Diabetes News / Recent Literature Review / Forth Quarter 2019

Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity   In this observational retrospective study, 2287 patients with obesity (BMI≥30 ) and type 2 diabetes who underwent metabolic surgery within the Cleveland Clinic Health System, were matched 1:5 to nonsurgical patients with diabetes and obesity. The primary end point was the incident of extended major adverse cardiovascular events (MACE, composite of 6 outcomes), defined a first all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy and atrial fibrillation. Secondary outcome included 3-component MACE (myocardial infarction, ischemic stroke and mortality). The median follow-up duration was 3.9 years. At the end of the study period, 385 (30.8%) patients in the surgical group and 3243 (44.7%) patients in the nonsurgical group experienced a primary end point (hazard ratio, HR 0.61, 95% CI, 0.55 – 0.69). All secondary putcomes showed significantly differences in favor of metabolic surgery. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (HR = 0.59, 95%CI, 0.48- 0.72). Metabolic surgery was also associated with a significant reduction of HbA1c (mean difference between groups1.1%), and use of noninsulin diabetes medication, insulin antihypertensive medications and lipid0lower therapies. In the 90 days after metabolic surgery, complications included bleeding requiring transfusion (n=68, 3.0 %), pulmonary adverse events (n=58, 2.5%), venous thromboembolism (n=4, 0.2%), cardiac events (n=17, 0.7%), and renal failure requiring dialysis (n=4, 0.2%) (Aminlan A et al, JAMA 2019;322:1271-1282)

Diabetes News/Recent Literature Review/ First Quarter 2018

Metformin Treatment in Patients with Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4 The safety of metformin was examined in moderate and severe chronic kidney disease (CKD)( stages 3A/3B and 4, eGFR 59-45, 44-30, and <15 mL/min/1.72 m2 , respectively). Three metformin doses were examined: 1,500mg (0.5 g in the morning [qam]+ 1g in the evening [qpm]) in CKD3A, 1,000 mg (0.5g qam + o.5 g qpm ) in CKD3B, and 500 mg (qam) in CKD 4. After 4 months on these regimens, patients displayed stable metformin concentrations that never exceeded the safe upper limit of 5.0 mg/L. Hyperlactatemia was absent, and HbA1c levels did not change.  The study provided solid basis for the continuing metformin treatment in patients with moderate or severe CKD, supporting the recent guidelines on metformin treatment, providing that the dose is adjusted to the eGFR (Lalau JD et al,  Diabetes Care 2018;43:547-553)

Diabetes News/Recent Literature Review/Forth Quarter 2018

Diabetes News/Recent Literature Review/Forth Quarter 201

Effect of atorvastatin on the elatic properties of arteries in patients with type 2 diabetes assessed by tonometry

Type 2 diabetes is associated with a marked increase of cadiovascullar events. In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Arterial stiffness, which is present as early as in impaired glucose metabolism, represents the link between diabetes and vascular events. Aortic pulse wave velocity (PWV), recorded by an applanation tonometer, is considered as an independent predictive factor of cardiovascular events.Aim of our study was to assess the effect of atorvastatin on the elastic properties of arteries in patients with type 2 diabetes and dyslipidemia.A total of 93 outpatients with type 2 diabetes who visited the Diabetes Center at the Laiko Hospital participated. The main inclusive criteria were: LDLc> 100 mg/dl, an adequate glycemic control (HbA1c 8.5 %), age 45-75 years, ankle-brachial pressure index >0.9 and absence of cardiovascular disease. Fifty subjects (17 men/33 women, mean age 60.78±8.19 years) were assigned to 10 mg atorvastatin daily and low-fat diet and 43 subjects (21 men/22 women, mean age 60.16±9.21 years) to low-fat diet only. Carotid-radial PWV (crPWV) and carotid-femoral PWV (cfPWV) were assessed using the SphygmoCor system (SphygmoCor AtCor Medical, Sidney, Australia). ΗbA1c, plasma lipids, hsCRp, fibrinogen, plasma osteoprotegerin (OPG) and metalloproteinase-9 (MMP-9) were assessed. The two groups were comparable regarding baseline clinical and laboratory characteristics, as well as baseline crPWV and cfPWV values. All patients were evaluated again at 3, 6 and 12 months, during which the same clinical examination, blood tests and PWV measurement were repeated.In the atorvastatin group, a significant reduction of crPWV was observed at 3 months of treatment by 3.50% (p100 mg/dl, σχετικά καλή γλυκαιμική ρύθμιση (HbA1c 0,9, και απουσία γνωστής μακροαγγειοπάθειας. Σε 50 ασθενείς (17 άντρες/33 γυναίκες, μέσης ηλικίας 60,78±8,19 ετών) έγινε έναρξη ατορβαστατίνης (10 mg ημερησίως) σε συνδυασμό με υπολιπιδαιμική δίαιτα, σύμφωνα με πρόσφατα δημοσιευμένες οδηγίες, και σε 43 ασθενείς (21 άντρες/22 γυναίκες, μέσης ηλικίας 60,16±9,21 ετών) χορηγήθηκε μόνο υπολιπιδαιμική δίαιτα. Η εκτίμηση της PWV μεταξύ καρωτίδας-κερκιδικής αρτηρίας (carotid-radial PWV, crPWV) και μεταξύ καρωτίδας-μηριαίας αρτηρίας (carotid-femoral PWV, cfPWV) έγινε με τη συσκευή SphygmoCor (SphygmoCor AtCor Medical, Sidney, Australia). Υπολογίστηκαν οι τιμές της HbA1c, των λιπιδίων ορού, της hsCRP, του ινωδογόνου, της οστεοπροτεγερίνης (ΟPG) και της μεταλλοπρωτεϊνάσης-9 (MMP-9). Οι δύο ομάδες ήταν συγκρίσιμες ως προς όλα τα25κλινικά κι εργαστηρικά χαρακτηριστικά, καθώς και ως προς τις αρχικές τιμές της crPWV και της cfPWV. Οι ασθενείς επανεκτιμήθηκαν ύστερα από 3, 6 και 12 μήνες. Σε κάθε επίσκεψη διενεργήθηκε η ίδια κλινική κι εργαστηριακή εξέταση, καθώς και μέτρηση της crPWV και cfPWV.Στην ομάδα των ασθενών που έλαβε ατορβαστατίνη παρατηρήθηκε στατιστικά σημαντική μείωση της crPWV μετά από 3 μήνες θεραπείας κατά 3,50% (p<0,05), μετά από 6 μήνες κατά 3,39% (p<0,05) και στους 12 μήνες κατά 6,26% (p=0,017). Παρόμοια, στους 3 μήνες θεραπείας σημειώθηκε μείωση της cfPWV κατά 6,09% (p=0,001), στους 6 μήνες κατά 8,02% (p<0,001) και στους 12 μήνες θεραπείας κατά 6,39% (p<0,001). Στην ομάδα των ασθενών που έλαβε μόνο δίαιτα, τόσο η crPWV όσο και η cfPWV δεν παρουσίασαν στατιστικά σημαντική βελτίωση. Στην ομάδα της ατορβαστατίνης παρατηρήθηκε επίσης στατιστικά σημαντική μείωση της ολικής χοληστερόλης, της LDLc και των τριγλυκεριδίων σε κάθε επίσκεψη (όλες οι τιμές p<0,05). Στην ομάδα των ασθενών υπό δίαιτα δεν διεπιστώθηκε σημαντική βελτίωση των λιπιδίων. Σε καμία από τις δύο ομάδες δεν παρατηρήθηκε στατιστικά σημαντική μεταβολή των υπολοίπων βιοχημικών παραμέτρων.Η παρούσα προοπτική μελέτη κατέδειξε για πρώτη φορά την ευεργετική επίδραση της ατορβαστίνης στις ελαστικές ιδιότητες τόσο των ελαστικών όσο και των μυϊκού τύπου αρτηριών σε ασθενείς με διαβήτη τύπου 2. Η βελτίωση αυτή ήταν εμφανής ήδη από τους πρώτους 3 μήνες θεραπείας και διατηρήθηκε καθόλη της διάρκεια της παρακολούθησης των 12 μηνώ

The effect of hyperhomocysteinemia on aortic distensibility in healthy individuals

Objective: Elevated plasma homocysteine (HCY) levels have been associated with increased risk for cardiovascular disease. Aortic distensibility and aortic pulse wave velocity (PWV) are indices of aortic elasticity. The potential effect of acute hyperhomocysteinemia (HHCY) on the elastic properties of the aorta in healthy individuals is not known. The aim of the present study was to determine the effect of acute methionine-induced HHCY on aortic distensibility and PWV in healthy individualsand the effect of acute HHCY on myocardial performance of the left ventricle (Tei index). Methods: Thirty healthy volunteers were included in this crossover study. An oral methionine (100 mg/kg) or water load was given in random order on separate days at weekly intervals. Aortic distensibility and Tei index were determined non-invasively by ultrasonography at baseline and 3 h after methionine or water consumption, while PWV was measured by applanation tonometry at baseline and every 1 h for the same time interval. Results: Oral methionine induced an increase in total plasma HCY concentrations (P &lt; 0.001), whereas HCY concentrations did not change after water consumption. Aortic distensibility decreased 3 h after methionine load (P &lt; 0.001) and Tei index increased (P &lt; 0.001), suggesting worsening compared with baseline values. Water consumption had no effect on aortic distensibility or Tei index values. PWV values did not change after either methionine or water consumption. Conclusions: Acute methionine-induced HHCY reduces aortic distensibility and worsens myocardial performance in healthy individuals. Further research is warranted to examine in the long term the direct effects of HHCY on cardiovascular function and the indirect effects on structural remodeling. (C) 2013 Elsevier Inc. All rights reserved

Effect of atorvastatin on baroreflex sensitivity in subjects with type 2 diabetes and dyslipidaemia

In this prospective study, we examined the effect of atorvastatin treatment on baroreflex sensitivity (BRS) in subjects with type 2 diabetes. A total of 79 patients with type 2 diabetes with dyslipidaemia were recruited. A total of 46 subjects were enrolled to atorvastatin 10 mg daily and low-fat diet and 33 patients to low-fat diet only. BRS was assessed non-invasively using the sequence method at baseline, 3, 6 and 12 months. Treatment with atorvastatin increased BRS after 12 months (from 6.46 +/- 2.79 ms/mmHg to 8.05 +/- 4.28 ms/mmHg, p = 0.03), while no effect was seen with low-fat diet. Further sub-analysis according to obesity status showed that BRS increased significantly only in the non-obese group (p = 0.036). A low dose of atorvastatin increased BRS in non-obese subjects with type 2 diabetes and dyslipidaemia after 1-year treatment. This finding emphasizes the beneficial effect of atorvastatin on cardiovascular system, beyond the lipid-lowering effects

Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection

Aims SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers 4 months after COVID-19 infection. Methods and results In a case-control prospective study, we included 70 patients 4 months after COVID-19 infection, 70 age- and sex-matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV), (v) global left and right ventricular longitudinal strain (GLS), and (vi) malondialdehyde (MDA), an oxidative stress marker, thrombomodulin and von Willebrand factor as endothelial biomarkers. COVID-19 patients had similar CFR and FMD as hypertensives (2.48 +/- 0.41 vs. 2.58 +/- 0.88, P = 0.562, and 5.86 +/- 2.82% vs. 5.80 +/- 2.07%, P = 0.872, respectively) but lower values than controls (3.42 +/- 0.65, P = 0.0135, and 9.06 +/- 2.11%, P = 0.002, respectively). Compared to controls, both COVID-19 and hypertensives had greater PBR5-25 (2.07 +/- 0.15 mu m and 2.07 +/- 0.26 mu m, P = 0.8 vs. 1.89 +/- 0.17 mu m, P = 0.001), higher PWV (carotid-femoral PWV 12.09 +/- 2.50 vs. 11.92 +/- 2.94, P = 0.7 vs. 10.04 +/- 1.80m/s, P = 0.036) and impaired left and right ventricular GLS (-19.50 +/- 2.56% vs. -19.23 +/- 2.67%, P = 0.864 vs. -21.98 +/- 1.51%, P = 0.020 and -16.99 +/- 3.17% vs. -18.63 +/- 3.20%, P = 0.002 vs. -20.51 +/- 2.28%, P &lt; 0.001). MDA and thrombomodulin were higher in COVID-19 ;patients than both hypertensives and controls (10.67 +/- 0.32 vs 1.76 +/- 0.03, P = 0.003 vs. 1.01 +/- 0.05 nmol/L, P = 0.001 and 3716.63 +/- 188.36 vs. 3114.46 +/- 179.18 pg/mL, P = 0.017 vs. 2590.02 +/- 156.51 pg/mL, P &lt; 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers. Conclusions SARS-CoV-2 may cause endothelial and vascular dysfunction linked to impaired cardiac performance 4 months after infection

Development and validation of SCOPE score: a clinical score to predict progression of COVID-19 pneumonia to severe respiratory failure

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions