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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.

ZusammenfassungDie unter der Kategorie „andere spezifische Diabetesformen“ zusammengefassten Störungen 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), medikamentös induzierte Diabetesformen (z. B. Antipsychotikatherapie, Glukokortikoidtherapie, HAART, Checkpoint-Inhibitoren, genetische Formen (z. B. i. R. eines MODY, neonataler Diabetes, Down-Syndrom, Klinefelter-Syndrom, Turner-Syndrom), pankreoprive Formen (z. B. postoperativ, Pankreatitis, Pankreastumoren, Hämochromatose, zystische Fibrose), Infektionen (z. B. kongenitale Rötelninfektion) und seltene autoimmune Formen (z. B. Stiffman-Syndrom). Die Diagnose der spezifischen Diabetesform kann die therapeutischen Erwägungen beeinflussen. Nicht nur pankreoprive Formen, sondern auch Typ 1 oder langjähriger Typ 2 Diabetes mellitus sind häufig mit einer exokrinen Pankreasinsuffizienz assoziiert.

Purpose Sodium-glucose cotransporter 2 inhibitor (SGLT2i) regulation, developed as treatment for patients with type 2 diabetes, can be imaged with the glucose analogue alpha-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me4FDG), a positron emission tomography (PET) tracer with a high affinity for SGLT1 and SGLT2 proteins. With regard to therapy effectiveness, we aimed to investigate whether clinical parameters or Me4FDG excretion could predict response to SGLT2i in patients with type 2 diabetes. Methods In a longitudinal, prospective study, 19 patients with type 2 diabetes underwent Me4FDG combined PET and magnetic resonance imaging (PET/MRI) scans at baseline and 2 weeks after initiation of therapy with SGLT2i, accompanied by the collection of blood and urine samples. Me4FDG-excretion was determined from the Me4FDG uptake in the bladder. Long-term response was determined by HbA1c level after 3 months; a strong response to the therapy was defined as a reduction of HbA1c by at least 10% from baseline. Results SGLT2i resulted in significantly increased Me4FDG excretion (4.8 vs. 45.0, P P r = 0.55 (P P = 0.005, OR 1.9). Conclusions Using Me4FDG-PET, we demonstrated for the first time renal SGLT2-related excretion before and after short-term SGLT2i treatment. In contrary to other clinical parameters, SGLT2-related excretion before treatment was a robust predictor of long-term HbA1c response in patients with type 2 diabetes, suggesting that therapy effectiveness is only dependent of endogenous SGLT2 processes.

AIMS To investigate the potential synergistic effects of combined exenatide (EXE) and dapagliflozin (DAPA) versus (PLAC) placebo and DAPA on hepatocellular lipid (HCL) reduction after 24 weeks of treatment. MATERIALS AND METHODS Thirty patients with type 2 diabetes were randomized to weekly EXE and daily DAPA (n = 16) or weekly PLAC and daily DAPA (n = 14). Inclusion criteria were glycated haemoglobin (HbA1c) 48 to 97 mmol/mol (6.5-11%), age 18 to 75 years, body mass index (BMI) ≥25 kg/m2 and metformin ≥1000 mg. The primary endpoint, HCL levels, were measured at baseline and after 24 weeks of treatment using magnetic resonance spectroscopy. Between-group effects were analysed using general linear models, adjusted for baseline outcome variables, age, sex and BMI. Within-group differences were assessed using a paired t-test. RESULTS After 24 weeks, HCLs were reduced in both treatment groups (absolute change from baseline: EXE + DAPA -4.4%, 95% confidence interval [CI] -8.2, -0.7, P

Summary Background Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed. Methods Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL‑C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL‑C goal while receiving stabilized LLT was assessed. Results A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL‑C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently. Conclusion The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases.

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.

Die vorliegende Leitlinie nimmt Bezug auf die Indikation und praktische Umsetzung der Insulintherapie bei Typ 2 Diabetes, insbesondere auch im Hinblick auf die unterschiedlichen Formen der Insulintherapie.

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.

Rauchen und Passivrauchen erhohen Diabetesinzidenz und Wahrscheinlichkeit fur Spatschaden deutlich. Rauchstopp kann zu Gewichtszunahme und erhohtem Diabetesrisiko fuhren, senkt aber trotzdem kardiovaskulare und Gesamtmortalitat. Eine Basisdiagnostik (Fagerstrom-Test, exhalatorisches CO) ist die Grundlage einer erfolgreichen Raucherentwohnung. An medikamentoser Unterstutzung stehen Varenicline, Nikotinersatztherapie und Bupropion zur Verfugung. Soziookonomische und psychische Faktoren spielen fur Rauchen und Rauchstopp eine wichtige Rolle. Moderater Alkoholkonsum senkt moglicherweise Diabetes- und kardiovaskulares Risiko. Selektionsbias und falsche Angaben konnten in Studien allerdings diese Wirkungen zu optimistisch erscheinen lassen. Dem steht ein dosisabhangiges Mehr an Krankheit und gesundheitlich eingeschrankten Lebensjahren gegenuber, v. a. durch Krebs, Lebererkrankungen und Infektionen.

Introduction Lixisenatide has been studied extensively in randomized clinical trials; however, data on its use in the real-life practice are scarce. Methods This study was a prospective, 26-week, multicenter, observational study conducted in Austrian diabetes centers and office-based practices to evaluate efficacy and safety of lixisenatide under real-life conditions in patients with type 2 diabetes. Results Out of 144 patients (mean BMI 36.4 kg/m2, disease duration 12.4 years), 113 completed the documentation at 6 months and 42% received basal insulin with or without oral antidiabetic drugs. The HbA1c declined from 8.7% (72 mmol/mol) to 7.9% (63 mmol/mol) and at study end 24.8% of the patients reached an HbA1c level below 7%. Fasting and postprandial glucose after lixisenatide administration were reduced by 27 ± 58 mg/dl and 45 ± 67 mg/dl, respectively. At study end body weight (− 4.5 ± 5.4 kg), triglycerides (− 10.8 ± 105 mg/dl), systolic blood pressure (− 4.8 ± 17.1 mmHg), and LDL cholesterol (− 3.7 ± 25 mg/dl) were reduced. The most commonly reported adverse events were gastrointestinal disorders (18.8%). Forty-three patients (30%) discontinued prematurely, mostly caused by lack of efficacy, occurrence of gastrointestinal disorders, and missing reimbursement. The average dose of insulin decreased slightly by 1.5 units (from 29.4 to 27.9). Conclusion Lixisenatide demonstrated a similar efficacy and safety profile under real-life conditions as previously shown in randomized clinical trials. Funding sanofi-aventis GmbH Austria.

Aims To investigate the potential synergistic effects of combined exenatide (EXE) and dapagliflozin (DAPA) versus (PLAC) placebo and DAPA on hepatocellular lipid (HCL) reduction after 24 weeks of treatment. Materials and methods Thirty patients with type 2 diabetes were randomized to weekly EXE and daily DAPA (n = 16) or weekly PLAC and daily DAPA (n = 14). Inclusion criteria were glycated haemoglobin (HbA1c) 48 to 97 mmol/mol (6.5‐11%), age 18 to 75 years, body mass index (BMI) ≥25 kg/m2 and metformin ≥1000 mg. The primary endpoint, HCL levels, were measured at baseline and after 24 weeks of treatment using magnetic resonance spectroscopy. Between‐group effects were analysed using general linear models, adjusted for baseline outcome variables, age, sex and BMI. Within‐group differences were assessed using a paired t‐test. Results After 24 weeks, HCLs were reduced in both treatment groups (absolute change from baseline: EXE + DAPA −4.4%, 95% confidence interval [CI] −8.2, −0.7, P

ObjectivesAim of this study was to examine trends over time in smoking status in men and women, and in subgroups, in Austria, a country with poor smoking regulation policies.Design and participantsTwo cross-sectional surveys (Austrian Health Interview Surveys for 2007 and 2014), each with more than 15 000 participants from the general population, aged ≥15 years.Outcome measuresPrevalence of self-reported daily smoking. ORs for daily smoking in subgroups, presented as results of logistic regression models, adjusted for sociodemographic variables and presence of chronic diseases.ResultsPrevalence of daily cigarette smoking was 26.0% for men in both years, and increased from 19.1% to 22.0% (pConclusionsThere has been a remarkable increase in smoking prevalence over the 7-year period in women in Austria, especially for those with chronic diseases, higher age, lower education and a migration background. Better political and clinical efforts are needed to reduce the high tobacco use in Austria.

IntroductionInhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI.MethodsPET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls.ResultsMTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; pSGLT2i, the lower was the glycated hemoglobin level 3 months after therapy initiation.ConclusionMTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2 weeks after therapy with SGLT2i begins. GRP in T2DMSGLT2i was associated with better long-term glycemic response 3 months after initiation of therapy.Trial registration numberNCT03557138.

OBJECTIVE The objective of this study was to evaluate the efficacy and safety of the dual sodium–glucose cotransporter 1 and 2 inhibitor sotagliflozin compared with placebo when combined with optimized insulin in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS In a double-blind, 52-week, international phase 3 trial, adults with T1D were randomized to placebo (n = 258) or once-daily oral sotagliflozin 200 mg (n = 261) or 400 mg (n = 263) after 6 weeks of insulin optimization. The primary outcome was change in HbA1c from baseline to 24 weeks. The first secondary end point was a composite of the proportion of patients with HbA1c RESULTS At 24 weeks, placebo-adjusted changes in HbA1c from baseline (7.8%) were −0.37% and −0.35% with sotagliflozin 200 and 400 mg, respectively (P < 0.001), and differences were maintained at 52 weeks. At 52 weeks, greater proportions of sotagliflozin-treated patients (200 mg: 25.67%; 400 mg: 26.62%) than placebo-treated patients (14.34%; P ≤ 0.001) met the composite end point, and sotagliflozin 400 mg reduced fasting plasma glucose (−0.87 mmol/L; P = 0.008), weight (−2.92 kg; P < 0.001), and total daily insulin dose (−8.2%; P = 0.001). In a 24-week continuous glucose monitoring (CGM) substudy, postprandial glucose decreased (P ≤ 0.009) and CGM demonstrated up to 3 h more time in the target range of 3.9–10.0 mmol/L with sotagliflozin. Treatment satisfaction increased and diabetes distress decreased with sotagliflozin (P < 0.05 vs. placebo). The frequency of documented hypoglycemia was lower with sotagliflozin, and severe hypoglycemia occurred by week 52 in 13 patients (5.0%), 13 patients (5.0%), and 6 patients (2.3%) treated with placebo and sotagliflozin 200 and 400 mg, respectively. DKA occurred in 0 of 258 patients, 6 of 261 patients (2.3%), and 9 of 263 patients (3.4%) in these respective groups. CONCLUSIONS In a 1-year study, sotagliflozin was associated with statistically significant HbA1c reductions. More episodes of DKA and fewer episodes of documented and severe hypoglycemia were observed in patients using sotagliflozin relative to those receiving placebo (ClinicalTrials.gov, NCT02421510).

INTRODUCTION: To assess the impact of duration of type 2 diabetes on glucose-lowering effectiveness of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin versus sulfonylureas (SUs) in a real-life setting. METHODS: Data were extracted from the large 1-year, observational EDGE study (N = 45,868). Patients receiving either DPP-4 inhibitor or any SU as add-on to monotherapy were selected (N = 36,164). Impact of the disease duration on change in glycated hemoglobin (HbA1c) levels was evaluated by using a linear multiple regression model. Descriptive statistics assessed the proportion of patients achieving the composite endpoint (HbA1c

PurposeTo report on the global quality of life (QOL) in people living with HIV (PLWHIV) and how a smoking cessation intervention influences the changes in QOL.MethodsParticipants were asked to fill out a questionnaire during visits to their HIV outpatient clinic consisting of sociodemographic information, general health data and the WHOQOL HIV-Bref. Exhaled carbon monoxide measurements were used to confirm the smoking status, based on which participants classified as smokers received a short 5 min structured intervention and were offered participation in a full smoking cessation programme consisting of five sessions. Follow-up was done 8 months after the baseline.ResultsOverall 447 (mean age = 45.5) participants took part with 221 being classified as smokers. A total of 165 (74.6%) participants received a short intervention and 63 (29.4%) agreed to participate in the full program. At baseline, differences in QoL were observed, where smokers had lower QoL in domains of physical (M = 16.1 vs. 15.3,p = 0.009) and psychological (M = 15.3 vs. 14.6,p = 0.021) well-being, independency level (M = 16.1 vs. 15.2,p = 0.003) and environment (M = 16.5 vs. 16.0,p = 0.036). At study end, 27 (12.2%) participants quit smoking; 12 (19.0%) participants of the full programme and 15 (14.7%) that received the short intervention. There were no significant differences in QoL between those that continued to smoke and quitters at follow-up.ConclusionQuality of life results may be used to better understand the underlying motivation of PLWHIV who start cessation programs. In order to reduce the high prevalence and health burden that smoking causes in PLWHIV, it is necessary to introduce effective interventions that can be used in the clinical settings.

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.

Smoking and second-hand smoke strongly increase incidence of diabetes and probability for its complications. Smoking cessation can lead to weight gain and increased diabetes risk; however, it decreases cardiovascular and total mortality. A basal diagnostics (Fagerström Test, exhaled CO) is the basis for successful smoking cessation. Supporting medication include Varenicline, Nicotine Replacement Therapy and Bupropion. Socio-economic as well as psychological factors play an important role for smoking and smoking cessation.Moderate consumption of alcohol possibly decreases risk for diabetes and cardiovascular diseases. Selection bias and underreporting in studies maybe contribute to a too optimistic view. On the other hand, alcohol increases in a dose dependant fashion excess morbidity and disability adjusted life years, especially by cancer, liver diseases and infections.

The heterogenous catagory "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e. g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART)), genetic forms of diabetes (e. g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down Syndrome, Klinefelter Syndrome, Turner Syndrome), pancreatogenic diabetes (e. g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

Objectives/Background Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels. Methods 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proBNP levels were studied by stratifying and through interaction analysis. Results During a median follow-up of 60 months, the primary endpoint occurred in 522 (26%) of patients. The median age was 63 years. A Cox regression analysis was adjusted for site of treatment, concomitant medication, age, gender, body mass index, glycated haemoglobin, duration of diabetes, glomerular filtration rate, cholesterol, and history of smoking and cardiac disease. Metformin was associated with a decreased risk in the cohort with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014) and a similar association was found for the interaction between metformin and NT-proBNP (p=0.001). There was neither an association for sulfonylureas nor a significant interaction between sulfonylureas and NT-proBNP. Conclusions Metformin is associated with beneficial cardiovascular outcomes in patients with diabetes only when (sub)clinical cardiovascular risk defined by NT-proBNP levels is present.

Introduction Traditional risk factors for cardiovascular diseases have been shown to have an even higher impact in the HIV infected population. Cardiovascular risk factors amongst people living with HIV treated in doctor's offices in Austria have not been documented before. Our study aimed to close this gap, focusing on dyslipidemia, diabetes mellitus and diabetes risk. Patients and methods After ethics approval, consecutive patients who visited their treating physicians for routine checks were enrolled. The lipid profile was assessed by measuring total cholesterol, triglycerides, HDL and apolipoprotein B and calculating LDL and non-HDL-cholesterol. The diabetes risk was calculated by measuring insulin and blood glucose levels and assessing insulin resistance and beta cell function using the HOMA-IR model. Results 522 patients were included in the analysis. 90.2% of the participants were on antiretroviral therapy. Two third had an impaired lipid profile, but dyslipidemia had been diagnosed only in 46.3% of the patients. There was a clear correlation between protease inhibitor use and pathologic blood lipids. Of the persons with dyslipidemia, 18.4% received lipid lowering drugs. 8 persons (1.6%) fulfilled the criteria for diabetes mellitus. Of those, 4 patients already had a diagnosed diabetes mellitus. 50.1% of the study participants showed an increased insulin resistance. Patients on nucleoside reverse transcriptase inhibitors had significantly higher markers for impaired glucose metabolism. Discussion We found a high percentage of increased insulin resistance, of impaired lipid profile and in contrast to this a low treatment rate with lipid lowering drugs in this cohort of people living with HIV.

Aim Posttransplantation diabetes mellitus (PTDM) is a common complication after renal transplantation leading to increased cardiovascular morbidity and mortality. In subjects with type 2 diabetes (T2DM) increased glycemic variability and poor glycemic control have been associated with cardiovascular complications. We therefore aimed at determining glycemic variability and glycemic control in subjects with PTDM in comparison to T2DM subjects. Methods In this observational study we analyzed 10 transplanted subjects without diabetes (Control), 10 transplanted subjects with PTDM, and 8 non-transplanted T2DM subjects using Continuous Glucose Monitoring (CGM). Several indices of glycemic control quality and variability were computed. Results Many indices of both glycemic control quality and variability were different between control and PTDM subjects, with worse values in PTDM. The indices of glycemic control, such as glucose mean, GRADE and M-value, were similar in PTDM and T2DM, but some indices of glycemic variability, that is CONGA, lability index and shape index, showed a markedly higher (i.e., worse) value in T2DM than in PTDM ( P value range: 0.001–0.035). Conclusions Although PTDM and T2DM subjects showed similar glycemic control quality, glycemic variability was significantly higher in T2DM. These data underscore potential important pathophysiological differences between T2DM and PTDM indicating that increased glycemic variability may not be a key factor for the excess cardiovascular mortality in patients with PTDM.

Sotagliflozin (SOTA) is a dual SGLT1 and SGLT2 inhibitor in development as adjunct therapy to insulin in T1D. In this double-blind, 52-week study, 782 adults with T1D treated with multiple daily insulin injections or pump therapy were randomized 1:1:1 to placebo (n=258), SOTA 200 mg (n=261) or SOTA 400 mg (n=263) once daily after 6 weeks of insulin optimization. Primary endpoint was change from baseline in A1C at Week 24. Other endpoints included A1C, documented hypoglycemia (DH), weight and FPG change at Week 52, patient (pt) reported outcomes (PROs) and net clinical benefit (NCB), assessing the proportion of pts with A1C Baseline characteristics were similar between groups. Compared with placebo, treatment with SOTA 200 or 400 mg improved A1C and pt satisfaction at Week 24 and reduced A1C, DH rate, weight, FPG and pt distress at Week 52 (Table). More pts achieved NCB in the SOTA arms vs. placebo (Table). Pts receiving SOTA 400 mg had the least SH events, but more genital mycotic infections, DKA and diarrhea than placebo. In conclusion, SOTA 200 and 400 mg were associated with statistically significant A1C reductions that were sustained (P Efficacy (mITT population) and Safety (safety population) ResultsPlacebo n=258SOTA 200 mg n=261SOTA 400 mg n=263Mean A1C at Baseline, after 6-week insulin optimization, %7.797.747.71Outcomes at Week 24A1C LSM difference from placebo, % ± SE (P-value)--0.37±0.(P Disclosure T. Danne: Speaker's Bureau; Self; A. Menarini Diagnostics. Advisory Panel; Self; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Dexcom, Inc.. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; DreaMed Diabetes, Ltd.. Research Support; Self; Insulet Corporation. Speaker's Bureau; Self; Menarini Group. B. Cariou: Board Member; Self; Amgen Inc.. Consultant; Self; Genfit. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Sanofi-Aventis, Regeneron Pharmaceuticals, Inc. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. M. Brandle: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Novo Nordisk Foundation. Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. H. Brath: Speaker's Bureau; Self; Abbott. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc., Pfizer Inc.. Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH. Board Member; Self; Austrian Diabetes Association. E. Franek: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Bristol-Myers Squibb Company, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Servier. J.A. Kushner: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc.. Consultant; Self; KNOW Foods, Inc. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc., Merck & Co., Inc. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. A.L. Peters: Advisory Panel; Self; Abbott, Bigfoot Biomedical. Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Eli Lilly and Company, Insulin Algorithms, JDRF, Lexicon Pharmaceuticals, Inc., Livongo Health. Research Support; Self; MannKind Corporation. Other Relationship; Self; Medscape. Advisory Panel; Self; Merck & Co., Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Omada Health, Inc., Optum Rx, Inc., Sanofi. Research Support; Self; T1D Exchange. Advisory Panel; Self; The Endocrine Society. Research Support; Self; The Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Spouse/Partner; Johnson & Johnson Diabetes Institute, LLC. S. Sawhney: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc., AstraZeneca, Pfizer Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation. P. Strumph: Employee; Self; Lexicon Pharmaceuticals, Inc.. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.. Board Member; Self; College Diabetes Network.

The objective of this study was to evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 and 2 inhibitor sotagliflozin compared with placebo when combined with optimized insulin in adults with type 1 diabetes (T1D).In a double-blind, 52-week, international phase 3 trial, adults with T1D were randomized to placebo (At 24 weeks, placebo-adjusted changes in HbAIn a 1-year study, sotagliflozin was associated with statistically significant HbA

The aim of this post hoc analysis of data from the Austrian subpopulation of the EDGE study was the evaluation of the effectiveness and tolerability of vildagliptin as an add-on to an existing oral antidiabetic (OAD) monotherapy versus a combination therapy with two OADs without vildagliptin in patients with inadequately controlled type 2 diabetes.In Austria, 422 patients were included. In the framework of regular visits (at baseline, about once per quarter, and at the study end, after 12 months), adverse events (AEs), courses, and changes of therapy were recorded. In addition to the primary end point defined in the primary study, i.e., a reduction of HbA1c by 0.3 % without hypoglycemia, weight gain ≥ 5 %, peripheral edema, or discontinuation due to gastrointestinal events, the most clinically relevant secondary end point, i.e., HbA1c reduction 7 % without hypoglycemia or ≥ 3 % increase in body weight after 12 months was used for the analysis of the Austrian data.The initial HbA1c of all enrolled patients was 8.3 ± 1.4 %. The mean reduction of HbA1c was - 1.1 % in the vildagliptin cohort and - 1.0 % in the comparator cohort. In the vildagliptin cohort, 56.4 % of patients, and in the comparator cohort, 45.9 % of patients, reached the primary end point (odds ratio: 1.53, p = 0.04). In the vildagliptin cohort, 18.7 % of patients, and in the comparator cohort, 16.9 % of patients, reached the secondary end point (odds ratio: 1.13, p = 0.68). The incidence of hypoglycemic events (two in each cohort), AEs (approximately 15 % in each cohort), and serious AEs (approximately 2 % in each cohort) was comparable between the two groups.In a "real-life" setting, the effectiveness of vildagliptin as second-line treatment is superior to comparator OADs with regard to a reduction in HbA1c of greater than 0.3 % from baseline without well-recognized side effects in patients with inadequately controlled type 2 diabetes (mean baseline HbA1c: 8.5 % (vildagliptin cohort) vs. 8.1 % (comparator cohort)).

Background/Aims: Diabetes mellitus type 2 (DMT2) is accompanied by systemic low-grade inflammation with elevated levels of interleukin-6 (IL-6), which is encoded by a gene (IL-6) previously shown to be regulated by DNA methylation. We investigated seven CpG sites in IL-6 in individuals with DMT2, obese individuals and lean controls. Further, the DMT2 group received the glucagon-like peptide 1 agonist liraglutide. Methods: Blood samples were taken at the beginning of the study and after 4 months. The DNA methylation was assessed using pyrosequencing. Results: Methylation levels at the CpG sites -664, -628 and +13 at the first sampling time point (T1) and at -666 and -664 at the second sampling time point (T2) correlated negatively with initial body weight in the DMT2 group. We found positive correlations for the obese and the lean control group. In the obese group, CpG +27 methylation at T1 correlated with initial body weight (r = 0.685; p = 0.014). In the lean group, CpG -664 at T1 (r = 0.874; p = 0.005) and CpG -628 at T2 (r = 0.632; p = 0.050) correlated with initial body weight. Conclusion: These findings are an informative basis for further studies to elucidate epigenetic mechanisms underlying DMT2. Additionally, our results might provide starting points for the development of biomarkers for prevention and therapy strategies.

Aims The current study aims to investigate practicability and effects of a combined dietary intervention with increased relative protein content supplemented with omega-3 polyunsaturated fatty acids (PUFA) on metabolic control and inflammatory parameters in a real life situation in type 2 diabetes patients. Methods In this observational study we advised thirty mostly obese patients with type 2 diabetes to follow a protein-enriched diet with carbohydrates of low glycemic index (low GI) and moderate fat reduction supplemented with omega-3 PUFA for 24 weeks. Primary efficacy parameter was the change in HbA1c; secondary parameters included changes in systemic inflammation (measured by ultrasensitive C-reactive protein, usCRP), body weight, waist circumference, fat mass. The study is registered at clinicaltrials.gov (NCT01474603). Results The dietary intervention significantly reduced the primary efficacy variable HbA1c from a baseline value of 63±11mmol/mol to 59±14mmol/mol ( P =0.033) and 56±12mmol/mol ( P =0.001) after 12 and 24 weeks, respectively. In addition, usCRP decreased significantly at 24 weeks ( P =0.039). Waist circumference, an important indicator for cardiometabolic-risk and silent inflammation, decreased from baseline 116.0±14.1cm to 114.9±13.5cm ( P =0.019), 114.0±14.4cm ( P =0.001), and 112.7±13.4cm ( P =0.049), after 3, 12 and 24 weeks, respectively. Conclusion Counseling a protein enriched and low glycemic index diet supplemented with long-chain omega-3 PUFA in a real-life clinical setting improves glycemic control and also reduces waist circumference and silent inflammation in overweight or obese patients with type 2 diabetes.

SCOPE Oxidative imbalance plays a key role in cancer induction and cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to find out if gallic acid (GA) prevents oxidative stress in diabetic patients. Therefore, we investigate its impact on oxidation of DNA bases and on other health-related macromolecules. METHODS AND RESULTS We perform an intervention study (n = 19) with GA and monitored alterations of the DNA stability in single cell gel electrophoresis (SCGE) assays in lymphocytes. Furthermore, a panel of health-related biomarkers is measured before and after consumption of GA (15 mg p-1 d-1 ) for 7 d. Significant reduction of oxidized purines (by 31%, p

Diabetes Mellitus type 2 (DM2) is associated with increased cancer risk. Instability of the genetic material plays a key role in the aetiology of human cancer. This study aimed to analyse genomic instability with the micronucleus cytome assay in exfoliated buccal cells depending on glycated haemoglobin (HbA1c) levels and medication in 146 female DM2 patients. The occurrence of micronuclei was significantly increased in DM2 patients compared to healthy controls. Furthermore, it was doubled in DM2 patients with HbA1c > 7.5% compared to subjects with HbA1c ≤ 7.5%. Positive correlations were found between micronuclei frequencies and HbA1c as well as fasting plasma glucose. Patients under insulin treatment showed a two-fold increase in micronuclei frequencies compared to subjects under first-line medication (no drugs or monotherapy with non-insulin medication). However, after separation of HbA1c (cut-off 7.5%) only patients with severe DM2 characterised by high HbA1c and insulin treatment showed higher micronuclei frequencies but not patients with insulin treatment and low HbA1c. We demonstrated that the severity of DM2 accompanied by elevated micronuclei frequencies predict a possible enhanced cancer risk among female DM2 patients. Therapy, therefore, should focus on a strict HbA1c control and personalised medical treatments.

AimIn this post hoc analysis of the EDGE study, we assessed the effectiveness and safety of vildagliptin versus other oral antidiabetes drugs (OADs) as add-on to first-line sulphonylurea (SU) therapy in patients who did not receive metformin in a real-life setting.MethodsThe primary endpoint was odds of achieving an HbA1c reduction of >0.3% without tolerability issues. Secondary endpoint was odds of achieving HbA1c

This study aimed to compare the frequencies of nuclear anomalies in buccal cells between diabetic and non-diabetic individuals and to assess the impact of a 'healthy diet'-a cornerstone in the treatment of diabetes. Seventy-six diabetic and 21 non-diabetic individuals participated in this parallel, randomised, intervention trial. All participants received information about the importance of a healthy diet, while participants randomly assigned to the intervention group received additionally 300g of vegetables and 25ml of plant oil rich in polyunsaturated fatty acids (PUFA) per day for 8 weeks. Cytogenetic damage in buccal cells was assessed at baseline and after 8 weeks using the buccal micronucleus cytome assay. Micronucleus (MN) frequency at baseline was significantly higher in participants with diabetes (0.58±0.30‰) compared with non-diabetic individuals (0.28±0.29‰). Further analysis of baseline data revealed significantly higher MN levels in participants of the highest tertile of waist circumference (+40%), fasting plasma glucose (+55%), glycated haemoglobin (+41%) and cardiovascular disease risk (+39%) relative to participants of the lowest tertile. The dietary intervention had no effect on MN frequencies. Glycated haemoglobin and biomarkers reflecting cytokinetic defect or acute cell death were reduced in both the intervention and 'information only' groups. The results of this study suggest a strong impact of abdominal obesity and glucose metabolism on genomic stability. Similar effects on nuclear anomalies were observed in the 'information only' group and the intervention group receiving vegetables and PUFA-rich plant oil.

Objectives: The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro–B-type natriuretic peptide (NT-proBNP).Backgro...

Aim Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale ‘pragmatic’ trials. Methods EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA1c > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA1c

Aims The aim of the present study was to evaluate a mobile health (mHealth) based remote medication adherence measurement system (mAMS) in elderly patients with increased cardiovascular risk treated for diabetes, high cholesterol and hypertension. Cardiovascular risk was defined as the presence of at least two out of the three risk factors: type 2 diabetes, hypercholesterolaemia and hypertension.

cope Type 2 diabetes is a multifactorial disease associated with increased oxidative stress, which may lead to increased DNA damage. The aim of this study was to investigate the effect of a healthy diet on DNA oxidation in diabetics and nondiabetics. Methods and results Seventy-six diabetic and 21 nondiabetic individuals participated in this study. All subjects received information about the benefits of a healthy diet, while subjects randomly assigned to the intervention group received additionally 300 g of vegetables and 25 mL PUFA-rich plant oil per day. DNA damage in mononuclear cells (Comet Assay), urinary excretion of 8-oxo-7-hydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and glycated hemoglobin (HbA1c) were measured at baseline, after 4, 8 (end of intervention), and 16 weeks. The intervention with vegetables and PUFA-rich oil led to a significant increase in plasma antioxidant concentrations. Diabetic individuals of the intervention group showed a significant reduction in HbA1c and DNA strand breaks. Levels of HbA1c were also improved in diabetics of the information group, but oxidative damage to DNA was not altered. Urinary 8-oxodG and 8-oxoGuo excretion remained unchanged in both groups. Conclusions This study provides evidence that a healthy diet rich in antioxidants reduces levels of DNA strand breaks in diabetic individuals.

BACKGROUND Diabetes has been linked epidemiologically to increased cancer incidence and mortality. Growth differentiation factor 15 (GDF-15) is increased in patients with diabetes and has recently been linked to the occurrence of cancer. We investigated whether circulating GDF-15 concentrations can predict the incidence of malignant diseases in a diabetic patient cohort already facing increased risk for cancer. METHODS We prospectively enrolled a total of 919 patients with type 2 diabetes and no history of malignant disease, who were clinically followed up for 60 months. GDF-15, N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline; an additional 4 cardiovascular biomarkers were determined for a subpopulation (n = 259). Study end point was defined as the first diagnosis of any type of cancer during the follow-up period. RESULTS During a median follow-up of 60 months, 66 patients (7.2%) were diagnosed with cancer. Baseline circulating GDF-15 concentrations were higher in patients that developed cancer over the follow-up period when compared to cancer-free patients. Increased GDF-15 concentrations were significantly associated with cancer incidence [crude hazard ratio (HR) per 1-IQR (interquartile range) increase 2.13, 95% CI 1.53–2.97, P < 0.001]. This effect persisted after multivariate adjustment with an adjusted HR of 1.86 (95% CI 1.22–2.84; P = 0.004). Among the 4 additionally tested cardiovascular markers in the subpopulation, only troponin T and C-terminal proendothelin-1 showed a significant association with future cancer incidence with unadjusted HRs of 1.71 (95% CI 1.28–2.28, P < 0.001) and 1.68 (95% CI 1.02–2.76, P = 0.042), respectively. CONCLUSIONS Increased circulating concentrations of GDF-15 are associated with increased cancer incidence in patients with type 2 diabetes.

Between 5 and 10% of the European population suffers from diabetes, and its prevalence is constantly rising, in Austria like in other countries. The main goals in the treatment of diabetes mellitus are the prevention of complications and organ damage, the prevention of severe hypo- and hyperglycaemia and the preservation of quality of life. Many patients with type 2 diabetes become insulin-dependent in the course of their disease. The application of a long acting insulin or insulin analogue is the simplest way of initiating an insulin therapy and is in accordance with current guidelines. Current scientific evidence shows that the use of long acting insulin analogues for type 2 diabetes; which can no longer be sufficiently controlled with oral antidiabetic agents, is simple, safe and efficacious. Thus, this treatment option should be available without any restrictions to physicians and patients in order to facilitate the beginning of an insulin regime. This position paper summarises up the current evidence concerning this subject.

Diabetes mellitus type 2 (DMT2) is accompanied by systemic low-grade inflammation with elevated levels of interleukin-6 (IL-6), which is encoded by a gene (IL-6) previously shown to be regulated by DNA methylation. We investigated seven CpG sites in IL-6 in individuals with DMT2, obese individuals and lean controls. Further, the DMT2 group received the glucagon-like peptide 1 agonist liraglutide.Blood samples were taken at the beginning of the study and after 4 months. The DNA methylation was assessed using pyrosequencing.Methylation levels at the CpG sites -664, -628 and +13 at the first sampling time point (T1) and at -666 and -664 at the second sampling time point (T2) correlated negatively with initial body weight in the DMT2 group. We found positive correlations for the obese and the lean control group. In the obese group, CpG +27 methylation at T1 correlated with initial body weight (r = 0.685; p = 0.014). In the lean group, CpG -664 at T1 (r = 0.874; p = 0.005) and CpG -628 at T2 (r = 0.632; p = 0.050) correlated with initial body weight.These findings are an informative basis for further studies to elucidate epigenetic mechanisms underlying DMT2. Additionally, our results might provide starting points for the development of biomarkers for prevention and therapy strategies.

Background Diabetes mellitus type 2 (DM2) is associated with increased oxidative stress and oxidative damage to DNA. An appropriate intake of antioxidants via the diet can improve this disturbed oxidative status [1]. Apples are the most widely consumed fruits in Europe and represent a major source of antioxidants due to their high polyphenol content [2]. Apple pomace as a polyphenol-rich byproduct of apple juice production could serve as a cheap and reliable tool for a nutraceutical with antioxidative properties.

Metabolic syndrome is associated with alterations in the structure of the gut microbiota leading to low-grade inflammatory responses. An increased penetration of the impaired gut membrane by bacterial components is believed to induce this inflammation, possibly involving epigenetic alteration of inflammatory molecules such as Toll-like receptors (TLRs). We evaluated changes of the gut microbiota and epigenetic DNA methylation of TLR2 and TLR4 in three groups of subjects: type 2 diabetics under glucagon-like peptide-1 agonist therapy, obese individuals without established insulin resistance, and a lean control group. Clostridium cluster IV, Clostridium cluster XIVa, lactic acid bacteria, Faecalibacterium prausnitzii and Bacteroidetes abundances were analysed by PCR and 454 high-throughput sequencing. The epigenetic methylation in the regulatory region of TLR4 and TLR2 was analysed using bisulfite conversion and pyrosequencing. We observed a significantly higher ratio of Firmicutes/ Bacteroidetes in type 2 diabetics compared to lean controls and obese. Major differences were shown in lactic acid bacteria, with the highest abundance in type 2 diabetics, followed by obese and lean participants. In comparison, F. prausnitzii was least abundant in type 2 diabetics, and most abundant in lean controls. Methylation analysis of four CpGs in the first exon of TLR4 showed significantly lower methylation in obese individuals, but no significant difference between type 2 diabetics and lean controls. Methylation of seven CpGs in the promoter region of TLR2 was significantly lower in type 2 diabetics compared to obese subjects and lean controls. The methylation levels of both TLRs were significantly correlated with body mass index. Our data suggest that changes in gut microbiota and thus cell wall components are involved in the epigenetic regulation of inflammatory reactions. An improved diet targeted to induce gut microbial balance and in the following even epigenetic changes of pro-inflammatory genes may be effective in the prevention of metabolic syndrome.

Background Low adiponectin levels are discussed as risk factor for cardiovascular events. This is of special importance in individuals with type 2 diabetes (T2DM) because they are at higher risk for cardiovascular diseases. The present study aimed to investigate the effect of two plant oils rich in polyunsaturated fatty acids (PUFA), with different content of omega-3 fatty acids, on adiponectin levels, glucose and lipid metabolism in T2DM individuals treated either with insulin or oral anti-diabetics (OAD). Methods Ninety-two subjects with T2DM [34 treated with insulin (T2DM-Ins) and 58 treated with OAD (T2DM-OAD)] participated in this randomised, double-blind, parallel intervention study. Individuals received either 9 g of nut oil (n-3:n-6 ratio: 1.3 : 6.1) or mixed oil (n-3:n-6 ratio: 0.6 : 5.7) per day for 10 weeks. The fatty acid profile, tocopherol, adiponectin levels and parameters regarding glucose and lipid metabolism were assessed at baseline, during and after the intervention. Results Compliance was confirmed by significant increases in γ-tocopherol and PUFA in both oil groups. An increase in adiponectin levels in T2DM-Ins participants (+6.84% in nut oil and +4.47% in mixed oil group after 10 weeks compared to baseline) was observed, albeit not significantly different from T2DM-OAD individuals (P = 0.051). Lipid and glucose metabolism were not affected by the intervention. Conclusions The present study provides evidence that a small and easy change in dietary behaviour towards better fat quality moderately increases adiponectin levels in T2DM-Ins subjects, independently of the administered plant oil.