https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.29367

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

Coronary artery disease (CAD) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. This process can be modified by lifestyle adjustments, pharmacological therapies, and invasive interventions designed to achieve disease stabilization or regression. The disease can have long, stable periods but can also become unstable at any time, typically due to an acute atherothrombotic event caused by plaque rupture or erosion. However, the disease is chronic, most often progressive, and hence serious, even in clinically apparently silent periods. The dynamic nature of the CAD process results in various clinical presentations, which can be conveniently categorized as either acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). The Guidelines presented here refer to the management of patients with CCS. The natural history of CCS is illustrated in Figure 1.

/pdf/2019-esc-guidelines-for-the-diagnosis-and-management-of-5b7mv2v506.pdf

2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes.

2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

A correction has been published: European Heart Journal, ehaa895, https://doi.org/10.1093/eurheartj/ehaa895

2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Mechanisms for insulin resistance: common threads and missing links.

Metabolic diseases such as type 2 diabetes (T2D) are linked to the development of fatty liver, steatohepatitis and liver fibrosis. We have previously described novel clusters of patients at risk for T2D. Three clusters (3, 5 and 6) either had a high risk to progress to T2D or to develop cardiorenal complications. While high-risk clusters differ in liver fat content, it remains unknown if they also harbor a different risk for hepatic fibrosis. Thus, we determined clinically applicable scores of liver fibrosis in 1115 subjects at risk for T2D from the TUEF/TULIP study, which were categorized into high-risk clusters (n=602). Liver fat content was determined by 1H-magnetic resonance spectroscopy. The AST-to-platelet-ratio index (APRI), fibrosis-4 score (FIB-4) and NAFLD fibrosis score (NFS) were used to determine fibrosis risk. ANCOVA model analysis adjusted for liver fat content was performed. Of the high-risk clusters (3: n= 83, 5: n= 203, 6: n= 316), cluster 6 had the highest BMI 44.1±9.7 kg/m² (vs. cluster 3: 29.7±3.1 kg/m², p<0.001 and cluster 5: 42.8.0±8.7, p=0.32) and cluster 5 had the highest liver fat content (13.4±8.8% vs. cluster 3: 8.0±6.5, p<0.001 and cluster 6: 9.0±6.7, p<0.001). All fibrosis scores correlated with liver fat content (e.g. FIB-4: r= 0.45, p< 0.0001). Although FIB-4, APRI and NFS were generally low, they were highest in cluster 5, but despite highest liver fat content, they did not differ from cluster 3 and 6 (e.g. FIB-4: cluster 5: 0.19±0.45 vs. cluster 3: 0.14±0.01, p=0.59 and cluster 6: 0.12±0.15, p=0.39). Interestingly, cluster 3 with the lowest liver fat content exhibited higher FIB-4 compared to cluster 6 (p=0.02). According to clinically applicable scores, the most insulin resistant cluster 5 has the highest FIB-4 score. The insulin deficient cluster 3 has a relatively high FIB-4 score despite relatively low liver fat content and BMI. Further studies are needed to investigate the clinical relevance of these findings.
 
 
 V.Minelli faiao: None. A.Peter: None. A.L.Birkenfeld: None. N.Stefan: Advisory Panel; Pfizer Inc., Research Support; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. R.Jumpertz von schwartzenberg: Other Relationship; Sanofi, Amgen Inc., Lilly, Novo Nordisk. A.Sandforth: None. S.Katzenstein: None. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. L.Fritsche: None. J.Machann: None. F.Schick: None. H.Häring: None. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi.


96-OR: Liver Fibrosis Scores in Novel Subclusters of Patients at Risk for Type 2 Diabetes

Der Begriff Prädiabetes beschreibt einen erhöhten, jedoch noch nicht im diabetischen Bereich liegenden Nüchternblutzuckerspiegel, einen erhöhten Blutzuckerspiegel nach 120 min in einem standardmäßig mit 75 g Glukose durchgeführten oralen Glukosetoleranztest oder beides. In die Definition der American Diabetes Association fließt zusätzlich das glykierte Hämoglobin A (HbA1c) ein. Die Häufigkeit des Prädiabetes nimmt stark zu. Die Progression von einer normalen Glukosetoleranz zu einem Diabetes ist ein kontinuierlicher Vorgang. Insulinresistenz und Insulinsekretionsstörung, deren gleichzeitiges Vorliegen den manifesten Diabetes charakterisiert, sind schon im prädiabetischen Stadium vorhanden. Der Prädiabetes geht mit einem erhöhten Diabetesrisiko einher; allerdings entwickeln bei Weitem nicht alle Menschen mit Prädiabetes einen Diabetes. Dennoch bleibt allein die Feststellung eines erhöhten Diabetesrisikos insofern relevant, als sie die Ergreifung von Maßnahmen zur Diabetesprävention erfordert. Als effektivste Strategie zur Behandlung des Prädiabetes hat sich eine strukturierte Lebensstilintervention erwiesen. Um deren Effizienz zu erhöhen, sollte sie möglichst ausschließlich denjenigen Menschen zur Verfügung gestellt werden, welche die größten Chancen haben, davon zu profitieren. Dazu müssten Menschen mit Prädiabetes nach ihrem Risikoprofil stratifiziert werden. In einer Population von Menschen mit erhöhtem Diabetesrisiko (Tübinger Diabetes-Familien-Studie) wurde eine Clusteranalyse vorgenommen, die 6 Cluster/Untergruppen ergab. Darunter wurden 3 Hochrisikountergruppen identifiziert. Zwei davon zeigen eine überwiegende Insulinsekretionsstörung bzw. überwiegende Insulinresistenz und ein hohes Diabetes- und kardiovaskuläres Risiko. Die dritte Gruppe weist ein hohes Nephropathierisiko und eine hohe Mortalität, aber ein relativ betrachtet niedrigeres Diabetesrisiko auf. Einen Prädiabetes kann man insgesamt noch nicht gezielt pathophysiologisch orientiert behandeln. Die neue – auf der Pathophysiologie basierende – Einteilung des Prädiabetes eröffnet nun neue Wege für die Diabetesprävention. Aktuell laufende und zukünftige Studien sollen die Annahme bestätigen, dass die Wirksamkeit etablierter bzw. noch nicht etablierter Präventionsmaßnahmen abhängig von der jeweiligen Untergruppe ist. 

Prädiabetes als therapeutische Herausforderung in der Inneren Medizin

Background Physical activity is a cornerstone in the prevention and treatment of type 2 diabetes and metformin is a first-line oral glucose-lowering drug. There is clinical evidence that health beneficial effects of exercise, like improvement of insulin sensitivity or increase in muscle mass, are blunted or even antagonized under metformin therapy. However, skeletal muscle has been poorly investigated in this context from a molecular perspective. 

Structural changes in human myotubes lead to impaired human myotube contractility under metformin treatment

Network targeted brain stimulation improves task performance in participants with overweight and obesity

Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-β1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover.

/pdf/extracellular-matrix-expression-in-human-pancreatic-fat-3ma2xek8.pdf

Andreas L. Birkenfeld

Papers

96-OR: Liver Fibrosis Scores in Novel Subclusters of Patients at Risk for Type 2 Diabetes

Prädiabetes als therapeutische Herausforderung in der Inneren Medizin

Structural changes in human myotubes lead to impaired human myotube contractility under metformin treatment

Network targeted brain stimulation improves task performance in participants with overweight and obesity

Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes