Practical management of dyslipidemia in the pediatric population with diabetes

Abstract

Early identification and timely treatment of dyslipidemia are fundamental pillars of cardiovascular prevention in individuals with diabetes. Atherosclerosis is a continuous process that begins during childhood and adolescence, and its progression is closely related to cumulative exposure to atherogenic lipoproteins. At the same time, diabetes accelerates the development of vascular disease through the interplay of chronic hyperglycemia, oxidative stress, low-grade inflammation, and endothelial dysfunction, all of which amplify the atherogenic effects of lipid abnormalities.

Elevated low-density lipoprotein cholesterol (LDL-C) is the most common quantitative lipid abnormality in type 1 diabetes. However, qualitative alterations in lipoproteins have also been described, including an increased proportion of small, dense LDL particles, impaired high-density lipoprotein (HDL) function, and elevated triglyceride-rich and remnant lipoproteins, all of which contribute to residual cardiovascular risk. In this context, emerging biomarkers such as apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)] have gained increasing attention as complementary tools for more accurate cardiovascular risk stratification.

The therapeutic approach should be comprehensive, focusing on optimization of glycemic control, promotion of cardioprotective dietary patterns, and regular physical activity. When lifestyle interventions are insufficient to achieve recommended LDL-C targets, pharmacological therapy should be initiated, as lipid-lowering treatment has demonstrated both efficacy and safety beginning in childhood. In recent years, advances in lipid-lowering therapies have expanded the therapeutic options for patients with high-risk hypercholesterolemia. In addition to statins and ezetimibe, bempedoic acid, an ATP-citrate lyase inhibitor, has been shown to significantly reduce LDL-C levels in adults with statin intolerance or established high cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, including evolocumab and alirocumab, achieve LDL-C reductions exceeding 50–60% and have demonstrated significant reductions in cardiovascular events in adults. More recently, inclisiran, a small interfering RNA (siRNA) targeting hepatic PCSK9 synthesis, has emerged as an attractive therapeutic option because of its twice-yearly dosing regimen. Although clinical experience with these agents in pediatric populations remains limited and they are not currently part of the routine management of dyslipidemia in children and adolescents with diabetes, they represent promising alternatives for selected patients, particularly those with familial hypercholesterolemia or very high cardiovascular risk.

Current evidence supports an early, multidisciplinary, and individualized preventive approach based on cardiovascular risk stratification, with the goal of reducing cumulative exposure to atherogenic lipoproteins and modifying the trajectory of cardiovascular disease from the earliest stages of life.