TNF-α induced pro-atherogenic alterations are amplified in endothelial cells chronically exposed to hyperglycemia in vivo. Liraglutide mitigates TNF-α effects and reduces cell stress/damage indicators, such as endothelial microvesicle (EMV) release. These results foster the notion that Liraglutide could exert a protective effect against hyperglycemia and inflammation triggered endothelial dysfunction.

Summary Pregnancies complicated by diabetes have largely increased in number over the last 50 years. Pregnancy is characterized by a physiologic increase in insulin resistance, which, associated with increased oxidative stress and inflammations, could induce alterations of glucose metabolism and diabetes. If not optimally controlled, these conditions have a negative impact on maternal and foetal outcomes. To date, one can resort only to diet and lifestyle to treat obesity and insulin resistance during pregnancy, and insulin remains the only therapeutic option to manage diabetes during pregnancy. However, in the last years, in a variety of experimental models, inositol and antioxidants supplementation have shown insulin‐sensitizing, anti‐inflammatory, and antioxidant properties, which could be mediated by some possible complementary mechanism of action. Different isomers and multiple combinations of these compounds are presently available: Aim of the present review article is to examine the existing evidence in order to clarify and/or define the effects of different inositol‐ and antioxidant‐based supplements during pregnancy complicated by insulin resistance and/or by diabetes. This could help the clinician's evaluation and choice of the appropriate supplementation regimen.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile. Area Covered: adverse events and the safety concerns most often emerged in trials with GLP-1RA namely, exenatide long acting release (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at comparing the safety profiles of molecules of these two classes. Expert opinion: GLP-1RA and SGLT2i, although each associated with different specific side effects, share a 'similar' safety profile and are both drugs relatively easy to handle. The potentially complementary mechanisms of action, the cardio and nephroprotective effects demonstrated by molecules of both classes, make these drugs potentially useful even in add on to each other.

Objective. Hypoglycemia is associated with increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes. Design. A non-randomised, mechanistic intervention study Methods. Insulin-treated patients with type 2 diabetes (n=21, [mean±SD] age 62.8±6.5 years, BMI 29.0±4.2 kg/m2, HbA1c 6.8±0.5% [51.0±5.4 mmol/mol]) and matched controls (n=21, age 62.2±8.3 years, BMI 29.2±3.5 kg/m2, HbA1c 5.3±0.3% [34.3±3.3 mmol/mol]) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: 1) fasting plasma glucose, 2) hyperglycemia (fasting plasma glucose+10 mmol/L) and 3) hyperinsulinemic hypoglycemia (plasma glucose<3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. Results. Both groups experienced progressively increasing heart rate corrected QT (Fridericia’s formula)) interval prolongations during hypoglycemia ([∆mean (95% CI)] 31 ms [16, 45] and 39 ms [24, 53] in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P=0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P=0.033 and P<0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia. Conclusions. In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrythmias and sudden cardiac death.