Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes
Atherosclerotic CVD is a major cause of death in individuals with type 1 diabetes mellitus (T1DM). However, conventional risk factors do not fully account for the increased risk. This study aimed to investigate whether serum proteins associate with diabetes status and the occurrence of CVD in T1DM....
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Elsevier
2025-02-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752500001X |
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| author | Baohai Shao Janet K. Snell-Bergeon Ian H. de Boer W. Sean Davidson Karin E. Bornfeldt Jay W. Heinecke |
| author_facet | Baohai Shao Janet K. Snell-Bergeon Ian H. de Boer W. Sean Davidson Karin E. Bornfeldt Jay W. Heinecke |
| author_sort | Baohai Shao |
| collection | DOAJ |
| description | Atherosclerotic CVD is a major cause of death in individuals with type 1 diabetes mellitus (T1DM). However, conventional risk factors do not fully account for the increased risk. This study aimed to investigate whether serum proteins associate with diabetes status and the occurrence of CVD in T1DM. We used isotope dilution-MS/MS to quantify 28 serum proteins in 228 subjects participating in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used linear regression to analyze the association between serum protein levels and T1DM status using 47 healthy controls and 134 T1DM patients without CVD and Cox proportional hazards regression to assess their prediction for incident CVD by a case-cohort study using a subcohort of 145 T1DM subjects and a total of 47 CVD events. Of the 28 serum proteins studied, five of them—alpha-2-macroglobulin (A2M), apolipoprotein A-IV, apolipoprotein L1, insulin-like growth factor 2, and phospholipid transfer protein—were significantly associated with T1DM status, with A2M being 1.6-fold higher in T1DM. After adjusting for potential confounders, A2M independently predicted incident CVD, with a mean hazard ratio of 3.3 and 95% CI of 1.8–6.1. In our study, A2M showed the largest increase in serum levels when comparing patients with T1DM to control subjects. A2M also predicted incident CVD, suggesting that it could serve as both a marker and possibly a mediator of atherosclerosis in T1DM. These findings emphasize the importance of specific serum proteins in assessing and managing CVD risk in T1DM. |
| format | Article |
| id | doaj-art-b3292b81be634efc8c013b2fbd3d41a2 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-b3292b81be634efc8c013b2fbd3d41a22025-02-02T05:26:36ZengElsevierJournal of Lipid Research0022-22752025-02-01662100741Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetesBaohai Shao0Janet K. Snell-Bergeon1Ian H. de Boer2W. Sean Davidson3Karin E. Bornfeldt4Jay W. Heinecke5Department of Medicine, University of Washington, Seattle, WA; For correspondence: Baohai Shao.Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CODepartment of Medicine, University of Washington, Seattle, WADepartment of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OHDepartment of Medicine, University of Washington, Seattle, WADepartment of Medicine, University of Washington, Seattle, WAAtherosclerotic CVD is a major cause of death in individuals with type 1 diabetes mellitus (T1DM). However, conventional risk factors do not fully account for the increased risk. This study aimed to investigate whether serum proteins associate with diabetes status and the occurrence of CVD in T1DM. We used isotope dilution-MS/MS to quantify 28 serum proteins in 228 subjects participating in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used linear regression to analyze the association between serum protein levels and T1DM status using 47 healthy controls and 134 T1DM patients without CVD and Cox proportional hazards regression to assess their prediction for incident CVD by a case-cohort study using a subcohort of 145 T1DM subjects and a total of 47 CVD events. Of the 28 serum proteins studied, five of them—alpha-2-macroglobulin (A2M), apolipoprotein A-IV, apolipoprotein L1, insulin-like growth factor 2, and phospholipid transfer protein—were significantly associated with T1DM status, with A2M being 1.6-fold higher in T1DM. After adjusting for potential confounders, A2M independently predicted incident CVD, with a mean hazard ratio of 3.3 and 95% CI of 1.8–6.1. In our study, A2M showed the largest increase in serum levels when comparing patients with T1DM to control subjects. A2M also predicted incident CVD, suggesting that it could serve as both a marker and possibly a mediator of atherosclerosis in T1DM. These findings emphasize the importance of specific serum proteins in assessing and managing CVD risk in T1DM.http://www.sciencedirect.com/science/article/pii/S002222752500001Xalpha-2-macroglobulinatherosclerosiscase-cohort designincident CVDCox proportional regressionmass spectrometry |
| spellingShingle | Baohai Shao Janet K. Snell-Bergeon Ian H. de Boer W. Sean Davidson Karin E. Bornfeldt Jay W. Heinecke Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes Journal of Lipid Research alpha-2-macroglobulin atherosclerosis case-cohort design incident CVD Cox proportional regression mass spectrometry |
| title | Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes |
| title_full | Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes |
| title_fullStr | Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes |
| title_full_unstemmed | Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes |
| title_short | Elevated levels of serum alpha-2-macroglobulin associate with diabetes status and incident CVD in type 1 diabetes |
| title_sort | elevated levels of serum alpha 2 macroglobulin associate with diabetes status and incident cvd in type 1 diabetes |
| topic | alpha-2-macroglobulin atherosclerosis case-cohort design incident CVD Cox proportional regression mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S002222752500001X |
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