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Lithium-ion batteries are sensitive to temperature changes over their life. High operational temperatures can negatively affect the battery and lead to capacity fade and lifespan reduction. Air-cooled thermal management systems are widely used in electrified vehicles. A novel air-cooled battery design is introduced. Aluminum fin cooling features are directly integrated onto prismatic cells rather than established by the use of an auxiliary polymer component. When the cells are arranged in a battery array, the on-cell features generate cooling channels. A forced-convection testbed is used to determine thermal management performance. Shear resistance experiments are used to measure the mechanical resistance of the battery cell assemblies. The study demonstrates that a configuration with parallel channel cell-wall integrated fins recovers the performance of the system with the standard polymer space but provides a 20% improvement in temperature uniformity under fan power control. This configuration, however, lacks mechanical resistance in the assembly. A poka-yoke based configuration with tapered channels enhanced by secondary fins provides mechanical resistances and also performs better in both flow and fan power control. This configuration maintains the cell maximum temperature as the assembly via polymer spacers but improves the temperature uniformity by 50%.

Bei der Behandlung des Typ-2-Diabetes kann der Arzt heute auf verschiedene Substanzklassen zuruckgreifen. Uber Starken und Schwachen dieser Substanzen und uber Konsequenzen fur die individualisierte Therapie informiert der folgende Beitrag.

Die subkutane Insulinpumpentherapie (CSII) stellt die zurzeit physiologischste Form der Insulinzufuhr dar. Patienten mit Typ-1-Diabetes profitieren besonders von einer Verbesserung des HbA1c-Werts (HbA1c: Glykohamoglobin Typ A1c), der Abnahme der Haufigkeit von Hypoglykamien und geringeren Glukoseschwankungen. Die optimierte Glukosekontrolle kann das Risiko fur diabetische Folgeerkrankungen reduzieren. Die CSII liefert eine optimale Basis zur Koppelung mit kontinuierlich messenden Glukosesensoren (CGM). Diese sensorunterstutzte Pumpentherapie (SuP) ist ein Schritt hin zu einem bereits in naher Zukunft verfugbaren geschlossenen System, der kunstlichen Bauchspeicheldruse.

Neue orale Antidiabetika (OAD) haben die Behandlung des Diabetes mellitus Typ 2 in den letzten Jahren komplexer gemacht. Vor dem Start einer Insulintherapie gibt es nun immer mehr Kombinationsmoglichkeiten fur eine zwei- und dreifach orale Therapie.

Die Insulinpumpentherapie (CSII) ist die bedarfsgerechteste Form der Insulinzufuhr. Patienten mit Typ-1-Diabetes profitieren besonders von einer Verbesserung des HbA1c-Werts, der Abnahme von Hypoglykamien und geringeren Glukoseschwankungen. Nachweislich verringert das das Risiko fur diabetische Folgeerkrankungen. Durch die Kopplung von Insulinpumpen mit dem kontinuierlichen Glukosemonitoring (CGM) zur Sensorunterstutzten Pumpentherapie (SuP) werden die Vorteile dieser Form der Insulinabgabe noch deutlicher. Damit ist auch ein erster Schritt zu einem geschlossenen System erfolgt. In diesem Artikel geht es um eine Darstellung von CSII und SuP und den Beleg ihrer Wirksamkeit.

Bei Patienten mit Typ-1-Diabetes ist ein Glukoseverlauf oberhalb physiologischer Bereiche mit der Entwicklung von mikro- und makrovaskularen Langzeitkomplikationen assoziiert. So ist es nachvollziehbar, dass aktuelle Leitlinien fur die Mehrzahl der Patienten eine moglichst normnahe Einstellung empfehlen, solange dies ohne eine relevante Zunahme von Hypoglykamien bzw. unter Ausschluss schwerer Hypoglykamien erreichbar ist. Ein solches Ziel ist eine grose Herausforderung fur Patienten und betreuende Diabetologen und Diabetesberater. Trotz diverser Verbesserungen bei den therapeutischen Optionen wahrend der letzten wenigen Jahrzehnte ist die Zahl der Patienten, die diese Therapieziele mit den derzeit kommerziell verfugbaren therapeutischen Optionen erreichen, noch immer nicht ausreichend. Erfreulicherweise ermoglichen neue Entwicklungen der letzten Jahre v. a im Bereich der Diabetestechnologie, zunehmend den Anteil im Zielbereich eingestellter Patienten zu erhohen. Hierzu tragen besonders die sukzessiv mehr zum Einsatz kommenden und immer verlasslicher arbeitenden kontinuierlichen Glukosemesssysteme bei. Gekoppelt mit einer Insulinpumpentherapie ermoglichen diese Messsysteme eine stabilere (geringe Glukosevariabilitat), bessere (HbA1c) und sicherere (Hypoglykamien) Einstellungsqualitat. Tatsachlich ist die Marktdurchdringung bei diesen Systemen in Deutschland weiterhin nur im einstelligen Prozentbereich und stellt daher noch immer ein bemerkenswertes bisher nicht genutztes Potenzial dar. Aktuellste Modelle fur diese sog. sensorunterstutzte Pumpentherapie (SUP) greifen bereits pradiktiv (vorubergehende, selbstandige Unterbrechung der Insulinabgabe und Wiederaufnahme der Basalrate) mithilfe eines Algorithmus in die Therapie ein, um sich anbahnende Hypoglykamien zu vermeiden. Der nachste logische Schritt ist das Insulinmanagement im Sinn eines artifiziellen Pankreas (AP) komplett zu automatisieren, d. h. einen Kreislauf von Glukosemessung und Insulinabgabe so zu etablieren, dass sich ein geschlossenes System, ein sog. Closed-loop-System (CL), ergibt. In den letzten beiden Jahren sind hier grose Fortschritte zu verzeichnen, mehrere Forschergruppen arbeiten an der Etablierung marktreifer Systeme. Dieser Beitrag basiert auf umfassenden Erfahrungen bei der Behandlung eines Typ-1-Diabetes-Patientenkollektivs sowie einer selektiven Literaturrecherche in der Datenbank PubMed zum Thema Closed-loop-Systeme bei Typ-1-Diabetes-mellitus.

Nahezu jeder vierte Deutsche ist zu dick – Tendenz zunehmend. Die Ursachen sind hinlanglich bekannt: zuviel Essen, zu wenig Bewegung. In Einzelfallen konnen aber auch weitere Erkrankungen dahinter stecken. Lesen Sie, welche Folgen das zu hohe Korpergewicht fur die Patienten haben kann, und was Sie ausschliesen mussen, bevor Sie zur Diat raten.

Bei Patienten mit Typ-1-Diabetes mellitus (T1DM) und Typ-2-Diabetes mellitus (T2DM) stellt die Hypoglykamie nach wie vor einen relevanten limitierenden Faktor fur die Erreichung des HbA1c-Zielwertes dar. Neben der akuten Notfallsituation hat die Hypoglykamie prognostische Relevanz hinsichtlich kardiovaskularer oder zerebrovaskularer Morbiditat bis hin zur Mortalitat. Symptomatische und v. a. schwere Hypoglykamien sind fur die betroffenen Patienten eine grose Belastung, auch stellen sie einen nicht unerheblichen Kostenfaktor fur das Gesundheitssystem dar. Mit der kontinuierlichen Glucosemessung (CGM) sind komplexe Ablaufe perihypoglykamischer Episoden besser nachvollziehbar. Auch konnte gezeigt werden, dass neben den offensichtlichen symptomatischen Hypoglykamien auch eine nicht unerhebliche Zahl an inapparenter Hypoglykamien auftreten, die u. a. mitverantwortlich sind fur die bei vielen Patienten vorliegende hohe Glucosevariabilitat und Instabilitat des Glucosestoffwechsels. Gefahrdet sind nicht nur Patienten mit T1DM, sondern v. a. Patienten mit langjahrigem T2DM unter einer Therapie mit Sulfonylharnstoffen oder Insulin. Ein weiterer behandelbarer Risikofaktor stellt eine gestorte Gegenregulation verbunden mit Hypoglykamiewahrnehmungsstorung dar. Ziel muss es sein, neben dem optimierten Management (Schulung) einen Schwerpunkt auf die Hypoglykamiepravention durch Optimierung und Vermeidung moglicher Ausloser oder Risikofaktoren zu setzen. Hierzu gehoren neben individualisierten Therapiezielen auch die Wahl effektiver, aber gleichzeitig in Hinsicht auf das Hypoglykamierisiko sicherer Therapiestrategien.

Braucht Ihr Patient Glukokortikoide, sollten Sie unbedingt seine Blutzuckerwerte im Blick behalten. Verschlechtert sich seine Glukosestoffwechsellage, mussen Sie aber auf die Gabe der Glukokortikoide nicht verzichten. Vielmehr muss die Diabetestherapie angepasst werden. Wie Sie dabei im Einzelfall vorgehen sollten, erlautert der Autor des nachfolgenden Beitrags.

Die Moglichkeit des kontinuierlichen Glucose-Monitorings („continuous glucose monitoring“, CGM) stellt einen der wesentlichen Therapiefortschritte in den vergangenen 15 Jahren dar. Sie kann fur diagnostische Zwecke (uber Tage bis Wochen) oder fur die dauerhafte Behandlung eingesetzt werden. Auch die klinische Entscheidungsfindung wird vom CGM-System unterstutzt, denn dieses gibt nicht nur die momentane Glucosekonzentration wieder, sondern ebenfalls den Trend und das Glucoseprofil wahrend einiger Stunden vor der jeweiligen Messung. Die Verwendung von CGM in Kombination mit der kontinuierlichen subkutanen Insulininfusion („continuous subcutaneous insulin infusion“, CSII) ermoglicht die sensorgestutzte Insulinpumpentherapie und die automatische Abschaltung der Insulininfusion, wenn der Patient bei niedrigen Glucosekonzentrationen nicht reagiert („low-glucose suspend“, LGS). Mit CGM lassen sich also die Stoffwechselkontrolle optimieren, die Ziel-HbA1c-Konzentrationen einhalten und gleichzeitig das Risiko fur hypoglykamische Ereignisse verringern.

Trotz verschiedener neuer Medikamente fur Menschen mit Typ-2-Diabetes-mellitus wie den Inkretinmimetika hat die Insulintherapie nicht an Wichtigkeit eingebust. Im Gegenteil: Auser einer guten Schulung der Patienten, auch im Hinblick auf gesunde Ernahrung, und der Blutzuckerselbstkontrolle ist die Insulintherapie ein essenzieller Baustein im sequenziellen Therapiekonzept von Menschen mit Typ-2-Diabetes [1].

Seit Ende 2012 steht in Deutschland eine neue Substanzklasse zur Therapie des Typ 2 Diabetes zur Verfugung. Das Wirkprinzip ist neu und beruht auf einer Modulation der Glukoseruckresorption im Harn durch Inhibition so genannter Sodium Glucose Linked Transporter (SGLT). Dadurch wird eine therapeutische Glukosurie induziert. Dies ist ein fur den Arzt ungewohnter Behandlungsansatz, der die Niere als Ort der Glukoseregulation in den therapeutischen Mittelpunkt stellt. Daher sind eine nahere Betrachtung der hierfur verantwortlichen renalen Mechanismen sowie eine Darstellung der Vor- und Nachteile dieser Medikamentengruppe sinnvoll.

ZusammenfassungEmpfehlungen zur Lebensstilmodifikation bilden die Basis aktueller Therapieempfehlungen bei Patienten mit Typ-2-Diabetes mellitus. Im Mittelpunkt steht zudem eine multifaktorielle, medikamentöse Therapiestrategie aller relevanter Risikofaktoren, um eine optimale Ereignisreduktion bei den Folgeerkrankungen zu erreichen. Bei der Therapie der Glukosestoffwechselstörung ist Metformin als Mittel der Wahl unumstritten, der Einsatz wird bereits bei Diagnosestellung empfohlen. Von den zusätzlich zur Verfügung stehenden antihyperglykämen Substanzen beleuchtet der Artikel jene Medikamente, die im Rahmen der Stoffwechseloptimierung ohne Gewichtszunahme und Hypoglykämiegefahr auskommen, nämlich Dipeptidylpeptidase 4-Inhibitoren, GLP1-Rezeptor-Agonisten und SGLT2-Inhibitoren. Alle Medikamente weisen ein günstiges kardiovaskuläres Risikoprofil auf. Für diese neueren, innovativen Substanzen stehen die Ergebnisse von Endpunktstudien jedoch noch aus.

Background The prevention of cardiovascular disease, including diastolic cardiac dysfunction with its high prevalence and ominous prognosis, is a therapeutic challenge for patients with type 2 diabetes. Both short and long-acting insulin analogues (AI) have been shown to reduce glucose variability and provide potential benefit for cardiovascular disease although the effects on cardiac function have not yet been evaluated. This long-term, prospective, randomized controlled trial in patients with type 2 diabetes (T2D) tested the hypothesis that a multiple daily injection regimen (MDI) with AI improves postmeal glucose excursions in comparison to human insulin (HI) and that the effects of AI improve diastolic cardiac function. Methods For 36 months, MDI treatment in 109 T2D patients was adapted every 3 months (targets: fasting glucose ≤ 110 mg/dl, postmeal glucose ≤ 150 mg/dl) in both groups: AI (insulin detemir and insulin aspart, n = 61) and HI (NPH-insulin and regular HI, n = 48). Diastolic cardiac function (myocardial velocity E’ using tissue Doppler imaging and the mitral inflow ratio E/A) and vascular function were assessed before and 2 h after a standardized breakfast (48 g carbohydrates). At baseline, both groups were comparable with regards to demographic, cardiac and metabolic data. Analysis of data included traditional statistics as well as the use of a multiple imputation technique shown in brackets [ ]. Results At 36 months, the primary endpoint, postmeal glucose, decreased by 20 ± 62 mg/dl, p = 0.038 [p = 0.021] with AI and increased insignificantly with HI (inter-group p = 0.032 [p = 0.047]) to postmeal glucose levels of 161 ± 39 with AI vs. 195 ± 54 mg/dl with HI (inter-group p = 0.002 [p = 0.010]) whereas the levels of fasting glucose and HbA1c were comparable. With AI, postmeal E’ improved by 0.6 ± 1.4 cm/s, p = 0.009 [p = 0.002] and fasting E’ by 0.4 ± 1.4 cm/s, p = 0.069 [p = 0.013], however, E’ remained unchanged with HI. These changes were consistent with those of the traditional parameter E/A. Conclusions MDI with AI results in better postmeal glucose control compared to HI. The treatment with AI is associated with improved diastolic cardiac function. ClinicalTrials.gov (NTC00747409)

This pilot study aimed to evaluate the application of a computer animated electronic patient information program (ePI) for people with type-2 diabetes mellitus. The ePI shall improve and perpetuate general and/or specific knowledge, compliance and motivation of type-2 diabetic patients as complementary to established, structured treatment and teaching programs.Patients and methods: A total of 16 patients with type-2 diabetes mellitus (50 % women, age 53.7 ± 17.0 years, diabetes duration 7.1 ± 6.5 years, weight 97.9 ± 17.8 kg, BMI 35.4 ± 4.5 kg/m2, HbA1c 7.8 ± 2.6 %, therapy: 56 % insulin therapy, 31 % oral antidiabetics, 12 % diet only) have been randomly selected at the municipal hospital Munich-Bogenhausen (Stadtisches Klinikum Munchen-Bogenhausen) and included in the study. All patients have participated in the computer animated information program, consisting of several modules covering the subjects of motivation and self-management, glucose metabolism, basics of therapy and pathophysiology of type-2 diabetes and after-diseases. All course contents are animated using audiovisual media and use interactive elements such as games, simulation and quizzes as learning control mechanisms concluding each module. To explore the increase of diabetes-related knowhow, attitude regarding the disease, program acceptance and assessment of the patients, a standardized set of questionnaires with 4 sections and a total of 40 items has been developed. Results: Upon program participation, 25 % of the patients stated to have no experience in computer usage, 13 % a little and 63 % moderate to strong. Internet experience (at least one contact) was reported by 81 % of participants. Quantitative analysis: Diabetes-related knowledge has been increased through the information program from 11.8 ± 2.2 to 17.7 ± 1.9 points (p = 0.002). Within the specific domains of knowledge, the following improvements have been observed (before vs. after): Diabetes Basics (1.4 ± 0.6 vs. 1.8 ± 0.4 points, p = 0.029), Pathophysiology (4.0 ± 1.0 vs. 5.1 ± 1.0 points, p < 0.005), Glucose Metabolism (2.4 ± 0.5 vs. 2.8 ± 0.4 points, p = 0.009), After-Diseases (1.9 ± 1.2 vs. 2.9 ± 0.3 points, p = 0.005) and Therapy (2.3 ± 0.7 vs. 2.7 ± 0.6 points, p = 0.054). Qualitative analysis: Program assessment by the patient (perceived quality, information transfer, ease of use) yielded an average of 1,4 points (“very good”) on a 6 points “Likert-Scale” (mean ± standard deviation [Median, Range]: Total course 1.4 ± 0.5 [1.0, 1.0 – 2.0], program quality 1.6 ± 0.6 [2.0, 1.0 – 3.0], ease of use and simplicity 1.2 ± 0.4 [1.0, 1.0 – 2.0], comprehensibility of information 1.3 ± 0.5 [1.0, 1.0 – 2.0], text 1.4 ± 0.5 [1.0, 1.0 – 2.0], readability 1.4 ± 0.7 [1.0, 1.0 – 3.0], voice 1.4 ± 0.5 [1.0, 1.0 – 2.0], acoustic comprehensibility 1,2 ± 0,4 [1.0, 1.0 – 2.0], seriousness and reliability 1.2 ± 0.4 [1.0, 1.0 – 2.0], quality of medical information 1.5 ± 0,.6 [1.0, 1.0 – 3.0], graphic illustrations 1,4 ± 0,5 [1.0, 1.0 – 2.0] and characters 1.4 ± 0.5 [1.0, 1.0 – 2.0]). The questionnaire to evaluate patients‘ acceptance of ePI yielded the following results: 100 % of the patients have graded the speed of information transfer and the degree of difficulty to be “appropriate”. All patients (100 %) have reported that their future enrollment in similar computer programs of this like was conceivable. 81 % have stated an increased motivation to “take better care of the diabetes”. All patients (100 %) have expressed that they wished their physician/hospital/health insurance company would provide such programs and only 25 % would not be willing to pay for such a service out of their own pocket. Discussion: Patients with type 2 diabetes mellitus highly accept the ePI. In regards of ease of use, comprehensibility and program offering, the evaluation has given very positive results. Program application leads to a significant increase in diabetes-related knowledge, compliance and motivation. Integration of the program in existing care plans appears reasonable and can improve their effectiveness and efficiency. Problem-oriented patient education can be complemented by the application of specific program modules.

Objective: To evaluate the effect of the long-acting basal insulin analog glargine compared with neutral protamine Hagedorn (NPH) insulin on the incidence of diabetic foot ulceration (DFU) in patients with diabetes in Germany. Method: A retrospective cohort study was performed using a representative German database (IMS Disease Analyzer) of patients with type 2 diabetes, who started a basal insulin therapy with either insulin glargine or NPH insulin, between July 2000 and September 2007, and continued this therapy for at least 24 months, and whose data were continuously documented. The occurrence of DFU was recorded beginning in the third year after therapy initiation and Kaplan-Meier curves were generated and compared using log-rank tests. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for the incidence of DFU. Results: Patients who fulfilled the inclusion criteria (n=23 395) had started either on insulin glargine (n=9638) or on NPH insulin (n=13 757). After adjustment for demographic and clinical variables, it was demonstrated that the relative risk to diabetes patients of developing DFS is 64% lower with insulin glargine than with NPH insulin therapy (HR=0.611; p=0.0405). Conclusion: The results suggest that, compared with NPH insulin, insulin glargine therapy significantly reduces the risk of DFS in patients with diabetes under real life conditions. Prospective long-term trials are needed to confirm these secondary data analysis results. Declaration of interest: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.

Im Jahr 2011 und Anfang 2012 wurde eine Reihe hoch interessanter Beitrage zum Thema Typ-1-Diabetes veroffentlicht. In der vorliegenden Ubersicht werden „Top-Publikationen“ aus den Bereichen Epidemiologie, Pravention, Insulintherapie, Insulinpumpentherapie, sensorunterstutzte Pumpentherapie (SUP) und neue Therapieoptionen vorgestellt. Die hohe Zahl wegweisender Publikationen war in den Themenbereichen Pravention und SUP auffallig. Zum Thema Pravention wurden uberwiegend Arbeiten auf dem Gebiet der Tertiarpravention publiziert. Die Ergebnisse zeigten keine Heilung, jedoch haufig eine Progressionshemmung. Die Publikationen im Bereich der SUP belegen die Uberlegenheit dieser Therapieform im Vergleich zur klassischen intensivierten konventionellen Insulintherapie (ICT) bzw. Pumpentherapie ohne Sensor, wenn der Sensor moglichst haufig getragen wird. Die Gesamtheit der vorliegenden Studien deutet darauf hin, dass sich diese Therapieform zum neuen Goldstandard bei Typ-1-Diabetes entwickeln kann.

Die Epidemie Diabetes mellitus ist im Zunehmen begriffen, wobei die altere Bevolkerung uberproportional betroffen ist. Die Therapie alterer, insbesondere geriatrischer Patienten, die in der Regel alter als 65 Jahre sind und alltagsrelevante Behinderungen aufweisen, die sich als Folge der Multimorbiditat entwickelt haben und die Lebensqualitat beeintrachtigen, unterscheidet sich zum Teil erheblich vom Rest der Typ-2-Patienten. Unterschiede zeigen sich sowohl bei der diabetologisch-pharmakologischen (orale Antidiabetika, Insuline) als auch in Hinsicht auf die praktische Behandlung, d. h. der Auswahl der Therapiestrategie. Zwar fehlen noch immer Outcome-Daten der Diabetestherapie speziell fur altere Patienten, doch haben die in den letzten Jahren publizierten Endpunktstudien bezuglich der Festlegung eines HbA1c-Ziels die Botschaft erbracht, dass Therapieziele abhangig vom einzelnen Patienten individuell festgelegt werden mussen. Hiervon profitieren gerade altere, geriatrische Patienten, fur die Individualitat in der Therapie besonderes relevant ist. Therapieziele sind zwar oftmals weniger streng fur altere oder geriatrische Patienten, dennoch wird – wegen der Bedenken vor Nebenwirkungen – die notwendige Therapie, vor allem eine Insulintherapie, trotz guter therapeutischer Optionen nicht selten zu spat oder nicht ausreichend konsequent umgesetzt. Die Ubersichtsarbeit beleuchtet den aktuellen Stand der medikamentosen Diabetestherapie speziell fur den alteren Patienten mit Typ-2-Diabetes-mellitus.

Das Ziel bei der Behandlung von Patienten mit Typ-2-Diabetes ist eine zeitgerechte, am individuellen Therapieziel des einzelnen Patienten ausgerichtete Therapie. Individuelle Therapieziele berucksichtigen insbesondere die Diabetesdauer, die Lebenserwartung, Begleiterkrankungen — hierbei besonders makrovaskulare Komplikationen, Neigung zu Hypoglykamien, die Compliance und die individuelle Fahigkeiten der Patienten.

Type 1 Diabetes mellitus (IDDM) results from an immune-mediated destruction of the pancreatic b-cells. The genetic predisposition is mainly confered by variations within MHC class II region on chromosome 6p as well as the CTLA4 gene located on chromosome 2q33. We analysed the transmission of HLA DQA1, DQB1, DRB1*04 alleles as well as an endogenous retroviral element (DQLTR3) in 130 families with a type 1 diabetic offspring in order to evaluate their role in genetic susceptibility to IDDM. Also the combined transmission of HLA and CTLA4 haplotypes was investigated. MHC class II alleles were typed using sequence-specific primer analysis. The presence or absence of DQLTR3 was defined by a nested PCR approach and CTLA4 microsatellite polymorphisms were detected with fluorescence-labeled primer on an automated sequencing system. By transmission distortion test we confirm the linkage of HLA DQA1*0501 DQB1*0201 (DR3 DQ2) as well as DQA1*0301 DQB1*0302 (DR4 DQ8) with IDDM. Whereas the combination with CTLA4 risk markers leads to the highest transmission rate on DR3 positive haplotypes, the predisposing CTLA4 variant does not modulate the risk on DR4 haplotypes. However, the absence of DQLTR3 on DR3, but its presence on DR4 haplotypes significantly increases the genetic risk for type 1 diabetes. Therefore predisposing MHC class II haplotypes are defined by distinct loci which differentially control genetic susceptibility. The combined transmission of protective CTLA4 and HLA DR3 as well as DR4 haplotypes confirms the dominant role of HLA class II polymorphisms in defining disease susceptibility to type 1 diabetes mellitus.

In people with type 2 diabetes (T2DM), hyper- glycemia has a negative impact on cardiac func- tion and cardiovascular risk. Benefi cial eff ects of improved postprandial glycemic control have been shown for cardiovascular risk only. To dem- onstrate these benefi cial eff ects on myocardial function, we investigated well-controlled T2DM patients on three insulin regimens with diff erent impact on postprandial glucose control. For 24 months, 61 T2DM participants in a randomized study had either conventional therapy (CT) with human premixed insulin b.d. (n = 20), intensi- fi ed therapy (ICT) with Lispro at meals and NPH at bedtime (n = 24), or supplementary therapy (SIT) with human regular insulin at meals (n = 17). Metabolism and cardiovascular function were assessed before and 2 hours after a standardized carbohydrate breakfast (48 g) using tissue Dop- pler to measure diastolic myocardial function (E ' ). Age, BMI, dose of insulin, cardiovascular disease, and medication were comparable between the groups. Hb1Ac was comparable with CT, ICT, and SIT (6.6 ± 0.6, 6.2 ± 0.6, and 6.4 ± 0.7 % ) and so was fasting glucose. Post-meal glucose increment was 60 ± 45 mg / dl with CT, but 15 ± 52 and 8 ± 58 mg / dl with ICT and SIT (p < 0.006). Ewas signifi cantly lower (p < 0.03) with CT (6.8 ± 1.0 cm / s) vs. ICT (7.7 ± 1.6) and SIT (7.8 ± 1.2 cm / s), and correlated with post-meal glucose (r = − 0.2644, p < 0.046). Intima-media thickness and arterial stiff ness parameters were higher in CT (p < 0.04). In T2DM patients, the long-term insulin regimens CT, ICT, and SIT achieved overall good metabolic control with signifi cant diff erences, however, in postpran- dial glucose increments. The regimens achieving better post-meal glucose control were associated with better myocardial / vascular function.

Type 2 diabetes mellitus is characterized by insulin resistance and by progressive beta-cell failure. Whereas insulin resistance is a more or less stable variable the progressive beta-cell failure is responsible for the necessary upgrading of therapy over the years - initially with oral antidiabetic agents normally. The indication for insulin therapy is given if oral agents fail, sometimes insulin therapy can be the primary choice. Actual guidelines line up basal insulin on the same level as sulfonylurea or glitazones after failure of metformin therapy. Basal insulin therapy in combination with oral agents is successful in patients with sufficient residual beta-cell function and delivers the possibility towards upgrading to a basal-bolus regimen if beta-cell function further decreases. The choice of the therapy regimen, the type of insulin should be defined by individual criteria, for example the blood glucose profile, age, date of diagnosis, concomitant diseases, individual capabilities, living conditions, compliance and the individual glucose targets.

The effects of thiazolidinediones on cardiac function are controversial in humans with type 2 diabetes (T2DM) and in animals. Given the high prevalence and prognostic relevance of diastolic myocardial dysfunction in T2DM, we tested the hypothesis that by reducing oxidative stress rosiglitazone, but not glimepiride, may improve diastolic function. This randomised cross-over study investigated 12 met-formin-treated T2DM patients without cardiovascular disease before and after 16 weeks of additional therapy with rosiglitazone (8 mg daily) or glimepiride (3 mg daily). Systolic and diastolic myocardial velocity (E’) were assessed with tissue Doppler. In spite of similar non-significant lowering of glycosylated haemoglobin (HbA1C), rosiglitazone, but not glimepiride, significantly improved E’ (p=0.04), reduced malondialdehyde (p=0.028), lowered high-sensitivity C-reactive protein (hsCRP) (p=0.019), and increased adiponectin (p=0.002). For rosiglitazone, multivariate regression analysis revealed malondialdehyde reduction as an independent determinant of treatment-induced improvement in E’. The rosiglitazone-induced improvements of diastolic function and oxidative stress may be of prognostic relevance in choosing therapy for T2DM patients without overt heart disease.

Aims: To assess the effects of a structured in-patient diabetes training programme in people with Type 2 diabetes mellitus on a basal-bolus regimen using insulin glargine or NPH insulin and rapid-acting insulin analogues with respect to glycaemic control, weight development and incidence of hypoglycaemia in an outpatient-clinic setting. Patients and Methods: This was a prospective, non-randomized, single centre, comparative observational study including 119 subjects. Pre-study treatment was a basal-bolus regimen with NPH insulin and a rapid-acting insulin analogue. Subjects either continued with NPH insulin (n = 56) or were switched over to insulin glargine (n=63) at the discretion of the investigator (aiming at equal numbers in each group). Patients then attended routine out-patient follow up visits for 18 months. Results: HbA1c in the insulin glargine group improved statistically significant by -0.49%; [95%Cl, -0.26, -0.71; p

BACKGROUND In patients with type 2 diabetes mellitus diastolic dysfunction is a frequent manifestation of myocardial disease with poor prognosis. The hypothesis that better glycemic control results in improved myocardial function was tested using tissue Doppler. METHODS During a short-term (3 weeks) and a long-term (52 weeks) study, metabolic control and myocardial function were evaluated in 33 and 50 patients, respectively, with type 2 diabetes. Systolic (Vs) and diastolic (Ve) myocardial velocity were assessed by tissue Doppler. In the short-term study, antidiabetic therapy was intensified in 25 patients (Int3) and compared to those eight individuals with unchanged therapy (Con3), similarly to the long-term study with Int52 (n = 39) and Con52 (n = 11). RESULTS In Int3, fasting serum glucose was reduced by 69+/-47 mg/dl (p < 0.01) compared to baseline and was associated with an increase of Ve from 8.0 +/- 1.6 to 8.8 +/- 1.6 cm/s (p < 0.01) and Vs from 6.2 +/- 1.1 to 6.6 +/- 1.3 cm/s, p < 0.04. In Con3, serum glucose and myocardial velocities were unchanged. In Int52, fasting serum glucose was reduced by 20 +/- 43 mg/dl (p < 0.017) compared to baseline and was associated with an increase of Ve from 7.6 +/- 1.3 to 8.3 +/- 1.7 cm/s (p < 0.002) and a similar trend in Vs (p < 0.07). In Con52, serum glucose and myocardial velocities remained unchanged. Evaluating pooled data, the changes of diastolic myocardial velocity correlated significantly with the changes of serum glucose (r = 0.49, p < 0.004 short- and r = 0.45; p < 0.002 long-term study, respectively). CONCLUSION In patients with type 2 diabetes subclinical diastolic myocardial dysfunction, measured as diastolic myocardial velocity by tissue Doppler, improves with better glycemic control.

Using modern echocardiography, we quantified the extent of global myocardial function and perfusion abnormalities in patients with type 2 diabetes and compared this with the hypothetically similar extent of impairments in patients with coronary artery disease (CAD). This case–control study (66 patients) compared four age-matched groups: control, type 2 diabetic, CAD, and diabetic subjects with CAD (DCAD) and left ventricular ejection fraction >50%. CAD patients had 1–2 vessel disease. Diastolic and systolic myocardial velocities were assessed with pulsed tissue Doppler. Global myocardial perfusion was assessed with contrast echocardiography as indices of capillary blood volume and myocardial blood flow at maximal vasodilatation. In CAD and DCAD patients, functional and perfusion parameters were additionally assessed in the territory with a normal coronary angiogram reading, providing a model for comparison with the global data from control and diabetic patients. Comparing diabetic with control subjects, myocardial velocity at early diastole was impaired (8.8±1.8 vs 10.1±1.7 cm/s; p=0.02) and correlated inversely with age, HbA1c and pulse pressure (R 2=0.761). Capillary blood volume (16.6±5.0 vs 24.4±4.9%) and blood flow (56±35 vs 114±40) were decreased (p=0.001). In CAD patients, myocardial velocity at early diastole was similarly decreased (p=0.02). CAD and DCAD patients were receiving more cardiovascular preventive therapy for the same extent of impaired global perfusion as in the less extensively treated diabetes group without CAD (p

AIM OF STUDY The aim of the study was to find to find out which factors are able to predict the disease-specific knowledge of in-patient diabetic patients and to characterize this group of patients. METHODS The disease-specific knowledge of diabetic patients of a Hospital in Munich, Germany (department of diabetology) was tested using a general questionnaire and a specific diabetes knowledge test. All data manipulation and statistical calculations were conducted with the statistical software package SAS (version 9.1). RESULTS On average type-1-diabetics achieved 73% of the possible points in the knowledge test, type-2-diabetics achieved 68% of total points. In bivariate analyses, using logistic regression, existence of diabetes related complications was a significant predictor of poor knowledge (OR = 4.36; 95%-KI: 1.38-13.77) in type-1-diabetics. Other factors, e. g. lack of diabetes education were associated with low test results but reached no statistical significance (OR = 6.13; 95%-KI: 0.67-56.42). In multivariate logistic regression (female) gender was a significant risk factor for low test results (OR = 7.66; 95%-KI: 1.18-49.8). In type-2-diabetics lack of diabetes education (OR = 3.86; 95%-KI: 1.51-9.84), low self-assessment of information about diabetes (OR = 3.90; 95%-KI: 1.36-11.21) and lack of knowledge about diabetes diet (OR = 4.06; 95%-KI: 1.60-10.28) were predictors of poor test results. The existence of diabetes related complications was associated with poor test results but showed no statistical significance in multivariate analysis (OR = 2.99; 95%-KI: 0.85-10.43). CONCLUSIONS There is a group of diabetic inward-patients that is less informed about diabetes and shows knowledge deficits in testing. These patients often lack diabetes education and show an unfavourable course of the disease, already having diabetes related complications. Type-2-diabetes patients who feel that they have poor information about their disease actually achieve lower results in knowledge testing. Efforts to assure diabetes education for these patients are essentially necessary.

HLA-DR4 is a primary disease association marker in type 1 diabetes mellitus (IDDM). We therefore analyzed the transmission of 228 DR4+ haplotypes in 183 families with an IDDM proband (95 from Germany and 88 from Belgium). In a separate case-control data set, we investigated the HLA-DRB1*04 and DQ allele distribution in 245 IDDM patients and 177 controls from Germany, all DR4 positive. HLA-DRB1 *0401 and *0402 linked to DQB1 *0302 were significantly more often transmitted to patients in the studied families (81% and 89%) in contrast to DRB1 *0401-DQB1 *0301 (33%). The case-control study of HLA-DQB1 *0302+ individuals revealed -DRB1 *0405 to be more frequent in patients with IDDM and HLA-DRB1 *0403 and -DRB1 *0404 to be less frequent. HLA-DQA1 *0102-DQB1 *0602 and -DQA1 *0501-DQB1 *0301 in trans complementation with DRB1 *0401-DQB1 *0302 were also significantly less frequent in IDDM patients (P

Major genetic susceptibility to type 1 diabetes mellitus maps to the human leukocyte antigen (HLA) region on chromosome 6p. During evolution, endogenous retroviral long terminal repeats (LTR) have been integrated at several sites within this region. We analyzed the presence of a solitary HERV-K LTR in the HLA DQ region (DQ-LTR3) and its linkage to DRB1, DQA1, and DQB1 haplotypes derived from 246 German and Belgian families with a patient suffering from type 1 diabetes mellitus. Segregation analysis of 984 HLA DQA1/B1 haplotypes showed that DQ-LTR3 is linked to distinct DQA1 and DQB1 haplotypes but is absent in others. The presence of DQ-LTR3 on HLA DQB1*0302 haplotypes was preferentially transmitted to patients from heterozygous parents (82%; P < 10(-6)), in contrast to only 2 of 7 DQB1*0302 haplotypes without DQ-LTR3. Also, the extended HLA DRB1*0401, DQB1*0302 DQ-LTR3-positive haplotypes were preferentially transmitted (84%; P < 10(-6)) compared with 1 of 6 DR-DQ matched DQ-LTR3 negative haplotypes. DQ-LTR3 is missing on most DQB1*0201 haplotypes, and those LTR3 negative haplotypes were also preferentially transmitted to patients (80%; P < 10(-6)), whereas DQB1*0201 DQ-LTR3-positive haplotypes were less often transmitted to patients (36%). Other DQA1/B1 haplotypes did not differ for DQ-LTR3 between transmitted and nontransmitted haplotypes. Thus, the presence of DQLTR3 on HLA DQB1*0302 and its absence on DQB1*0201 haplotypes are independent genetic risk markers for type 1 diabetes.

Although some of the susceptibility to Graves' disease is conferred by genes in the human leucocyte antigen (HLA) region on the short arm of chromosome 6, other genetic factors must also predispose. Among the cytokines involved in thyroid autoimmunity interferon-gamma (IFN-gamma) plays a key role in the pathogenesis of Graves' disease. We therefore analyzed the first intron of the IFN-gamma gene for a dinucleotide (CA) repeat polymorphism on chromosome 12q. Two hundred two Caucasian patients with Graves' disease and 214 Caucasian controls were analyzed by polymerase chain reaction (PCR) and subsequent polyacrylamide gel electrophoresis technique: eight different alleles designated as IFN-gamma*1 to IFN-gamma*8 could be differentiated. Among Graves' disease patients IFN-gamma*5 (12.9% vs. 6.8%, p0.04) was significantly more frequent whereas IFN-gamma*2 (2.5% vs. 9.8%, p0.002) was significantly less frequent. Patients positive for the genetic susceptibility marker HLA DQA1*0501 had significantly more IFN-gamma*3 alleles (13.6% vs. 2.6%, p0.009) and IFN-gamma*5 alleles (22.1% vs. 7.6%, p0.03) compared with DQA1*0501 positive controls. Also, among patients with endocrine ophthalmopathy IFN-gamma*3 (17.9% vs. 4.2%, p8 x 10(-6)) and IFN-gamma*5 (18.9% vs. 7.0%, p0.003) were significantly more frequent compared with controls. Although a significant association of IFN-gamma microsatellite polymorphism was observed, only a small proportion of Graves' disease patients have these markers. Thus, it is likely that the detected microsatellite polymorphisms play only a minor role in the susceptibility to Graves' disease.

Using the ARGUS detector at the e+e− storage ring DORIS II at DESY, we have found evidence for the production of the excited charmed baryon state Λc(2593)+ in the channel Λc+π+π−. Its mass was determined to be (2594.6±0.9±0.4) MeV/c2, and the natural width measured to be Γ = (2.9−2.1−1.4+2.9+1.8) MeV. The production cross section times the branching ratios of σ(e+e− → Λc(2593)+X) × Br(Λc(2593)+ → Λc+π+π−) × Br(Λc+ → pK−π+) was measured to be (0.25−0.13+0.24 ±0.13) pb. The fractions of Λc(2593)+ decays proceeding through the Σc0π+ and Σc++π− channels were determined to be 0.29±0.10±0.11 and 0.37±0.12±0.13, respectively.

The genetic susceptibility to Graves' disease and type 1 (insulin-dependent) diabetes mellitus is conferred by genes in the human leukocyte antigen region on the short arm of chromosome 6, but several other genes are presumed to determine disease susceptibility. Among those candidate genes is the cytotoxic T lymphocyte antigen 4 (CTLA4) located on chromosome 2q33 in man. We investigated the distribution of the CTLA4 exon 1 polymorphism (49 A/G) in Graves' disease and IDDM. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in the leader peptide of the expressed protein and was analyzed by PCR, single strand conformation polymorphism, and restriction fragment length polymorphism analysis in 305 patients with Graves' disease, 293 patients with IDDM, and 325 controls. Patients with Graves' disease had significantly more Ala alleles than controls, both as homozygotes (21% vs. 13%) and as heterozygotes (53% vs. 46%), and less Thr as homozygotes (26% vs. 42%; P < 2 x 10(-4). The phenotypic frequency of Ala-positive patients (73%) was significantly higher than of controls (58%; P = 10(-4); relative risk = 2). Patients with IDDM also had significantly more Ala alleles as homozygotes (19%) or heterozygotes (50%; P = 0.01). In conclusion, an alanine at codon 17 of CTLA4 is associated with genetic susceptibility to Graves' disease as well as to IDDM.

In recent years, the treatment of type 1 diabetes has changed significantly. An important diagnostic and therapeutic support tool is the continuous glucose monitoring (CGM) showing its best performance when used in combination with an insulin pump therapy. Before the availability of CGM the consideration of glucose regulation and therapeutic success was based solely on selectively measured blood glucose levels and HbA1c. In contrast to the blood glucose measurements CGM measures in the interstitial fluid and opens a new dimension of diabetes therapy, we call it "glucose dynamics". The knowledge of the continuous glucose course and its trends has proved to be a highly relevant additional parameter which in practical terms has a particularly stabilizing influence on blood glucose profiles. CGM therefore offers the option of a fine-tuning of metabolic control by experienced heath care professionals and the patient, making blood glucose control in general and unplanned activities and problems in everyday life better controllable. However, despite the tremendous potential of CGM in combination with a pump therapy the basic settings of an effective pump therapy are crucial. Particularly the right basal insulin coverage as the first step is the key issue for success. With support of CGM there is an enormous potential to facilitate the adjustment and optimization of insulin pump therapy.

We aimed to identify predictors of hypoglycaemia in patients with poorly controlled type 2 diabetes treated with a single daily bolus of insulin glulisine on top of insulin glargine and oral antidiabetic drugs (basal-plus regimen).We retrospectively analysed four large basal-plus trials including 713 patients (47% female) with type 2 diabetes, mean age of 59.9 ± 9.5 years and diabetes duration of 11 ± 7.0 years. Predictors for symptomatic, severe and nocturnal hypoglycaemia were identified by multivariate logistic regression analyses, calculation of odds ratios (ORs) and Wald 95% confidence intervals (CIs).Mean numbers of hypoglycaemic events per year were 4.64 ± 11.4 (symptomatic 60 mg/dl), 0.59 ± 2.28 (nocturnal) and 0.03 ± 0.22 (severe). A total of 44.5% of patients reached the composite endpoint of glycated haemoglobin (HbA1c)7.0% plus no severe hypoglycaemia, and 26.7% reached the composite of HbA1c7.0% plus no symptomatic hypoglycaemia. Predictors of nocturnal and symptomatic hypoglycaemia were female gender (OR 1.82; 95% CI 1.07-3.11 and OR 1.89; 95% CI 1.31-2.78), diabetes duration10 versus5 years (OR 2.61; 95% CI 1.03-6.59 and OR 2.01; 95% CI 1.15-3.51) and higher basal insulin dose (per unit of increase) (OR 1.01; 95% CI 1.00-1.03 and OR 1.01; 95% CI 1.00-1.02). Conversely, a higher body mass index (BMI) (27-30 vs.27 kg/m(2) and30 vs.27 kg/m(2) ) conferred a reduced risk of symptomatic hypoglycaemia with an OR of 0.53 (95% CI 0.31-0.90) and an OR of 0.61 (95% CI 0.39-0.97).Female gender, a long diabetes duration and higher basal insulin dose were predictors of hypoglycaemia, while protection was provided by BMI 30. These results may help to successfully establish basal-plus insulin regimen in individual patients on their transition from basal-only to basal-bolus treatment.

Since end of 2012 a new therapeutical approach for the treatment of type 2 diabetes is available in Germany. It relies on the modulation of glucose re-absorption in the kidney by inhibition of so called Sodium Glucose Linked Transporters (SGLT) thereby leading to therapeutical glucosuria. Putting the kidney in the centre of therapeutical approach of glucose regulation is unfamiliar for physicians. Therefore, it is helpful to elucidate the underlying renal mechanisms and to present the advantages and disadvantages of this new therapeutic class.

The prevalence and prognostic importance of diastolic dysfunction in type 2 diabetes has only recently been appreciated. We tested the hypothesis that in insulin treated type 2 diabetes (D), carbohydrate consumption induces oxidative stress resulting in further impairment of diastolic function beyond structural myocardial stiffness. The effects of a pure carbohydrate breakfast (48 g) on oxidative stress and cardiac function were studied in the fasting and postmeal states in subjects without hypertension or overt cardiac disease (moderately well controlled D, n=21 and controls without D, n=20). Studied variables included systolic and early diastolic (E') myocardial velocities, traditional metabolic and hemodynamic parameters, serum nitrotyrosine, and sVCAM-1. In D compared to control subjects, the postmeal increase (∆) in glucose (1.44±2.78 vs. 0.11±0.72 mmol/l, p=0.04) and ∆nitrotyrosine (0.34±0.37 vs. -0.23±0.47 nM/l, p