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AimsPsoriasis has been associated with increased cardiovascular (CV) risk. We investigated whether markers of CV function and their change after treatment have a prognostic value for adverse outcomes.Methods and resultsIn a prospective study, at baseline and after 6 months of treatment with biological agents, we assessed in 298 psoriasis patients (i) left ventricular global longitudinal strain (GLS) and (ii) carotid-femoral pulse wave velocity (PWV), to evaluate their prognostic value for major adverse cardiovascular events (MACEs), including coronary artery disease, stroke, hospitalization for heart failure, and all-cause death over a 4-year follow-up period. During follow-up, 26 (8.7%) MACEs were recorded. By univariate analysis, decreasing absolute GLS values [hazard ratio (HR): 0.73, P < 0.001], decreasing GLS change after treatment (HR: 0.53, P = 0.008), and increasing PWV values (HR: 1.16, P = 0.049) were associated with adverse outcomes. Baseline GLS and its change post-treatment remained independent predictors of adverse events after adjusting for several confounders (P < 0.05). The addition of baseline GLS and its absolute change post-treatment to SCORE2 increased Harrell’s C from 0.882 to 0.941. By multivariable analysis, for each 1% increase in absolute baseline GLS values, the risk of MACE decreased by 33% and for each 1% absolute increase of GLS post-treatment compared with the baseline value, the risk of MACE decreased by 58%.ConclusionGlobal longitudinal strain has an independent and additive prognostic value to SCORE2 for adverse CV events in psoriasis, providing timely decision-making for intensive anti-inflammatory treatment and aggressive modification of risk factors to reduce CV risk.

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 µm and 2.07 ± 0.26 µm, P = 0.8 vs. 1.89 ± 0.17 µm, P = 0.001), higher PWV (carotid-femoral PWV 12.09 ± 2.50 vs. 11.92 ± 2.94, P = 0.7 vs. 10.04 ± 1.80 m/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 < 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 < 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.

Recent reports have shown a strong association between obesity and the severity of COVID-19 infection, even in the absence of other comorbidities. After infecting the host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a hyperinflammatory reaction through the excessive release of cytokines, a condition known as “cytokine storm,” while inducing lymphopenia and a disrupted immune response. Obesity is associated with chronic low-grade inflammation and immune dysregulation, but the exact mechanisms through which it exacerbates COVID-19 infection are not fully clarified. The production of increased amounts of cytokines such as TNFα, IL-1, IL-6, and monocyte chemoattractant protein (MCP-1) lead to oxidative stress and defective function of innate and adaptive immunity, whereas the activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome seems to play a crucial role in the pathogenesis of the infection. Endothelial dysfunction and arterial stiffness could favor the recently discovered infection of the endothelium by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic microenvironment in obesity could provide a link for the increased cardiovascular events in these patients. The successful use of anti-inflammatory agents such as IL-1 and IL-6 blockers in similar hyperinflammatory settings, like that of rheumatoid arthritis, has triggered the discussion of whether such agents could be administrated in selected patients with COVID-19 disease.

Background There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn’s disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn’s disease. Methods The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn’s disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited. Results 138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn’s disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn’s disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605). Conclusions Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn’s disease is promising but warrants further investigation. Trial registration: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.

Insulin resistance (IR) is associated with a higher rate of type 1 diabetes (T1D) complications. We aimed to examine the relationship between estimated glucose disposal rate (eGDR), a readily available marker of IR in clinical practice and early predictor biomarkers of macrovascular and microvascular complications in patients with T1D.A cross-sectional study.A total of 165 consecutive patients with T1D free of cardiovascular, eye, and renal complications were included in the study from 2016 to 2020. Participants were characterized as insulin resistant if their eGDR value was ≤ 8 mg/kg/min. Pulse wave velocity (PWV) and global longitudinal strain (GLS) were used as surrogates for subclinical atherosclerosis and left ventricular systolic dysfunction (LVSD), respectively. Four previously standardized tests based on the calculation of heart rate variability (HRV) were used to evaluate subclinical cardiac autonomic neuropathy (CAN). Early nephropathy was assessed by assessing urinary albumin to creatinine ratio (ACR).The population sample (n = 165) included a majority of female patients (63%) and had a median age of 32 years (24-43), median disease duration of 14 years ( ± 9.5-21.5), a median BMI value of 23.7 kg/mIn patients with T1D, insulin resistance, as measured by eGDR, correlates well with early CVD predictors and CAN. These associations appear independent of the effects of gender, aging, and disease duration.

The regenerative potential of platelet lysate (PL) and platelet gel (PG) is mediated by the release of platelets (PLTs) growth factors. The aim of this study was the evaluation of the PL production utilizing low volume single Cord Blood Units (CBUs) and the comparison of the biomolecule content between PLs obtained from intermediate and high volume CBUs.CBUs (n = 90) with volumes greater than 50 ml and initial platelet count 150 × 10CBPL was produced from low volume single CBUs and contained 3.4 ± 0.3 ×10This study provided significant evidence regarding the utilization of the low volume CBUs for the production of CB derivatives, thus can serve as healing mediators in regenerative medicine approaches.

There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.

Funding Acknowledgements Type of funding sources: None. Background and Aims Patients with stroke are at high risk to develop cardiovascular complications. We assessed endothelial glycocalyx, aortic elastic properties, left atrial and ventricular function in patients with lacunar, atherosclerotic and stroke of undetermined source (ESUS). Patients and methods In 75 patients (age 55.2 ± 10.6) with acute cerebral stroke (25 lacunar, 20 atherosclerotic and 30 ESUS) and 20 controls with similar risk factors, we measured: (1) perfused boundary region (PBR) of the sublingual arterial microvessels (range 5–25 µm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity (PWV), central systolic blood pressure (cSBP), and augmentation index (AIx), (3) Left atrial (LA) strain using speckle-tracking imaging, and (4) left ventricular global longitudinal strain. Results Compared with controls, patients with stroke had higher PWV (11.38 ± 3.62 vs 9.51 ± 1.57 m/sec, p = 0.045), PBR (2.10 ± 0.27 vs 1.94 ± 0.20, p = 0.039) and central SBP (139.64 ± 26.31 vs 116.36 ± 37.23 mmHg, p = 0.039), while ventricular (-17.902 ± 3.77 vs - 19.87 ± 1.17%, p = 0.025) and atrial deformation (24.8 ± 9.99 vs 39.05 ± 2.08%, p LA reservoir strain was more reduced in ESUS patients compared to other 2 stroke types (ESUS 21.7 ± 6.6%, Lacunar 25.6 ± 13.2%, atherosclerotic 22.3 ± 7.8%, P Regarding endothelial glycocalyx, PBR5-9 (the smallest vessels with diameter 5-9 μm) was higher in patients with ESUS than in the other two types of stroke (ESUS 1.22 ± 0.12 μm, LACUNAR 1.19 ± 0.12 μm, ATHEROSCLEROTIC 1.15 ± 0.09 μm, p PWV was significantly higher in patients with atherosclerotic stroke (15.57 ± 5.50 m/sec, p = 0.007), while in patients with lacunar it was mildly elevated (10.53 ± 3.22 m/sec) and in ESUS patients it was moderately increased (11.7 ± 3 m/sec). Conclusions Patients with stroke have impaired atrial strain, endothelial glycocalyx and arterial elasticity, compared with controls. Arterial stiffness is more affected in atherosclerotic stroke, while LA deformation and glycocalyx of small size micro vessels are more affected in ESUS patients.

The aim of this study was to assess the effect of the COVID-19 lockdown periods on the metabolic control of patients with type 2 diabetes (T2D) in three academic diabetes centers in Greece. There was a slight improvement in BMI, blood pressure and lipid values while the remaining parameters remained stable.

Aim Endothelial glycocalyx is involved in the clinical course of atherogenesis. The purpose of this study was to investigate whether disturbance of glycocalyx integrity is related with increased cardiovascular risk. Methods Perfused Boundary Region (PBR), a marker of glycocalyx integrity, was measured non-invasively in sublingual microvessels with a diameter ranging from 5–25 μm using a dedicated camera (Sideview, Darkfield Imaging). Increased PBR indicates reduced glycocalyx thickness. We measured baseline PBR in 400 apparently healthy subjects, without established cardiovascular disease. We prospectively monitored the occurrence of major cardiovascular events (MACE-death, myocardial infarction, stroke and heart failure hospitalization) during a 6-year follow-up period using electronic records and clinic visits. Results Forty-three MACE were documented during follow-up. Subjects with PBR at 5–9 μm microvessel diameter greater than 1.15 μm (mean value of the study cohort) had 2-fold higher risk for MACE than those with lower PBR in a model including sex, age, hyperlipidemia, diabetes, hypertension, current smoking, family history of coronary artery disease and treatment with ACEi/ARBs or lipid lowering agents (hazard ratio (HR): 2.49; 95% CI: 1.23–5.02, p=0.011, net reclassification improvement (NRI): 25%; C-statistic: 0.738). PBR5-9 ≥1.15 was an independent and additive predictor of outcome when added in a model including SCORE, risk factors not included in SCORE (diabetes, family history of CAD) and medication (HR: 2.48 NRI: 23.8%, C-statistic increase from 0.629 to 0.678, for all cardiac events and HR: 4.19, NRI: 33.1%, C-statistic increase from 0.654 to 0.734 for death myocardial infarction and stroke, p Conclusion Endothelial glycocalyx integrity is an independent and additive predictor to atherosclerotic risk factors for adverse outcome at 6 years follow-up in individuals without diagnosed cardiovascular disease. Funding Acknowledgement Type of funding sources: None.

Background/Introduction Biomarkers of oxidative stress burden are found increased in Type-2 diabetes mellitus (T2DM) patients. An imbalance between oxidative and antioxidative plasma factors is implicated in the pathway of cardiovascular disease in diabetics. Novel antidiabetic agents with cardioprotective effects are glucagon like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). Purpose We investigated the effect of liraglutide (GLP1-RA),empagliflozin (SGLT-2i) and their combination on plasma levels of oxidative and antioxidative factors. Methods A hundred-sixty T2DM patients were randomly assigned and received: a) insulin (n=40), b) liraglutide (n=40), c) empagliflozin (n=40) and d) the combination liraglutide and empagliflozin (n=40) for 1 year. We measured at baseline and after 1 year of treatment the following antioxidative markers: a) Reducing Power (RP), b) 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), c) Total Antioxidant Capacity (TAC) and also Thiobarbituric acid reactive substances (TBARS) as a marker of oxidative burden. Results After 1 year of treatment all subjects achieved successful glycemic regulation, as estimated by Hemoglobin A1c (HbA1c) levels (8±0.5 vs 6.65±0.5, p Conclusion One year treatment with the GLP1-RA liraglutide and SGLT2i empagliflozin resulted in improvement of plasma levels of oxidative and antioxidative biomarkers compared to administration of insulin and the changes were more outstanding in patients that received the combination of GLP1-RA and SGLT2i, despite similar glycemic regulation in all participants. Thus the favorable cardiovascular effects of these novel factors may be partly explained by alterations in equilibrium between oxidative and antioxidative circulating biomarkers. Funding Acknowledgement Type of funding sources: None.

Background/Introduction The phosphodiesterase 4 inhibitor apremilast is an approved treatment option for psoriasis. Purpose We aimed to investigate the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis. Methods Ninety patients with psoriasis were randomized to receive apremilast (n=30), anti-tumor necrosis factor-a (etanercept, n=30), or cyclosporine treatment (n=30). At baseline and 4 months post-treatment, we measured: (1)Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm using a dedicated camera (Sidestream Dark Field imaging, Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. Perfused microvascular density (PMD), an index of microvascular perfusion, was also measured. (2)Pulse wave velocity (PWV - Complior; ALAM Medical) and central systolic blood pressure (cSBP), and (3)LV global longitudinal strain (GLS) and percent difference between peak twisting and untwisting at mitral valve opening (%dpTw-UtwMVO) using speckle-tracking echocardiography. Results Compared with baseline, PBR20–25 decreased only after apremilast treatment (−13% at 4 months, P Conclusions In psoriasis, apremilast confers a greater improvement of endothelial glycocalyx, microvascular perfusion and LV myocardial function compared with etanercept or cyclosporine treatment. Apremilast restores glycocalyx integrity and thus reduces vascular permeability to pro-inflammatory molecules. This may explain the beneficial effects of apremilast on COVID-19. Funding Acknowledgement Type of funding sources: None.

Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction plays a major role in cardiometabolic disease through insulin resistance, lipotoxicity, and, eventually, oxidative stress and chronic inflammation. We review the literature concerning the aforementioned mechanisms as well-established risk factors for adverse COVID-19 outcomes. We especially focus on data regarding the underlying endothelial effects of SARS-CoV-2 infection, including direct damage and increased vascular leakage through a hyper-inflammatory cascade and diminished nitric oxide bioavailability. Interestingly, an increased incidence of hypoalbuminemia has been observed in patients with severe COVID-19, especially those with underlying cardiometabolic disease. Importantly, low albumin levels present a strong, positive association with poor disease outcomes. Therefore, in this review article, we highlight the important role of cardiovascular risk factors on endothelium integrity and the possible link of endothelial damage in the hypoalbuminemia-associated adverse prognosis of COVID-19 patients.

We investigated whether disturbance of glycocalyx integrity is related with increased cardiovascular risk. In 600 healthy subjects, we measured perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter ranging 5-25 µm using a dedicated camera (Sideview Darkfield Imaging). Increased PBR indicates reduced glycocalyx thickness. We prospectively monitored the occurrence of cardiovascular events (MACE-death, myocardial infarction, and stroke) during a 6-year follow-up. Fifty-seven MACE were documented. Increased values of PBR5-25 predicted higher risk for MACE in a model including sex, age, hyperlipidemia, diabetes, hypertension, smoking, family history of coronary disease, treatment with ACEi/ARBs, or lipid-lowering agents (hazard ratio (HR), 6.44, p = 0.011; net reclassification improvement (NRI), 28%; C-statistic: 0.761). PBR5-25 was an independent and additive predictor of outcome when added in a model including the European Heart SCORE, diabetes, family history of CAD, and medication (HR, 4.71; NRI: 39.7%, C-statistic from 0.653 to 0.693; p lt; 0.01).Glycocalyx integrity is an independent and additive predictor to risk factors for MACE at 6-year follow-up in individuals without cardiovascular disease. ClinicalTrials.govIdentifier:NCT04646252. PBR5-25 was an independent and additive predictor of adverse cardiovascular events in a model including the European Heart SCORE, diabetes, family history of coronary disease, and medication (HR: 4.71, NRI: 39.7%, C-statistic from 0.653 to 0.693; p lt; 0.01, NRI:37.9%).

BackgroundFamilial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (PPARG) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce.Case PresentationWe present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARGGlu157Gly variant. After six months of metreleptin treatment, HbA1c decreased from 10 to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl.ConclusionsThis case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.

Hyperglycemia is a common manifestation in the course of severe disease and is the result of acute metabolic and hormonal changes associated with various factors such as trauma, stress, surgery, or infection. Numerous studies demonstrate the association of adverse clinical events with stress hyperglycemia. This article briefly describes the pathophysiological mechanisms which lead to hyperglycemia under stressful circumstances particularly in the pediatric and adolescent population. The importance of prevention of hyperglycemia, especially for children, is emphasized and the existing models for the prediction of diabetes are presented. The available studies on the association between stress hyperglycemia and progress to type 1 diabetes mellitus are presented, implying a possible role for stress hyperglycemia as part of a broader prognostic model for the prediction and prevention of overt disease in susceptible patients.

Background Bullous pemphigoid is the most common bullous chronic autoimmune skin disease. Recent studies have suggested dipeptidyl-peptidase 4 inhibitors as possible predisposing agents of bullous pemphigoid. The objective of our study was to prospectively estimate the association between gliptins and the development of bullous pemphigoid. Methods We conducted a prospective study which included all patients diagnosed with biopsy-proven bullous pemphigoid in the Dermatology Department of our hospital between April 1, 2009 and December 31,2019. The diagnosis of bullous pemphigoid was based on specific clinical, histological and immunological features. Results Overall 113 consecutive patients (age 75 ± 13 years, 62 females) with the diagnosis of bullous pemphigoid were enrolled. Seventy-six patients (67.3%) suffered from type 2 Diabetes and 52 (46%) were treated with dipeptidyl-peptidase 4 inhibitors. The most frequent prescribed gliptin was vildagliptin, being administered to 45 cases (39.8% of total patients enrolled, 86.5% of the patients treated with gliptins). Gliptins were withdrawn immediately after the diagnosis of bullous pemphigoid, which together with steroid administration led to remission of the rash. Conclusions This study revealed that treatment with dipeptidyl-peptidase 4 inhibitors, especially vildagliptin, is significantly associated with an increased risk of bullous pemphigoid development.

Background: Familial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (PPARG) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce. Case presentation: We present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARGGlu157Gly variant. After six months of metreleptin treatment HbA1c decreased from 10% to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl. Conclusions: This case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as a difficult-to-classify and manage diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.

Funding Acknowledgements Type of funding sources: None. Background/Introduction: Type-2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure. Purpose We investigated the effect of novel antidiabetic drugs, glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on myocardial function. Methods A hundred-sixty T2DM patients (age: 58 ± 10years) were randomized to insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40) or their combination (GLP-1RA + SGLT-2i) (n = 40) as add-on to metformin. We measured at baseline and 1 year post-treatment: a) global LV longitudinal strain (GLS), systolic (GLSR) and diastolic (GLSR E) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial work index (GWI), global constructive (GCW) and global wasted work (GWW) derived by pressure-myocardial strain loops using speckle tracking imaging. Results After 1 year of treatment, all patients improved GLS, GCS, GRS and pUtwVel (p Conclusions One year treatment with GLP-1RA or combination of GLP-1RA and SGLT-2i resulted in a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT-2i treatment, independently of glycemic control in T2DM. All patients (n = 160) Insulin (n = 40) GLP-1RA (n = 40) SGLT-2i (n = 40) GLP-1RA + SGLT-2i (n = 40) p-value GLS, % Baseline -16.4 ± 3.7 -16.4 ± 3.5 -16.2 ± 3.5 -17 ± 4 -16 ± 4 0.139 1 year -17.9 ± 3.9 -17.6 ± 4.2 -18.3 ± 3.5 -17.4 ± 3.4 -18.4 ± 4.7 0.003 GWI, mmHg% Baseline 1538 ± 430 1644 ± 416 1510 ± 403 1536 ± 535 1463 ± 362 0.116 1 year 1692 ± 412 1696 ± 377 1730 ± 318 1568 ± 456 1772 ± 499 0.006 pTw, deg Baseline 15.7 ± 6 16 ± 5.1 15.6 ± 5 15.2 ± 6 16.1 ± 8 0.910 1 year 14.6 ± 5.1 15.4 ± 5.4 14.4 ± 5.4 14.7 ± 4.6 14 ± 5 0.034 pUtwVel, deg/s Baseline -104 ± 42 -100 ± 44 -107 ± 41 -101 ± 28 -111 ± 54 0.550 1 year -116 ± 49 -107 ± 55 -114 ± 45 -108 ± 38 -134 ± 61 0.017 Table

Background/Introduction Type-2 diabetes mellitus (T2DM) exacerbates mechanisms of atherosclerosis and heart failure. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on LV myocardial function of T2DM patients. Methods A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40) as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) global LV longitudinal strain (GLS), systolic (LongSr) and diastolic (LongSrE) strain rate, global circumferential (GCS) and radial (GRS) strain, peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel), b) global myocardial global work index (GWI), global constructive (GCW) and global wasted myocardial work (GWW) derived by pressure-myocardial strain loops using speckle tracking imaging. Results At 4 and 12 months post-treatment, all patients improved GLS, GCS, GRS and pUtwVel (p Conclusions Twelve-month treatment with GLP-1RA or combination of GLP-1RA and SGLT-2i showed a greater improvement of myocardial deformation and effective cardiac work than insulin or SGLT-2i treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

Background/Introduction Type-2 diabetes mellitus (T2DM) is associated with endothelial and myocardial dysfunction. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on vascular and cardiac function of T2DM patients. Methods A hundred-sixty T2DM patients were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40) as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (marker of glycocalyx thickness), b) pulse wave velocity (PWV), central systolic blood pressure (cSBP), c) global LV longitudinal (GLS), circumferential (GCS) and radial (GRS) strain, d) the ratio PWV/GLS, as an index of ventricular-arterial interaction, e) myocardial work index (GWI) using speckle tracking imaging. Results Twelve months post-treatment, all patients improved PBR, PWV, GLS, GCS and GRS (p Conclusions Twelve-month treatment with GLP-1RA, SGLT-2i and their combination showed a greater improvement of vascular markers and effective cardiac work than insulin in T2DM. The combined therapy was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

Background/Introduction Type-2 diabetes mellitus (T2DM) is associated with endothelial and arterial dysfunction. Purpose We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i)and their combination on endothelial and arterial function of T2DM patients. Methods A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40)as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25μm) using Sideview Darkfield imaging. Increased PBR indicates reduced glucocalyx thickness, b) pulse wave velocity (PWV-Complior), central systolic blood pressure (cSBP) and augmentation index (AI) of the aortic pulse wave. Results Twelve months post-treatment, all patients improved PBR, PWV and AI (p Conclusions Twelve-month treatment with SGLT-2i and its combination with GLP-1RA, showed a greater improvement on arterial elastic properties than GLP1RA or insulin treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately. Funding Acknowledgement Type of funding source: None

In recent decades there has been an alarming increase in the prevalence of obesity in patients with type 1 diabetes leading to the development of insulin resistance and cardiometabolic complications, with mechanisms poorly clarified. While bariatric surgery has long been considered an effective treatment option for patients with type 2 diabetes, the evidence regarding its benefits on weight loss and the prevention of complications in T1DM patients is scarce, with controversial outcomes. Bariatric surgery has been associated with a significant reduction in daily insulin requirement, along with a considerable reduction in body mass index, results which were sustained in the long term. Furthermore, studies suggest that bariatric surgery in type 1 diabetes results in the improvement of comorbidities related to obesity including hypertension and dyslipidemia. However, regarding glycemic control, the reduction of mean glycosylated hemoglobin was modest or statistically insignificant in most studies. The reasons for these results are yet to be elucidated; possible explanations include preservation of beta cell mass and increased residual function post-surgery, improvement in insulin action, altered GLP-1 function, timing of surgery, and association with residual islet cell mass. A number of concerns regarding safety issues have arisen due to the reporting of peri-operative and post-operative adverse events. The most significant complications are metabolic and include diabetic ketoacidosis, severe hypoglycemia and glucose fluctuations. Further prospective clinical studies are required to provide evidence for the effect of bariatric surgery on T1DM patients. The results may offer a better knowledge for the selection of people living with diabetes who will benefit more from a metabolic surgery.

Despite high-quality evidence highlighting metabolic surgery as an effective treatment option for type 2 diabetes mellitus (T2DM), the number of patients receiving bariatric surgery (BS) remains low. Since the introduction of the Diabetes Surgery Summit II (DSS-II) eligibility criteria, data on eligibility rates for BS in T2DM cohorts remain scarce. The aims of the present study were to examine in a real-world clinical setting: (i) what is the percentage of T2DM patients visiting diabetes outpatient clinics who meet the DSS-II eligibility criteria, (ii) how many of these have been informed about the option of BS, and (iii) what are the characteristics associated with eligibility and awareness of BS. Demographic, anthropometric, clinical and socioeconomic data were obtained for all patients with T2DM who were consecutively examined in the outpatient clinics of three large-volume university hospitals (n = 1167). A medical registry form was completed to screen for BS eligibility. Patients were considered eligible if the recommendation by DSS-II criteria was either to “consider” or “recommend” BS. Eligible patients were further inquired whether they had ever been informed about the option of BS by their physicians. The advanced DiaRem score (ADRS) was applied to eligible patients to assess their probability of achieving postoperative T2DM remission. A significant percentage of T2DM patients who are routinely assessed in outpatient clinics meet the DSS-II eligibility criteria (15.3%). Eligible patients are younger and more obese, have a shorter T2DM duration, worse glycaemic control and better renal function, compared to non-eligible ones. Among eligible patients, only 39.3% have been medically informed about the option of BS. Informed patients are younger and more severely obese than non-informed ones. A significant percentage of non-informed patients (35%) have an ADRS ≤10, indicating a considerable probability for T2DM remission after BS, and are thus deprived of this opportunity due to lack of appropriate medical counseling. Screening and awareness of BS remain an unmet need in current T2DM management. Future research should focus on intensifying screening for BS eligibility at every medical visit and promoting evidence-based clinical recommendations for patients expected to benefit the most.

Diabetes Mellitus type 1 (T1DM) is a chronic disease that requires patients' self-monitoring and self-management to achieve glucose targets and prevent complications. Telenursing implicates technology in the interaction of a specialized nurse with patients with chronic diseases in order to provide personalized care and support.To evaluate the effect of telenursing on T1DM patients' compliance with glucose self-monitoring and glycemic control.Randomized controlled study.Outpatient Department of Diabetes, Endocrinology and Metabolism of a University Hospital in Northern Greece.Ninety-four T1DM patients were recruited and randomized in two groups by a random number generator. The intervention group (N = 48) was provided with telenursing services. A specialized nurse made a weekly contact via telephone motivating patients to frequently measure blood glucose and adopt a healthy lifestyle. The control group (N = 46) received standard diabetes advice and care in the clinic. The primary outcome was the effect of the intervention in glucose control and glucose variability. The secondary outcome was the effect on frequency of self-monitoring. SPSS 20.0 was used for data analysis.The two groups did not differ in age, sex, physical activity or initial HbA1c. In the intervention group, blood glucose significantly decreased at the end of the study in all predefined measurements, compared to control group: morning (93.18 ± 13.30 mg/dl vs. 105.17 ± 13.74 mg/dl, p 0.005), pre-prandial (114.76 ± 9.54 mg/dl vs. 120.84 ± 4.05 mg/dl, p 0.005), post-prandial (193.35 ± 25.36 mg/dl vs. 207.84 ± 18.80 mg/dl, p 0.005), and HbA1c decreased significantly over time in the intervention group (8.3 ± 0.6% at the beginning of the study vs. 7.8 ± 1% at the end of the study, p = 0.03). In the intervention group there were also fewer omitted glucose measurements than in the control group.Patients in the intervention group achieved better glucose control and more frequent self-monitoring than patients in routine care in the clinic. The findings of our study indicate that telenursing can motivate T1DM patients to better control their disease.

Background: stress hyperglycemia (SH) is a relatively frequent finding in pediatric patients. The purpose of this prospective observational study was to identify the prevalence of pediatric SH and its associated risk factors in Greece. Methods: A total of 1005 patients without diabetes who were admitted consecutively for acute illness in a Pediatric Emergency Department were included in the study. Medical history, anthropometric measurements, blood glucose levels, and the medication administered were recorded. A questionnaire was distributed to parents regarding medical and perinatal history and sociodemographic characteristics. Results: There were 72 cases of SH on admission (7.2%) and 39 (3.9%) during hospitalization. Mean age was 6.4 years; 50.3% were male. SH on admission was associated with oral corticosteroid therapy (21.1% vs. 4.7%, p < 0.001), inhaled corticosteroids (12.7% vs. 3%, p < 0.001), and inhaled β2-agonists (30.6% vs. 10.7%, p < 0.001). In-hospital hyperglycemia was associated with oral corticosteroids (adjusted OR = 3.32), inhaled corticosteroids (OR = 10.03) and inhaled β2-agonists (OR = 5.01). Children with asthma were 5.58 and 7.86 times more likely to present admission and in-hospital hyperglycemia, respectively. Conclusions: This is the first report of SH prevalence in pediatric patients in Greece. Asthma, corticosteroids, and β2-agonists significantly increase the risk of SH. No parental factors seem to predispose to SH.

Patients with type 1 diabetes mellitus (T1DM) present signs of atherosclerosis and endothelial dysfunction earlier compared to healthy individuals. The evidence regarding the efficacy of continuous subcutaneous insulin infusion (CSII) in vascular function in T1DM are scarce. The aim of this study is to determine whether insulin intensification with CSII improves arterial stiffness and endothelial function in T1DM compared to multiple daily insulin (MDI) injections. Thirty patients with T1DM were included in our study. Fifteen patients with poor glycemic control were transitioned from MDI to CSII and were reviewed immediately prior (baseline) and six months after the initiation of CSII. Fifteen patients, matched for sex, age and glycemic control, remained on intensified treatment with MDI (control group). In all patients at each visit we measure a) Carotid-femoral PWV b) central systolic blood pressure (cSBP) c) perfused boundary region (PBR) of the sublingual arterial microvessels. Both groups had similar cardiovascular markers and HbA1c at baseline (p>0.05). After a six month treatment period, patients on CSII improved HbA1c (7.9±1.5% vs 7.35±0.7%, p0.05), PWV (8±2.3 vs. 8±1.9m/s, p>0.05) and cSBP (115±15.2 vs. 115.7±15.4 mmHg, p>0.05) in patients who remained on MDI, despite improvement of HbA1c (8±1.1% vs 7.36±0.8%, p

Glucagon like peptide-1 analogues (GLP-1A) and sodium-glucose co-transporter 2 (SGLT2) are used in the treatment of type 2 diabetes mellitus (T2DM) We investigated whether the effects of treatment with GLP-1A and SGLT2 and their combination on vascular and cardiac function. Methods A hundred twenty, patients with type 2 diabetes were randomized to receive the insulin +/− metformin (n=30), GLP-1A, liraglutide (n=30), the SGLT-2, empagliflozin (n=30) or their combination (GLP-1R+SGLT-2) for 3 months (n=30). We measured at baseline and after treatment a) pulse wave velocity (PWV), central systolic blood pressure (cSBP) b) the perfusion boundary region (PBR-micrometers) of the sublingual arterial microvessels, as a marker of endothelial glycocalyx thickness. c) global LV longitundinal strain (GLS), peak LV untwisting velocity and global myocardial work index (GWI) derived by pressure–myocardial strain loops using speckle tracking imaging and PWV to GLS ratio, as a marker of ventricular-arterial coupling Results All treatment groups had similar vascular and cardiac markers, glucose levels and HbA1 at inclusion (p>0.05). After treatment, all patients had improved GLS, PWV and increased LV twisting-untwisting velocities (p N=120 Insulin GLP-1A SGLT-2 GLP-1A + SGLT-2 P 3-months N=30 N=30 N=30 N=30 PBR, μm 2.27±0.3 2.17±0.3 2.17±0.3 1.99±0.2 Conclusion Three-month treatment with GLP-1A, SGLT-2 and their combination showed a greater improvement of vascular markers, ventricular-arterial coupling and effective cardiac work than insulin treatment in type 2 diabetes.

Background: Poor glycaemic control affects myocardial function. We investigated changes in endothelial function and left ventricular (LV) myocardial deformation in poorly controlled type 2 diabetics before and after glycaemic control intensification. Methods: In 100 poorly-controlled diabetic patients (age: 51 ± 12 years), we measured at baseline and at 12 months after intensified glycaemic control: (a) Pulse wave velocity (PWV, Complior), (b) flow-mediated dilatation (FMD, %) of the brachial artery, (c) perfused boundary region (PBR) of the sublingual arterial micro-vessels (side-view dark-field imaging, Glycocheck), (d) LV global longitudinal strain (GLS), peak twisting (pTw), peak twisting velocity (pTwVel), and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, where the ratio of PWV/GLS was used as a marker of ventricular-arterial interaction, and (e) Malondialdehyde (MDA) and protein carbonyls (PCs) plasma levels. Results: Intensified 12-month antidiabetic treatment reduced HbA1c (8.9 ± 1.8% (74 ± 24 mmol/mol) versus 7.1 ± 1.2% (54 ± 14 mmol/mol), p = 0.001), PWV (12 ± 3 versus 10.8 ± 2 m/s), PBR (2.12 ± 0.3 versus 1.98 ± 0.2 μm), MDA, and PCs, meanwhile, the treatment improved GLS (−15.2 versus −16.9%), PWV/GLS, and FMD% (p &lt, 0.05). By multi-variate analysis, incretin-based agents were associated with improved PWV (p = 0.029), GLS (p = 0.037), PBR (p = 0.047), and FMD% (p = 0.034), in addition to a reduction of HbA1c. The patients with a final HbA1c ≤ 7% (≤ 53 mmol/mol) had greater reduction in PWV, PBR, and markers of oxidative stress, with a parallel increase in FMD and GLS, compared to those who had HbA1c &gt, 7% (&gt, 53 mmol/mol). Conclusions: Intensified glycaemic control, in addition to incretin-based treatment, improves arterial stiffness, endothelial glycocalyx, and myocardial deformation in type 2 diabetes after one year of treatment.