Νέα μέθοδος αντιμετώπισης των χρόνιων διαβητικών ελκών, βασισμένη στη θεραπεία με RGTA matrix: μία τυχαιοποιημένη, ελεγχόμενη μελέτη

Τα έλκη αποτελούν συχνή επιπλοκή του σακχαρώδους διαβήτη (ΣΔ). Τα διαβητικά έλκη χαρακτηρίζονται από αυξημένη δραστηριότητα πρωτεϊνών που διασπούν την εξωκυττάρια θεμέλια ουσία (ΕΘΟ) και δυσχεραίνουν την επούλωση. Τα matrix therapy regenerating agents (RGTA) (CACIPLIQ) είναι χημικά κατασκευασμένα πολυμερή που έχουν σχεδιαστεί ειδικά για να αντικαταστήσουν τη θειική ηπαράνη στα έλκη και έτσι να μιμούνται τη δράση της, προστατεύοντας τις πρωτεΐνες της ΕΘΟ από την αποδόμηση. Στόχος της παρούσας εργασίας ήταν η αξιολόγηση της αποτελεσματικότητας και της ασφάλειας χορήγησης CACIPLIQ σε χρόνια διαβητικά έλκη. Στη μελέτη συμπεριλήφθηκαν 27 ασθενείς με ΣΔ και ενεργό νευροπαθητικό έλκος άκρου ποδός που είχε διάρκεια >6 εβδομάδες. Η μελέτης διήρκησε 16 εβδομάδες και η πρώτη επίσκεψη πραγματοποιήθηκε 2 εβδομάδες πριν την έναρξη της παρέμβασης, ενώ η τελευταία επίσκεψη πραγματοποιήθηκε 4 εβδομάδες μετά το τέλος της παρέμβασης. Συνολικά 13 άτομα τυχαιοποιήθηκαν στην ομάδα που αντιμετωπίσθηκε με τη συνήθη αγωγή και 14 άτομα στην ομάδα που έλαβε επιπλέον CACIPLIQ με τη μορφή εναιωρήματος. Οι ασθενείς των δυο ομάδων δεν διέφεραν σημαντικά ως προς τα δημογραφικά, τα κλινικά και τα εργαστηριακά χαρακτηριστικά τους στην έναρξη της μελέτης. Δεν παρατηρήθηκε σημαντική διαφορά μεταξύ των δυο ομάδων στο πρωτογενές καταληκτικό σημείο που αφορούσε τον αριθμό των ελκών με > 80% μείωση στο μέγεθος του έλκους 10 εβδομάδες μετά τη χορήγηση του εξεταζόμενου φαρμάκου (P = 0.936). Επίσης, δεν παρατηρήθηκε σημαντική διαφορά στα δευτερογενή καταληκτικά σημεία, συμπεριλαμβανομένου και των ανεπιθύμητων συμβαμάτων. Συμπερασματικά, η προσθήκη CACIPLIQ στην καθιερωμένη αγωγή σε νευροπαθητικά έλκη ατόμων με ΣΔ δεν επηρεάζει σημαντικά την έκβαση των ελκών σε σύγκριση με τη συνήθη αγωγή.Ulcers are a common complication of diabetes mellitus (DM). In diabetic ulcers, there is increased activity of proteins that disrupt the extracellular matrix (ECM) and impair wound healing. Matrix therapy regenerating agents (RGTA) (CACIPLIQ) are chemically formulated polymers specifically designed to replace heparin sulfate in ulcers and thereby mimic its action by protecting ECM proteins. The aim of this study was to evaluate the efficacy and safety of CACIPLIQ in chronic neuropathic diabetic ulcers. A total of 27 patients with DM and active foot neuropathic ulcer lasting >6 weeks were recruited. The duration of the study was 16 weeks; the first visit was 2 weeks before the intervention and the last visit was 4 weeks after the end of the intervention. A total of 13 of these patients were randomized to standard care and 14 to CACIPLIQ via spraying as add on standard care. The patients of the two groups did not differ significantly in their demographic, clinical and laboratory characteristics at baseline. No significant difference was found between the two groups regarding the primary endpoint (number of ulcers with >80% reduction in ulcer size 10 weeks after administration of CACIPLIQ) (P = 0.936). Additionally, there was no statistically significant difference in secondary endpoints, including adverse events. In conclusion, the addition of CACIPLIQ to standard wound care in neuropathic diabetic foot ulcers does not impact wound healing in comparison with the standard wound care

SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects

Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the latest class of antidiabetic medication that inhibit the absorption of glucose from the proximal tubule of the kidney and hence cause glycosuria. Four SGLT2i are currently commercially available in many countries: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT2i reduce glycated hemoglobin by 0.5%–1.0% and have shown favorable effects on body weight, blood pressure, lipid profile, arterial stiffness and endothelial function. More importantly, SGLT2i have demonstrated impressive cardioprotective and renoprotective effects. The main mechanisms underlying their cardioprotective effects have been attributed to improvement in cardiac cell metabolism, improvement in ventricular loading conditions, inhibition of the Na+/H+ exchange in the myocardial cells, alteration in adipokines and cytokines production, as well as reduction of cardiac cells necrosis and cardiac fibrosis. The main adverse events of SGLT2i include urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Concerns have also been raised about the association of SGLT2i with lower limb amputations, Fournier gangrene, risk of bone fractures, female breast cancer, male bladder cancer, orthostatic hypotension, and acute kidney injury

Liver cirrhosis-effect on QT interval and cardiac autonomic nervous system activity.

AIM: To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy (CAN). METHODS: A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval (QTc) and their dispersions (dQT, dQTc) were measured and calculated using a computer-based program. The diagnosis of CAN was based upon the battery of the tests proposed by Ewing and Clarke and the consensus statements of the American Diabetes Association. CAN was diagnosed when two out of the four classical Ewing tests were abnormal. RESULTS: QT, QTc and their dispersions were significantly longer (P < 0.01) in patients with cirrhosis than in controls. No significant differences in QT interval were found among the subgroups according to the etiology of cirrhosis. Multivariate regression analysis after controlling for age, gender and duration of cirrhosis demonstrated significant association between QT and presence of diabetes mellitus [standardized regression coefficient (beta) = 0.45, P = 0.02] and treatment with diuretics (beta = 0.55, P = 0.03), but not with the Child-Pugh score (P = 0.54). Prevalence of CAN was common (54.9%) among patients with cirrhosis and its severity was associated with the Child-Pugh score (r = 0.33, P = 0.02). Moreover, patients with decompensated cirrhosis had more severe CAN that those with compensated cirrhosis (P = 0.03). No significant association was found between severity of CAN and QT interval duration. CONCLUSION: Patients with cirrhosis have QT prolongation. Treatment with diuretics is associated with longer QT. CAN is common in patients with cirrhosis and its severity is associated with severity of the disease

Rare diabetic neuropathies: It is not only distal symmetrical polyneuropathy

The prevalence of diabetes mellitus is increasing at an epidemic level, leading to a consequent increase of its chronic complications, including neuropathy. Diabetic neuropathy constitutes a heterogeneous group of disorders with distinct clinical presentations and pathophysiological mechanisms. These distinct forms may be categorised according to their clinical presentation as symmetrical (distal symmetrical polyneuropathy, autonomic and acute sensory neuropathy) and focal or multifocal (radiculoplexus neuropathies, entrapment syndromes, cranial palsies and other mononeuropathies). Additionally, people with diabetes may have neuropathies due to causes other than diabetes. The commonest forms of diabetic neuropathy are distal symmetrical polyneuropathy and autonomic neuropathy. However, clinicians should be aware that people with diabetes may suffer from less common forms of neuropathy and should be able to recognise their symptoms and signs. The recognition of the rare diabetic neuropathies is crucial, as they often lead to different clinical outcomes and require different management. The aim of the present narrative, non-systematic review is to outline the rare types of diabetic neuropathies. (c) 2021 Elsevier B.V. All rights reserved

The effect of vitamin D supplementation on mortality and intensive care unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression

Aims The aim of this systematic review and meta-analysis was to investigate the effect of vitamin D supplementation on mortality and admission to intensive care unit (ICU) of COVID-19 patients. Methods A systematic search of PubMed, Google Scholar, Embase, Web of Science and medRxiv with terms relative to vitamin D supplementation and COVID-19 was conducted on 26 March 2021. Comprehensive Meta-Analysis software was used for the quantitative assessment of data and random-effects model was applied. To investigate the association between the dose of vitamin D and the outcomes of interest, meta-regression analysis was performed. Results Two thousand and seventy-eight patients from nine studies with data on mortality were included (583 received vitamin D supplementation, while 1495 did not). Sixty-one (10.46%) individuals in the treated group died, compared to 386 (25.81%) in the non-treated group (odds ratio [OR]: 0.597; 95% CI: 0.318-1.121; p = 0.109). Eight hundred and sixty patients from six studies with data on ICU admission were included (369 received vitamin D supplementation, while 491 did not). Forty-five (12.19%) individuals in the treated group were admitted to ICU, compared to 129 (26.27%) in the non-treated group (OR: 0.326; 95% CI: 0.149-0.712; p = 0.005). No significant linear relationship between vitamin D dose and log OR of mortality or log OR of ICU admission was observed. Conclusion This meta-analysis indicates a beneficial role of vitamin D supplementation on ICU admission, but not on mortality, of COVID-19 patients. Further research is urgently needed to understand the benefit of vitamin D in COVID-19

Immunogenicity of SARS-CoV-2 BNT162b2 Vaccine in People with Diabetes: A Prospective Observational Study

The mRNA-based BNT162b2 vaccine has demonstrated high efficacy against severe SARS-CoV-2. However, data regarding immune response in people with diabetes mellitus (DM) after vaccination with the BNT162b2 vaccine are limited. In this prospective observational study, we examined humoral immune response in participants with and without DM after vaccination with the BNT162b2 mRNA vaccine. A total of 174 participants (58 with and 116 without diabetes, matched for age) were included. Antibodies were measured 21 days after the first dose, 7–15 days after the second dose, and 70–75 days after the second and before the third dose of the vaccine. Antibodies were measured by an anti-SARS-CoV-2 receptor-binding domain IgG (Abs-RBD-IgG) assay by a chemiluminescent microparticle immune assay; values > 50 AU/mL are considered protective from severe disease. Almost 17% of participants with DM did not develop adequate humoral immune response to the BNT162b2 mRNA vaccine after the first dose; however, it was high and similar after the second dose in both participants with and without DM and remained so almost 2 months after the second dose of the vaccine. Geometric mean values of Abs-RBD-IgG were not significantly different between participants with and without DM during the study. At least two doses of the BNT162b2 vaccine are necessary to ensure adequate and sustainable immune response in people with DM

Low prevalence of rheumatoid arthritis among patients with pre-existing type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is a non-autoimmune disease characterized by chronic hyperglycemia and increased non-enzymatic glycation of amino groups. Glycation occurs through a series of events eventually leading to the formation of irreversible “advanced glycation end-products” (AGEs). AGEs may affect the function of long-lived proteins, including cytokines, immunoglobulins and their receptors, resulting in a “less active” immune system. We aimed to test the hypothesis that a common inflammatory chronic disease, such as rheumatoid arthritis (RA), in which the earliest event is an inflammatory response to unknown stimulus, has a lower prevalence in these patients than in normoglycemic, non-diabetic subjects. Methods: In this study, we compared the prevalence of RA in a prospectively followed outpatient cohort of patients with T2DM patients (n=1,630) with a control, matched, non-diabetic population (n=1,630). Results: Among non-diabetic controls, 13 patients (prevalence 0.80%) with RA were identified. An almost 3-fold lower prevalence of RA (0.25%) was found in consecutive patients with T2DM (P=0.029). Most of the RA cases among participants with T2DM were diagnosed early after diabetes onset. The onset of RA in patients with T2DM occurred at significantly older age (64 +/- 15 years) as compared to the non-diabetes group (48 +/- 18 years; P=0.004). Conclusions: The prevalence of RA is lower and occurs in an older age in patients with pre-existing T2DM in comparison with people without T2DM