Imbalance between oxidative stress burden and antioxidant capacity is implicated in the course of atherosclerosis among type 2 diabetic patients. We addressed the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP1-RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on levels of oxidant and antioxidant biomarkers. We recruited a total of 160 type 2 diabetics, who received insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40), or their combination (GLP-1RA+SGLT-2i) (n = 40). We measured at baseline, at 4 and at 12 months of treatment: (a) Thiobarbituric Acid Reactive Substances (TBARS), (b) Malondialdehyde (MDA), (c) Reducing Power (RP), (d) 2,2¢-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS) and (e) Total Antioxidant Capacity TAC). Dual treatment resulted in significant improvement of TBARS, MDA, and ABTS at four months compared with the other groups (p < 0.05 for all comparisons). At twelve months, all participants improved TBARS, MDA, and ABTS (p < 0.05). At 12 months, GLP1-RA and GLP-1RA+SGLT2-i provided a greater reduction of TBARS (−8.76% and −9.83%) compared with insulin or SGLT2i (−0.5% and 3.22%), (p < 0.05). GLP1-RA and GLP-1RA+SGLT-2i showed a greater reduction of MDA (−30.15% and −31.44%) compared with insulin or SGLT2i (4.72% and −3.74%), (p < 0.05). SGLT2i and GLP-1RA+SGLT2-i showed increase of ABTS (12.87% and 14.13%) compared with insulin or GLP1-RA (2.44% and −3.44%), (p < 0.05). Only combined treatment resulted in increase of TAC compared with the other groups after 12 months of treatment (p < 0.05).12-month treatment with GLP1-RA and SGLT2i resulted in reduction of biomarkers responsible for oxidative modifications and increase of antioxidant biomarker, respectively. The combination treatment was superior and additive to each separate agent and also the beneficial effects appeared earlier.

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 < 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 > 7% (> 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.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is regarded as a liver manifestation of metabolic syndrome. It is linked to insulin resistance, obesity, and diabetes mellitus, all of which increase the risk of cardiovascular complications. Endothelial dysfunction (EnD) constitutes the main driver in the progression of atherosclerosis and coronary artery disease (CAD). Several pathophysiological alterations and molecular mechanisms are involved in the development of EnD in patients with NAFLD. Our aim is to examine the association of NAFLD and CAD with the parallel assessment of EnD, discussing the pathophysiological mechanisms and the genetic background that underpin this relationship. This review delves into the management of the condition, exploring potential clinical implications and available medical treatment options to facilitate the deployment of optimal treatment strategies for these patients.

Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are cardioprotective drugs. We investigated their effects on left atrial function, a major determinant of cardiac diastolic dysfunction in type 2 diabetes mellitus. We also explored the association of changes in arterial stiffness with those of the LA strain after treatment. Materials and Methods: A total of 200 patients (59.5 ± 9.1 year old, 151 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n = 50 served as controls), liraglutide (n = 50), empagliflozin (n = 50) or their combination (liraglutide + empagliflozin) (n = 50). We measured at baseline and 6 months post-treatment: (a) left atrial and global left ventricular longitudinal strain by speckle tracking echocardiography; (b) pulse wave velocity (PWV) and central systolic blood pressure. Results: At baseline, there was a correlation of the LA reservoir strain with PWV (r = −0.209, p = 0.008), central SBP (r = −0.151, p = 0.030), EF (r = 0.214, p = 0.004) and GLS (r = −0.279, p = 0.009). The LA reservoir change 6 months post-treatment was correlated with the PWV change in all groups (r = −0.242, p = 0.028). The LA reservoir change 6 months post-treatment was correlated with the GLS change in all groups (r = −0.322, p = 0.004). Six months after intervention, patients treated with liraglutide, empagliflozin and their combination improved the left atrial reservoir strain (GLP1RA 30.7 ± 9.3 vs. 33.9 ± 9.7%, p = 0.011, SGLT2i 30 ± 8.3 vs. 32.3 ± 7.3%, p = 0.04, GLP1&SGLT2i 29.1 ± 8.7 vs. 31.3 ± 8.2, p = 0.007) compared to those treated with insulin (33 ± 8.3% vs. 32.8 ± 7.4, p = 0.829). Also, patients treated with liraglutide and the combination liraglutide and empagliflozin had improved left atrial conduction strain (p < 0.05). Empagliflozin or the combination liraglutide and empagliflozin showed a greater decrease of PWV and central and brachial systolic blood pressure than insulin or GLP-1RA. (p < 0.05). Conclusions: Impaired aortic elastic properties are associated with a decreased LA strain in type 2 diabetics. Treatment with liraglutide, empagliflozin and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with the improvement of arterial and myocardial functions.

Context The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known. Objective To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study. Results Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months (P < .05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (−6% vs −4%, P = .048 and −11% vs −9%, P = .039), augmentation index (AIx) (−59% vs −52%, P = .041 and −70% vs −57%, P = .022), and pulse wave velocity (PWV) (−6% vs −3.5%, P = .019 and −12% vs −10%, P = .036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores. Conclusion Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD.

Familial partial lipodystrophy (FPLD) is a rare syndrome in which a patient’s phenotype is not merely dependent on the specific genetic mutation, but it is also defined by a combination of other demographic, environmental and genetic factors. In this prospective observational study in a Greek referral center, we enrolled 39 patients who fulfilled the clinical criteria of FPLD. A genetic analysis was conducted, which included sequence and deletion/duplication analyses of the LMNA and PPRARG genes, along with anthropometric and metabolic parameters. The treatment responses of patients who were eligible for treatment with metreleptin were evaluated at 3 and 12 months. In most of the patients, no significant changes were detected at the exon level, and any mutations that led to changes at the protein level were not associated with the lipodystrophic phenotype. On the contrary, various changes were detected at the intron level, especially in introns 7 and 10, whose clinical significance is considered unknown. In addition, treatment with metreleptin in specific FPLD patients significantly improved glycemic and lipidemic control, an effect which was sustained at the 12-month follow-up. More large-scale studies are necessary to clarify the genetic and allelic heterogeneity of the disease, along with other parameters which could predict treatment response.