Teresa Buckner1, Baohai Shao2, Robert H Eckel3, Jay W Heinecke2, Karin E Bornfeldt4, Janet Snell-Bergeon5. 1. Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: teresa.buckner@cuanschutz.edu. 2. Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA, USA. 3. Division of Endocrinology, Metabolism and Diabetes, and Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 4. Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA, USA. 5. Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Abstract
BACKGROUND: Apolipoprotein C3 (APOC3) is a risk factor for incident coronary artery disease in people with type 1 diabetes (T1D). The pathways that link elevated APOC3 levels to an increased risk of incident cardiovascular disease in people with T1D are not understood. OBJECTIVE: To explore potential mechanisms, we investigated the association of APOC3 with insulin resistance and coronary artery calcium (CAC). METHODS: In a random subcohort of participants with T1D from Coronary Artery Calcification in Type 1 Diabetes (n = 134), serum APOC3, high-density lipoprotein (HDL)-associated APOC3, and retinol binding protein 4 (RBP4; a potential marker of insulin resistance) were measured by targeted mass spectrometry. We used linear regression to evaluate associations of serum APOC3 and HDL-APOC3 with APOB, non-HDL cholesterol, serum- and HDL-associated RBP4, and estimated insulin sensitivity and logistic regression to evaluate association with presence of CAC, adjusted for age, sex, and diabetes duration. RESULTS: Serum APOC3 correlated positively with APOB and non-HDL cholesterol and was associated with increased odds of CAC (odds ratio: 1.68, P = .024). Estimated insulin sensitivity was not associated with serum- or HDL-RBP4 but was negatively associated with serum APOC3 in men (ß estimate: -0.318, P = .0040) and decreased odds of CAC (odds ratio: 0.434, P = .0023). CONCLUSIONS: Serum APOC3 associates with increased insulin resistance and CAC in T1D.
BACKGROUND: Apolipoprotein C3 (APOC3) is a risk factor for incident coronary artery disease in people with type 1 diabetes (T1D). The pathways that link elevated APOC3 levels to an increased risk of incident cardiovascular disease in people with T1D are not understood. OBJECTIVE: To explore potential mechanisms, we investigated the association of APOC3 with insulin resistance and coronary artery calcium (CAC). METHODS: In a random subcohort of participants with T1D from Coronary Artery Calcification in Type 1 Diabetes (n = 134), serum APOC3, high-density lipoprotein (HDL)-associated APOC3, and retinol binding protein 4 (RBP4; a potential marker of insulin resistance) were measured by targeted mass spectrometry. We used linear regression to evaluate associations of serum APOC3 and HDL-APOC3 with APOB, non-HDL cholesterol, serum- and HDL-associated RBP4, and estimated insulin sensitivity and logistic regression to evaluate association with presence of CAC, adjusted for age, sex, and diabetes duration. RESULTS: Serum APOC3 correlated positively with APOB and non-HDL cholesterol and was associated with increased odds of CAC (odds ratio: 1.68, P = .024). Estimated insulin sensitivity was not associated with serum- or HDL-RBP4 but was negatively associated with serum APOC3 in men (ß estimate: -0.318, P = .0040) and decreased odds of CAC (odds ratio: 0.434, P = .0023). CONCLUSIONS: Serum APOC3 associates with increased insulin resistance and CAC in T1D.
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