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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.

ZusammenfassungZu Diabetestechnologien abseits von Insulinpumpen und Glukosesensoren zählen Verfahren, welche einerseits das Diabetesselbstmanagement und andererseits die medizinische Betreuung, therapeutische Anpassungen und Schulungen durch Diabetesfachpersonen unterstützen. Diabetes-Apps sind in einer großen Anzahl und Vielfalt in den App-Stores für unterschiedliche Systeme verfügbar. Die Funktionalitäten variieren, und nur einige Apps bringen im klinischen Alltag einen Mehrwert im Sinne einer automatisierten Insulindokumentation (in Verbindung mit Smartpens), Insulindosiskalkulation oder Bereitstellung therapierelevanter Informationen bezüglich der Mahlzeitenzusammensetzung. Die seit kurzem am Markt verfügbaren Smartpens entsprechen grundsätzlich konventionellen, wiederbefüllbaren Insulinpens, sind jedoch um die Möglichkeit, die Dosis und den Zeitpunkt einer Insulingabe zu speichern, erweitert. Die dokumentierten Insulinabgaben ermöglichen in Zusammenschau mit den Glukosewerten eine detailliertere Analyse mit Darstellung und Objektivierung von Optimierungspotenzialen. Eine weitere Unterstützung für Menschen mit Diabetes stellen Apps mit hinterlegten Mahlzeitendatenbanken und der Möglichkeit der Mahlzeitendokumentation dar, die auch in der Adipositastherapie verwendet werden. Die technologische Weiterentwicklung der Kamerasysteme und Sensoren von Smartphones führen zudem zu immer genaueren Möglichkeiten einer automatisierten Erkennung der Mahlzeitenzusammensetzung. Bei all der Euphorie über die zunehmenden und mannigfaltigen Möglichkeiten neuer Diabetestechnologien muss der Fokus weiterhin auf deren Bedienungsfreundlichkeit und Anwendbarkeit durch eine möglichst große Anzahl von Personen mit Diabetes gerichtet bleiben. Ebenso muss der Umgang mit durch Apps erhobenen Gesundheitsdaten und cloudbasierten Anwendungen die regulatorischen Standards und damit den Schutz des Individuums erfüllen und v. a. akzeptieren.

Aim To cluster adults with diabetes using variables from real-world clinical care at manifestation. Materials and Methods We applied hierarchical clustering using Ward's method to 56 869 adults documented in the prospective Diabetes Follow-up Registry (DPV). Clustering variables included age, sex, body mass index (BMI), HbA1c, diabetic ketoacidosis (DKA), components of the metabolic syndrome (hypertension/dyslipidaemia/hyperuricaemia) and beta-cell antibody status. Time until use of oral antidiabetic drugs (OADs), use of insulin, chronic kidney disease (CKD), cardiovascular disease (CVD), retinopathy or neuropathy were assessed using Kaplan–Meier analysis and Cox regression models. Results We identified eight clusters: four clusters comprised early diabetes onset (median age 40-50 years) but differed with regard to BMI, HbA1c, DKA and antibody positivity. Two clusters included adults with diabetes onset aged in their early 60s who met target HbA1c, but differed in BMI and sex distribution. Two clusters were characterized by late diabetes onset (median age 69 and 77 years) and comparatively low BMI, but differences in HbA1c. Earlier insulin use was observed in adults with high HbA1c, and earlier OAD use was observed in those with high BMI. Time until CKD or CVD was shorter in those with late onset, whereas retinopathy occurred earlier in adults with late onset and high HbA1c, and in adults with early onset, but high HbA1c and high percentage of antibody positivity. Conclusions Adult diabetes is heterogeneous beyond classical type 1/type 2 diabetes, based on easily available variables in clinical practice using an automated clustering algorithm that allows both continuous and binary variables.

Zusammenfassung100 Jahre nach Einführung der Insulintherapie haben sich durch pharmakologische Weiterentwicklung der Insuline mit vielfältigen Wirkdauern, aber auch Veränderungen der Applikations- und Messmöglichkeiten, die angewendeten Insulintherapien insbesondere in den letzten 20 Jahren stark verändert, hin zu einer häufigeren Anwendung von Insulinanaloga, insbesondere bei Patienten mit T1DM 1. Bei Typ-2-DM ergibt sich mit unterschiedlichen Strategien der Insulintherapie auch in Kombination mit oralen Antidiabetika für die Patienten ein breites Spektrum an Formen der Insulintherapie. Durch die verschiedenen Applikationsformen und Insuline zeigt sich eine kleine, aber signifikante Verbesserung der Blutzuckereinstellung, aber vor allem eine Individualisierung der Diabetestherapie.

To assess the prevalence of elevated liver enzymes and associated diabetes-related comorbidities in type 2 diabetes (T2D).Between 2010 and 2019, 281 245 patients with T2D (aged 18-75 years) from 501 Diabetes Prospective Follow-up (DPV) centres were evaluated, resulting in analysis of 51 645 patients with complete data on demographics and liver enzymes.Elevated liver enzymes were found in 40.2% of all patients. However, only 8.6% of these patients had International Classification of Diseases-10 codes for nonalcoholic fatty liver disease and/or nonalcoholic steatohepatitis. Adjusted for age, sex, diabetes duration, body mass index and glycated haemoglobin, a higher prevalence of arterial hypertension (P 0.0001), dyslipidaemia (P 0.0001), peripheral artery disease (P = 0.0029), myocardial infarction (P = 0.0003), coronary artery disease (P = 0.0001), microalbuminuria (P 0.0001) and chronic kidney disease (P 0.0001) was seen in patients with elevated versus normal liver enzymes. The prevalence of elevated liver enzymes was lowest in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors or a combination of SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists.Elevated liver enzymes are common in patients with T2D and clearly correlate with a higher prevalence of clinically relevant comorbidities. Assessing liver enzymes should be standard clinical routine in T2D due to a possible predictive role for comorbidities and complications.

This is a single-center prospective cohort study including 199 consecutive patients with T2D, PAD (mean age 62.3 ± 7.2 years; 62.8% males), and preoperative CACS and CCTA undergoing PFA and followed-up over 1 year.Over a period of 1 year follow-up, a total of 35 (17.6%) participants died. The area under ROC curve to predict mortality for the CACS was 0.835 (95% CI:0.769-0.900), for CCTA 0.858 (95% CI:0.788-0.927). After adjustment for confounders, compared to no-stenosis on CCTA (reference), the risk of all-cause mortality in non-obstructive coronary atery disease (CAD) increased (HR = 1.38, 95% CI [0.75-12.86],ip/i= .284), 1-vessel obstructive CAD (HR = 8.13, 95% CI [0.87-75.88],ip/i= .066), 2-vessels (HR = 10.94, 95% CI [1.03-115.8],ip/i= .047), and 3-vessels (HR = 45.73, 95% CI [4.6-454.7],ip/i= .001) respectively. Increasing levels of CACS tended to be associated with increased risk of all-cause mortality (HR = 1.002, 95% CI [1.0-1.003],ip/i= .061). 61/95 patients with obstructive CAD underwent coronary revascularization.Coronary artery calcium score and CCTA have a high predictive value for 1-year all-cause mortality in T2D patients undergoing minor amputations and may be considered for preoperative risk assessment allowing timely preventive interventions.

T helper 9 cells (TH9) are key drivers of allergic tissue inflammation. They are characterized by the expression of type 2 cytokines, such as IL-9 and IL-13, and the peroxisome proliferator-activated receptor gamma (PPAR-γ) transcription factor. However, the functional role of PPAR-γ in human TH9 cells remains unknown. Here, we demonstrate that PPAR-γ drives activation-induced glycolysis, which, in turn, specifically promotes the expression of IL-9, but not IL-13, in an mTORC1-dependent manner. In vitro and ex vivo experiments on skin samples of allergic contact dermatitis showed that the PPAR-γ-mTORC1-IL-9 pathway was active in TH9 cells in human skin inflammation. Additionally, we found that tissue glucose levels were dynamically regulated in acute allergic skin inflammation, suggesting that in situ glucose availability is linked to distinct immunological signals in vivo. Furthermore, paracrine IL-9 induced the lactate transporter MCT1 in IL-9R+ TH cells, where it increased aerobic glycolysis and proliferative capacity. Taken together, our findings delineate a hitherto unknown relationship between PPAR-γ-dependent glucose metabolism and the pathogenic effector function of human TH9 cells.Graphical abstract

Aim: To develop a non-invasive machine learning (ML) approach to detect hypoglycemia during real car driving based on driving (CAN) , and eye and head motion (EHM) data. Methods: We logged CAN and EHM data in 21 subjects with type 1 diabetes (18 male, 41 ± yrs, A1c 6.8 ± 0.7 % [51 ± 7 mmol/mol]) during driving in eu- (EU) and hypoglycemia (< 3.0 mmol/L, HYPO) . Participants drove in a car (Volkswagen Touran) supervised by a driving instructor on a closed test-track. Using CAN and EHM data, we built ML models to predict the probability of the driver being in HYPO. To make our approach applicable to different generations of cars, we present 3 ML models: first, a model combining CAN+EHM, representing the modern car with integrated camera. Second, a CAN model using driving data only, since modern cars are not generally equipped with EHM tracking. Third, anticipating that autonomous driving will limit the role of CAN data in the future, we tested a model solely based on EHM. Results: Mean BG in EU and HYPO was 6.3 ± 0.8 mmol/L and 2.5 ± 0.5 mmol/L (p< 0.001) , respectively. The model CAN+EHM achieved an area under the receiver operating characteristic curve of 0.88 ± 0.05, sensitivity of 0.70 ± 0.30, and specificity of 0.83 ± 0.in detecting HYPO. Further results are in Fig. 1. Conclusion: We propose ML-based approaches to non-invasively detect HYPO from driver behavior, applicable to contemporary cars and anticipating developments in automotive technology. Disclosure V.Lehmann: None. E.Fleisch: None. T.Kowatsch: Advisory Panel; Pathmate Technologies AG, Research Support; CSS Insurance, Stock/Shareholder; Pathmate Technologies AG. S.N.Lagger: None. M.Laimer: None. F.Wortmann: None. C.Stettler: None. T.Zueger: None. M.Maritsch: None. M.Notter: None. S.Schallmoser: None. C.Bérubé: None. C.Albrecht: None. M.Kraus: None. S.Feuerriegel: None. Funding Swiss National Science Foundation (SNF CRSII5_183569) , Swiss Diabetes Foundation, Diabetes Center Berne, Automobile Club Switzerland (ACS) , Federal Department of Defence, Civil Protection and Sport (DDPS) and Department of Research of the University Hospital Berne

Diagnosis, Prevention and Treatment of Cardiovascular Disease in People with Diabetes and Prediabetes Abstract. Diabetes is associated with an increased cardiovascular risk. In addition to optimizing glycemia, timely diagnosis and stringent control of cardiovascular risk factors is essential for individuals with diabetes. Therapeutic options include lifestyle-optimization, individualized drug therapy and targeted treatment of concomitant or secondary cardiovascular disease. Cardiovascular disease occurs more often in individuals with diabetes and includes heart failure, atrial fibrillation, coronary heart disease and sudden cardiac death. The correct choice of antidiabetic drugs and interventions can control cardiovascular risk factors, reduce cardiovascular risk and treat concomitant or secondary diseases in a targeted manner. This review is intended to provide guidance on diagnosis, treatment and choice of therapy for individuals with type 2 diabetes without and with concomitant or secondary cardiovascular disease.

Zusammenfassung. Mit dem künstlichen Pankreas (auch closed-loop-System genannt) wird der jahrzehntelange Traum einer automatisierten Insulindosierung Realität. Das System steuert die subkutane Insulinzufuhr automatisch anhand eines Kontrollalgorithmus, der Bezug nimmt auf die aktuelle Glukosekonzentration. Closed-loop-Systeme werden seit 2011 bei Patienten mit Typ-1-Diabetes in klinischen Studien getestet. Dabei konnten gegenüber der konventionellen Pumpentherapie deutliche Reduktionen von Über- und Unterzuckerungen sowie eine geringere Blutzuckervariabilität erreicht werden. Im Jahre 2016 wurde das erste hybrid-closed-loop-System zur Therapie des Typ-1-Diabetes von den amerikanischen Behörden zugelassen. Hybrid-closed-loop-Systeme arbeiten noch nicht vollautomatisch. Nutzer müssen bei der Insulindosierung für Mahlzeiten und Korrekturen aktiv mitwirken. Herausforderungen wie der verzögerte Wirkungseintritt subkutan verabreichten Insulins und das Tragen einer Vielzahl medizinischer Geräte am Körper bleiben weiterhin bestehen. Die folgende Übersichtsarbeit illustriert den aktuellen Stand der Entwicklung von closed-loop-Systemen in der Diabetestherapie. Dabei wird auf das Therapie-Konzept, die einzelnen technischen Komponenten, die Evidenzlage sowie auf heute oder in naher Zukunft verfügbare Systeme eingegangen.

Objective To estimate the prevalence of diabetes due to diseases of the exocrine pancreas (DEP) using data of the multicentre diabetes patient follow-up registry. Moreover, we aimed at comparing individuals with diabetes due to DEP to individuals with type 1 and type 2 diabetes. Methods Individuals with DEP, type 1 or type 2 diabetes ≥18 years of age were studied. We aggregated the most recent treatment year per patient and used propensity scores to match diabetes due to DEP to type 1 and type 2 diabetes. Matching was conducted one-to-one with sex, age, diabetes duration, migration background and the German index of socioeconomic deprivation as covariates. Results We identified 7,093 (1.6%) individuals with diabetes due to DEP. In the matched cohort DEP-type 1 diabetes we observed a similar daily insulin dose (0.62 IU/kg (95% confidence interval:0.60–0.63), 0.60 IU/kg (0.58–0.62)) and significant differences regarding microvascular (41.0% (39.7–42.2), 45.3% (44.0–46.6)), and macrovascular disease (16.6% (15.7–17.6), 14.7% (13.8–15.6)). HbA1c (8.2% (8.1–8.3), 7.9% (7.8–8.0)), daily insulin dose (0.60 IU/kg (0.58–0.62), 0.56 IU/kg (0.54–0.58)) and event rates of severe hypoglycemia (23.9 events/100 PY (21.4–26.8), (9.5 events/100 PY (8.0–11.2)) were significantly higher in individuals with diabetes due to DEP compared to type 2 diabetes. Conclusions Using registry data, rare diabetes types such as diabetes due to DEP can be studied with a significant sample size. Our study identified differences and similarities between adult individuals with DEP related diabetes and type 1 or type 2 diabetes.

Summary Background Bariatric surgery is a treatment option for patients with severe obesity and improves parameters of cardiovascular and/or metabolic disease. Carotid intima media thickness (C-IMT) is a surrogate measure of subclinical atherosclerosis. Previous studies showed short to mid-term arrest and even regression of C‑IMT progression following bariatric surgery. We aimed to investigate the long-term effect of weight loss on C‑IMT progression 10 years after bariatric surgery in comparison to a population-based control cohort. Methods In total, 21 eligible patients were examined preoperatively, at 5 and 10 years after bariatric surgery. Anthropometric parameters, plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), insulin, and glucose were assessed at all three study visits. C‑IMT was measured via B‑mode scans of the common carotid artery. C‑IMT progression was measured in an age-matched and BMI-matched cohort selected from the population-based Bruneck study to compare with changes in C‑IMT progression after bariatric surgery. Results C‑IMT remained stable over the 10-year observation period after bariatric surgery. The control cohort showed a significant C‑IMT progression over 10 years. The difference in C‑IMT progression over 10 years was significant (p Conclusion Weight loss induced by bariatric surgery halts the natural progression of C‑IMT over a 10-year observation period.

Das kunstliche Pankreas (auch Closed-loop-System genannt) bringt uns dem jahrzehntelangen Traum einer automatisierten Insulindosierung einen Schritt naher. Das System steuert die subkutane Insulinzufuhr mit einem Kontrollalgorithmus entsprechend der Glukosekonzentration. Die Studienlage zeigt, dass damit die Blutzuckerkontrolle und Lebensqualitat Betroffener deutlich verbessert werden konnen. Vollautomatische Closed-loop-Systeme sind jedoch noch nicht erhaltlich. Patienten mussen bei der Insulindosierung fur Mahlzeiten und Korrekturen zusatzlich aktiv mitwirken. Die folgende Ubersichtsarbeit zeigt den aktuellen Entwicklungsstand des kunstlichen Pankreas in der Diabetestherapie auf.

Aims To examine the association of frozen shoulder (FS) with demographic and diabetes-related outcomes in individuals with type 1 (T1D) or type 2 (T2D) diabetes aged ≥30 years. Materials and methods Multivariable logistic regression models, adjusted for demographics were used to calculate the proportion of FS in association with age, gender, diabetes duration, body mass index (BMI), haemoglobin A1C (HbA1c) and diabetes treatment. Results The unadjusted percentage of FS was higher in T1D compared to T2D (0.22% vs. 0.06%). In T1D, adjusted regression models revealed higher prevalence of FS in women than men (0.26 [0.20–0.34] % vs. 0.15 [0.11–0.21] %, p=0.010). No significant relationship of age and BMI with FS was found in both diabetes types. Longer diabetes duration was associated with a higher proportion of FS in T1D (p7% was related to a higher proportion of FS compared to HbA1c ≤7% (0.25 [0.19–0.32] vs. 0.12 [0.08–0.20] %, p=0.007), while an inverse relationship was found in T2D (HbA1c ≤7%: 0.08 [0.07–0.10] vs. HbA1c >7%: 0.05 [0.04–0.06] %, p=0.001). Conclusions Different associations of FS with gender and HbA1c were observed for T1D and T2D; however, longer diabetes duration increases the risk for FS independent of diabetes type. Musculoskeletal diseases are still underreported in individuals with diabetes and awareness should be raised for FS as a specific diabetes complication.

OBJECTIVE To investigate temporal trends and contemporary use of insulin pump therapy and glucose monitoring in type 1 diabetes. RESEARCH DESIGN AND METHODS In a population-based study, we analyzed the use of insulin pump therapy, continuous glucose monitoring (CGM), and self-monitoring of blood glucose (SMBG) from 1995 to 2017 in patients with type 1 diabetes identified from the Diabetes Prospective Follow-up (DPV) database in Germany and Austria. Patients were stratified by age, sex, migration background, and country. RESULTS Among 96,547 patients with type 1 diabetes (median age 17.9 years, 53% males), the percentage using insulin pump therapy increased from 1% in 1995 to 53% in 2017, with the highest rates in the youngest patients (92% in preschoolers, 74% in children, 56% in adolescents aged CONCLUSIONS Since 1995, insulin pump use has continuously increased, and insulin pump therapy is now standard in patients aged

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes, based on current evidence.

Diagnosis, Prevention and Treatment of Cardiovascular Disease in People with Diabetes and Prediabetes

Background: Awareness of fatty liver disease in people with diabetes is low and reliable epidemiological data on diabetes and liver enzymes are scarce. This population-based analysis of the DPV database assessed the prevalence of elevated liver enzymes and associated diabetes related comorbidities in type 2 diabetes (T2D). Methods: This analysis comprises 281,245 patients with T2D between the age of 18 and 75 years from 501 diabetes centers from January 2010 until December 2019. Among these, complete demographic and concomitant data on liver enzymes were available in a total of 51,645 patients. Findings: Elevated liver enzymes were found in 40·2% of all patients. In contrast, only 8·6% of these patients were ICD-10 coded as nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH), respectively. After adjustment for age, sex, diabetes duration, BMI, and HbA1c, a higher prevalence of arterial hypertension (p

Aims To analyse time-trends in BMI, obesity and cardiometabolic risk in adults with type 1 diabetes (T1DM) from the Diabetes Prospective Follow-up registry DPV. Methods Data from 62,519 individuals with T1DM (age ≥ 18 years, BMI ≥ 18.5 kg/m2) were analysed. Multivariable regression models were used to determine time-trends in BMI, obesity and cardiometabolic risk and to identify predictors for increasing BMI. Results were compared to the NCD Risk Factor Collaboration (NCD-RisC) data for Germany. Results Between 1999 and 2018 mean BMI increased from 25.0 kg/m2 to 26.2 kg/m2 in individuals with T1DM. This trend was most pronounced in young and middle-aged individuals (>21–55 years of age) and in those with higher baseline BMI. Insulin dose and diabetes duration were associated with increasing BMI. Between 1999 and 2016, the prevalence of obesity increased 1.8-fold in individuals with T1DM and 1.4-fold among the German population, respectively (NCD-RisC). Approximately 50–70% of individuals with obesity were insufficiently treated for hypertension and/or dyslipidaemia. Conclusion In adults with T1DM the prevalence of obesity is increasing at a faster pace than in the German population. BMI needs to be closely monitored, particularly during young adulthood, and cardiovascular risk factors need to be controlled better to prevent CVD and premature death.

OBJECTIVE While the adjustment of insulin is an established strategy to reduce the risk of exercise-associated hypoglycemia for individuals with type 1 diabetes, it is not easily feasible for those treated with ultra-long-acting basal insulin. The current study determined whether pre-exercise intake of fructose attenuates the risk of exercise-induced hypoglycemia in individuals with type 1 diabetes using insulin degludec. RESEARCH DESIGN AND METHODS Fourteen male adults with type 1 diabetes completed two 60-min aerobic cycling sessions with or without prior intake (30 min) of 20 g of fructose, in a randomized two-period crossover design. Exercise was performed in the morning in a fasted state without prior insulin reduction and after 48 h of standardized diet. The primary outcome was time to hypoglycemia (plasma glucose ≤3.9 mmol/L) during exercise. RESULTS Intake of fructose resulted in one hypoglycemic event at 60 min compared with six hypoglycemic events at 27.5 ± 9.4 min of exercise in the control condition, translating into a risk reduction of 87.8% (hazard ratio 0.12 [95% CI 0.02, 0.66]; P = 0.015). Mean plasma glucose during exercise was 7.3 ± 1.4 mmol/L with fructose and 5.5 ± 1.1 mmol/L in the control group (P < 0.001). Lactate levels were higher at rest in the 30 min following fructose intake (P < 0.001) but were not significantly different from the control group during exercise (P = 0.32). Substrate oxidation during exercise did not significantly differ between the conditions (P = 0.73 for carbohydrate and P = 0.48 for fat oxidation). Fructose was well tolerated. CONCLUSIONS Pre-exercise intake of fructose is an easily feasible, effective, and well-tolerated strategy to alleviate the risk of exercise-induced hypoglycemia while avoiding hyperglycemia in individuals with type 1 diabetes on ultra-long-acting insulin.

Background White coat adherence (WCA) is defined as an increased adherence to treatment regimens directly before a visit with a healthcare provider. Little is known on the effect of WCA on glucose control in adult patients with diabetes mellitus. Methods The present study is based on 618 CGM-observations of 276 patients with diabetes treated between January 2013 and July 2018. The analysis compares data from the 3 days prior to a visit (p1) with the preceding 25 days (p2). Results Sensor use was higher during p1 than p2 (92.8±7.3% vs 88.8±7.5%; p 7% [53mmol/mol]. Conclusion This study reveals a WCA effect on pre-visit glucose control in adult patients with diabetes. The effect was most pronounced in patients with moderate to poor glycemic control. In these patients, analysis of CGM data should encompass a minimum of 1 to 2 weeks prior to a consultation., Diabetes Research and Clinical Practice, 168

Diabetes is a proinflammatory and prothrombotic condition that increases the risk of vascular complications. The aim of this study was to develop a diabetic microvascular flow model that allows to study the complex interactions between endothelial cells, blood cells and plasma proteins and their effects on clot formation. Primary human cardiac microvascular endothelial cells from donors without diabetes or donors with diabetes (type 1 or type 2) were grown in a microfluidic chip, perfused with non-diabetic or diabetic whole blood, and clot formation was assessed by measuring fibrin deposition in real time by confocal microscopy. Clot formation in non-diabetic whole blood was significantly increased in the presence of endothelial cells from donors with type 2 diabetes compared with cells from donors without diabetes. There was no significant difference in clot formation between non-diabetic and diabetic whole blood. We present for the first time a diabetic microvascular flow model as a new tool to study clot formation as a result of the complex interactions between endothelial cells, blood cells and plasma proteins in a diabetes setting. We show that endothelial cells affect clot formation in whole blood, attributing an important role to the endothelium in the development of atherothrombotic complications.

Background The prevalence of patients with concomitant cardiovascular disease and diabetes mellitus (DM) is increasing rapidly. We aimed to compare the effectiveness of current cardiac rehabilitation (CR) programs across seven European countries between elderly cardiac patients with and without DM. Methods 1633 acute and chronic coronary artery disease (CAD) patients and patients after valve intervention with an age 65 or above who participated in comprehensive CR (3 weeks to 3 months, depending on centre) were included. Peak oxygen uptake (VO2 peak), body mass index, resting systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), and glycated haemoglobin (HbA1c) were assessed before start of CR, at termination of CR (variable time point), and 12 months after start of CR, with no intervention after CR. Baseline values and changes from baseline to 12-month follow-up were compared between patients with and without DM using mixed models, and mortality and hospitalisation rates using logistic regression. Results 430 (26.3%) patients had DM. Patients with DM had more body fat, lower educational level, more comorbidities, cardiovascular risk factors, and more advanced CAD. Both groups increased their VO2 peak over the study period but with a significantly lower improvement from baseline to follow-up in patients with DM. In the DM group, change in HbA1c was associated with weight change but not with change in absolute VO2 peak. 12-month cardiac mortality was higher in patients with DM. Conclusions While immediate improvements in VO2 peak after CR in elderly patients with and without DM were similar, 12-month maintenance of this improvement was inferior in patients with DM, possibly related to disease progression. Glycemic control was less favourable in diabetic patients needing insulin in the short- and long-term. Since glycemic control was only related to weight loss but not to increase in exercise capacity, this highlights the importance of weight loss in obese DM patients during CR. Trial registration NTR5306 at trialregister.nl; trial registered 07/16/2015; https://www.trialregister.nl/trial/5166