The role of qualification and quality management in the prescription of antipsychotics and potentially inappropriate medication (PIM) in nursing home residents in Germany: results of the HIOPP-3-iTBX study.

BACKGROUND: Nursing home residents (NHR) show high rates of polypharmacy. The HIOPP-3-iTBX study is the first cRCT on medication optimization in nursing homes (NH) in Germany. The intervention did not result in a reduction of PIM and/or antipsychotics. This analysis looks at structure quality in the HIOPP-3-iTBX study participants. AIMS: Evaluation of structure quality as part of a cluster-randomized controlled intervention study. METHODS: Structure quality in multiprofessional teams from n = 44 NH (n = 44 NH directors, n = 91 family doctors (FD), and n = 52 pharmacies with n = 62 pharmacists) was assessed using self-designed questionnaires at baseline. Main aspects of the questionnaires related to the qualification of participants, quality management, the medication process and size of the facilities. All completed questionnaires were included. number of PIM/antipsychotics was drawn from the baseline medication analysis in 692 NHR. Data were analyzed by descriptive statistics and mixed model logistic regression. RESULTS: The presence of a nurse with one of the additional qualifications pain nurse or Zertifiziertes Curriculum (Zercur) Geriatrie in the participating NH was associated with a lower risk for the prescription of PIM/antipsychotics. No association between any characteristic in the other participants at baseline was observed. CONCLUSIONS AND DISCUSSION: The results support the known role of nursing qualification in the quality and safety of care. Further studies need to look more closely at how use is made of the additional qualifications within the multiprofessional teams. Perspectively, the results can contribute to the development of quality standards in NH in Germany.

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Polymyalgia Rheumatica.

BACKGROUND: Polymyalgia rheumatica (PMR) is among the most common inflammatory rheumatic diseases in older adults. Presumed risk factors include female sex, previous infections, and genetic factors. No epidemiological data on PMR in Germany have been available until now. METHODS: This review is based on publications retrieved by a selective literature search in PubMed. Moreover, the administrative incidence and prevalence of PMR in the years 2011-2019 was determined from data of the AOK Baden-Württemberg statutory health insurance carrier for insurees aged 40 and older. In addition, we quantified the number of consultations with physicians involved in the diagnosis. RESULTS: The annual age- and sex-standardized incidence and prevalence of PMR from 2011 to 2019 were 18.6/100 000 persons and 138.8/100 000 persons, respectively. The incidence was higher in women than in men (21.8/100 000 vs. 12.8/100 000 persons per year). 60% of the cases were diagnosed in primary care practices. The treatment of PMR with orally administered glucocorticoids usually results in a treatment response within a few days to weeks. Approximately 43% of patients experience recurrent symptoms within a year, requiring adjustment of the glucocorticoid dose. For older patients with impaired physical ability, additional non-pharmacological treatment with exercise programs plays an important role. CONCLUSION: PMR usually takes an uncomplicated course under treatment and can be managed in primary care, but these patients are often multimorbid and require frequent follow-up. Along with research on the etiology of the disease, further studies are needed to identify the risk factors for a chronic course and to evaluate the potential effects of non-pharmacological measures.

[The Logic Model - a rationale for an encompassing evaluation framework of the German Competence Centers for Postgraduate Medical Education in general practice]. / Das Logische Modell als Grundlage für ein strukturiertes Konzept der Evaluation und Qualitätssicherung der Kompetenzzentren Weiterbildung Allgemeinmedizin.

BACKGROUND: The Competence Centers for Postgraduate Medical Education (KW) established throughout Germany represent complex programs to increase the efficiency and quality of postgraduate medical education in general practice. So-called Logic Models serve as the framework for evaluations and quality management processes of complex programs in many areas. The aim of this article is to develop such a model, using the example of the Competence Center in Baden-Württemberg (KWBW) in order to structure its complex program logic and use it as a framework for future evaluations and quality management processes. METHODS: The adaptation of the Logic Model to the KWBW took place in an informal, nominal group process with employees and participants of the program. RESULTS: We identified 76 core elements of the KWBW. These core elements were classified in one of the five pillars of the Logic Model (input, activity, output, outcome and impact) and categorized according to fields of action and target groups. DISCUSSION: The Logic Model, which was developed using the KWBW as an example, identifies and structures important core elements of a complex postgraduate medical training program for the first time. It seems to be well suited for visualizing the internal logic of this complex program and the interaction of the various elements within the KWBW. It can thus be used as the basis for a comprehensive and systematic evaluation concept and for quality assurance. CONCLUSION: The model is also a prerequisite for comparative research questions of other university programs for postgraduate medical education and thus offers an opportunity for cooperative development efforts. This article therefore contributes to promoting quality in continuing medical training.

Drug Safety for Nursing-Home Residents-Findings of a Pragmatic, Cluster-Randomized, Controlled Intervention Trialin 44 Nursing Homes.

BACKGROUND: The safety of drug use by nursing-home residents can be impaired by polypharmacy, potentially inappropriate medications (PIM), and neuroleptics, as well as by a lack of adequate interprofessional coordination in the nursing home. The goal of the HIOPP-3-iTBX Trial was to improve drug safety in nursing-home residents, including a reduction of PIM and/or neu - roleptic use, by means of a complex interprofessional intervention. METHODS: This cluster-randomized, controlled trial was performed in nursing homes in Germany. Residents over age 65 were included in the trial. The intervention was carried out over six months and consisted of four elements: a drug review by trained pharmacists, educational sessions for general practitioners and nurses, a drug safety toolbox, and change management seminars for members of the three participating professions. The nursing homes in the control group continued to provide usual care. The primary endpoint was the prescription of at least one PIM and/or at least two neuroleptic drugs simultaneously. The secondary endpoints were the incidence of falls and hospitalizations, quality of life, and health-care costs. This trial is registered in the German Clinical Trials Registry (DRKS00013588). RESULTS: 44 nursing homes with 862 residents were randomized, 23 of them (with 452 residents) to the intervention group and 21 (with 410 residents) to the control group. 41% of all nursing-home residents initially took at least one PIM and/or at least two neuroleptic drugs simultaneously. Follow-up data (including, among other things, the current drug regimen) were obtained for 773 residents. The intention-to-treat analysis continued to show no difference between the intervention group and the control group with respect to the primary endpoint. CONCLUSION: This trial of an intervention to improve drug safety in nursing homes led neither to reduced prescribing of PIM and/or neuroleptic drugs, nor to any improvement in the overall health status of the nursing-home residents.

Developing a seminar curriculum for the Competence Center for General Practice in Baden-Wuerttemberg - a progress report.

Aim: The seminar program of the KWBW Verbundweiterbildungplus® is offered by the Competence Center for Postgraduate Medical Education in Baden-Württemberg (KWBW) for physicians specializing in general practice (GP trainees). Attendance is a voluntary one comprised of 48 curricular units of 45 minutes each per GP trainee. This seminar program is meant to be attended in parallel to the postgraduate medical education in clinic or practice. The intention behind this project was to develop objectives, topics and a feasible structure for a seminar curriculum while taking time and financial constraints into account. Method: The Kern cycle was applied in an open, modified nominal group consensus technique in the form of an iterative process. Participating were 17 experts from the departments of general practice at the universities in Freiburg, Heidelberg, Tuebingen and Ulm, plus a pediatrician. Results: The main objective was defined as empowering GP trainees to independently provide high-quality primary care, including in rural areas. A basic curriculum was defined based on relevant frameworks, such as the 2018 Model Regulation for Postgraduate Medical Training (Musterweiterbildungsordnung/MWBO) and the Competency-based Curriculum General Practice (KCA). Overall, the seminar curriculum has 62 basic modules with 2 curricular units each (e.g. Basic Principles of General Practice, Chest Pain, Billing) and another 58 two-unit modules on variable topics (e.g. digitalization, travel medicine) adding up to 240 (124+116) curricular units. A blueprint with a rotation schedule for all of the teaching sites in Baden-Württemberg allows regular attendance by n=400 GP trainees over a period of five years, with individual variability in terms of program length. Conclusion: The model entails a five-year, flexible program to accompany the postgraduate medical education in general practice which can also be implemented in multicenter programs and those with high enrollments. The model's focus is on acquisition of core competencies for general practice. Despite the current shift to eLearning seminars due to SARS-CoV, the program's implementation is being continued, constantly evaluated, and used to further develop the KWBW Verbundweiterbildungplus® program.

[Lessons learned: Challenges faced in the recruitment process for the cluster-randomized nursing home study HIOPP-3 iTBX]. / "Lessons learned" ­ Herausforderungen im Rekrutierungsprozess in der cluster-randomisierten Pflegeheimstudie "HIOPP-3 iTBX".

INTRODUCTION: The cluster-randomized multicenter HIOPP-3 iTBX study ('General Practitioners' Initiative to optimize Medication safety for Nursing Home Residents - using an interprofessional toolbox') aims to improve medication safety in nursing home residents through a complex interprofessional intervention focusing on neuroleptics and potentially inadequate medications. A stepwise recruitment process was used for all study participants (nursing homes, general practitioners, pharmacists, nursing home residents). The aim of this article is to describe the underlying recruitment strategy, the results of the recruitment and the measures undertaken to recruit the necessary number of participants. METHODS: The recruitment strategy and the response rates of nursing homes, general practitioners, pharmacists and nursing home residents are described. Measures to improve recruitment at the study sites and reasons for refusal to participate were documented. RESULTS: The response rate in nursing homes was 8.4 % (n=44). Of the pharmacists contacted by these nursing homes 70.3 % (n=52) participated, and 43.5 % (n=91) of all contacted general practitioners. Twenty-three (33.0 %) nursing homes had to be excluded from the study because no interprofessional team could be formed. Of all nursing home residents under the care of the participating general practitioners 862 (43,5%) persons and/or their caregivers gave consent to participate in the study. The recruitment for the study took 14 months. In the course of recruitment, recruitment strategies had to be adapted to local circumstances at the study sites. Reasons for non-participation varied between the different groups. DISCUSSION AND CONCLUSION: The main challenge in the HIOPP-3 iTBX study was to form interprofessional teams in each cluster. A stepwise, partly dependent recruitment process in a large group of potential participants presents organizational challenges that should be taken into account while planning the study. In order to reach the calculated sample size in the HIOPP-3 iTBX study, a pragmatic and flexible approach, adapted to local circumstances, was required. Further studies may benefit from the experiences made in the HIOPP-3 iTBX study.

The teaching and learning environment of a primary care medical student clinical attachment ("Famulatur") - a qualitative study on experiences of students and primary care physicians in Germany.

Aim: Following changes in licensing regulations for doctors ("Approbationsordnung") in 2012, a 4-week clinical attachment ("Famulatur") in primary care is now mandatory for all medical students in Germany. To date, it has not been studied how the Famulatur in primary care is perceived by the learner or the teacher. The aim of this study was to explore the experiences of both medical students and primary care physicians (PCPs) with regard to the teaching and learning situation in the Famulatur in primary care. Methods: A qualitative analysis of semi-structured interviews with 12 students from the medical faculty in Tübingen, Germany, and 17 PCPs from this region, was performed. Interview material was analyzed following content analysis according to Mayring. Results: In addition to considering the variety of tasks expected of the students and the optimal time for the Famulatur during the medical curriculum, the main themes of the interviews were the strengths, weaknesses and suggestions for improvement of the Famulatur. The Famulatur was predominantly perceived positively, although it being obligatory was criticized. In particular, the 1:1 supervision and the extended duration (compared to the first curricular primary care placement ("Blockpraktikum")) were positively evaluated. PCPs and students were critical of the lack of a learning and educational Famulatur framework, which would have enabled earlier orientation and alignment of each party. Conclusion: The Famulatur offers good learning opportunities for medical students and provides an insight into primary care, which is typically seen positively; it appears to heighten enthusiasm for primary care within budding doctors. Even if the obligation should cease in "The Master Plan for Medical Studies 2020" (Masterplan Medizinstudium 2020), it would be beneficial to optimize the primary care Famulatur; the development of a student logbook and learning objectives could be helpful, for example in the form of portfolios.

Improving cooperation between general practitioners and dermatologists via telemedicine: study protocol of the cluster-randomized controlled TeleDerm study.

BACKGROUND: Internationally, teledermatology has proven to be a viable alternative to conventional physical referrals. Travel cost and referral times are reduced while patient safety is preserved. Especially patients from rural areas benefit from this healthcare innovation. Despite these established facts and positive experiences from EU neighboring countries like the Netherlands or the United Kingdom, Germany has not yet implemented store-and-forward teledermatology in routine care. METHODS: The TeleDerm study will implement and evaluate store-and-forward teledermatology in 50 general practitioner (GP) practices as an alternative to conventional referrals. TeleDerm aims to confirm that the possibility of store-and-forward teledermatology in GP practices is going to lead to a 15% (n = 260) reduction in referrals in the intervention arm. The study uses a cluster-randomized controlled trial design. Randomization is planned for the cluster "county". The main observational unit is the GP practice. Poisson distribution of referrals is assumed. The evaluation of secondary outcomes like acceptance, enablers and barriers uses a mixed-methods design with questionnaires and interviews. DISCUSSION: Due to the heterogeneity of GP practice organization, patient management software, information technology service providers, GP personal technical affinity and training, we expect several challenges in implementing teledermatology in German GP routine care. Therefore, we plan to recruit 30% more GPs than required by the power calculation. The implementation design and accompanying evaluation is expected to deliver vital insights into the specifics of implementing telemedicine in German routine care. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00012944 . Registered prospectively on 31 August 2017.

[Prescription of Benzodiazepines and Z-Drugs by German General Practitioners: A Cross-Sectional Study]. / Verordnung von Benzodiazepinen und Z-Drugs in hausärztlichen Praxen ­ eine Querschnittanalyse.

BACKGROUND: Due to their addictive potential, benzodiazepine (BZ) and non-benzodiazepine-agonists (NBZ, so-called Z-drugs) should be taken no longer than 6 weeks. BZ and NBZ are primarily prescribed by general practitioners (GPs). Therefore, we aimed to analyze GPs' data on the patients collective, the amount of BZ/NBZ prescribed and the rate of private prescriptions. METHODS: We analyzed person years of 2-year intervals from 2009 to 2014 of the primary care CONTENT register that contains routine data from 31 general practitioners' practices. We classified BZ/NBZ prescriptions according to risk groups. The association of BZ/NBZ prescription and potential influencing factors was analyzed by calculating the odds ratio with 95% confidence interval (and corresponding p-value) on the basis of a multiple logistic regression model (adjusted by age, sex and type of health insurance). All patients with drug prescription with and without BZ/NBZ-prescription were compared. RESULTS: Almost 5% of patients with drug prescriptions received at least one prescription of BZ/NBZ during 1 year of observation. On average these patients were older (67.5 vs. 48 years respectively) and the proportion of women was higher than in the comparison group (69 vs. 58%). About one-third of these patients received more than 600 mg diazepam equivalent dose per person year (according to a 2-month daily intake of more than 10 mg diazepam). About one-third of the prescriptions were private prescriptions. A number of variables were significantly associated with the prescription of BZ/NBZ (e. g. age, gender, diagnosis codes, practices). CONCLUSION: The results provide valuable information about BZ/NBZ prescription routines in general practice. For continuous medical education as well as the development of interventions to reduce the use of BZ/NBZ, patient characteristics (e. g. sex, age, comorbidities, type of insurance) as well as different prescription routines (e. g. private prescriptions, reason and frequency of prescriptions, guideline orientation) should be considered.

[Active participation in research and teaching during post-graduate GP training: perspectives of future general practitioners]. / Aktiv in Forschung und Lehre in der Weiterbildung Allgemeinmedizin ­ Perspektiven der nachrückenden Ärztegeneration.

BACKGROUND: Academic institutions of general practice at German medical faculties have grown during the past years. This leads to an increase in the need of qualified young researchers and teachers in general practice (GP). Little is known about the interest in research and teaching skills and their training among general practice trainees and young GPs. RESEARCH QUESTION: This cross-sectional survey among GP trainees and young GPs examined 1. if there is an interest in the training in research and teaching skills during post-graduate GP training, 2. which fostering and hindering factors have an effect on this interest and 3. which roles are attributed to academic institutions of general practice. METHODS: A web-based cross-sectional study was performed among members of "Verbundweiterbildungplus", a network of GP trainees, as well as "Junge Allgemeinmedizin Deutschland", the German network of young GPs. Descriptive analysis was conducted. RESULTS: 148 GP trainees and young GPs participated in the study, 76% (n=109) of them were GP trainees. There was interest in a position in research and teaching during post-graduate GP training among 55% (n=78). Factors associated with the interest in a position in research and teaching during post-graduate GP training were (MV 5-point Likert scale ± SD): compatibility of clinical work and research/teaching and of family and career (4.4±0.8; 4.7±0.6 respectively). The roles of academic institutions of general practice were attributed to training of medical students (4.6±0.6), post-graduate GP training (4.5±0.7) and research (4.5±0.7). GP trainees assessed the importance of training in research and teaching skills during post-graduate GP training and of the compatibility of family and career differently from young GPs (3.7±1.0 vs. 4.1±0.8 p=0.027; 4.8±0.5 vs. 4.3±0.9, p=0.016). Those interested in a position in research and teaching during post-graduate GP training showed a stronger interest in specific training in research skills (3.7±1.1 vs. 2.8±1.1, p<0.001), a future clinical position in a research practice (3.8±1.2 vs. 2.5±1.2, p<0.001) and as a lecturer at an academic institution of general practice (4.3±0.9 vs. 3.9±1.1, p=0.04). DISCUSSION: There is an interest in professional involvement in research and teaching during post-graduate GP training among GP trainees and young GPs. For those interested, structured concepts (e.g. "clinician scientist") need to be developed in order to facilitate the combination of clinical work and a position in research and teaching during post-graduate GP training. In doing so, the existing potential could be better exploited and more future GPs could be involved in research and teaching.

Polypharmacy-an Upward Trend with Unpredictable Effects.

BACKGROUND: Guideline-oriented treatments can lead to polypharmacy, i.e., the simultaneous long-term use of multiple drugs. Polypharmacy mainly affects elderly patients. The goal of this review is to survey the current scientific evidence about polypharmacy, focusing on clinical endpoints, and to point out implications for medical practice and research. METHODS: This selective literature review is based on pertinent publications that were retrieved by a selective search in PubMed employing the terms "polypharmacy AND general practice." Selected references were considered as well. RESULTS: In Germany, polypharmacy currently affects approximately 42% of persons over age 65, with an ongoing upward trend. 20-25% of these patients receive potentially inappropriate drugs. Approximately 86% of the daily doses of drugs taken by persons over age 65 are prescribed by general practitioners. There is inconsistent evidence on the question whether polypharmacy affects clinical endpoints such as mortality. It cannot be determined with certainty whether polypharmacy itself, or the underlying multimorbidity, is the reason for worse clinical outcomes. Lists, instruments, and guidelines such as PRISCUS (a list of potentially inappropriate drugs for elderly patients), FORTA (Fit fOR The Aged), MAI (the Medication Appropriateness Index), and the Hausärztliche Leitlinie Multimedikation (a German-language guideline on polypharmacy for general practitioners) can help physicians take care of patients who are taking multiple drugs. It has not yet been proven, however, that their use has any effect on clinical outcomes. CONCLUSION: The decision whether to keep giving a drug or to discontinue it must always be made individually on the basis of current treatment goals; drug lists and a pertinent general practitioners' guideline can be useful aids in decision-making. Efforts to pay more attention to multimorbidity and polypharmacy in future studies and guidelines are deserving of support.

Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner.

Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.

Offspring sex determines the impact of the maternal ACE I/D polymorphism on maternal glycaemic control during the last weeks of pregnancy.

UNLABELLED: HYPOTHESIS/ INTRODUCTION: : We recently demonstrated that fetal sex may affect maternal glycaemic control in genetically prone mothers. We tested the hypothesis that fetal sex/fetal Y/X chromosomes might affect maternal glycaemic control during pregnancy depending on the maternal angiotensin converting enzyme (ACE) I/D polymorphism. MATERIAL AND METHODS: : One thousand, three hundred and thirty-two Caucasian women without pre-existing diabetes and pre-existing hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycaemic control was analysed by measuring total glycated haemoglobin at birth. Correction for confounding factors and multiple testing was done. RESULTS: : Maternal ACE I/D polymorphism showed significant interaction with fetal sex concerning maternal total glycated haemoglobin. Total glycated haemoglobin in DD mothers delivering boys was 6.42 ± 0.70% vs. 6.21 ± 0.66% in DD mother delivering girls (p < 0.005), whereas the II carrying mothers showed the opposite effect. II mothers delivering a girl had a higher (p = 0.044) total glycated haemoglobin at birth (6.40 ± 0.80%) compared to II mothers delivering boys (6.21 ± 0.81%). There was no interaction of the ACE I/D polymorphism and fetal sex with respect to new onset proteinuria, new onset edema and pregnancy-induced hypertension. CONCLUSIONS: : Maternal glycaemic control during the last weeks of pregnancy seems to be influenced by an interaction of the ACE I/D genotyp and fetal sex.

New evidence for the fetal insulin hypothesis: fetal angiotensinogen M235T polymorphism is associated with birth weight and elevated fetal total glycated hemoglobin at birth.

BACKGROUND: Low birth weight is associated with an increased risk of cardiovascular events in later life. Insulin resistance is a key finding in adult patients with cardiovascular diseases. The neonatal phenotype of an individual with insulin resistance might be low birth weight, as insulin influences fetal growth. The renin-angiotensin-aldosterone system has been associated with cardiovascular disease and insulin resistance. We analyzed whether fetal polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme genes influence birth weight and/or fetal total glycated hemoglobin (fTGH), a surrogate parameter of fetal insulin resistance at birth. METHOD: In 1132 white women delivering singletons, neonatal umbilical blood samples and clinical data of the mothers and newborns were obtained. Newborns were genotyped with respect to the AGT M235T and angiotensin-converting enzyme insertion/deletion polymorphism. RESULTS: The AGT M235T TT polymorphism is associated with reduced birth weight (TT: 3288 g versus TM + MM: 3435 g, P < 0.05). Furthermore, newborns with a high percentage of fTGH (>6.5%) are more likely to have the TT genotype than those with normal fTGH (

Interaction of maternal peroxisome proliferator-activated receptor gamma2 Pro12Ala polymorphism with fetal sex affects maternal glycemic control during pregnancy.

It was suggested that fetal sex may substantially affect maternal glycemic control during pregnancy in genetically susceptible mothers. The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is known to affect glycemic control and may act in a sex-specific manner. This polymorphism is thus an attractive candidate to test this hypothesis using a second independent functionally relevant polymorphism. We analyzed the impact of fetal sex on maternal glycemic control during pregnancy in relation to the maternal PPARgamma2 Pro12Ala polymorphism. Two-thousand fourteen Caucasian women without preexisting diabetes and preexisting hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycemic control was analyzed by measuring total glycated hemoglobin at birth. Correction for confounding factors and multiple testing was considered in the analysis. The maternal PPARgamma2 Pro12Ala polymorphism without consideration of fetal sex had no effect on blood pressure, new onset of proteinuria and total glycated hemoglobin at delivery. Mothers carrying both G alleles (GG genotype) delivering a girl had a higher (P = 0.015) total glycated hemoglobin (6.81 or - 0.50%) versus mothers carrying the same alleles but delivering boys (5.85 + or - 0.58%). Comparing mothers with the GG genotype delivering girls with mothers with CC or CG genotypes also delivering girls (6.32 + or - 0.72%) revealed a significantly higher maternal total glycated hemoglobin at delivery in the former group (P < 0.009). Fetal sex/sex chromosomes may substantially affect maternal glycemic control in mothers who are carriers of the GG alleles of the PPARgamma2 Pro12Ala polymorphism.