Journal Article

Secretory Acid Sphingomyelinase in Children and Adolescents With Type 1 Diabetes

Redaelli, Francesca Chiara, Macedoni, Maddalena, Mameli, Chiara, Ferrigno, Cristina, Perrotta, Cristiana, Zecchini, Silvia, Zuccotti, Gianvincenzo, Napoli, Alessandra, Petitti, Agnese, Clementi, Emilio, Bolchini, Alice, Biejat, Paulina Roux, Arcari, Alessandro

2026

Overview

The activity of acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, has been found to be increased in a variety of human diseases. Studies conducted on animal and cellular models showed that sphingolipids and ASMase play a central role in the pathogenesis of type 1 diabetes (T1D) and T1D-related vascular damage. Currently, no studies have investigated the role of ASMase activity in pediatric patients with T1D. Therefore, we conducted a cross-sectional study to evaluate the activity of the secretory form of ASMase (S-ASMase) in the serum of patients with T1D aged 2-16 years in comparison with a control group (healthy subjects matched for age, gender, and pubertal stage). We recruited children and adolescents affected by T1D (including patients with new-onset and established T1D) aged 2-16 years and healthy normal-weight subjects with normal timing of puberty (matched for age, gender, and pubertal stage), who were consecutively admitted-as outpatients-to our institution for screening purposes. Serum lipid profile, glycated hemoglobin (HbA1c), and urine albumin-creatinine ratio (uACR) were assessed in all T1D patients. S-ASMase activity was measured in all study participants through a colorimetric assay. In total, 68 T1D patients and 51 healthy controls were recruited in this study. None of the T1D patients had T1D-related complications. No difference in S-ASMase activity was observed between subjects with T1D and healthy controls. However, when T1D patients were stratified according to the duration of diabetes, we found a significantly higher activity of S-ASMase in patients with new-onset T1D (recruited within 1 week after the disease diagnosis) as compared to that observed in patients with established T1D. In all patients with T1D, S-ASMase activity correlated positively with HbA1c and triglyceride levels, while it correlated negatively with total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels. However, there were no significant differences in S-ASMase activity between T1D patients with new-onset disease who presented with diabetic ketoacidosis (DKA; n = 12) and T1D patients with new-onset disease who did not present with DKA (n = 13). Our study evaluated, for the first time, the in vivo activity of S-ASMase in a pediatric cohort of patients with T1D. In pediatric patients with new-onset T1D, we found a significantly higher S-ASMase activity as compared to that observed in patients with established T1D. In all T1D patients, the positive correlation between S-ASMase activity, HbA1c, and triglyceride levels, as well as the negative correlation between S-ASMase activity and HDL-C levels, suggests a potential role played by sphingolipids in T1D pathophysiology. Further mechanistic studies are needed to better elucidate the role of S-ASMase in patients with T1D at different stages of the disease.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Acids / Adolescent / Age / Albuminuria - urine / Blood pressure / Body mass index / Case-Control Studies / Child / Child, Preschool / Children & youth / Cholesterol / Creatinine - urine / Cross-Sectional Studies / Diabetes / Diabetes Mellitus, Type 1 - blood / Diabetes Mellitus, Type 1 - enzymology / Diabetic ketoacidosis / Diabetic retinopathy / Disease / Enzymes / Female / Gender / Glycated Hemoglobin - analysis / Glycated Hemoglobin - metabolism / Humans / Hypertension / Insulin / Laboratories / Lipids - blood / Male / Obesity / Overweight / Patients / Pediatrics / Software / Sphingomyelin Phosphodiesterase - blood / Sphingomyelin Phosphodiesterase - metabolism / Standard scores / Statistical analysis / Teenagers / Urine / Variance analysis