Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

A variety of different drugs with distinct approaches are available for the treatment of type 2 diabetes. Different treatment options, as well as new developments, are needed, since an acceptable quality of glucose control often requires drug combinations. Furthermore, type 2 diabetes is known as a heterogeneous disease that is characterized by different phases and individual characteristics, such as risk profiles and contraindications. In particular the impact of antihyperglycemic therapies on cardiovascular risk, body weight and the risk for hypoglycemia is important, but also the consideration of other co-morbidities, occupational and social aspects plays a role. So far, each therapeutic step is based on lifestyle-interventions and, if possible, metformin. Dipeptidylpeptidase 4 (DPP 4) inhibitors und glucagon-like peptid 1 (GLP 1) mimetics represent a new important tool in the differential therapy of type 2 diabetes. The advantage of incretin-based concepts is an improvement of glucose quality without induction of hypoglycemia and additional weight gain. It is, however, still not known, whether these advantages will still be seen in end point studies, e. g. concerning the cardiovascular risk.

Besides classical antidiabetic goals the contemporary diabetology more intensely focuses on the reduction of cardiovascular risk factors of type 2 diabetic patients. Especially, potentially deleterious consequences of insulin therapies are debated, since avoiding hypoglycemic events and the possibility of weight loss represent advantageous cardiovascular effects of an antidiabetic therapy. On the other hand, a large proportion of patients receive insulin treatment during progression of the disease. In order to improve the cardiovascular risk profile of these patients, the combination of insulin with additional oral antidiabetic treatment should be considered. Positive effects are yielded, if the combination allows an optimized glucose control without an increase of hypoglycemic events or weight gain, or if the insulin dose and the body weight can be reduced. Options of such insulin based combination treatments and their potential cardiovascular impact are discussed.

Glycemic and body weight control are two outstanding goals in the treatment of patients with type 2 diabetes that often are not appropriately achieved. This observational study evaluates whether treatment by quality controlled diabetes centers generates an improvement in this regard and focuses on associations with different therapies. Data of 9.294 type 2 diabetic patients (mean age 66.9±11.6 years, mean diabetes duration 12.4±9.2 years) from 103 German diabetes centers were assessed by a standardized, prospective, computer-based diabetes care and outcome documentation system (DPV-Wiss-database). Therapeutic concepts included lifestyle intervention (n=1.813), oral antidiabetics (OAD, n=1.536), insulin (n=4.504) and insulin plus OAD (n=1.441). HbA1c and body weight were compared before and after a stable therapeutical period of 1.07±0.3 years. Change in HbA1c (%): all patients 7.4±1.6-7.0±1.3, lifestyle intervention 7.5±1.9-6.9±1.5, OAD 6.7±1.1-6.5±1.0, insulin 7.6±1.6-7.2±1.4, insulin plus OAD 7.5±1.5-7.2±1.3; each p≤0.05. Change in body weight (kg): all patients +0.08±0.07, n. s.; lifestyle intervention -0.28±0.20, OAD -0.56±0.13, each p<0.05 [metfomin -0.77±0.21, sulfonylurea drugs -0.75±0.34, each p<0.05; glitazones +0.62±0.70, α-glucosidase inhibitors -0.22±0.76, each n. s.], insulin +0.27±0.10, insulin plus OAD +0.63±0.14, each n. s. In summary, lifestyle, metformin or sulfonylurea drug treatment resulted in HbA1c-values below 7.0% plus a significant weight reduction. Insulin treatment-associated concepts resulted in HbA1c-values slightly above 7.0% without body weight alterations. These "real life" data underline that a specialised and quality controlled diabetes care is able to achieve significant treatment results even in patients with disease progression and a high proportion of insulin therapies.

Objective: Mice deficient of the serotonin transporter (5-HTT ko) mice have a reduced brain serotonin content and develop late-onset obesity. To elucidate the pathophysiology of this obesity, we analyzed the expression of the interrelated weight-regulatory molecules: brain-derived neurotrophic factor (BDNF) and leptin receptor (LR) in brain areas associated with nutrition and activity. Research Design and Methods: We investigated feeding behavior, physical activity and metabolic parameters of 5-HTT ko and wild-type mice and measured the expression of BDNF and LR in brain areas associated with nutrition and activity using quantitative real-time PCR. The influence of age, gender and fasting was analyzed. Results: Male 5-HTT ko mice developed obesity without hyperphagia from the age of 5 months. Physical activity was reduced in old male, but not old female, 5-HTT ko mice. The BDNF gene expression in frontal cortex was elevated in young, but reduced in old 5-HTT ko mice. Fasting failed to increase the BDNF gene expression in frontal cortex of young 5 HTT ko mice and in the hypothalamus in old 5-HTT ko mice. The fasting-induced hypothalamic increase of LR was absent in both young and old 5-HTT ko mice. Conclusions: We propose that low brain serotonin level due to the 5-HTT ko genotype leads to reduced physical activity and low BDNF, which together with the lack of fasting-induced hypothalamic BDNF and LR production results in late-onset obesity. Although lack of the 5-HTT is a genetic vulnerability factor for obesity, female gender is protective.

Fragestellung: Patienten mit einer koronaren Eingefäß-Erkrankung unterscheiden sich in der Regel hinsichtlich kardiovaskulärer Ereignisrate, Prognose und Notwendigkeit einer koronaren Bypass-Versorgung von Patienten mit einer Mehrgefäß-Erkrankung. In der Studie wurde untersucht, ob sich Patienten mit Ein- bzw. Mehrgefäß-Erkrankung bzgl. kardio-metabolischer Parameter, insbesondere dem Glucosestoffwechsel, unterscheiden.

Fragestellung: Glucosestoffwechselstörungen und das Entstehen einer koronaren Herzerkrankung (KHK) sind eng miteinander assoziiert. Um das Vorliegen einer Glucosestoffwechselstörung zu untersuchen, wird bei Patienten mit einer KHK ohne bekannten Diabetes mellitus die Durchführung eines oralen Glucosetoleranztests (OGTT) empfohlen (ESC 2007, DDG 2008).

Fragestellung: Adipositas gilt als eigenständiger kardiovaskulärer Risikofaktor. Neben einer guten Stoffwechselkontrolle stellt die Gewichtsreduktion bei Übergewicht ein wichtiges Ziel einer mikro- und makrovaskulär orientierten Diabetestherapie dar. Auf Basis der DPV-Wiss-Datenbank wurde untersucht, welchen Einfluss verschiedene Diabetestherapien auf den Stoffwechsel und auf das Gewicht haben.

Die Synkope ist ein häufiges Symptom in der Notaufnahme. Meist hat sie eine gutartige Ursache und bedarf keines langwierigen stationären Aufenthaltes. Ein risikoadaptiertes und strukturiertes Vorgehen hilft, für jeden synkopierten Patienten eine optimale Strategie zu finden. Lebensgefährliche Ursachen einer Synkope müssen unverzüglich ausgeschlossen und nichtsynkopale Bewusstseinsstörungen stets differenzialdiagnostisch bedacht werden. Patienten mit hohem Risiko für eine schwerwiegende Gesundheitsstörung wie z. B. einer strukturellen Herzerkrankung als Ursache der Synkope müssen identifiziert und der notwendigen weiteren Diagnostik zugeführt werden. Patienten ohne erhöhtes Risiko können ambulant weiter betreut werden.

Severe arterial hypertension is a hallmark of Cushing syndrome which occurs in 80% of the patients. Additionally, persistent cortisol excess induces obesity, hyperinsulinemia with disturbed glucose tolerance and dyslipidemia which all contribute to the development of hypertension and its deleterious sequelae. Cortisol effects are mediated through diversely distributed intracellular glucocorticoid and mineralocorticoid receptors which are protected by the 11-beta-hydroxysteroiddehydrogenase type 2 in cells of some organs (i.e. kidney) but not in other. A highly complex clinical picture evolves in case of hypercortisolism due to the ubiquitous distribution of steroid receptors with different affinity and binding capacities for glucocorticoids. The present review focuses on the cortisol induced changes in blood pressure regulation which contribute to the development of hypertension.

Apoptotic mechanisms in proximal renal tubular epithelial cells (PTEC) are crucial in the pathogenesis of acute kidney injury. We investigated whether insulin alters anti-apoptotic signalling in human PTEC. Cells were deprived of insulin for 0, 24 or 48 h and then stimulated with insulin for 0 or 5 min. Apoptosis was induced by camptothecin incubation. Insulin receptor kinase (IR-kinase) activity, phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-1-associated PI3-kinase (p85), Ser273-phosphorylation of Akt and caspase-3 activity (C3-activity) were determined. Insulin stimulation increased the activity of IR-kinase, IRS-1 phosphorylation, p85 association with IRS-1 and Ser273-phosphorylation of Akt by at least 250%, respectively and decreased the C3-activity by 45% (p < 0.01, respectively). Deprivation of insulin for 24 and 48 h reduced basal and insulin-stimulated IR-kinase activity, IRS-1 phosphorylation, p85 association with IRS-1 and Ser273-phosphorylation of Akt by 30-40% and increased C3-activity by 15-20% (p < 0.01, respectively). Incubation with camptothecin increased C3-activity by 250-300% (p < 0.001). Subsequent insulin stimulation reversed the camptothecin induced increase of C3-activity. Our data indicate that apoptosis in PTEC is regulated by the insulin dependent PI3-kinase/Akt pathway. The enhancement of tubular-specific cell survival signals might represent a potential therapeutic tool for the protection of renal function in acute kidney injury.

Calpains are a family of non-lysosomal cytoplasmatic cysteine proteases. Since calpain 10 (CAPN10), a member of the calpain family of proteases, has been found to represent a putative diabetes susceptibility gene, it was argued that calpains may be involved in the development of type 2 diabetes. The functional role of calpains in insulin signaling and/or insulin action is, however, not clear. We investigated the effects of the calpains 1 and 2 inhibitor PD151746 on insulin signaling and insulin action in human hepatoma G2 cells (HepG2). HepG2 cells were incubated without (-PD) or with (+PD) 5.33 micromol/l PD151746 for different times and then stimulated with 100 nmol/l insulin for 0 (t(0)), 5 (t(5)), 15 (t(15)), 30 (t(30)), 45 (t(45)), and 60 (t(60)) min. After solubilization of the cells, insulin receptor kinase activity, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-1-associated phosphatidylinositol-3 kinase (PI3-kinase), PI3-kinase activity, Thr(308) phosphorlyation of Akt, amount of protein tyrosine phosphatase-epsilon (PTPepsilon), and glycogen synthase activity were determined. Incubation with PD151746 resulted in a significant reduction of insulin-stimulated glycogen synthesis compared with cells not pre-incubated with the calpain inhibitor (-PD: t(0), 4.90 +/- 1.20%; t(5), 5.90 +/- 1.02%; t(15), 5.29 +/- 0.95%; t(30), 5.60 +/- 1.10%; t(45), 5.52 +/- 0.90%; t(60), 5.67 +/- 0.97%;+PD: t(0), 4.56 +/- 1.10%; t(5), 6.16 +/- 1.05%; t(15), 7.52 +/- 1.09%; t(30), 7.68 +/- 1.10%; t(45), 8.28 +/- 0.89%; t(60), 7.69 +/- 0.98%; P < 0.05). Incubation with PD151746 significantly increased the protein amount of PTPepsilon in the cells after 12 h (-PD: t(1), 0.85 +/- 0.18 RU (Relative unit); t(8), 0.87 +/- 0.18 RU; t(12), 0.9 +/- 0.13 RU; +PD: t(1), 0.92 +/- 0.21 RU; t(8), 1.1 +/- 0.15 RU; t(12), 1.34 +/- 0.16 RU; P < 0.05). Calpain inhibition with PD151746 had no effect on the insulin stimulation of the investigated insulin signaling parameters. These results in HepG2 cells suggest that calpains play a role in the hepatic regulation of insulin-stimulated glycogen synthesis independent of the PI3-kinase/Akt signaling pathway.

Fragestellung: Die Adipositas spielt eine wesentliche Rolle bei der Entstehung makrovaskulärer Komplikationen des Menschen mit Typ 2 Diabetes. Das Erreichen einer Gewichtsreduktion ist deshalb neben der Normoglykämie ein wichtiges Ziel der Diabetestherapie. Auf Basis der DPV-Wiss-Datenbank wurde untersucht, welchen Einfluss verschiedene Diabetestherapien auf den Stoffwechsel und auf das Gewicht haben.

Einleitung: BZSM und Insulin Dosisanpassung gelten als anerkannte Bestandteile eines modernen Diabetes Selbstmanagements. Ziele: Die Effektivität einer BZSM für die BZ Einstellung soll unter Alltagsbedingungen ermittelt werden.

In Europe, hantavirus infections usually present as hemorrhagic fever with renal syndrome and its mild form nephropathia epidemica, while clinical cases with severe pulmonary affections are extremely rare and appear to be confined to infections by New World hanta viruses in the Americas. We report on a female patient from Northern Germany, who suffered primarily from severe acute respiratory distress syndrome-like pulmonary failure due to Dobrava hantavirus infection that was complicated by acute renal insufficiency.

BACKGROUND:The increasing prevalence of diabetes mellitus and its long-term complications are associated with an expanding social medical problem. In order to originate an established teaching and training program on a physician-based level in short time, three specialist diabetes centers from Lübeck transferred their concept to a diabetes organization based on 17 physicians who had only rarely undertaken any diabetes teaching before. We investigated the achievement and effectiveness of this concept in a prospective multicenter evaluation one year after the patients had received structured diabetes teaching by the organization.PATIENTS AND METHODS:Physicians and their teaching staff were trained by the specialists from the diabetes centers according to an official agreement. Patients were treated by each practice, while the diabetes teaching was done centrally by the organization through a diabetes assistant/dietician based on a modified official diabetes teaching and training program (ZI-program). 230 of 250 patients (120 male, 110 female) were reinvestigated one year after they had received the teaching. The group consisted of 179 non-insulin-treated (NIB; 94 via physicians, 85 via specialists) and 51 insulin-treated (IB; 19 via physicians, 32 via specialists) participants.RESULTS:The average age of NIB was 60.4+/-9.8 years, while IBs were 68.8+/-7.3 years old. HbA (1c) values were reduced in both groups, NIB and IB, by approximately 1% (NIB: 7.59+/-1.97% to 6.59+/-1.84%; IB: 8.47+/-1.35% to 7,36+/-1,38 %; p < 0,001). In the NIB-group the BMI was reduced by 0,64+/-0,14 kg x m (-2), whereas it was increased in the IB-group by 0.33+/-0.24 kg x m(-2) (NIB: 30.55+/-0.40 to 29.91+/-0.39 kg x m(-2), p < 0.001; IB: 28.83+/-0.74 to 29.16+/-0.75 kg x m(-2), p = 0.82).CONCLUSION:The transfer of established teaching and training concepts of specialist diabetes centers to a newly founded, physician-based diabetes organization resulted in a broad, effective and long-lasting medical care of patients with type 2 diabetics treated without or with insulin. The results are superior to those of other evaluations based on diabetes training ZI-programs.

Viral RNA was amplified by reverse transcription-PCR from a patient suffering from hemorrhagic fever with renal syndrome (HFRS) in Germany. The virus strain could be assigned to the Dobrava hantavirus (DOBV). This is the first molecular identification of human infection by DOBV in central Europe and the first proof that a virus strain related to the DOBV-Aa lineage, carried by Apodemus agrarius rodents, is able to cause HFRS.