期刊
CARDIOVASCULAR DIABETOLOGY
卷 14, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12933-015-0266-4
关键词
AGEs; A1c; DCCT/EDIC; Coronary artery calcium; Intima media thickening; Cardiac indices
资金
- NIDDK [DK-79432, JDRF 17-2010-318]
- National Institutes of Health [1982-93]
- Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease [U01 DK094176, U01 DK094157]
- National Eye Institute
- National Institute of Neurologic Disorders and Stroke
- Genetic Clinical Research Centers Program
- Clinical Translational Science Center Program, Bethesda, Maryland, USA
Background: We recently reported strong associations between eight skin collagen AGEs and two solubility markers from skin biopsies obtained at DCCT study closeout and the long-term progression of microvascular disease in EDIC, despite adjustment for mean glycemia. Herein we investigated the hypothesis that some of these AGEs (fluorescence to be reported elsewhere) correlate with long-term subclinical cardiovascular disease (CVD) measurements, i.e. coronary artery calcium score (CAC) at EDIC year 7-9 (n = 187), change of carotid intima-media thickness (IMT) from EDIC year 1 to year 6 and 12 (n = 127), and cardiac MRI outcomes at EDIC year 15-16 (n = 142). Methods: Skin collagen AGE measurements obtained from stored specimens were related to clinical data from the DCCT/EDIC using Spearman correlations and multivariable logistic regression analyses. Results: Spearman correlations showed furosine (early glycation) was associated with future mean CAC (p < 0.05) and CAC > 0 (p = 0.39), but not with CAC score < 100 vs. > 100. Glucosepane and pentosidine crosslinks, methylglyoxal hydroimidazolones (MG-H1) and pepsin solubility (inversely) correlated with IMT change from year 1 to 6(all P < 0.05). Left ventricular (LV) mass (cMRI) correlated with MG-H1, and inversely with pepsin solubility (both p < 0.05), while the ratio LV mass/end diastolic volume correlated with furosine and MG-H1 (both p < 0.05), and highly with CML (p < 0.01). In multivariate analysis only furosine (p = 0.01) was associated with CAC. In contrast IMT was inversely associated with lower collagen pepsin solubility and positively with glucosepane, Conclusions: In type 1 diabetes, multiple AGEs are associated with IMT progression in spite of adjustment for A1c implying a likely participatory role of glycation and AGE mediated crosslinking on matrix accumulation in coronary arteries. This may also apply to functional cardiac MRI outcomes, especially left ventricular mass. In contrast, early glycation measured by furosine, but not AGEs, was associated with CAC score, implying hyperglycemia as a risk factor in calcium deposition perhaps via processes independent of glycation.
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