OBJECTIVE:Anorexia nervosa (AN) is a severe mental disorder that is characterized by restriction of energy intake, low weight, and endocrine abnormalities. One of the known endocrine changes in relation to underweight is in the GH/IGF-I axis. The aim of the study was (a) to investigate longitudinal characteristics of the IGF-I-change during therapy and weight gain in adult AN, (b) to determine relationships between IGF-I and leptin, (c) to characterize patients with weak and pronounced hormonal reactions to underweight.DESIGN:Data was assessed from 19 AN patients. Over the first two months, serum IGF-I concentrations were assessed on a weekly basis; thereafter on a monthly basis. The trend of IGF-I values over time was analyzed using individual growth models.RESULTS:In total, n = 177 IGF-I measurements were analyzed. IGF-I increased significantly dependent on BMI (slope = 20.81, p < 0.001), not modulated by duration of disease. The increase in IGF-I was significantly related to the increase in leptin concentrations over time (slope = 15.57, p < 0.001). Patients with a weaker hormonal reaction to underweight were significantly older compared to patients with a pronounced hormonal reaction (t(17) = 3.07, p = 0.007).CONCLUSIONS:During treatment, IGF-I change is clearly related to BMI as well as to leptin. Age appears to be associated with the IGF-I response to underweight.

OBJECTIVE:The protein hormone adiponectin promotes metabolic and psychological health. The aim of the study was to track changes in adiponectin levels in response to weight gain and to assess associations between adiponectin and psychological aspects in patients with anorexia nervosa (AN).METHODS:To investigate if adiponectin levels depend on AN severity, data were assessed from 11 inpatients with a very low body mass index (BMI) and a high chronicity (high severity group; HSS), and nine with less severe symptoms (LSS). During the course of treatment, serum adiponectin concentrations were assessed on a weekly basis along with BMI. Psychological variables (i.e., depression, anxiety, stress, and AN-specific symptoms) were obtained by means of electronic diaries. Longitudinal regressions and correlations were calculated to evaluate the temporal course of adiponectin and its relationship with psychological self-ratings.RESULTS:At the beginning adiponectin was not increased in HSS patients (p = .56), and only marginally elevated in LSS patients (p = 0.07) compared with controls. In HSS patients, adiponectin increased along with BMI during the first treatment phase (i.e., when the BMI of patients was below 16 kg/m2) and thereafter decreased with further weight gain. In LSS patients, adiponectin was not associated with BMI increase. Furthermore, adiponectin was strongly negatively correlated with psychological self-ratings when the BMI of patients was above 16 kg/m2, i.e., higher levels of adiponectin were related to lower ratings of depression, anxiety, and AN-specific symptoms.DISCUSSION:The study connects previous varying results by indicating that the course of adiponectin is dependent on BMI and symptom severity. Similarly, associations of adiponectin and psychological health depended on BMI.

Background Leptin, a hormone secreted by adipose tissue, appears to play a major role in the homeostasis of body weight and psychobiological processes associated with anorexia nervosa (AN). However, there is scarce data on its exact influence on this disorder, in particular data over time. Objective The present study addresses whether leptin changes during inpatient treatment play a role for treatment outcome and psychological factors in underweight AN patients. Methods In order to understand whether leptin’s role differs in relation to AN severity, data were assessed from 11 patients with a very low BMI and a higher chronicity (high severity group; HSS; mean BMI at the beginning of the study = 13.6; mean duration of illness = 5.1 years) vs. nine with less severe symptoms (LSS; mean BMI = 16.2; mean duration of illness = 3.7 years). During the course of treatment, serum leptin concentrations were assessed weekly while weight (BMI) was assessed twice per week. Concomitantly, psychological variables were obtained by means of electronic diaries. Unconditional linear growth models were calculated to evaluate the temporal course of leptin in relation to BMI. For HSS patients, two phases of treatment (BMI < 16 and BMI ≥ 16 kg/m2) were investigated. Results Leptin increased significantly with BMI in both groups of patients. For HSS patients, the increase of leptin in the first treatment phase did not predict later increases in BMI. Furthermore, the relationship of leptin and psychological factors was modulated by symptom severity. In HSS patients, higher leptin levels were associated with greater feelings of depression, anxiety, and stress whereas in LSS patients a higher leptin level showed the trend to be associated with lower psychological symptom burden. Conclusions Our results suggest that leptin changes are differently associated with weight gain and psychological symptoms depending on the severity of starvation.

Objective The role of emotion dysregulation with regard to the psychopathology of anorexia nervosa (AN) is increasingly discussed. It is both assumed that AN symptoms have an impact on difficulties in tolerating aversive emotions and that—conversely—emotion dysregulation influences AN. To date, such conclusions are drawn on the basis of cross-sectional data not allowing for inferences on the temporal dynamics. The current study investigates the longitudinal interaction between emotional intolerance and core AN symptoms over the course of inpatient treatment by comparing patients with high (BMI<15 kg/m2) vs. low symptom severity (HSS vs. LSS). Method The study adopted a longitudinal, process-oriented design with N = 16 analysed electronic diaries. Throughout the course of their inpatient treatment, the patients answered questions daily about emotional intolerance and their AN-specific cognitions and behaviours. The temporal dynamics between emotional intolerance and these variables were analysed using a multivariate time series approach. Results The time series of the processes under investigation adequately reflected the individual treatment courses. The majority of significant linear time trends was found for HSS patients. Most importantly, analysis revealed significant temporal interactions between emotional intolerance and AN symptoms in almost 70% of HSS patients. Thereby, up to 37% of variance in eating restraint and up to 23% in weight concern could be attributed to changes in emotional intolerance. Conclusions The findings support the notion that intolerable unpleasant emotions in severely affected AN patients influence their psychopathology. Additionally, time series analysis outlined the inter-individual heterogeneity of psychosomatic treatment courses of AN patients.

Objective: The aim of the study was to investigate the characteristics of the awakening salivary cortisol in patients with anorexia nervosa (AN) using a time series design. We included ten AN inpatients, six with a very low BMI (high symptom severity, HSS group) and four patients with less severe symptoms (low symptom severity, LSS group).Methods: Patients collected salivary cortisol daily upon awakening. The number of collected saliva samples varied across patients between n = 65 and n = 229 (due to the different lengths of their inpatient stay). In addition, before retiring, the patients answered questions daily on the handheld regarding disorder-related psychosocial variables. The analysis of cortisol and diary data was conducted by using a time series approach.Results: Time series showed that the awakening cortisol of the AN patients was elevated as compared to a control group. Cortisol measurements of patients with LSS essentially fluctuated in a stationary manner around a constant mean. The series of patients with HSS were generally less stable; four HSS patients showed a non stationary cortisol awakening series. Antipsychotic medication did not change awakening cortisol in a specific way. The lagged dependencies between cortisol and depressive feelings became significant for four patients. Here, higher cortisol values were temporally associated with higher values of depressive feelings.Conclusions: Upon awakening, the cortisol of all AN patients was in the standard range but elevated as compared to healthy controls. Patients with HSS appeared to show less stable awakening cortisol time series compared to patients with LSS. (C) 2016 Elsevier B.V. All rights reserved.

symptoms during everyday life on an 11-point Likert scale [from ‘very dissatisfied’ (0) to ‘very satisfied’ (10)], i.e. aggressiveness, impulsiveness, concentration, hypersomnia, sensation of hunger, and agitation. Furthermore, the numbers of eating attacks and losses of control were documented, and physical activity was assessed by a pedometer counting daily steps. As part of the self-assessment, the patient was asked every evening which medication he believed to have received this day. Additionally, on 4 days a week, the patient performed a cancellation test (d2-R), which is validated for the assessment of attention and concentration and suited to quantify attention deficits in ADHD patients [4] . The test was performed under supervision 2 h after drug intake, when maximum improvement in performance was expected [3] . Because of possible learning effects upon repetitive testing, the time to perform the d2-R test was reduced according to the test manual [4] . The primary statistical evaluation was a time series analysis, as described earlier [5] , using SAS version 9.3 (SAS Institute Inc., Cary, N.C., USA). The level of significance was set at p ≤ 0.05. This N-of-1 randomized controlled trial found no evidence for an ability of methylphenidate to improve ADHD symptoms in this patient on long-term treatment. However, the subjectively assumed intake of methylphenidate was correlated with a better general condition (p = 0.005) and higher subjective power of concentration (p = 0.007). Aggressiveness (p = 0.029), impulsiveness (p = 0.020), the sensation of hunger (p = 0.041), and the number of eating attacks (p = 0.012) were all negatively correlated with the assumed but not with the actual methylphenidate intake. Indeed, there is evidence that the belief that one receives active treatment sometimes predicts subjective responses better than the actual treatment [6] . Interestingly, the subjectively perceived improved concentration was not substantiated in better d2-R performance, which is in agreement with findings in healthy prescription stimulant-naive college students, who reported enhanced subjective arousal when assuming methylphenidate intake, while cognitive performance was in fact unchanged [7] . Although biased by numerous factors, the post hoc assessment of subjective well-being was a likely critical element of this trial because it helped to reveal that methylphenidate and expected beneficial effects did not coincide. Interestingly, the patient assumed an intake of methylphenidate twice as often as of placebo ( fig. 2 ), and particularly at the beginning of the trial, he was convinced that he recognized methylphenidate effects immediately, and tended to explain his behavior accordingly (‘I had an eating attack, since I had received placebo’). Thereafter, the patient became more and more confused regarding drug exposure, which shifted his focus gradually from a medication-centered view towards a state of imWe cared for a 27-year-old patient with an 18-year history of attention deficit hyperactivity disorder (ADHD) on long-term treatment with methylphenidate whose dose had been gradually increased from 40 to 140 mg/day during the previous 9 years, with an additional 10-mg ‘on-demand’ rescue dose for eating attacks or aggressive feelings ( fig. 1 ). The comprehensive psychological assessment confirmed a methylphenidate overuse in combination with an extensive psychological dependence complicated by a family environment that powerfully reinforced his abuse. Considering that nonresponse manifests in 20–30% of patients on methylphenidate [1] , the appropriateness of methylphenidate therapy was doubted and a dose reduction and drug discontinuation recommended, which was rejected by the patient because he was afraid of symptom exacerbation. Consequently, an N-of-1 randomized controlled trial was suggested to test the ability of methylphenidate to improve the ADHD symptoms in this individual [2] . In contrast to several earlier outpatient and inpatient withdrawal attempts, which had all failed, the patient welcomed this individualized treatment approach as a cooperative venture with the physician and was motivated to participate. After consultation of the local ethics committee and obtaining informed consent from the patient, the methylphenidate dose was gradually reduced to the recommended maximum dose of 80 mg/day. Subsequently, methylphenidate and identically looking placebo were administered in a randomized double-blind multiple-crossover fashion for 32 days, each day using either the drug or placebo ( fig. 1 ). Taking into account the patient’s fluctuating symptom severity, randomization was designed in blocks, each comprising 1 day of methylphenidate and 1 day of placebo treatment. The short half-life of methylphenidate, the rapid onset of action, and the disappearance of the effect within 1 day enabled a daily switch between placebo and the active drug [3] . Every evening, the patient assessed his self-perceived health status by rating his general condition and the most troubling Received: February 24, 2014 Accepted after revision: June 4, 2014 Published online: October 16, 2014

The diagnosis of microscopic lymph node metastasis in lung cancer is challenging despite the constant advances in tumor staging. The analysis of the methylation status of certain genes in lymph node samples could improve the diagnostic capability of conventional cyto-histological methods. The aim of this study was to demonstrate the feasibility of methylation studies using cytological lymph node samples.A prospective study including 88 patients with a diagnosis or strong suspicion of non-small cell lung cancer, in which an echobronchoscopy was performed on mediastinal or hilar lymph nodes for diagnosis and/or staging purposes. DNA was extracted from cytological lymph node samples and sodium bisulfite modification was performed. Methylation studies for p16/INK4a and SHOX2 were accomplished by MS-qPCR and pyrosequencing.The methodology used in our study yielded optimal/good DNA quality in 90% of the cases. No differences in DNA concentration were observed with respect to the lymph node biopsied and final diagnosis. Methylation analyses using MS-qPCR and pyrosequencing were not possible in a small number of samples mainly due to low DNA concentration, inadequate purity, fragmentation and/or degradation as a consequence of bisulfite conversion.Methylation quantification using MS-qPCR and pyrosequencing of cytological lymph node samples obtained using echobronchoscopy is feasible if an appropriate DNA concentration is obtained, notably contributing to the identification of epigenetic biomarkers capable of improving decision making for the benefit of potentially curable lung cancer patients.El diagnóstico de la afectación metastásica ganglionar en el cáncer de pulmón constituye un problema, a pesar de los avances en la estadificación. La determinación del estado de metilación en ganglios podría mejorar la capacidad de las técnicas citohistológicas para detectar afectación metastásica. Nuestro objetivo fue demostrar la viabilidad de realizar estudios de metilación en muestras ganglionares citológicas.Estudio prospectivo que incluyó 88 pacientes con diagnóstico o alta sospecha de cáncer de pulmón no microcítico, en los que se realizó una punción citológica por ecobroncoscopia de adenopatías mediastínicas y/o hiliares. Se extrajo ADN a partir de muestras citológicas ganglionares y se realizó el tratamiento con bisulfito de sodio. Los estudios de metilación se realizaron por qPCR-MS y pirosecuenciación en los genes p16/INK4a y SHOX2.La metodología empleada permitió obtener ADN de características óptimas/buenas en el 90% de los casos. No se observaron diferencias en la concentración de ADN respecto a la estación ganglionar ni al diagnóstico final. Los análisis por qPCR-MS y pirosecuenciación no fueron posibles en un reducido número de muestras debido a baja concentración de ADN, además de la inadecuada pureza, fragmentación y/o degradación debido al tratamiento con bisulfito de sodio.La cuantificación de la metilación por técnicas como qPCR-MS o pirosecuenciación en muestras ganglionares obtenidas por ecobroncoscopia resulta viable siempre y cuando se logre obtener una concentración adecuada de ADN, contribuyendo a la búsqueda de biomarcadores epigenéticos que mejoren la toma de decisiones en el cáncer de pulmón potencialmente curable en beneficio del paciente.

The aim of this study was to examine the features and changes of the cortisol awakening response (CAR) in patients with anorexia nervosa (AN) with severe and less severe symptoms over the course of inpatient treatment. Our study included n = 20 AN patients who received treatment at the University Hospital, Heidelberg. N = 11 patients were admitted at a psychosomatic and internal-medicine ward that specialized in the treatment of AN patients with a very low BMI (patient group with high symptom severity, HSS). The mean BMI of these patients was 13.2 kg/m2 (SD = 1.4) at the beginning of the study and 16.9 kg/m2 (SD = 1.7) at the end. N = 9 patients were treated at a psychotherapeutic ward where AN patients with less severe symptoms are admitted (patient group with low symptom severity, LSS). The mean BMI of these latter patients was 16.3 kg/m2 (SD = 0.89) at the beginning of the study and 17.1 kg/m2 (SD = 0.65) at the end. Salivary cortisol was measured on two consecutive days respectively, both at the beginning and the end of the study. At the beginning of the study, patients with HSS had a significantly lower mean CAR compared to patients from the LSS group (3.4 nmol/l vs. 11.4 nmol/l). At the end of the study, the mean CAR of patients from the HSS group was still significantly lower compared to the mean CAR of patients with LSS (2.0 nmol/l vs. 9.2 nmol/l). Results indicate that AN patients with severe symptoms exhibit a lower CAR compared to AN patients with less severe symptoms.

Objective: Anorexia nervosa (AN) is a serious eating disorder marked by self-induced underweight. In patients with AN, the avoidance of emotions appears to be a central feature that is reinforced during the acute state of the disorder. This single case study investigated the role of emotional avoidance of a 25-year-old patient with AN during her inpatient treatment. Method: Throughout the course of 96 days, the patient answered questions daily about her emotional avoidance, pro-anorectic beliefs, perfectionism, and further variables on an electronic diary. The patient's daily self-assessment of emotional avoidance was described in terms of mean value, range, and variability for the various treatment phases. Temporal relationships between emotional avoidance and further variables were determined using a time series approach (vector autoregressive (VAR) modelling). Results: Diary data reflect that the patient's ability to tolerate unpleasant emotions appeared to undergo a process of change during inpatient treatment. Results of the time series analysis indicate that the more the patient was able to deal with negative emotions on any one day ( t—1), the less she would be socially avoidant, cognitively confined to food and eating, as well as feeling less secure with her AN, and less depressive on the following day (t). Conclusions: The findings show that for this patient emotional avoidance plays a central role in the interacting system of various psychosocial variables. Replication of these results in other patients with AN would support the recommendation to focus more on emotional regulation in the treatment of AN.

BACKGROUND: The aim of the study was to determine predictors that influence health-related quality of life (HRQOL) in a large cohort of elderly diabetes patients from primary care over a follow-up period of five years. METHODS AND RESULTS: At the baseline measurement of the ESTHER cohort study (2000-2002), 1375 out of 9953 participants suffered from diabetes (13.8%). 1057 of these diabetes patients responded to the second-follow up (2005-2007). HRQOL at baseline and follow-up was measured using the SF-12; mental component scores (MCS) and physical component scores (PCS) were calculated; multiple linear regression models were used to determine predictors of HRQOL at follow-up. As possible predictors for HRQOL, the following baseline variables were examined: treatment with insulin, glycated hemoglobin (HbA1c), number of diabetes related complications, number of comorbid diseases, Body-Mass-Index (BMI), depression and HRQOL. Regression analyses were adjusted for sociodemographic variables and smoking status. 1034 patients (97.8%) responded to the SF-12 both at baseline and after five years and were therefore included in the study. Regression analyses indicated that significant predictors of decreased MCS were a lower HRQOL, a higher number of diabetes related complications and a reported history of depression at baseline. Complications, BMI, smoking and HRQOL at baseline significantly predicted PCS at the five year follow-up. CONCLUSIONS: Our findings expand evidence from previous cross-sectional data indicating that in elderly diabetes patients, depression, diabetes related complications, smoking and BMI are temporally predictive for HRQOL.

Objective: The aim of the study was to assess the longitudinal association between cardiovascular risk factors including albuminuria and other variables (e.g. awareness of hypertension, number of types of antihypertensive drugs, comorbidity), and health-related quality of life (HRQOL) in a large cohort of patients with hypertension, over a follow-up period of 5 years. Methods: Nine thousand nine hundred and fifty-three participants of the ESTHER (Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen) study – a population-based cohort study of middle-aged and older adults aged 50–74 years at baseline – were recruited by general practitioners (GPs) in 2000–2002 and included in the follow-up (2005–2007). HRQOL at baseline and follow-up was measured using the Short-Form General Health Survey (SF-12). Mental component scores (MCS) and physical component scores (PCS) were calculated. Multiple linear regression models were used to determine longitudinal predictors of HRQOL at follow-up. Results: Four thousand, two hundred and three patients with hypertension (98.2%) responded to the SF-12 both at baseline and after 5 years and were therefore included in the study. Smoking status, BMI, diabetes, macroalbuminuria, comorbid diseases, history of depression, and lower HRQOL at baseline predicted lower PCS at the 5-year follow-up. Lower MCS after 5 years was predicted by smoking status, dyslipidaemia, a reported history of depression, and HRQOL at baseline. No significant association was detected between awareness of hypertension and any HRQOL component score after 5 years. Conclusions: Macroalbuminuria and other variables related to increased cardiovascular risk have a negative impact on PCS. Suggestions of a link of treatment and awareness of hypertension with HRQOL from previous cross-sectional studies are not supported by our longitudinal findings.

BACKGROUND:The prevalence rate of mental disorders in severely obese patients appears to be high. In the Department of Psychosomatic Medicine, Heidelberg, we established a short outpatient group intervention for severely obese patients with an affective, anxiety, and/or eating disorder who either are not able to make a clear decision for an intensive weight loss program or who have already decided to undergo bariatric surgery but are advised to attend a support group before surgery. The aim of the group intervention was to reduce depressive symptoms and, in indecisive patients, to enhance the motivation of the patients for engagement in further intensive treatment programs, including bariatric surgery.METHODS:Descriptive data of the first two intervention groups are provided. The treatment program and topics of the group sessions are explained. Time series analysis methods are used to investigate the development of a single patient during the intervention program.RESULTS:Initially, 16 patients joined the group program; ten of these attended the group therapy to completion. The remaining ten patients showed clinically relevant reduction in depression levels and improvement in mental quality of life. Results of the single-case time series analysis indicate that the temporal relationship between eating behavior and depression changed during treatment.CONCLUSIONS:The group program, as outlined, could be a useful intervention for severely obese patients with comorbid depression, anxiety, or eating disorder. A gap in the health care system is thus bridged by this short intervention that can encourage further treatment decisions such as bariatric surgery.

OBJECTIVE:With the increasing prevalence of multiple conditions in older age, the high prevalence of mental disorders, and the many social challenges facing elderly people, a high-risk patient group in need of interdisciplinary (biological, psychological, and social) care is emerging. The INTERMED interview is an integrative assessment method that identifies patients with complex health care needs. The aim of this study was to develop and evaluate the INTERMED for the Elderly (IM-E), specifically for use in populations of elderly persons.METHODS:In focus groups conducted with the authors of the original INTERMED, the variables and anchor points that had to be adjusted to the needs and situation of the elderly and to the demands of a population-based study were discussed and altered. The final version of the IM-E was conducted with 42 elderly persons. Participants were doubly scored by two trained raters; the interrater reliability [intraclass correlation coefficient (ICC) (2,1)] was calculated.RESULTS:The IM-E was well accepted by the elderly persons interviewed. ICCs for the various domains of the IM-E ranged between .87 and .95, while the ICC for the sum score was .95. Regarding the cutoff point of 20/21 for patients with complex health care needs, a κ of .75 was achieved.CONCLUSIONS:The IM-E is a reliable integrative assessment instrument. It is well suited for epidemiological settings to adequately describe the percentage of elderly patients with complex health care needs. In clinical settings, it can be used to identify elderly patients in need of interdisciplinary care.

Einleitung: Der Zuwachs der älteren Bevölkerung führt zu einem Anstieg der Prävalenz chronischer Erkrankungen wie Diabetes mellitus. Bis 2030 wird durch zunehmende Urbanisierung und das Altern der Weltbevölkerung mit 366 Millionen Erkrankten weltweit gerechnet. Ziel einer optimierten Diabetestherapie ist u.a. ein Erhalt der gesundheitsbezogenen Lebensqualität (LQ). Bekannte Einflussfaktoren der gesundheitsbezogenen LQ bei Diabetes sind das Geschlecht und die Anzahl der Spätfolgen. Für Stoffwechselkontrolle und Art der Therapie liegen widersprüchliche Daten vor. Bisherige Erkenntnisse basieren zumeist auf Querschnittsanalysen von Patientenkollektiven. Populationsbezogene längsschnittliche Untersuchungen an Erwachsenen/Älteren unter Berücksichtigung physiologischer Parameter stehen aus. Methoden: In der ESTHER-Studie wurde bei 1375 Diabetikern die gesundheitsbezogene Lebensqualität über den SF-12 erhoben – zur Baseline, nach 2 Jahren und in einem 5-Jahres Follow-Up. Zusätzlich wurden soziodemographische Daten, Komorbiditäten, Gesundheitsverhalten, körperliche Aktivität und die aktuelle Medikation abgefragt sowie physiologische Parameter gemessen. Die Lebensqualität der Diabetiker fünf Jahre nach Einschluss in die Studie wurde über eine lineare Regression mit Prädiktoren der Baseline-Messung modelliert. Ergebnisse: Ein signifikant positiver Zusammenhang mit der psychischen LQ nach 5 Jahren fand sich für die LQ bei Baseline (p<0,001)), signifikant negative Zusammenhänge fanden sich für die Blutzuckereinstellung (p=0,01), die Anzahl der Komplikationen (p=0,03) und eine depressive Komorbidität (p=0,01). Weitere identifizierte Prädiktoren der körperlichen Lebensqualität bei Diabetes werden im Rahmen der bisher vorhandenen Literatur diskutiert. Diskussion: Die gesundheitsbezogene LQ ist ein relevantes Outcomekriterium in klinischen und epidemiologischen Studien. Es ist sinnvoll, bei Erhebungen in der älteren Bevölkerung ergänzend krankheitsspezifische Erhebungsinstrumente zur Erfassung der Lebensqualität einsetzen, um die Mechanismen der Einschränkung des Wohlbefindens differenzierter erfassen und Interventionsstudien an klinischen Kollektiven durchführen zu können. Neben der Erhebung der bekannten Risikofaktoren bei Diabetes sollte zusätzlich die psychische Komorbidität erfasst und differenziert untersucht werden, da sie einen relevanten Einfluss auf das Wohlbefinden und das Auftreten von Folgeerscheinungen bei Diabetes mellitus hat.