Heparanase is the predominant enzyme that cleaves heparan sulfate, the main polysaccharide in the extracellular matrix. While the role of heparanase in sustaining the pathology of autoimmune... Show moreHeparanase is the predominant enzyme that cleaves heparan sulfate, the main polysaccharide in the extracellular matrix. While the role of heparanase in sustaining the pathology of autoimmune diabetes is well documented, its association with metabolic syndrome/type 2 diabetes attracted less attention. Our research was undertaken to elucidate the significance of heparanase in impaired glucose metabolism in metabolic syndrome and early type 2 diabetes. Here, we report that heparanase exerts opposite effects in insulin-producing (i.e., islets) vs. insulin-target (i.e., skeletal muscle) compartments, sustaining or hampering proper regulation of glucose homeostasis depending on the site of action. We observed that the enzyme promotes macrophage infiltration into islets in a murine model of metabolic syndrome, and fosters beta-cell-damaging properties of macrophages activated in vitro by components of diabetogenic/obese milieu (i.e., fatty acids). On the other hand, in skeletal muscle (prototypic insulin-target tissue), heparanase is essential to ensure insulin sensitivity. Thus, despite a deleterious effect of heparanase on macrophage infiltration in islets, the enzyme appears to have beneficial role in glucose homeostasis in metabolic syndrome. The dichotomic action of the enzyme in the maintenance of glycemic control should be taken into account when considering heparanase-targeting strategies for the treatment of diabetes. Show less
Huang, Z.L.; Lum, E.; Jimenez, G.; Semwal, M.; Sloot, P.; Car, J. 2019
BackgroundSmartphone apps are becoming increasingly popular for supporting diabetes self-management. A key aspect of diabetes self-management is appropriate medication-taking. This study aims to... Show moreBackgroundSmartphone apps are becoming increasingly popular for supporting diabetes self-management. A key aspect of diabetes self-management is appropriate medication-taking. This study aims to systematically assess and characterise the medication management features in diabetes self-management apps and their congruence with best-practice evidence-based criteria.MethodsThe Google Play and Apple app stores were searched in June 2018 using diabetes-related terms in the English language. Apps with both medication and blood glucose management features were downloaded and evaluated against assessment criteria derived from international medication management and diabetes guidelines.ResultsOur search yielded 3369 Android and 1799 iOS potentially relevant apps; of which, 143 apps (81 Android, 62 iOS) met inclusion criteria and were downloaded and assessed. Over half 58.0% (83/143) of the apps had a medication reminder feature; 16.8% (24/143) had a feature to review medication adherence; 39.9% (57/143) allowed entry of medication-taking instructions; 5.6% (8/143) provided information about medication; and 4.2% (6/143) displayed motivational messages to encourage medication-taking. Only two apps prompted users on the use of complementary medicine. Issues such as limited medication logging capacity, faulty reminder features, unclear medication adherence assessment, and visually distracting excessive advertising were observed during app assessments.ConclusionsA large proportion of diabetes self-management apps lacked features for enhancing medication adherence and safety. More emphasis should be given to the design of medication management features in diabetes apps to improve their alignment to evidence-based best practice. Show less
Deseive, S.; Straub, R.; Kupke, M.; Broersen, A.; Kitslaar, P.H.; Stocker, T.J.; ... ; Hausleiter, J. 2019
Background: To investigate the impact of diabetes on coronary artery total plaque volume (TPV) and adverse events in long-term follow-up.Methods: One-hundred-and-eight diabetic patients were... Show moreBackground: To investigate the impact of diabetes on coronary artery total plaque volume (TPV) and adverse events in long-term follow-up.Methods: One-hundred-and-eight diabetic patients were matched to 324 non-diabetic patients, with respect to age, sex, body-mass index, hypertension, smoking habits, LDL and HDL cholesterol, family history for CAD as well as aspirin and statin medication. In all patients, TPV was quantified from coronary CT angiographies (CTA) using dedicated software. All-cause mortality, acute coronary syndrome and late revascularisation ( > 90 days) served as combined endpoint.Results: Patients were followed for 5.6 years. The endpoint occurred in 18 (16.7%) diabetic and 26 (8.0%) nondiabetic patients (odds ratio 2.3, p = 0.03). Diabetic patients had significantly higher TPV than non-diabetic patients (55.1 mm 3 [IQR: 6.2 and 220.4 mm(3)] vs. 24.9 mm 3 [IQR: 0 and 166.7 mm(3)], p = 0.02). A TPV threshold of 110.5 mm(3) provided good separation of diabetic and non-diabetic patients at higher and lower risk for adverse events. Noteworthy, diabetic and non-diabetic patients with a TPV < 110.5 mm(3) had comparable outcome (hazard ratio: 1.3, p = 0.59), while diabetic patients with TPV > 110.5 mm(3) had significantly higher incidence of adverse events (hazard ratio 2.3, p = 0.03) compared to non-diabetic patients with TPV > 110.5 mm(3). There was incremental prognostic value in diabetic and non-diabetic patients over the Framingham Risk Score (Integrated Discrimination Improvement: 0.052 and 0.012, p for both < 0.05).Conclusion: Diabetes is associated with significantly higher TPV, which is independent of other CAD risk factors. Quantification of TPV improves the identification of diabetic patients at higher risk for future adverse events. Show less
Staels, W.; Verdonck, Y.; Heremans, Y.; Leuckx, G.; Groef, S. de; Heirman, C.; ... ; Leu, N. de 2018
Conclusions: The incidence of AITD among T1D patients is high, but stable among all ages and independent of diabetes duration. (C) 2016 Elsevier Inc. All rights reserved.
Background and purpose: The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment... Show moreBackground and purpose: The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome.Material and methods: A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS).Results: No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2 years; p = 0.01) and PFS (58% versus 37% at 2 years and a median PFS of 41 months versus 15 months; p = 0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p = 0.02 and 0.03).Conclusions: Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial. (C) 2016 Elsevier Ireland Ltd. All rights reserved. Show less
Berg, R. van den; Mook-Kanamori, D.O.; Donga, E.; Dijk, M. van; Dijk, J.G. van; Lammers, G.J.; ... ; Biermasz, N.R. 2016
