The Role of Asymmetric Dimethylarginine and Lipoprotein Associated Phospholipase A2 in Children and Adolescents with Dyslipidemia

Background: The pathophysiologic mechanisms which lead to cardiovascular (CV) events begin early in childhood. Atherosclerosis is recognized as a process of chronic and dynamic vascular inflammation induced primarily by endothelial dysfunction. Asymmetric dimethylarginine (ADMA) and lipoprotein associated phospholipase A2 (Lp-PLA2) are considered markers of early atherosclerosis and predictors of late complications in adults. Objectives: To establish the relationship between ADMA, Lp-PLA2 and traditional biochemically determined markers in children and adolescents with dyslipidemia. Material and Methods: The study population consisted of 102 children, 57 males/45 females, with a median age of 9.9 years. Seventy-one out of 102 had dyslipidemia (LDL-C levels ≥ 130 mg/dl). Lipid levels were estimated after an overnight fasting. LDL-C concentration was directly measured. ADMA and Lp-PLA2 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using STATA for Windows v8.5. Results: ADMA was significantly positively correlated with all TC, LDL-C and non-HDL-C. Even small changes of the ADMA concentration were found to be followed by corresponding alterations in lipid levels. A positive correlation of borderline significance between Lp-PLA2 and LDL-C or non- HDL-C was observed. In addition, ADMA and Lp-PLA2 were significantly correlated. A strong correlation between Lp-PLA2 and dyslipidemia or lipid levels could not be established, probably due to the size and heterogeneity of our sample. Conclusions: A relationship of ADMA and Lp-PLA2 levels with biochemical markers associated with long-term risk of atherosclerosis in children and adolescents is supported. The assessment of these two biomarkers combined may improve CV risk prediction and future management strategies in the pediatric population.

Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment

The last few years important changes have occurred in the field of diabetes treatment.The priority in the therapy of patients with diabetes is not glycemic control per se rather an overall management of risk factors,while individualization of glycemic target is suggested.Furthermore,regulatory authorities now require evidence of cardiovascular(CV)safety in order to approve new antidiabetic agents.The most novel drug classes,i.e.,sodium-glucose transporter 2 inhibitors(SGLT2-i)and some glucagon-like peptide-1 receptor agonists(GLP-1 RA),have been demonstrated to reduce major adverse CV events and,thus,have a prominent position in the therapeutic algorithm of hyperglycemia.In this context,the role of previously used hypoglycemic agents,including dipeptidyl peptidase 4(DPP-4)inhibitors,has been modified.DPP-4 inhibitors have a favorable safety profile,do not cause hypoglycemia or weight gain and do not require dose uptitration.Furthermore,they can be administered in patients with chronic kidney disease after dose modification and elderly patients with diabetes.Still,though,they have been undermined to a third line therapeutic choice as they have not been shown to reduce CV events as is the case with SGLT2-i and GLP-1 RA.Overall,DPP-4 inhibitors appear to have a place in the management of patients with diabetes as a safe class of oral glucose lowering agents with great experience in their use.

Origin and therapy for hypertriglyceridaemia in type 2 diabetes

Hypertriglyceridaemia(HTG) is a risk factor for cardiovascular disease(CVD) in type 2 diabetes and is caused by the interaction of genes and non-genetic factors, specifically poor glycaemic control and obesity. In spite of statin treatment, residual risk of CVD remains high in type 2 diabetes, and this may relate to HTG and atherogenic dyslipidemia. Treatment of HTG emphasises correcting secondary factors and adverse lifestyles, in particular, diet and exercise. Pharmacotherapy is also required in most type 2 diabetic patients. Statins are the first-line therapy to achieve recommended therapeutic targets of plasma low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol. Fibrates, ezetimibe and n-3 fatty acids are adjunctive treatment options for residual and persistent HTG. Evidence for the use of niacin has been challenged by non-significant CVD outcomes in two recent large clinical trials. Further investigation is required to clarify the use of incretin-based therapies for HTG in type 2 diabetes. Extreme HTG, with risk of pancreatitis, may require insulin infusion therapy or apheresis.New therapies targeting HTG in diabetes need to be tested in clinical endpoint trials. The purpose of this review is to examine the current evidence and provide practical guidance on the management of HTG in type 2 diabetes.