Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction – TSR). We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects of sleep disruption.

Hematopoietic stem cell transplantation (HSCT) is a curative treatment option for selected diseases of the hematopoietic system. In the context of HSCT, bloodstream infections caused by Gram-negative bacteria (GNB) significantly contribute to morbidity and mortality. Antibiotic treatment of bloodstream infections with carbapenem-resistant (CR) GNB presents a particular challenge. As a part of our infection control management, the admission of a patient who was known to be colonized with a CR Acinetobacter baumannii triggered an active weekly screening of all patients to determine the prevalence and potential transmission of CR GNB and CR Acinetobacter baumannii in particular. Over a 3 month period a total of 71 patients were regularly screened for colonization with CR GNB. Including the index patient, a total of three patients showed CR GNB colonization representing a prevalence of 4.2%. Nosocomial transmission of CR Acinetobacter baumannii or other CR GNB was not observed. However, the index patient developed a subsequent bloodstream infection with the CR Acinetobacter baumannii, therefore empiric antibiotic therapy based on the known resistance profile was initiated. A weekly prevalence screening for CR GNB might be an effective monitoring tool for potential transmission, may enhance existing infection control management concepts and may support the decision making for empiric antibiotic therapy.

Die rasante Entwicklung der Diabetesforschung hat viele neue Medikamente und Therapiestrategien auf den Weg gebracht, die das Potenzial haben, auch unabhängig von einer Diabeteserkrankung wirksam zu sein. So gibt es neue Erkenntnisse zu SGLT-2-Inhibitoren bei Herz-und chronischer Niereninsuffizienz. Auch die Weiterentwicklung inkretinbasierter Medikamente und duale GIP/GLP-1-Rezeptoragonisten sind vielversprechend. ABKÜR ZUNGEN MI Myokardinfarkt SGLT-2 sodium-glucose linked transporter-2 GLP-1 Glucagon-like Peptide-1 LVEF linksventrikuläre Ejektionsfraktion MACE major adverse cardiovascular events (schwere kardiovaskuläre Ereignisse) HFrEF Heart Failure with reduced Ejection Fraction HFpEF Heart Failure with preserved Ejection Fraction HHI Hospitalisierung aufgrund einer Herzinsuffizienz CV-Tod kardiovaskulärer Tod GIP Glucose-Dependent Insulinotropic Polypeptide ACE Angiotensin-converting enzyme AT 1 Angiotensin 1 SNAC sodium N-[8-(2-hydroxybenzoyl) amino caprylate G-BA gemeinsamer Bundesausschuss eGFR geschätzte glomeruläre Filtrationsrate EMA European Medicines Agency (Europäische Arzneimittel-Agentur) NVL Nationale Versorgungsleitlinie Einleitung FALLBEISPIEL 1 Anamnese -Symptomatik -Labor Ein 67-jähriger Patient (182 cm, 106 kg (BMI 32,0) stellt sich hausärztlich mit seit 3 Wochen bestehender Polyurie und Polydipsie mit einer Trinkmenge von 3-4 Litern vor. Darüber hinaus beklagt er eine Leistungsschwäche und Belastungsdyspnoe.

ZUSAMMENFASSUNGDie rasante Entwicklung der Diabetesforschung hat viele neue Medikamente und Therapiestrategien auf den Weg gebracht, die das Potenzial haben, auch unabhängig von einer Diabeteserkrankung wirksam zu sein. So gibt es neue Erkenntnisse zu SGLT-2-Inhibitoren bei Herz- und chronischer Niereninsuffizienz. Auch die Weiterentwicklung inkretinbasierter Medikamente und duale GIP/GLP-1-Rezeptoragonisten sind vielversprechend.