Abstract
OBJECT: Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD), with increased risk already observed in the prediabetic state. This study aimed to investigate the association of insulin sensitivity, secretion, and clearance with subclinical atherosclerosis in a randomly selected cohort of Swedish adults aged 50-64 years without known diabetes. MATERIAL AND METHODS: For this cross-sectional analysis, data from the Umeå site of the Swedish CArdioPulmonary BioImage Study (SCAPIS) were used, which included 2507 individuals aged 50-64 years. After applying exclusion criteria, 2054 participants remained. Insulin sensitivity, secretion, and clearance were calculated using an oral glucose tolerance test (OGTT). Atherosclerosis was assessed by coronary computed tomography angiography (CCTA) and carotid ultrasound, yielding coronary artery calcification scores (CACS), coronary segment involvement scores (SIS), and total carotid plaque counts. Ordinal regression models analyzed associations between insulin measures and atherosclerosis, adjusting for cardiovascular risk factors. RESULTS: Lower insulin sensitivity, as measured by the GUTT index, was associated with higher CACS and SIS, but not with carotid plaque count. No significant relationship was found between insulin secretion (Insulinogenic Index) and any atherosclerotic marker. Reduced insulin clearance was associated with CACS and SIS in unadjusted analyses; however, these associations did not persist after multivariable adjustment. CONCLUSION: In individuals without diabetes, insulin resistance is associated with markers of subclinical coronary atherosclerosis, reinforcing its role in early CVD. Insulin secretion or clearance are not directly associated with measures of subclinical atherosclerosis in this population but may contribute indirectly via effects on circulating insulin levels.