2726-LB: Association of Ceramide Score (CERT1) with Insulin Sensitivity and Secretion in a Healthy Biracial Cohort

Introduction and Objective: Ceramides are bioactive sphingolipids implicated in cardiometabolic disease. The Ceramide Risk Score Test (CERT1) predicts cardiovascular risk and is derived from four ceramide species: ceramide (d18:1/16:0), ceramide (d18:1/18:0), ceramide (d18:1/24:1), and ceramide (d18:1/24:0). We examined associations between CERT1 and insulin dynamics in normoglycemic adults from a biracial cohort. Methods: Sphingolipids were measured from the plasma of 240 healthy Black and White participants in the POP-ABC study (mean age 43.1±12.1 yr; BMI was 29.4±6.2 kg/m²; Fasting glucose 91.4±6.9 mg/dl), and CERT1 scores were calculated. Associations were examined with demographic, anthropometric, and metabolic variables, including BMI, glucose measures, lipid profile, insulin sensitivity index (ISI), acute insulin response to glucose (AIR), and metabolic syndrome scores. Results: CERT1 was positively correlated with AIR but not ISI in the overall cohort (r=0.18, P=0.018). Women (r=0.29, P=0.002) and participants aged 45-65 years (r=0.22, P=0.022) showed strong positive associations between CERT1 and AIR, and inverse association with ISI (women r=-0.22; P=0.034; age 45-60 yr r=-0.27; P=0.014). CERT1 was not associated with BMI, glucose, or lipid levels. Conclusion: Among normoglycemic subjects with overweight/obesity, higher CERT1 scores were significantly associated with decreased insulin sensitivity and compensatory insulin secretion, particularly in women and older adults. The basis of the apparent age/gender specificity of the CERT1 associations with insulin dynamics remains to be elucidated. Disclosure N. Mandal: None. F.B. Stentz: None. S. Dagogo-Jack: Consultant; Current; Abbott, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk. Funding NIH/NIDDK (R01DK128129)