volunteers an evaluated with the profile-tracking device TKC 300 Hommeltester in order to derive data about the inter-and intraindividual fluctuations. To determine the precision of this method 6 roughness parameters and I of waviness of each replica were repetitively evaluated. The practicability was tested introducing minimal changes in the experimental set-up. Further, the effect of urea-containing creme on the skins topography was investigated in a double-blind clinical setting on a collective of 11 patients. Results: The precision of this method is shown by nearly unchanged topographic parameters. Moreover, our data show smaller intra- than interindividual fluctuations of roughness (R[suba]) and waviness (W[subt]), being an important demand for clinical investigations. Conclusion: In this paper we demonstrate that the parameters of both roughness as well as the recently introduced waviness can be conveniently evaluated with a high degree of precision with the direct profilometry. [ABSTRACT FROM AUTHOR]