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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.

Hypoglycemia has been associated with complications from the vasculature. The contributing effects of oxidative stress (OS) on these actions have not been sufficiently studied, especially in daily, routine clinical practice. We examined the association of hypoglycemia encountered in daily clinical practice with biomarkers of OS and endogenous antioxidant activity in persons with diabetes [type 1 (T1D) or type 2 (T2D)], as well as individuals without diabetes, with a history of hypoglycemia. Several biomarkers of OS (MDA, ADMA, ox-LDL, 3-NT, protein carbonyls, 4-HNE, TBARS) and antioxidant capacity (TAC, superoxide scavenging capacity, hydroxyl radical scavenging capacity, reducing power, ABTS) were measured. Blood was drawn at the time of hypoglycemia detection and under euglycemic conditions on a different day. A total of 31 participants (mean age [±SD] 52.2 ± 21.1 years, 45.2% males) were included in the study. There were 14 (45.2%) persons with T2D, 12 (38.7%) with T1D, and 5 (16.1%) without diabetes. We found no differences in the examined biomarkers. Only TBARS, a biomarker of lipid peroxidation, showed lower values during hypoglycemia (p = 0.005). This finding needs confirmation in more extensive studies, given that MDA, another biomarker of lipid peroxidation, was not affected. Our study suggests that hypoglycemia encountered in daily clinical practice does not affect OS.

Oxidative stress plays an important role in the pathogenesis of diabetes. We investigated oxidative stress and nitrite/nitrate concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDRs) of diabetic patients with normal oral glucose tolerance test (OGTT) results, 40 subjects with abnormal OGTT results (dysglycaemic) and 20 subjects with normal OGTT results (normoglycaemic). Malondialdehyde (MDA), protein carbonyls (PCs), nitrite/nitrate plasma levels, the perfused boundary region (PBR—Glycocheck) of the sublingual microvessels, a marker of glycocalyx integrity, coronary flow reserve (CFR) and left ventricular global longitudinal strain (GLS) were assessed at 0 and 120 min of the OGTT. Insulin sensitivity was evaluated using Matsuda and the insulin sensitivity index (ISI). In all subjects, there were no significant changes in MDA or PC after the OGTT (p > 0.05). Compared with normoglycaemic subjects, FDRs and dysglycaemic subjects had significantly decreased nitrite/nitrate levels (−3% vs. −24% vs. −30%, respectively), an increased PBR and reduced CFR and GLS at 120 min (p < 0.05). The percent reduction in nitrite/nitrate was associated with abnormal Matsuda and ISI results, reversely related with the percent increase in PBR (r = −0.60) and positively related with the percent decrease in CFR (r = 0.39) and GLS (r = 0.48) (p < 0.05). Insulin resistance is associated with reduced nitric oxide bioavailability and coronary and myocardial dysfunction in FDRs and dysglycaemic subjects.

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.

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.

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.

Background/Introduction COVID-19 infection has been associated with increase arterial stiffness, endothelial dysfunction, and impairment in coronary and cardiac performance. Inflammation and oxidative stress have been suggested as possible pathophysiological mechanisms leading to vascular and endothelial deregulation after COVID-19 infection. Purpose The objective of our study is to evaluate premature alterations in arterial stiffness, endothelial, coronary, and myocardial function markers four months after SARS-CoV-2 infection. Methods We conducted a case-control prospective study, including 70 patients four months after COVID-19 infection, 70 age- and sex-matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness b) flow-mediated dilation (FMD), c) coronary Flow Reserve (CFR) by Doppler echocardiography d) pulse wave velocity (PWV) and central systolic (SBP) e) global LV longitudinal strain (GLS) by speckle tracking imaging and f) malondialdehyde (MDA) as oxidative stress marker. Results COVID-19 patients had similar CFR and FMD with hypertensives (2.48±0.41 vs 2.58±0.88, p=0.562, 5.86±2.82% vs 5.80±2.07%, p=0.872 respectively), but lower CFR and FMD than controls (3.42±0.65, p=0.0135 9.06±2.11%, p=0.002 respectively) Both COVID-19 and hypertensive group had greater PBR than controls (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). COVID-19 patients and hypertensives had higher PWV and central SBP than controls (PWVcf 12.09±2.50 and 11.92±2.94, p=0.7 vs 10.04±1.80 m/sec, p=0.036). COVID-19 patients and hypertensives had impaired values of GLS compared to controls (−19.50±2.56% and −19.23±2.67%, p=0.864 vs −21.98±1.51%, p=0.020). Increased PBR5–25 was associated with increased SBP central which in turn was related with impaired GLS (p Conclusions SARS-CoV-2 may cause impaired coronary microcirculatory, endothelial and vascular deregulation which remain four months after initial infection and are associated with reduced cardiac performance. The 10-fold increase of MDA compared to healthy individuals four months after COVID-19 infection indicate oxidative stress as possible pathophysiological mechanism. Funding Acknowledgement Type of funding sources: None.

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.

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%).

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: 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.

Chronic inflammation and increased oxidative stress are contributing factors to many non-communicable diseases. A growing body of evidence indicates that dietary nutrients can activate the immune system and may lead to the overproduction of pro-inflammatory cytokines. Fatty acids as macronutrients are key players for immunomodulation, with n-3 polyunsaturated fatty acids having the most beneficial effect, while polyphenols and carotenoids seem to be the most promising antioxidants. Psoriasis is a chronic, immune-mediated inflammatory disease with multifactorial etiology. Obesity is a major risk factor for psoriasis, which leads to worse clinical outcomes. Weight loss interventions and, generally, dietary regimens such as gluten-free and Mediterranean diet or supplement use may potentially improve psoriasis’ natural course and response to therapy. However, data about more sophisticated nutritional patterns, such as ketogenic, very low-carb or specific macro- and micro-nutrient substitution, are scarce. This review aims to present the effect of strictly structured dietary nutrients, that are known to affect glucose/lipid metabolism and insulin responses, on chronic inflammation and immunity, and to discuss the utility of nutritional regimens as possible therapeutic tools for psoriasis and psoriatic arthritis.

Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.

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

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.