Search

ZusammenfassungLebensstil, insbesondere regelmäßige körperliche Aktivität, ist ein wichtiger Bestandteil in der Prävention und Therapie des Typ 2 Diabetes mellitus und sollte fester Bestandteil jeglicher Betreuung von Patient:innen sein. Es besteht breiter Konsens, dass eine effiziente Diabetes-Prävention und Therapie in den meisten Fällen auch von einer Modifikation des Lebensstils begleitet sein muss.Ziele der Förderung der körperlichen Aktivität sind zunächst das Training des Herz-Kreislaufsystems, Kräftigung der Muskulatur, Steigerung des Energieumsatzes und die Reduktion von Inaktivität. Für einen substanziellen gesundheitlichen Nutzen sind wöchentlich mindestens 150 min aerobe körperliche Aktivität mit mittlerer oder höherer Intensität und zusätzlich muskelkräftigende Bewegungen erforderlich.Das Ausmaß des positive Effektes von Bewegung steht in direktem Verhältnis zum Grad der erreichten kardiorespiratorischen Fitness, und kann nur durch entsprechendes Training aufrechterhalten werden. Körperliches Training ist in jedem Alter für beide Geschlechter wirksam und effektiv. Durch die Reduktion der Insulinresistenz und funktionelle Verbesserung der Insulinsekretion hat körperliches Training positiven Einfluss auf die Glykämie und zusätzlich wird das kardiovaskuläre Risiko gesenkt.Im Speziellen hat Training nicht nur positiven Einfluss auf die Glykämie durch Verbesserung der Insulinresistenz und funktionelle Verbesserung der Insulinsekretion zu nehmen, sondern ist auch in der Lage, das kardiovaskuläre Risiko zu senken.Inaktivität per se gilt unabhängig vom Konstrukt der körperlichen Aktivität als Risikofaktor. Insbesondere langandauernde sitzende Tätigkeit soll vermieden werden.Standardisierte, regionale und angeleitete Bewegungsprogramme sind bestens geeignet, um ein ausreichendes wöchentliches Ausmaß an gesundheitsfördernder körperlicher Aktivität zu erreichen. Zusätzlich fordert die Österreichische Diabetes Gesellschaft die Position der Bewegungsberater:in als fixen Bestandteil eines multidisziplinären Behandlungsansatzes. Leider gab es in den letzten Jahren weder im Aufbau standardisierter Bewegungsangebote noch in der Bewegungsberatung erfolgsversprechende Entwicklungen.

ZusammenfassungBereits vor mehr als 30 Jahren forderte die St. Vincent Deklaration, dass Schwangere mit vorbestehendem Diabetes mellitus vergleichbare Schwangerschaftsergebnisse wie gesunde Frauen erreichen sollen. Dennoch bestehen bei Frauen mit konzeptionell manifestem Diabetes nach wie vor höhere Komplikationsraten und eine höhere perinatale Morbidität und Mortalität. Eine fehlende oder zumindest unzureichende Schwangerschaftsplanung und präkonzeptionelle Betreuung mit Optimierung der Stoffwechsellage vor Konzeption ist dafür verantwortlich. Alle Frauen mit Diabetes sollen im Selbstmanagement der Insulintherapie mit Anpassungen der Insulindosis geschult sein und eine stabile Stoffwechsellage vor Schwangerschaftsbeginn aufweisen. Eine Schilddrüsendysfunktion, Hypertonie oder diabetische Komplikationen vor der Konzeption sollten ausgeschlossen bzw. adäquat behandelt sein, um das Risiko einer möglichen Progression der Komplikationen und Begleiterkrankungen sowie insgesamt mütterliche und fetale Risiken zu minimieren. Ein Ziel der mütterlichen Stoffwechselkontrolle ist das Erreichen von Normoglykämie und normalen HbA1c-Werten, falls dies ohne Risiko für Hypoglykämien möglich ist, da eine schlechte Blutzuckereinstellung mit diabetischer Embryopathie und diabetischer Fetopathie assoziiert ist. Das Hypoglykämierisiko ist speziell bei Typ 1 Diabetes mellitus in der Frühschwangerschaft deutlich erhöht, nimmt aber mit den hormonellen Veränderungen und der Zunahme der Insulinresistenz im Schwangerschaftsverlauf deutlich ab. Eine weltweit steigende Adipositasprävalenz führt zusätzlich zu einem Anstieg von Müttern mit Typ 2 Diabetes. Dieser Trend ist auch bei Frauen mit Typ 1 Diabetes zu beobachten und aggraviert die Metabolik und die perinatalen Ergebnisse. Eine funktionelle, intensivierte Insulintherapie mit multiplen täglichen Insulininjektionen oder eine Insulinpumpentherapie tragen neben dem vermehrten Einsatz des kontinuierlichen Glukosemonitorings zum Erreichen einer guten mütterlichen Stoffwechselkontrolle vor und während der Schwangerschaft bei. Orale Antidiabetika (Metformin) können vor allem bei Typ 2 Diabetes und Adipositas helfen die Insulinsensitivität zu verbessern und dadurch den Insulinbedarf zu vermindern, sollten jedoch aufgrund der Plazentagängigkeit und ungewissen Langzeitergebnissen bei den Nachkommen mit Bedacht (shared decision making) verordnet werden. Aufgrund des erhöhten Präeklampsierisikos bei Frauen mit Diabetes in der Schwangerschaft ist hier ein frühes Screening zu empfehlen. Regelmäßige und engmaschige geburtshilfliche Kontrollen in einem spezialisierten Zentrum und bei spezialisierten Fachärzt:innen sowie interdisziplinäre Zusammenarbeit werden empfohlen um eine gute Stoffwechseleinstellung und gesunde Entwicklung des Kindes zu sichern.

ZusammenfassungDie Hyperglykämie ist wesentlich an der Entstehung der Spätkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten/Patientinnen beteiligt. Während Lebensstilmaßnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benötigen im Verlauf die meisten Patienten/Patientinnen mit Typ 2 Diabetes eine medikamentöse Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit, die Effektivität sowie substanzspezifische, kardiovaskuläre Effekte der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten für die klinische Praxis zusammengestellt.

ZusammenfassungDiese Leitlinie repräsentiert die Empfehlungen der Österreichischen Diabetes Gesellschaft (ÖDG) zur Nutzung von Diabetes-Technologie (Insulinpumpentherapie; kontinuierliche Glukosemesssysteme, CGM; Hybrid Closed Loop Systeme, HCL; Automated Insulin Delivery Systeme, AID, Diabetes-Apps) und den Zugang zu diesen technologischen Innovationen für Menschen mit Diabetes mellitus. Die Leitlinie wurde basierend auf aktueller wissenschaftlicher Evidenz erstellt.

ZusammenfassungDiabetesschulung und Selbstmanagement nehmen eine zentrale Rolle in der Diabetesbetreuung ein. Das dabei angestrebte Patient:innen-Empowerment zielt auf die aktive Beeinflussung des Diabetesverlaufs durch Selbstkontrolle und Therapieanpassung sowie die Befähigung der Betroffenen, den Diabetes in ihren Alltag zu integrieren und an ihre Lebensumstände entsprechend anzupassen. Eine Diabetesschulung ist allen Personen mit Diabetes zugänglich zu machen. Um ein strukturiertes und validiertes Schulungsprogramm anbieten zu können, sind adäquate personelle, räumliche, organisatorische und finanzielle Voraussetzungen nötig. Neben dem Zuwachs an Wissen über die Erkrankung konnte gezeigt werden, dass eine strukturierte Diabetesschulung ergebnisorientiert Parameter wie Blutzucker, HbA1c, Blutfette, Blutdruck und Körpergewicht positiv beeinflussen kann. Neuere Schulungsmodelle betonen neben der Ernährung die körperliche Bewegung als wichtigen Bestandteil der Lebensstil-Therapie und bedienen sich interaktiver Methoden, um die persönliche Verantwortung herauszuarbeiten. Spezifische Situationen (z. B. verminderte Hypoglykämie-Erkennung, Krankheit, Reisen), das Auftreten diabetischer Folgeerkrankungen und der Einsatz technischer Geräte wie Glukosesensor-Systeme und Insulinpumpen bedürfen zusätzlicher Schulungsmaßnahmen unterstützt durch adäquate elektronische Hilfsmittel (Diabetes-Apps, Diabetes-Web-Portale). Neue Erkenntnisse belegen den Nutzen telemedizinischer oder internetbasierter Dienste für die Diabetesprävention und das Diabetesmanagement.

ZusammenfassungGestationsdiabetes (GDM) wird als Glukosetoleranzstörung definiert, die erstmals in der Schwangerschaft festgestellt wird. GDM ist mit einer erhöhten feto-maternalen Morbidität sowie Langzeitkomplikationen bei Mutter und Kind assoziiert. Frauen, die die Kriterien eines manifesten Diabetes mellitus bereits in der Frühschwangerschaft erfüllen (Nüchternplasmaglukose ≥ 126 mg/dl, Spontanglukosemessung ≥ 200 mg/dl oder HbA1c ≥ 6,5 % vor der 20. Schwangerschaftswoche) sollen als Schwangere mit manifestem Diabetes klassifiziert und ebenso behandelt werden. Ein Screening auf unerkannten Typ 2 Diabetes bei der ersten pränatalen Kontrolle wird besonders bei Frauen mit hohem Risiko (Anamnese eines GDM/Prädiabetes, Fehlbildungen, Totgeburt, wiederholte Aborte oder Geburtsgewicht über 4500 g in früheren Schwangerschaften, Adipositas, metabolisches Syndrom, Alter > 35 Jahre, bei Gefäßerkrankungen, Auftreten von Diabetessymptomen wie Glukosurie, ethnische Zugehörigkeit zu Gruppen mit hohem Risiko [arabisch, S und SO-asiatisch, lateinamerikanisch]) empfohlen. GDM wird durch einen oralen Glukosetoleranztest (oGTT, 120 min; 75 g Glukose) oder durch Nüchternplasmaglukose ≥ 92 mg/dl diagnostiziert. Bei hohem Risiko kann ein oGTT bereits im ersten Trimenon sinnvoll sein, zwischen der 24.–28. Schwangerschaftswoche muss dieser Test aber in jedem Fall bei allen Schwangeren mit bis dahin unauffälligen Glukosewerten im Rahmen der Mutter-Kind-Pass-Untersuchung durchgeführt werden. Nach WHO Empfehlungen basierend auf der „Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study“ liegt ein GDM vor, wenn die Plasmaglukose nüchtern 92 mg/dl, nach 60 min 180 mg/dl oder nach 120 min 153 mg/dl überschreitet (Internationale Konsensuskriterien). Ein einziger erhöhter Wert ist für die Diagnose ausreichend und bedarf bereits einer strikten Stoffwechselkontrolle. Nach bariatrischer Operation wird aufgrund der Gefahr einer postprandialen Hypoglykämie die Durchführung eines oGTT nicht empfohlen. Alle Frauen mit GDM müssen eine Ernährungsberatung erhalten und ihre Blutzuckerwerte (4 Messzeitpunkte) regelmäßig kontrollieren. Ebenso sollte, falls nicht kontraindiziert, die körperliche Aktivität erhöht werden. Falls die Blutzuckerspiegel nicht im Therapiezielbereich liegen (nüchtern 1c oder oGTT) erfolgen (Evidenzklasse B). Alle Frauen sollen über ihr deutlich erhöhtes Risiko für Typ 2 Diabetes, das höhere kardiovaskuläre Risiko, sowie über entsprechende Präventionsmaßnahmen, informiert werden. Dazu gehören Lebensstilmaßnahmen, wie Gewichtsreduktion bei Übergewicht, gesunde Ernährung und ausreichend körperliche Aktivität (Evidenzklasse A). Auch die Kinder sollen hinsichtlich einer unauffälligen Entwicklung regelmäßig nachuntersucht werden, da in rezenten Untersuchungen höheres Risiko für Übergewicht und Adipositas sowie erhöhte Glukoseparameter festgestellt wurden. Wenn möglich sollte die gesamte Familie über Lebensstilmaßnahmen zur Aufrechterhaltung/Verbesserung der Gesundheit informiert werden.

Challenges for athletes with type 1 diabetes are numerous. To find the individual balance between energy intake and consumption and adequate insulin treatment without risking severe hypoglycemia or hyperglycemia is a demanding task. Nevertheless, people with type 1 diabetes are active in various sports, both individually and as members of teams (1,2). We report on the first athlete with type 1 diabetes ever to finish solo what is probably the hardest bicycle race worldwide—the Race Across America (RAAM). The U.S. race stretches from Oceanside, CA, to Annapolis, MD, over ~3,000 miles and 170,000 vertical feet and has to be finished within 12 days.

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

Gestationsdiabetes (GDM) wird als Glukosetoleranzstorung definiert, die erstmals in der Schwangerschaft entdeckt wird. GDM ist mit einer erhohten fetomaternalen Morbiditat sowie Langzeitkomplikationen bei Mutter und Kind assoziiert. Frauen, die die Kriterien eines manifesten Diabetes bereits in der Fruhschwangerschaft erfullen (Nuchternplasmaglukose >126 mg/dl, Spontanglukosemessung uber 200 mg/dl oder HbA1c > 6,5 % vor der 20. Schwangerschaftswoche), sollen als Schwangere mit manifestem Diabetes klassifiziert und ebenso behandelt werden. Ein Screening auf unerkannten Typ-2-Diabetes bei der ersten pranatalen Kontrolle wird besonders bei Frauen mit hohem Risiko (Anamnese eines GDM oder Pradiabetes; Fehlbildungen, Totgeburt, wiederholte Aborte oder Geburtsgewicht uber 4500 g in fruheren Schwangerschaften; Adipositas, metabolisches Syndrom, Alter uber 35 Jahre, bei Gefaserkrankungen, Auftreten von Diabetessymptomen wie Glukosurie, ethnische Zugehorigkeit zu Gruppen mit hohem Risiko [arabisch, S‑ und SO-Asien, Lateinamerika]) empfohlen (Evidenzklasse B). GDM wird durch einen oralen Glukosetoleranztest (OGTT) oder durch Nuchternplasmaglukosekonzentrationen uber 92 mg/dl diagnostiziert. Bei hohem Risiko kann ein OGTT (120 min; 75 g Glukose) bereits im ersten Trimenon sinnvoll sein, ist aber in jedem Fall bei allen Schwangeren mit bis dahin unauffalligen Glukosewerten zwischen der 24. und 28. Schwangerschaftswoche vorgeschrieben (Evidenzklasse B). Auf Basis der „Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study“ und nach den aktuellen WHO-Empfehlungen liegt ein GDM vor, wenn der Nuchternplasmaglukosewert 92 mg/dl, der 1‑Stunden-Wert 180 mg/dl oder der 2‑Stunden-Wert 153 mg/dl uberschreiten (OGTT; Internationale Konsensuskriterien). Ein einziger erhohter Wert ist fur die Diagnose ausreichend und bedarf bereits einer strikten Stoffwechselkontrolle. Nach bariatrischer Operation wird aufgrund der Gefahr einer postprandialen Hypoglykamie die Durchfuhrung eines OGTT nicht empfohlen. Alle Frauen mit GDM erhalten eine Ernahrungsberatung und mussen ihre Blutzuckerwerte regelmasig kontrollieren. Ebenso sollte, falls nicht kontraindiziert, die korperliche Aktivitat erhoht werden. Falls die Blutzuckerspiegel nicht im Therapiebereich liegen (nuchtern

Bereits vor 30 Jahren forderte die St. Vincent Deklaration, dass Schwangere mit vorbestehendem Diabetes mellitus vergleichbare Schwangerschaftsergebnisse wie gesunde Frauen erreichen sollen. Dennoch bestehen bei Frauen mit konzeptionell manifestem Diabetes nach wie vor hohere Komplikationsraten und eine hohere perinatale Morbiditat und Mortalitat. Eine fehlende oder zumindest unzureichende Schwangerschaftsplanung und prakonzeptionelle Betreuung mit Optimierung der Stoffwechsellage vor Konzeption sind dafur verantwortlich. Alle Frauen mit Diabetes sollen im Selbstmanagement der Insulintherapie mit Anpassungen der Insulindosis geschult sein und eine stabile Stoffwechsellage vor Schwangerschaftsbeginn aufweisen. Eine Schilddrusendysfunktion, Hypertonie oder diabetische Komplikationen vor der Konzeption sollten ausgeschlossen bzw. adaquat behandelt sein, um das Risiko einer moglichen Progression der Komplikationen und Begleiterkrankungen sowie insgesamt mutterliche und fetale Risiken zu minimieren. Ein Ziel der mutterlichen Stoffwechselkontrolle ist das Erreichen von Normoglykamie und normalen HbA1c-Werten, falls dies ohne Risiko fur Hypoglykamien moglich ist, da eine schlechte Blutzuckereinstellung mit diabetischer Embryopathie und diabetischer Fetopathie assoziiert ist. Das Hypoglykamierisiko ist speziell bei Typ 1 Diabetes mellitus in der Fruhschwangerschaft deutlich erhoht, nimmt aber mit den hormonellen Veranderungen und der Zunahme der Insulinresistenz im Schwangerschaftsverlauf deutlich ab. Eine weltweit steigende Adipositaspravalenz fuhrt zusatzlich zu einem Anstieg von Muttern mit Typ 2 Diabetes. Dieser Trend ist auch bei Frauen mit Typ 1 Diabetes zu beobachten und aggraviert die Metabolik und die perinatalen Ergebnisse. Eine funktionelle, intensivierte Insulintherapie mit multiplen taglichen Insulininjektionen oder eine Insulinpumpentherapie tragen zum Erreichen einer guten mutterlichen Stoffwechselkontrolle wahrend der Schwangerschaft bei. Orale Antidiabetika (Metformin) konnen vor allem bei Typ 2 Diabetes und Adipositas helfen die Insulinsensitivitat zu verbessern, sollten jedoch aufgrund der Plazentagangigkeit und ungewissen Langzeitergebnissen bei den Nachkommen mit Bedacht verordnet werden.

Metabolische Erkrankungen beeinflussen das Leben von Mannern und Frauen in den verschiedenen Lebensabschnitten in unterschiedlicher und vielfaltiger Weise und stellen eine grose Herausforderung fur das Gesundheitssystem dar. Die behandelnden Arztinnen und Arzte sind mit den unterschiedlichen Bedurfnissen von Mannern und Frauen im klinischen Alltag konfrontiert. Geschlechtsspezifische Unterschiede beeinflussen Screening, Diagnose und Behandlungsstrategien sowie die Entwicklung von Komplikationen und die Mortalitatsraten. Veranderungen im Glukose- und Lipidstoffwechsel, die Regulation von Energiehaushalt und Korperfettverteilung sowie damit assoziierte kardiovaskulare Erkrankungen werden stark von Steroid- und Sexualhormonen beeinflusst. Zusatzlich spielen Erziehung, Einkommen und psychosoziale Faktoren eine wichtige Rolle bei der Entstehung von Adipositas und Diabetes und mussen bei geschlechtsspezifischer Betrachtung mitberucksichtigt werden. Manner weisen im jungeren Alter und bei niedrigerem BMI ein hoheres Risiko fur Typ-2-Diabetes auf als Frauen, die wiederum von einem starken Anstieg im Risiko fur Diabetes-assoziierte kardiovaskulare Erkrankungen nach der Menopause betroffen sind. Frauen durften durch Diabetes auch etwas mehr Lebensjahre verlieren als Manner, wobei die hohere Mortalitat hauptsachlich auf vaskulare Komplikationen zuruckgefuhrt werden kann. Bei Mannern mit Diabetes scheint dafur der Mortalitatsanstieg durch Krebs gewichtiger als bei Frauen zu sein. Bei Frauen sind Pradiabetes und Diabetes meist mit mehr vaskularen Risikofaktoren assoziiert wie erhohte Inflammationsparameter, prothrombotische Veranderungen und hoherem Blutdruck. Sie weisen deshalb ein relativ hoheres vaskulares Risiko auf. Frauen sind ofter stark ubergewichtig und weniger korperlich aktiv, obwohl sie sogar noch mehr als Manner von einem hoheren Bewegungsausmas in ihrer Gesundheit und Lebenserwartung profitieren durften. In Gewichtsreduktionsprogrammen verlieren Manner haufig mehr Gewicht als Frauen. Frauen und Mannern profitieren gleich gut von Praventionsprogrammen mit etwa 40 % Risikoreduktion fur Typ-2-Diabetes nach 3 Jahren. Langzeitdaten konnten bisher eine Reduktion der allgemeinen und kardiovaskularen Mortalitat nur bei Frauen zeigen. Frauen weisen ofter eine gestorte Glukosetoleranz, Manner hingegen erhohte Nuchternblutzuckerspiegel auf. Eine Anamnese eines Gestationsdiabetes oder PCOS sowie hohere Androgenspiegel stellen bei Frauen, das Vorhandensein einer erektilen Dysfunktion oder erniedrigter Testosteronspiegel bei Mannern, wichtige geschlechtsspezifische Diabetesrisikofaktoren dar. Viele Studien zeigen des Weiteren, dass Frauen in der Therapie weniger oft die Zielwerte fur HbA1c, LDL-Cholesterin oder Blutdruck erreichen, wobei die Ursachen unklar sind. Generell sollen in der medikamentosen Behandlung geschlechtsspezifische Unterschiede in der Wirkung, Pharmakokinetik und in den Nebenwirkungen mehr Beachtung finden.

Die unter der Kategorie „andere spezifische Diabetesformen“ zusammengefassten Storungen des Glukosestoffwechsels stellen pathophysiologisch und therapeutisch eine sehr heterogene Krankheitsgruppe dar. Umfasst werden Diabetesformen, die im Rahmen von anderen endokrinologischen Erkrankungen auftreten (z. B. Akromegalie, Cushing-Syndrom), pankreoprive Formen (z. B. postoperativ, Pankreatitis, Pankreastumoren, Hamochromatose, zystische Fibrose), medikamentos induzierte Diabetesformen (z. B. Antipsychotikatherapie, Glukokortikoidtherapie, HAART), genetische Formen (z. B. i. R. eines MODY, neonataler Diabetes, Down-Syndrom, Klinefelter-Syndrom, Turner-Syndrom), Infektionen (z. B. kongenitale Rotelninfektion) und seltene autoimmune Formen (z. B. Stiffman-Syndrom). Nicht nur pankreoprive Formen, sondern auch Typ 1 oder langjahriger Typ 2 Diabetes mellitus sind haufig mit einer exokrinen Pankreasinsuffizienz assoziiert.

Background: To be able to compare continuous glucose monitoring (CGM) systems, they have to be worn in parallel by the same subjects. This study evaluated the performance and usability of three different CGM systems in direct comparison. Method: In this open, prospective study at two sites, 54 patients with diabetes wore three CGM systems each (Dexcom G5™ Mobile CGM system [DG5], Guardian™ Connect system [GC], and a Roche CGM system [RCGM]) in parallel for 6 or 7 days in a mixed inpatient and outpatient setting. Capillary comparison measurements were performed using a self-monitoring of blood glucose (SMBG) system. During study site visits, glucose excursions were induced. Performance of the systems was evaluated by calculating mean absolute relative differences (MARD, calculated as absolute differences for glucose concentrations Results: Overall MARD was 10.1 ± 2.1 for DG5, 11.5 ± 4.2 for GC, and 11.9 ± 5.6 for RCGM. Performance improved in all systems after the first day of use. All systems showed >99% of values within zones A and B of the consensus error grid. Overall, all CGM systems showed a small negative bias compared to SMBG. Usability of the systems differed regarding patch adhesion rate, failure rate, and patient rating. Most patients preferred GC, but in general all systems were rated positively. Conclusion: All three CGM systems showed similar overall accuracy in this direct comparison, but small differences were observed with regard to specific glucose ranges and usability aspects.

Aims/hypothesis Evidence for the effectiveness of interstitial glucose monitoring in individuals with type 1 diabetes using multiple daily injection (MDI) therapy is limited. In this pre-specified subgroup analysis of the Novel Glucose-Sensing Technology and Hypoglycemia in Type 1 Diabetes: a Multicentre, Non-masked, Randomised Controlled Trial’ (IMPACT), we assessed the impact of flash glucose technology on hypoglycaemia compared with capillary glucose monitoring. Methods This multicentre, prospective, non-masked, RCT enrolled adults from 23 European diabetes centres. Individuals were eligible to participate if they had well-controlled type 1 diabetes (diagnosed for ≥5 years), HbA1c ≤ 58 mmol/mol [7.5%], were using MDI therapy and on their current insulin regimen for ≥3 months, reported self-monitoring of blood glucose on a regular basis (equivalent to ≥3 times/day) for ≥2 months and were deemed technically capable of using flash glucose technology. Individuals were excluded if they were diagnosed with hypoglycaemia unawareness, had diabetic ketoacidosis or myocardial infarction in the preceding 6 months, had a known allergy to medical-grade adhesives, used continuous glucose monitoring (CGM) within the previous 4 months or were currently using CGM or sensor-augmented pump therapy, were pregnant or planning pregnancy or were receiving steroid therapy for any disorders. Following 2 weeks of blinded (to participants and investigator) sensor wear by all participants, participants with sensor data for more than 50% of the blinded wear period (or ≥650 individual sensor results) were randomly assigned, in a 1:1 ratio by a central interactive web response system (IWRS) using the biased-coin minimisation method, to flash sensor-based glucose monitoring (intervention group) or self-monitoring of capillary blood glucose (control group). The control group had two further 14 day blinded sensor-wear periods at the 3 and 6 month time points. Participants, investigators and staff were not masked to group allocation. The primary outcome was the change in time in hypoglycaemia (

This retrospective chart review study evaluated the effectiveness of the FreeStyle Libre Flash Glucose Monitoring SystemTM when used by adults with type 2 diabetes (T2DM) as their standard of care in a real-world setting. This study aimed to determine the effect of FreeStyle Libre when used for between 3 months to 6 months on HbA1c. The study population included adults on a basal-bolus insulin regimen for at least 1 year who had been using FreeStyle Libre regularly for at least 3 months (either self-funded or prescribed) and with HbA1c between 8.0 and 12.0% (64 to 108 mmol/mol). Pregnant patients were excluded, as were patients on dialysis. A total of 92 records from insulin using patients with T2DM from 6 hospital sites in Austria were included in this chart review. On average, HbA1c was 8.8±0.8% (72.2±8.9 mmol/mol), prior to FreeStyle Libre use, age was 64.4±9.7 years, BMI was 30.8±5.5 kg/m2 and average duration of insulin use 7.6±5.6 years (mean±SD), 79.3% of patients were on oral antidiabetic medications (metformin, TZD, DPP-4 or SGLT) and 54.3% were male. CVD and renal complications were reported by 34.8% and 27.2% of patients, respectively. HbA1c results were recorded between 91 to 194 days from the start of use of FreeStyle Libre, between September 2014 and July 2018. To minimise selection bias, all patients that had used FreeStyle Libre for at least 3 months from each study site were included in the analysis. After at least 3 months of using FreeStyle Libre, HbA1c (primary outcome) was significantly reduced by 0.9±0.8% (mean±SD); p Disclosure P. Fasching: None. H. Brath: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Novo Nordisk Inc., Servier. Speaker’s Bureau; Self; Amgen Inc., Ascensia Diabetes Care, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk Inc., Pfizer Inc., Sanofi. C. Ebenbichler: None. J.K. Mader: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Prediktor Medical, Roche Diabetes Care, Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Dexcom, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; decide Clinical Software GmbH. C. Schelkshorn: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. Speaker’s Bureau; Self; Abbott, Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Self; Lilly Diabetes. R. Weitgasser: Research Support; Self; Abbott.

The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.

BACKGROUND: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.METHODS: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.RESULTS: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1).CONCLUSIONS: The 16 diabetic kidney disease-associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.

Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain(COL4A3)gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of DKD, including albuminuria and end-stage renal disease. Three other loci are in or near genes with known or suggestive involvement in DKD(BMP7)or renal biology (COLEC11andDDR1). The 16 DKD-associated loci provide novel insights into the pathogenesis of DKD, identifying potential biological targets for prevention and treatment.

Hyperglycemia significantly contributes to micro- and macrovascular complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets in regard of optimal therapeutic efficacy and high therapeutic safety is of great importance. In this guideline we present the best and most current evidence-based clinical practice data for healthcare professionals.

Zusammenfassung Dieses Positionspapier zur Anwendung der subkutanen Insulinpumpentherapie (CSII) bei Diabetes mellitus basiert auf aktueller Evidenz zu Sicherheit und Vor-und Nachteile der CSII, insbesondere im Hinblick auf glykämische Kontrolle, Hypoglykämie, ketoazidotische Entgleisung, Lebensqualität und Anwendung in der Schwangerschaft. Dieser Artikel beinhaltet die Empfehlungen der Österreichischen Diabetesgesellschaft für die klinische Anwendung der Insulinpumpentherapie bei Kindern, Jugendlichen und Erwachsenen.

Background and Aims: Apolipoprotein C3 (ApoC3) is a key regulator of triglyceride metabolism via its inhibitory effects on lipolysis and hepatic remnant uptake. Emerging evidence indicate that ApoC3 is an independent risk factor for cardiovascular events. The fact that glucose and insulin regulates ApoC3 expression raises the role of ApoC3 and cardiovascular risk in diabetes. We, therefore, investigated ApoC3 and its association with cardiovascular disease (CVD) in patients with and without diabetic nephropathy. Methods: This cross-sectional and prospective analysis was part of the prospective, ongoing Finnish Diabetic Nephropathy (FinnDiane) Study. Between 1994 and 2015 data were obtained from 3926 type 1 diabetes (T1D) patients at more than 80 hospitals or health centers across Finland. ApoC3 levels were explored by groups of albuminuria, CKD stages, presence of CVD as well as prediction of CVD and death. Survival curves were calculated by Cox regression analysis. Results: At baseline, normo-, micro- and macroalbuminuria were present in 71.7%, 13.8% and 14.5% of the population (n=3926, females 48%, age 37.8±12.2 years, diabetes duration 23.2±13 years, HbA1c 8.4±1.5%). CKD stage 3-5 was diagnosed in 14.3%. Coronary heart disease or stroke (CVD) were present in 5.5% at baseline, while 16.3% developed CVD during 15-year follow-up. Compared to normoalbuminuria ApoC3 was elevated in the presence of micro- (p=0.013) or macroalbumiuria (p Conclusions: Baseline ApoC3 levels were elevated in T1D patients with micro- and macroalbuminuria, with impaired renal function, and with CVD. ApoC3 also predicted the development of CVD and death during follow-up. Disclosure L. Stechemesser: None. C. Forsblom: None. R. Weitgasser: None. P. Groop: Other Relationship; Self; AstraZeneca, AbbVie Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medscape, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi.

Aims:Estimate the costs associated with flash glucose monitoring as a replacement for routine self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes mellitus (T2DM) using intensive insulin, from a UK National Health Service (NHS) perspective.Methods:The base-case cost calculation used the frequency of SMBG and healthcare resource use observed in the REPLACE trial. Scenario analyses considered SMBG at the flash monitoring frequencies observed in the REPLACE trial (8.3 tests per day) and a real-world analysis (16 tests per day).Results:Compared with 3 SMBG tests per day, flash monitoring would cost an additional £585 per patient per year, offset by a £776 reduction in healthcare resource use, based on reductions in emergency room visits (41%), ambulance call-outs (66%) and hospital admissions (77%) observed in the REPLACE trial. Per patient, the estimated total annual cost for flash monitoring was £191 (13.4%) lower than for SMBG. In the scenarios based on acquisition cost alone, flash monitoring was cost-neutral versus 8.3 SMBG tests per day (5% decrease) and cost-saving at higher testing frequencies.Conclusion:From a UK NHS perspective, for patients with T2DM using intensive insulin, flash monitoring is potentially cost-saving compared with routine SMBG irrespective of testing frequency. Keywords

Background Type 2 diabetes is a chronic disease associated with poorer health outcomes and decreased health related quality of life (HRQoL). The aim of this analysis was to explore the impact of a disease management programme (DMP) in type 2 diabetes on HRQoL. A multilevel model was used to explain the variation in EQ-VAS. Methods A cluster-randomized controlled trial—analysis of the secondary endpoint HRQoL. Our study population were general practitioners and patients in the province of Salzburg. The DMP “Therapie-Aktiv” was implemented in the intervention group, and controls received usual care. Outcome measure was a change in EQ-VAS after 12 months. For comparison of rates, we used Fisher’s Exact test; for continuous variables the independent T test or Welch test were used. In the multilevel modeling, we examined various models, continuously adding variables to explain the variation in the dependent variable, starting with an empty model, including only the random intercept. We analysed random effects parameters in order to disentangle variation of the final EQ-VAS. Results The EQ-VAS significantly increased within the intervention group (mean difference 2.19, p = 0.005). There was no significant difference in EQ-VAS between groups (mean difference 1.00, p = 0.339). In the intervention group the improvement was more distinct in women (2.46, p = 0.036) compared to men (1.92, p = 0.063). In multilevel modeling, sex, age, family and work circumstances, any macrovascular diabetic complication, duration of diabetes, baseline body mass index and baseline EQ-VAS significantly influence final EQ-VAS, while DMP does not. The final model explains 28.9% (EQ-VAS) of the total variance. Most of the unexplained variance was found on patient-level (95%) and less on GP-level (5%). Conclusion DMP “Therapie-Aktiv” has no significant impact on final EQ-VAS. The impact of DMPs in type 2 diabetes on HRQoL is still unclear and future programmes should focus on patient specific needs and predictors in order to improve HRQoL. Trial registration Current Controlled trials Ltd., ISRCTN27414162

Background: Imprecise carbohydrate counting as a measure to guide the treatment of diabetes may be a source of errors resulting in problems in glycemic control. Exact measurements can be tedious, leading most patients to estimate their carbohydrate intake. In the presented pilot study a smartphone application (BEAR), that guides the estimation of the amounts of carbohydrates, was used by a group of diabetic patients. Methods: Eight adult patients with diabetes mellitus type 1 were recruited for the study. At the beginning of the study patients were introduced to BEAR in sessions lasting 45 minutes per patient. Patients redraw the real food in 3D on the smartphone screen. Based on a selected food type and the 3D form created using BEAR an estimation of carbohydrate content is calculated. Patients were supplied with the application on their personal smartphone or a loaner device and were instructed to use the application in real-world context during the study period. For evaluation purpose a test measuring carbohydrate estimation quality was designed and performed at the beginning and the end of the study. Results: In 44% of the estimations performed at the end of the study the error reduced by at least 6 grams of carbohydrate. This improvement occurred albeit several problems with the usage of BEAR were reported. Conclusions: Despite user interaction problems in this group of patients the provided intervention resulted in a reduction in the absolute error of carbohydrate estimation. Intervention with smartphone applications to assist carbohydrate counting apparently results in more accurate estimations.

Aims To estimate the costs associated with a flash glucose monitoring system as a replacement for routine self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes mellitus (T1DM) using intensive insulin, from a UK National Health Service (NHS) perspective. Methods The base-case cost calculation was created using the maximum frequency of glucose monitoring recommended by the 2015 National Institute for Health and Care Excellence guidelines (4–10 tests per day). Scenario analyses considered SMBG at the frequency observed in the IMPACT clinical trial (5.6 tests per day) and at the frequency of flash monitoring observed in a real-world analysis (16 tests per day). A further scenario included potential costs associated with severe hypoglycaemia. Results In the base case, the annual cost per patient using flash monitoring was £234 (19%) lower compared with routine SMBG (10 tests per day). In scenario analyses, the annual cost per patient of flash monitoring compared with 5.6 and 16 SMBG tests per day was £296 higher and £957 lower, respectively. The annual cost of severe hypoglycaemia for flash monitoring users was estimated to be £221 per patient, compared with £428 for routine SMBG users (based on 5.6 tests/day), corresponding to a reduction in costs of £207. Conclusions The flash monitoring system has a modest impact on glucose monitoring costs for the UK NHS for patients with T1DM using intensive insulin. For people requiring frequent tests, flash monitoring may be cost saving, especially when taking into account potential reductions in the rate of severe hypoglycaemia.

Background: This study aimed to explore if group-based peer support as an additional component to a disease management programme (DMP) in type 2 diabetes can reduce the number of prescribed drugs; hospital admissions; and length of hospital stay and therefore be a cost-effective model. Methods: Controlled study based on a secondary data analysis of a cluster randomized trial. Our study population was general practitioners and patients in the province of Salzburg. The 24-months intervention consisted of regular group meetings facilitated by trained peer supporters. The groups exercised together, discussed diabetes related topics, and received support by professionals. Data was anonymously collected on clusters through the statutory health insurance. Results: Data were available of 118 (82.5%,17 clusters of the patients in the original randomized trial) participants in the intervention and 143 (77.3%,19 clusters) in the control groups. The length of hospital stay was shorter in the intervention groups compared with controls. The mean difference during the 24-month study period was −40.13 days (95% CI − 78.54 to − 1.71, P = 0.041) in favour of the intervention groups. No differences were seen in the number of prescribed drugs and hospital admission. Estimated yearly savings by reducing the length of hospital stay was €1660.60 per patient. Conclusion: A group-based peer support programme as an additional component of a DMP in type 2 diabetes is a promising approach to optimize diabetes care and to enhance lifestyle interventions in primary care. Peer support seems to reduce length of hospital stay and could therefore be a cost-effective model.

Hypoglycemia is a frequent side effect induced by insulin treatment of type 1 (T1DM) and type 2 diabetes (T2DM). Limited data exist on the associated healthcare resource use and patient impact of hypoglycemia, particularly at a country-specific level. This study investigated the effects of self-reported non-severe hypoglycemic events (NSHE) on use of healthcare resources and patient wellbeing.Patients with T1DM or insulin-treated T2DM diabetes from seven European countries were invited to complete four weekly questionnaires. Data were collected on patient demographics, NSHE occurrence in the last 7 days, hypoglycemia-related resource use, and patient impact. NSHE were defined as events with hypoglycemia symptoms, with or without blood glucose measurement, or low blood glucose measurement without symptoms, which the patient could manage without third-party assistance.Three thousand, nine hundred and fifty-nine respondents completed at least one wave of the survey, with 57% completing all four questionnaires; 3827 respondents were used for data analyses. Overall, 2.3% and 8.9% of NSHE in patients with T1DM and T2DM, respectively, resulted in healthcare professional contact. Across countries, there was a mean increase in blood glucose test use of 3.0 tests in the week following a NSHE. Among respondents who were employed (48%), loss of work-time after the last hypoglycemic event was reported for 9.7% of NSHE. Overall, 10.2% (daytime) and 8.0% (nocturnal) NSHE led to work-time loss, with a mean loss of 84.3 (daytime) and 169.6 (nocturnal) minutes among patients reporting work-time loss. Additionally, patients reported feeling tired, irritable, and having negative feelings following hypoglycemia.Direct comparisons between studies must be interpreted with caution because of different definitions of hypoglycemia severity, duration of the studies, and methods of data collection.NSHE were associated with use of extra healthcare resources and work-time loss in all countries studied, suggesting that NSHE have considerable impact on patients/society.

Aims Hypoglycaemia presents a barrier to optimum diabetes management but data are limited on the frequency of hypoglycaemia incidents outside of clinical trials. The present study investigated the rates of self-reported non-severe hypoglycaemic events, hypoglycaemia awareness and physician discussion of events in people with Type 1 diabetes mellitus or insulin-treated Type 2 diabetes mellitus. Methods People in seven European countries aged >15 years with Type 1 diabetes or insulin–treated Type 2 diabetes (basal-only, basal-bolus and other insulin regimens) were recruited via consumer panels, nurses, telephone recruitment and family referrals. Respondents completed four online questionnaires. The first questionnaire collected background information on demographics and hypoglycaemia-related behaviour, whilst all four questionnaires collected data on non-severe hypoglycaemic events in the preceding 7 days. Results Analysis was based on 11 440 respondent-weeks from 3827 respondents. All participants completed the first questionnaire and 57% completed all four. The mean number of events/respondent–week was 1.8 (Type 1 diabetes) and 0.4–0.7 (Type 2 diabetes, with different insulin treatments) corresponding to annual event rates of 94 and 21–36, respectively. A total of 63% of respondents with Type 1 diabetes and 49–64% of respondents with Type 2 diabetes, treated with different insulin regimens, who experienced hypoglycaemic events, reported impaired hypoglycaemia awareness or unawareness. A high proportion of respondents rarely or never informed their general practitioner/specialist about hypoglycaemia: 65% (Type 1 diabetes) and 50–59% (Type 2 diabetes). Overall, 16% of respondents with Type 1 diabetes and 26% of respondents with Type 2 diabetes reported not being asked about hypoglycaemia during routine appointments. Conclusion Non-severe hypoglycaemic events are common amongst people with Type 1 diabetes and insulin–treated Type 2 diabetes in real-world settings. Many rarely or never inform their general practitioner/specialist about their hypoglycaemia and the real burden of hypoglycaemia may be underestimated.

Die Hyperglykamie ist wesentlich an der Entstehung mikro- als auch makrovaskularer Spatkomplikationen bei an Diabetes mellitus Typ 2 erkrankten Patienten beteiligt. Wahrend Lebensstilmasnahmen die Eckpfeiler jeder Diabetestherapie bleiben, benotigen im Verlauf die meisten PatientInnen mit Typ 2 Diabetes eine medikamentose Therapie. Bei der Definition individueller Behandlungsziele stellen die Therapiesicherheit bzw. die Effektivitat der Therapie die wichtigsten Faktoren dar. In dieser Leitlinie haben wir die rezenten evidenzbasierten Daten fur die klinische Praxis zusammengestellt.

Aim. Testing the effectiveness of peer support additionally to a disease management programme (DMP) for type 2 diabetes patients.Methods. Unblinded cluster-randomised controlled trial (RCT) involving 49 general practices, province of Salzburg, Austria. All patients enrolled in the DMP were eligible,n=337participated (intervention: 148 in 19 clusters; control: 189 in 20 clusters). The peer support intervention ran over 24 months and consisted of peer supporter recruitment and training, and group meetings weekly for physical exercise and monthly for discussion of diabetes related topics.Results. At two-year follow-up, adjusted analysis revealed a nonsignificant difference inHbA1cchange of 0.14% (21.97 mmol/mol) in favour of the intervention (95% CI −0.08 to 0.36%,p=0.22). Baseline values were 7.02 ± 1.25% in the intervention and 7.08 ± 1.25 in the control group. None of the secondary outcome measures showed significant differences except for improved quality of life (EQ-5D-VAS) in controls (4.3 points on a scale of 100; 95% CI 0.08 to 8.53,p=0.046) compared to the intervention group.Conclusion. Our peer support intervention as an additional DMP component showed no significant effect onHbA1cand secondary outcome measures. Further RTCs with a longer follow-up are needed to reveal whether peer support will have clinically relevant effects.Trial Registration. This trial has been registered with Current Controlled Trials Ltd. (ISRCTN10291077).

The sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor involved in the regulation of lipid and glucose metabolism and has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). We aimed to confirm associations of the SREBF-1 gene with T2DM in an Austrian population and to study possible associations with diabetes-related quantitative traits. We genotyped a diabetic cohort (n=446) along with a control group (n=1524) for a common C/G variation that is located in exon 18c (rs2297508) and has been associated with obesity and T2DM in French populations. Body mass index (BMI), indices of insulin sensitivity and β-cell function, plasma adiponectin, T2DM and single-nucleotide polymorphism rs2297508. Genotype distributions associated with rs2297508 differed by T2DM status (P=0.0045), but not by BMI. The variant G allele was associated with a modest, but significant, increase in the prevalence of T2DM after adjustment for age, sex and BMI (G/G: odds ratios (OR) (95% confidence intervals)=1.45 (0.99–2.11) and G/C: OR=1.37 (1.04–1.81)). In a cross-sectional population of non-diabetic subjects, associations of rs2297508 genotypes with plasma adiponectin levels adjusted for age, sex and BMI (P=0.0017) were observed in that the risk G/G genotype displayed the lowest adiponectin levels. We observed associations of rs2297508 with T2DM prevalence and plasma adiponectin. SREBP-1c has been implicated in the regulation of adiponectin gene expression. Our results therefore raise the possibility that sequence variations at the SREBF-1 gene locus might contribute to T2DM risk, at least in part, by altering circulating adiponectin levels.

The cholesteryl ester transfer protein (CETP) is responsible for the exchange of triglycerides and cholesteryl esters between lipoprotein particles leading to an increased hepatic clearance of HDL-cholesteryl esters. A high CETP activity reduces serum HDL levels, whereas persons without CETP activity have high HDL levels. We investigated the association of the TaqIB CETP polymorphism and various parameters of the insulin resistance syndrome in a cross sectional population based study. We included 1029 persons without known cardiovascular disease or diabetes mellitus consecutively enrolled in our SAPHIR program (Salzburg Atherosclerosis Prevention program in persons with a High Infarction Risk). Numerous clinical and laboratory data were accomplished. Insulin sensitivity was measured by a short insulin tolerance test. The TaqIB CETP polymorphism was determined by PCR, TaqI restriction and electrophoresis. 35.2% were homozygous for the prevalence (B1B1), 46.7% were heterozygous (B1B2), and 18.1% homozygous for the absence (B2B2) of the restriction site. HDL cholesterol and apolipoprotein A1 were lower and small dense low-density lipoproteins (sdLDL) higher in B1B1 compared to B2B1 and B2B2 persons. In women, we found a significant interaction effect between CETP genotype and adiposity for HDL cholesterol. B1B1 women with a BMI and a waist circumference above the median had 9.7 mg/dl lower HDL than B1B2 and 9.1 mg/dl lower HDL than B2B2 women (P0.001). In men, no interaction effect but a marked genotype to HDL correlation was found. There was a high CETP effect on sdLDL detected in men (P = 0.001). B1B1 men had sdLDL in 36%, B1B2 in 24.6%, and B2B2 in only 14.5%. Men with adiposity and insulin resistance had twice as many sdLDL as insulin sensitive men. We found a significant sex specific effect of the TaqIB CETP polymorphism on the insulin resistance parameters HDL-cholesterol and sdLDL in an Austrian population based study.

Background: Newer glucose meters are easier to use, but direct comparisons with older instruments are lacking. We wished to compare analytical performances of four new and four previous generation meters.Methods: On average, 248 glucose measurements were performed with two of each brand of meter on capillary blood samples from diabetic patients attending our outpatient clinic. Two to three different lots of strips were used. All measurements were performed by one experienced technician, using blood from the same sample for the meters and the comparison method (Beckman Analyzer 2). Results were evaluated by analysis of clinical relevance using the percentage of values within a maximum deviation of 5% from the reference value, by the method of residuals, by error grid analysis, and by the CVs for measurements in series.Results: Altogether, 1987 blood glucose values were obtained with meters compared with the reference values. By error grid analysis, the newer devices gave more accurate results without significant differences within the group (zone A, 98–98.5%). Except for the One Touch II (zone A, 98.5%), the other older devices were less exact (zone A, 87–92.5%), which was also true for all other evaluation procedures.Conclusions: New generation blood glucose meters are not only smaller and more aesthetically appealing but are more accurate compared with previous generation devices except the One Touch II. The performance of the newer meters improved but did not meet the goals of the latest American Diabetes Association recommendations in the hands of an experienced operator.

Background Disease management programmes (DMPs) are costly and impose additional work load on general practitioners (GPs). Data on their effectiveness are inconclusive. We therefore conducted a cluster-randomised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care. Methods All GPs of Salzburg-province were invited to participate. After cluster-randomisation by district, all patients with diabetes type 2 were recruited consecutively from 7-11/2007. The DMP, consisting mainly of physician and patient education, standardised documentation and agreement on therapeutic goals, was implemented in the intervention group while the control group received usual care. We aimed to show superiority of the intervention regarding metabolic control and process quality. The primary outcome measure was a change in HbA1c after one year. Secondary outcomes were days in the hospital, blood pressure, lipids, body mass index (BMI), enrolment in patient education and regular guideline-adherent examination. Blinding was not possible. Results 92 physicians recruited 1489 patients (649 intervention, 840 control). After 401 ± 47 days, 590 intervention-patients and 754 controls had complete data. In the intention to treat analysis (ITT) of all 1489 patients, HbA1c decreased 0.41% in the intervention group and 0.28% in controls. The difference of -0.13% (95% CI -0.24; -0.02) was significant at p = 0.026. Significance was lost in mixed models adjusted for baseline value and cluster-effects (adjusted mean difference -0.03 (95% CI -0.15; 0.09, p = 0.607). Of the secondary outcome measures, BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments (-0.53 kg/m²; 95% CI -1.03;-0.02; p = 0.014 and -0.10 mmol/l; 95% CI -0.21; -0.003; p = 0.043). Additionally, more patients received patient education (49.5% vs. 20.1%, p < 0.0001), eye- (71.0% vs. 51.2%, p < 0.0001), foot examinations (73.8% vs. 45.1%, p < 0.0001), and regular HbA1c checks (44.1% vs. 36.0%, p < 0.01) in the intervention group. Conclusion The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction, but does not significantly improve metabolic control for patients with type 2 diabetes mellitus. Whether the small benefit seen in secondary outcome measures leads to better patient outcomes, remains unclear. Trial Registration Current Controlled trials Ltd., ISRCTN27414162.

Background Due to its rising prevalence type 2 diabetes plays an important role concerning population health in Austria and other western countries. In various studies deficiencies in the care of diabetic patients have been revealed. These deficiencies may be overcome by disease-management-programmes (DMPs), but international experience shows that the effectiveness of DMPs is inconsistent. In particular large programmes designed by state-affiliated public health insurances have not been evaluated in randomized controlled trials (RCTs). We are therefore conducting a large scale RCT of the Austrian DMP for type 2 diabetic patients in the province of Salzburg to evaluate the programme regarding its effects on metabolic control, guideline adherent care and the quality of life of diabetic patients. Methods/Design The study is open for participation to all GPs and internists in the province of Salzburg. Physicians are randomized before recruitment of patients with the districts of Salzburg as clusters of randomisation. A total of over 1200 patients with type 2 diabetes will then be recruited. In the intervention group the DMP is applied for one year. Controls receive usual care. Endpoints are a decrease in HbA1c in the intervention group > 0,5% compared to controls, a higher percentage of patients with required diagnostic measures according to guidelines, improved cardiovascular risk profile and higher quality of life scores within one year. Current status of the study 98 Physicians agreed to participate in the study. 96 of them recruited 1494 patients, 654 in the intervention and 840 in the control group. Trail Registration This trial has been registered with Current Controlled Trials Ltd. (ISRCTN27414162).

Objectives: In the face of the ongoing discussion on the criteria for the diagnosis of gestational diabetes (GDM), we aimed to examine whether the criteria of the Fourth International Workshop Conference of GDM (WC) select women and children at risk better than the World Health Organization (WHO) criteria. Design and Setting: This was a prospective longitudinal open study in five tertiary care centers in Austria. Patients and Outcome Measures: The impact of risk factors, different thresholds (WC vs. WHO), and numbers of abnormal glucose values (WC) during the 2-h, 75-g oral glucose tolerance test on fetal/neonatal complications and maternal postpartum glucose tolerance was studied in 1466 pregnant women. Women were treated if at least one value according to the WC (GDM-WC1) was met or exceeded. Results: Forty-six percent of all women had GDM-WC1, whereas 29% had GDM-WHO, and 21% of all women had two or three abnormal values according to WC criteria (GDM-WC2). Eighty-five percent of the GDM-WHO were also identified by GDM-WC1. Previous GDM [odds ratio (OR) 2.9], glucosuria (OR 2.4), preconceptual overweight/obesity (OR 2.3), age 30 yr or older (OR 1.9), and large-for-gestational age (LGA) fetus (OR 1.8) were the best independent predictors of the occurrence of GDM. Previous GDM (OR 4.4) and overweight/obesity (OR 4.0) also independently predicted diabetes postpartum. GDM-WC1 had a higher rate of obstetrical complications (LGA neonates, neonatal hypoglycemia, cesarean sections; P < 0.001) and impaired postpartum glucose tolerance (P < 0.0001) than GDM-WHO. Conclusion: These results suggest the use of more stringent WC criteria for the diagnosis of GDM with the initiation of therapy in case of one fasting or stimulated abnormal glucose value because these criteria detected more LGA neonates with hypoglycemia and mothers with impaired postpartum glucose metabolism than the WHO criteria.

Background: Patients and medical personnel are eager to use blood glucose meters that are easy to handle and fast acting. We questioned whether accuracy and precision of these new, small and light weight devices would meet analytical laboratory standards and tested four meters with the above mentioned conditions. Methods: Approximately 300 capillary blood samples were collected and tested using two devices of each brand and two different types of glucose test strips. Blood from the same samples was used for comparison. Results were evaluated using maximum deviation of 5% and 10% from the comparative method, the error grid analysis, the overall deviation of the devices, the linear regression analysis as well as the CVs for measurement in series. Results: Of all 1196 measurements a deviation of less than 5% resp. 10% from the reference method was found for the FreeStyle (FS) meter in 69.5% and 96%, the Glucocard X Meter (GX) in 44% and 75%, the One Touch Ultra (OT) in 29% and 60%, the Wellion True Track (WT) in 28.5% and 58%. The error grid analysis gave 99.7% for FS, 99% for GX, 98% for OT and 97% for WT in zone A. The remainder of the values lay within zone B. Linear regression analysis resembled these results. CVs for measurement in series showed higher deviations for OT and WT compared to FS and GX. Conclusions: The four new, small and fast acting glucose meters fulfil clinically relevant analytical laboratory requirements making them appropriate for use by medical personnel. However, with regard to the tight and restrictive limits of the ADA recommendations, the devices are still in need of improvement. This should be taken into account when the devices are used by primarily inexperienced persons and is relevant for further industrial development of such devices.

TCF7L2 variants have been consistently associated with type 2 diabetes (T2D) in populations of different ethnic descent. Among them, the rs7903146 T allele is probably the best proxy to evaluate the effect of this gene on T2D risk in additional ethnic groups. In the present study, we investigated the association between the TCF7L2 rs7903146 polymorphism and T2D in Moroccans (406 normoglycemic individuals and 504 T2D subjects) and in white Austrians (1,075 normoglycemic individuals and 486 T2D subjects). Then, we systematically reviewed the association of this single nucleotide polymorphism (SNP) with T2D risk in a meta-analysis, combining our data with data from previous studies. The allelic odds ratios (ORs) for T2D were 1.56 [1.29-1.89] (p = 2.9 x 10(-6)) and 1.52 [1.29-1.78] (p = 3.0 x 10(-7)) in Moroccans and Austrians, respectively. No heterogeneity was found between these two different populations by Woolf test (chi (2) = 0.04, df = 1, p = 0.84). We found 28 original published association studies dealing with the TCF7L2 rs7903146 polymorphism in T2D. A meta-analysis was then performed on 29,195 control subjects and 17,202 cases. No heterogeneity in genotypic distribution was found (Woolf test: chi (2) = 31.5, df = 26, p = 0.21; Higgins statistic: I2 = 14.1%). A Mantel-Haenszel procedure was then performed to provide a pooled odds ratio (OR) of 1.46 [1.42-1.51] (p = 5.4 x 10(-140)). No publication bias was detected, using the conservative Egger's regression asymmetry test (t = -1.6, df = 25, p = 0.11). Compared to any other gene variants previously confirmed by meta-analysis, TCF7L2 can be distinguished by its tremendous reproducibility of association with T2D and its OR twice as high. In the near future, large-scale genome-wide association studies will fully extend the genome coverage, potentially delivering other common diabetes-susceptibility genes like TCF7L2.

Peroxisome proliferator–activated receptor coactivator-1α (PGC-1α) is a transcriptional coactivator implicated in transcriptional programs of hepatic gluconeogenesis, oxidative phosphorylation, and insulin release by β-cells. To study associations of the PGC-1α gene locus with carbohydrate metabolism and type 2 diabetes in humans, we identified several polymorphisms in the promoter region that were located in a haplotype block distinct from a second haplotype block containing part of intron 2 and extending beyond exon 13. Each block contained five common haplotypes. Oral glucose tolerance testing revealed associations of promoter haplotype combinations with 30- and 60-min postload plasma glucose levels, whereas haplotypes in both blocks were associated with indexes of β-cell function. The associations of promoter haplotypes are supported by functional studies showing that some polymorphisms are located in transcription factor binding sites and affect transactivation in an allele-specific manner. By comparing patients with type 2 diabetes and control subjects, we observed borderline significant differences of four-loci haplotype distributions in the downstream haplotype block. Moreover, the haplotype that was associated with the strongest insulin response to glucose conferred the lowest risk of type 2 diabetes (P < 0.01). Thus, the PGC-1α gene locus influences carbohydrate metabolism and contributes to type 2 diabetes in the population studied.

Obesity is frequently associated with type 2 diabetes. We previously observed an association of a functional G/A polymorphism in the uncoupling protein 2 (UCP2) promoter with obesity. The wild-type G allele was associated with reduced adipose tissue mRNA expression in vivo, reduced transcriptional activity in vitro, and increased risk of obesity. On the other hand, studies in animal and cell culture models identified pancreatic β-cell UCP2 expression as a main determinant of the insulin secretory response to glucose. We therefore ascertained associations of the −866G/A polymorphism with β-cell function and diabetes risk in obesity. We show here that the pancreatic transcription factor PAX6 preferentially binds to and more effectively trans activates the variant than the wild-type UCP2 promoter allele in the β-cell line INS1-E. By studying 39 obese nondiabetic humans, we observed genotype differences in β-cell function; wild-type subjects displayed a greater disposition index (the product of insulin sensitivity and acute insulin response to glucose) than subjects with the variant allele (P < 0.03). By comparing obese subjects with and without type 2 diabetes, we observed genotype-associated differences in diabetes prevalence that translated into a twofold age-adjusted risk reduction in wild-type subjects. Thus, the more common UCP2 promoter G allele, while being conducive for obesity, affords relative protection against type 2 diabetes.

OBJECTIVE: HELLP syndrome is a severe form of preeclampsia, characterized by hemolysis (H), elevated liver enzymes (EL), and low platelets (LP), whose pathogenesis is unclear. Autoimmunity is thought to play an important role. After the observation of development of type 1 diabetes in a patient with HELLP syndrome, we assumed a possible disease association based on autoimmune reactions. RESEARCH DESIGN AND METHODS: We examined 70 women with HELLP syndrome for the presence of autoimmune markers and glucose intolerance. Free thyroxine, triiodothyronine, thyroid-stimulating hormone, anti-thyroglobulin antibodies, thyroperoxidase antibodies, thyrotropin receptor antibodies, antinuclear antibodies (ANAs) and anti-DNA, islet cell antibodies, GADA, an oral glucose tolerance test, and HbA1c were determined postpartum. Patients with positive autoimmune markers or glucose intolerance were prospectively followed and repeated testing was performed. There were 60 women with a normal course of pregnancy matched for age, BMI, and number of pregnancies, which served as a control group. RESULTS: From the HELLP patients, 22 (31%) compared with only 6 (10%) control subjects had autoimmune antibodies (P < 0.01). There were 16 HELLP patients (23%) who exhibited only 1 kind of autoantibody (5 ANA, 9 thyroid antibodies, and 2 GADA), whereas in 6 HELLP patients (8.5%) 2 different antibodies were found. In all but 4 patients of the study group, these antibodies disappeared during 3 +/- 1.5 years of follow-up. Glucose intolerance was detected in 22 (31%) of the HELLP patients, 17 of them had impaired glucose tolerance (IGT), and 5 had diabetes, whereas only 4 subjects (6.5%) with IGT at postpartum were found in the control group (P < 0.01). During the follow-up, 2 HELLP patients were still diabetic and another 2 HELLP patients (1 GADA positive) had IGT versus 1 control subject. CONCLUSIONS: Our data give evidence that HELLP syndrome is associated with various autoimmune antibodies and glucose intolerance. Because glucose intolerance and/or autoimmune markers persisted during long-term follow-up in 6 patients with HELLP syndrome versus 1 in the control group, it may become advisable to reexamine patients with HELLP syndrome for detection of diabetes and autoimmune disorders.

Chronic insulin therapy improves but does not restore impaired insulin-mediated muscle glucose uptake in human diabetes or muscle glucose uptake, transport, and transporter translocation in streptozocin diabetic rats. To determine whether this inability is due to inadequate insulin replacement, we studied fasted streptozocin-induced diabetic Lewis rats either untreated or after islet transplantation under the kidney capsule. Plasma glucose was increased in untreated diabetics and normalized by the islet transplantation (110 +/- 5, 452 +/- 9, and 102 +/- 3 mg/dl in controls, untreated diabetics, and transplanted diabetics, respectively). Plasma membrane and intracellular microsomal membrane vesicles were prepared from hindlimb skeletal muscle of basal and maximally insulin-stimulated rats. Islet transplantation normalized plasma membrane carrier-mediated glucose transport Vmax, plasma membrane glucose transporter content, and insulin-induced transporter translocation. There were no differences in transporter intrinsic activity (Vmax/Ro) among the three groups. Microsomal membrane GLUT4 content was reduced by 30% in untreated diabetic rats and normal in transplanted diabetics, whereas the insulin-induced changes in microsomal membrane GLUT4 content were quantitatively similar in the three groups. There were no differences in plasma membrane GLUT1 among the groups and between basal and insulin stimulated states. Microsomal membrane GLUT1 content was increased 60% in untreated diabetics and normalized by the transplantation. In conclusion, an adequate insulin delivery in the peripheral circulation, obtained by islet transplantation, fully restores the muscle glucose transport system to normal in streptozocin diabetic rats.

BackgroundThe pivotal role of mitochondria in energy production and free radical generation suggests that the mitochondrial genome could have an important influence on the expression of multifactorial age related diseases. Substitution of T to C at nucleotide position 16189 in the hypervariable D-loop of the control region (CR) of mitochondrial DNA (mtDNA) has attracted research interest because of its suspected association with various multifactorial diseases. The aim of the present study was to compare the frequency of this polymorphism in the CR of mtDNA in patients with coronary artery disease (CAD, n = 482) and type 2 diabetes mellitus (T2DM, n = 505) from two study centers, with healthy individuals (n = 1481) of Middle European descent in Austria.Methodology and principal findingsCR polymorphisms and the nine major European haplogroups were identified by DNA sequencing and primer extension analysis, respectively. Frequencies and Odds Ratios for the association between cases and controls were calculated. Compared to healthy controls, the prevalence of T16189C was significantly higher in patients with CAD (11.8% vs 21.6%), as well as in patients with T2DM (11.8% vs 19.4%). The association of CAD, but not the one of T2DM, with T16189C remained highly significant after correction for age, sex and body mass index (BMI) and was independent of the two study centers.Conclusions and significanceOur results show for the first time a significant association of T16189C with CAD in a Middle European population. As reported in other studies, in patients with T2DM an association with T16189C in individuals of European decent remains questionable.