Empagliflozin is known to reduce cardiovascular events in type 2 diabetes patients, the mechanisms underlying this effect are not completely understood. To date there is no data available on the effects of empagliflozin on markers of myocardial function. This study evaluates possible influences of empagliflozin on NT-proBNP serum levels as a strong biomarker for the development of heart failure in type 2 diabetes.

Aim: To study the influence of an amino acid (AA) and chromium picolinate (CrPic) enriched table water on glucose response in healthy controls and early diabetes patients.

Liraglutide and linagliptin are novel drugs for the treatment of diabetes. Antioxidative and neuroprotective effects have been described for both compounds. However, it is not yet known, whether these mechanisms are also protective against diabetic retinal neurodegeneration. We assessed the antioxidative and neuroprotective capabilities of liraglutide and linagliptin as well as the signaling pathways involved, by using C. elegans as a model for glucose-induced neurodegeneration. C. elegans were cultivated under conditions, which mimic clinical hyperglycemia, and treated with 160 mu mol/l liraglutide or 13 mu mol/l linagliptin. Oxidative stress was reduced by 29 or 78 % and methylglyoxal-derived advanced glycation endproducts (AGEs) by 33 or 22 %, respectively. This resulted in an improved neuronal function by 42 or 60 % and an extended mean lifespan by 9 or 11 %, respectively. Antioxidative and AGE reducing effects of liraglutide and linagliptin were not dependent on v-akt murine thymoma viral oncogene homologue 1/forkhead box O1 (AKT1/FOXO). Neuroprotection by liraglutide was AKT1/FOXO dependent, yet AKT1/FOXO independent upon linagliptin treatment. Both liraglutide and linagliptin exert neuroprotective effects in an experimental model for glucose-induced neurodegeneration, however, the signaling pathways differ in the present study. Further pharmacological intervention with these pathways may help to delay the clinical onset of diabetic retinopathy by preserving neuronal integrity.

Traditionelle Chinesische Medizin (TCM) enthält Sekundärmetabolite mit protektiven Eigenschaften. Sijunzi-Tang-Dekokt (SJZTD), Si-Wu-Tang-Dekokt (SWTD) und Liuwei-Dihuang-Dekokt (LWDHD) enthalten Phytamine mit antioxidativen und neuroprotektiven Wirkungen, die überwiegend durch Catalase, Glutathionperoxidase und Superoxiddismutase bzw. Bcl-2/Bax und Caspase-3 vermittelt werden. Darüber hinaus beeinflussen die neuroprotektiven Phytamine von SJZTD, SWDT und LWDHD den PI3K/AKT/MAPK-, AKT/FOXO- bzw. Cytochrom-c-Signalweg. Über die systemische Wirkung von kompletten TCM-Dekokten ist hingegen nur wenig bekannt.

Objective: Current guidelines for the treatment of type 2 diabetes focus on pharmacological treatment of glucose and cardio-vascular risk factors. The aim of this prospective randomized controlled intervention study was to examine the effects of a psychosocial intervention on clinical endpoints and risk factors in patients with type 2 diabetes and early diabetic kidney disease.Methods: 110 patients were randomized to receive an 8-week mindfulness-based stress reduction (MBSR) training (n = 53) compared to standard care (n = 57). The study was carried out open-labelled and randomization was performed computer-generated in a 1:1 ratio. Primary outcome of the study was the change in urinary albumin excretion (albumin-creatinine-ratio, ACR); secondary outcomes were metabolic parameters, intima media thickness (IMT), psychosocial parameters and cardiovascular events.Results: 89 patients (42 in control group and 47 in intervention group) were analysed after 3 years of follow-up. After 1 year, the intervention group showed a reduction of ACR from 44 [16/80] to 39 [20/71] mg/g, while controls increased from 47 [16/120] to 59 [19/128] mg/g (p = 0.05). Parallel to the reduction of stress levels after 1 year, the intervention-group additionally showed reduced catecholamine levels (p < 0.05), improved 24 h-mean arterial (p < 0.05) and maximum systolic blood pressure (p < 0.01), as well as a reduction in IMT (p < 0.01). However, these effects were lost after 2 and 3 years of follow-up.Conclusions: This is the first study to show that a psychosocial intervention improves cardiovascular risk factors in high risk type 2 diabetes patients.

Aims/hypothesis: Ceanorhabditis elegans (C. elegans) was used as a model organism to study effects of the glucagon-like peptide-1 (GLP-1) analogue liraglutide, which is known to have neuroprotective effects. Experimental hyperglycemia caused neuronal dysfunction in C. elegans and reduced lifespan by increased reactive oxygen species (ROS) formation. Liraglutide enhanced the reduced lifespan and showed neuroprotective effects under high glucose conditions. These effects correlated with a reduction of ROS formation. In C. elegans, a key regulator for development, longevity and stress response is DAF-16/FOXO regulated, which is involved in stress resistance via up-regulation of catalase and MnSOD, two antioxidant enzymes involved in the detoxification of ROS. The purpose of this study is to evaluate potential molecular mechanisms underlying the effects of liraglutide.

Einführung: Endotheliale Vorläuferzellen (EPC) lassen sich aus peripherem Blut isolieren und differenzieren. In tierexperimentellen Studien wurde gezeigt, dass EPC zur Gefäßregeneration beitragen und Gefäßschäden vorbeugen. Die Anzahl aus dem peripheren Blut differenzierender EPC konnte als Risikoindikator für kardiovaskuläre Komplikationen in mehreren Studien gezeigt werden Hierbei korreliert eine verminderte Anzahl von EPC mit einem erhöhten kardiovaskulären Risiko. In vitro konnten wir in Vorarbeiten belegen, dass Insulin und insbesondere Glargin die Differenzierung von EPC und die EPC – vermittelte Angiogenese fördert.

Fragestellung: Beruht die therapeutische Wirkung von Humaninsulin nur auf der Senkung des Blutzuckers, oder werden zusätzlich protektive zelluläre Signalwege durch Humaninsulin unter Kulturbedingungen mit einer hohen Glukosekonzentration aktiviert?

Aims: C. elegans was used as a model organism to study effects of glucagon-like peptide-1 (GLP-1) analogue liraglutide, which is known to have neuroprotective effects, on glucose driven changes of lifespan and neuronal function. The short lifespan, good accessibility and strong homologies between human and C. elegans insulin signal transduction system offers excellent opportunities to study molecular mechanisms being responsible for these changes. In C. elegans, high glucose conditions impair neuronal function and reduce lifespan, likely driven by formation of advanced glycation end products (AGEs). In addition, GLP-1 homologue can be found in C. elegans. Aim of the study was to study effects of liraglutide on C. elegans with respect to lifespan and neuronal function under standard (ST) and high glucose (HG) conditions. Relative head motility, body angular velocity and body bending frequency were used as a parameter of neuronal function or damage, respectively.

Pathogenesis of late diabetic complications is influenced by a complex interplay of multiple exogenous and intrinsic factors. The well characterised nematode Caenorhabditis elegans is an ideal model to study causes of diabetic polyneuropathy because of its easily accessible nervous system. A repertoire of methods allows the assessment of both morphological and functional glucotoxic damages as well as reduction of lifespan, thereby helping to examine the influence of different pathways and mechanisms on neurodegeneration. Its insulin signalling system allows to directly visualize effects of insulin on high glucose induced neuronal damage, leading to a better understanding of diabetic polyneuropathy.

Aims/hypothesis: Ceanorhabditis elegans (C. elegans) lacks a vascular system and is therefore a good model to discriminate mechanisms of glucose-mediated tissue damage involving the diabetic retina. Erythropoietin has been identified as prosurvival, angiogenic and neuroprotective factor in the diabetic retina via its ability to inhibit apoptosis through anti-apoptotic pathways such as PI3K-Akt pathway which negatively regulates FOXO transcription factors. We determined the function of erythropoietin in glucose-induced nerve cell dysfunction in C. elegans with respect to lifespan, neuronal function and ROS formation under high glucose conditions and evaluated the potential molecular mechanisms underlying these effects with relation to the diabetic retina.

Fragestellung: Bei Kultivierung von C. elegans unter erhöhter Glukose-Konzentration ist die Akkumulation von Deletionen mitochondrialer DNA (dmtDNA) signifikant verstärkt. Die Entstehung von dmtDNA ist mit der Bildung mitochondrialer reaktiver Sauerstoffspezies (mtROS) assoziiert und wird durch die Präsenz von Apurin/Apyrimidin (AP)-Stellen begünstigt. Die AP-Endonuclease APE1 ist das zentrale Enzym des mitochondrialen DNA-Reparatursystems von AP-Stellen und wird ortholog als exo-3 in C. elegans exprimiert. Ziel dieser Studie war es, den Einfluss von exo-3 und mtROS auf die gesamtzelluläre ROS-Bildung, das Auftreten morphologischer Veränderungen des Nervensystems, die Beeinträchtigung neuronaler Funktionen und die Lebensspanne zu untersuchen.

Fragestellung: Methylglyoxal (MG) ist ein bei Diabetes mellitus vermehrt entstehender reaktiver Metabolit, der an der Entstehung diabetischer Spätschäden beteiligt ist. Bislang wurde angenommen, dass er ausschließlich nicht-enzymatisch entsteht. Daneben wurde in Bakterien und Hefen ein durch die Methylglyoxalsynthase (MGS) katalysierter Pathway beschrieben. Unsere Arbeitsgruppe konnte schließlich die Existenz eines MGS-Homologs in Caenorhabditis elegans zeigen. Dieses sollte in Funktion und Regulation charakterisiert werden.

Renin-angiotensin system blockade retards the progression of diabetic and non-diabetic chronic kidney disease of the native kidneys. Though most patients suffer from a significant renal insufficiency (Chronic kidney disease stage III) and a concomitant heart disease after renal transplantation, there is Up to now no evidence supporting the use of inhibitors of the renin-angiotensin system in these patients. We wish to summarize the available evidence on the use of inhibitors of the renin-angiotensin system after renal transplantation. We specifically discuss potential beneficial as well as adverse effects of a renin-angiotensin system blockade. In addition, we review their influence on morphologic and biochemical markers as well as on renal function, graft and patient survival after renal transplantation.

Type 2 diabetes and impaired glucose tolerance are an increasing burden not only for affected patients, but also for the whole health care system. The pathophysiology of diabetes and its late complications are far from being understood with hyperglycaemia being only the last sign of a long lasting and complex metabolic dysfunction. One major problem in finding therapeutic targets is the fact that the cellular disorders responsible for the development of diabetes involve phylogenetically ancient repair mechanisms. This is one of the reasons why therapeutic targeting of these mechanisms is difficult with the exception of life-style interventions which are, however, limited by individual compliance. In addition, the impact of many therapeutic agents on the entire organism is not well understood. Blood glucose control cannot be considered aEurozhigh tech" medicine and requires non-medical personnel to reach defined blood glucose targets. Non-adherence to treatment and life-style changes, however, facilitate the interaction of patients and medical personnel and individuals with diabetes are therefore often considered themselves to aEurozblame" for being affected by diabetes. Finally, generating treatment guidelines is extremely difficult as clinical studies targeting vascular endpoints need more than 10 years to become informative, partly due to the so-called glycaemic memory.

This Study examined a possible association of the G > C polymorphism at nucleotide -174 in the promoter region of the interleukin-6 (IL-6) gene (rs1800795) with the prevalence of diabetic complications in 235 patients with type I and 498 patients with type 2 diabetes. Genotyping was performed Using polymerase chain reaction (PCR) and Subsequent cleavage by Nla III restriction endonuclease. Analyzing all diabetic patients together demonstrated that 301 patients (41.1%) carried the GG genotype, 114 (15.6%) the CC genotype, and 318 (43.3%) were heterozygous for the GC genotype. However, there was no correlation of any of the genotypes with the prevalence of diabetic nephropathy or diabetic neuropathy, but subjects with the CC genotype had a significantly higher prevalence of diabetic retinopathy compared to patients with the GC and GG genotype (p=0.016). This association was mainly lost when a logistic regression model was adjusted for diabetes duration (p=0.07). Consistently, a weak but not significant association of the polymorphism with diabetic retinopathy was observed when type 1 and type 2 diabetic patients were analyzed separately (patients with type I diabetes: p=0.12: patients with type 2 diabetes: p=0.09). Analogically, no association of the polymorphism was found for diabetic nephropathy or diabetic neuropathy in these groups. In conclusion these data Suggest no major influence of the -174G > C variant in the promoter region of the IL-6 gene on the development of microvascular complications in patients with diabetes.

The outcome of simultaneous pancreas–kidney (SPK) transplantation in type 1 diabetes has dramatically improved in recent years because of optimized surgical techniques and new immunosuppressive drug regimens. Normoglycemia is followed by stabilization or even regression of diabetic lesions, i.e., of heart and kidneys. However, these effects are only visible after more than five yr of normoglycemia (achieved by a functioning allograft). This is also a likely explanation for the conflicting results of studies that investigated patient or kidney graft survival in SPK transplantation compared to kidney transplantation alone. Most studies had too short follow‐up periods, i.e., less than five yr, to compare effectively different transplant strategies in patients with type 1 diabetes and therefore failed to discover a survival benefit in favor of simultaneously transplanted patients. Recent data now indicate that, with a longer follow‐up, there is an increasing survival benefit for simultaneously transplanted patients compared to patients who received a single kidney transplant. This is paralleled by the comparison of simultaneously transplanted patients to patients who received a single kidney transplant from a living donor. A survival benefit for the combined procedure was here visible after 10 yr of follow‐up. We give a short overview on SPK transplantation, with a focus on the effects of this procedure on diabetic complications as well as patient and kidney graft survival.

Der Diabetes mellitus Typ 2, sowohl in seinen Vorstufen als auch in seinen Endstufen, ist eine zunehmende Belastung für die betroffenen Menschen und das Gesundheitssystem. Seine Pathophysiologie ist bis heute nicht gut verstanden, denn die Hyperglykämie ist nur das letzte Zeichen von unterschiedlichen und sehr komplexen metabolischen Störungen, die wiederum nicht eine alleinige, sondern verschiedenste Ursachen besitzen. Besonders problematisch für therapeutische Ansätze ist die Tatsache, dass diejenigen Reaktionen, die zum Diabetes mellitus und seinen Komplikationen beitragen, zelluläre Reaktionen sind, die zum Teil phylogenetisch alte Reparaturmechanismen darstellen und somit durchaus positive Effekte innehaben. Dies ist eine der Ursachen, warum mit der Ausnahme von Lebensstilinterventionen (die aber nicht jedem möglich sind), therapeutische Ansätze, die an diesen Mechanismen ansetzen, schwierig durchzuführen sind. Zudem gibt es eine Vielzahl unterschiedlichster Therapieformen, deren Wirkung auf den Gesamtorganismus nur mäßig untersucht ist. Nicht zuletzt ist eine gute Einstellung des Blutzuckers keine hochtechnisierte Medizin, sondern erfordert im Gegenteil den Einsatz von nichtärztlichem Personal (in einer Zeit, in der die Gesellschaft vor allen Dingen „High-tech-Medizin“ – auch mit Hochleistungsmedizin verwechselt – finanzieren möchte). Kompliziert wird der Umgang des Arztes und der Gesellschaft mit dem Diabetes mellitus dadurch, dass es sich nicht definieren lässt, inwieweit jemand tatsächlich durch mangelnde Bewegung und falsches Essverhalten selber „schuld“ an seiner Erkrankung ist. Schließlich wird das Erstellen von verbindlichen Leitlinien auch dadurch extrem erschwert, dass durch das „Blutzuckergedächtnis“ („glycaemic memory“) Therapiestudien erst nach deutlich mehr als 10 Jahren wirklich aussagefähig sind.