Familial Hypercholesterolemia in Pediatric Patients With Type 1 Diabetes: Double Challenge for Diagnosis and Treatment.

Abstract

Familial hypercholesterolemia (FH) and type 1 diabetes (T1D) are both common and without adequate treatment, lead to premature atherosclerosis and cardiovascular events. We identified children with T1D and probable FH and analyzed their lipid-lowering therapy (LLT). This retrospective cohort study was based on the Diabetes Prospective Follow-Up registry, analyzing data of 41,992 children (2014-2023) with pediatric T1D from 384 European centers. Classification of probable FH was >2× LDL cholesterol (LDL-C) >4.9 mmol/L and of possible FH, >2× LDL-C >4.1 mmol/L and ≤4.9 mmol/L. A total of 31,862 patients consistently had LDL-C <4.1 mmol/L, 416 (1.2%) had possible FH, and 195 (0.56%) had probable FH. Compared with the LDL-C <4.1 mmol/L cohort, the possible FH and probable FH groups had higher BMI standard deviation scores (0.73 and 0.55 vs. 0.27, P < 0.00001) and higher HbA1c (8.2% [66 mmol/mol]) and 8.3% [67 mmol/L] vs. 7.5% [58 mmol/mol], P < 0.00001) and were more often female (57% and 62% vs. 44%, P < 0.00001). Odds ratios for LDL-C 2× >4.9 mmol/L were 3.85 (95% CI 2.6-5.7) for HbA1c >9% (>75 mmol/mol), 2.12 (1.48-3.04) for HbA1c 7.5-9% (58-75 mmol/mol), 2.10 (1.56-2.81) for female sex, and 1.47 (1.08-2.02) for BMI >70th percentile. In the possible FH and probable FH groups, 20% and 29% were receiving LTT, respectively. The prevalence of probable FH was high (1 in 215 children) in pediatric T1D. We assume that the majority are affected by genetic FH, modified by HbA1c and BMI. Despite the very high risk for premature atherosclerosis in patients with FH and T1D, only one-third receive LLT.