Abstract 13186: Factors Associated With Dysglycemia and Type 2 Diabetes Mellitus Onset in Familial Hypercholesterolemia

Abstract

Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant monogenic disorder characterized by high blood LDL-C and cardiovascular disease (CVD). Type 2 diabetes mellitus (T2DM) is an independent cause of CVD and there is evidence that FH is associated with a lower frequency of its development. On the other hand, lipid lowering therapy (LLT) may increase T2DM risk. Goals: Evaluate the risk of dysglycemia and T2DM development in a cohort of molecularly proven FH individuals. Methods: This is a prospective analysis of a population enrolled on a genetic cascade screening program evaluated from March 2011 to January 2022. FH diagnosis was confirmed by molecular testing of variants in LDLR, APOB and PCSK9. Dysglycemia and T2DM diagnoses were done according to the ADA Criteria or use of any antidiabetic drugs. Results: 790 FH patients were included (age 45.5±15.0 years, 56.8% female, baseline LDL-C 198±74 mg/dL), 96.6% had LDLR variants. The prevalence of T2DM was 13.3% and 67.4% were taking LLT at baseline . There were 206 (26%) new cases of T2DM or dysglycemia after a median 51-month follow-up . In multivariate Cox regression analysis age (HR:1.026, CI95%: 1.014-1.038, p=0.000) , body mass index (HR: 1.062, CI95%: 1.035-1.090, p=0.000) and current smoking (HR: 2.005, HR: 1.337-3.008, p=0.001) were independently associated with T2DM and dysglycemia, while metformin use was associated with a lower risk (HR: 0.147, CI95%: 0.076-0.284, p=0.000). History of previous CVD, use of lipid lowering therapy at baseline, high intensity LLT , or type of molecular defect were not associated with higher T2DM/dysglycemia risk. Conclusions: In this cohort of molecularly proven FH subjects, T2DM affected more than 1 in 10 people at baseline. Previous CVD and classical risk factors but neither molecular defects nor lipid lowering therapy were associated with T2DM/dysglycemia onset.