INTRODUCTION Type 2 diabetes mellitus(T2DM) as one of the most common chronic diseases globally, which is related with high risk of mortality and incident heart failure1-3. The potential pathomechanism of diabetic myocardial damage might results in diffuse myocardial fibrosis. Fibrosis might be potential associated with abnormal metabolic, especially hyperglycemia4. The Extracellular volume fraction (ECV), native T1 and postcontrast T1 obtained by cardiac magnetic resonance (CMR) T1-mapping techniques could noninvasively detect myocardial fibrosis, and ECV have been as an effect biomarker for evaluate diffuse myocardial fibrosis5-7. The purposes of this study were: (i) the relationship between the T1 mapping parameters and T2DM in cardiac indicators and hyperglycemia; (ii) the relationship among ECV in diabetic individuals and the level of glycosylated hemoglobin (HbAlc) and duration of diabetes.

METHODS Sixty-Two T2DM patients (45males, age 58.5±13.19 years) and 20 health controls (13 males, age 57.65±9.87 years) who underwent CMR were prospectively enrolled. Patients with history of myocardial infarction and other organic heart disease or had contraindication of CMR were excluded. The T1 mapping were performed for all of patients and controls to obtain native T1 value, postcontrast T1 value and calculated ECV value. According to HbAlc, all the 62 T2DM patients were classified in high HbAlc level group (HbA1c (%) ≥7.0; n=32) and low HbAlc level group (HbA1c (%) <7.0; n=30); according to duration of diabetes, all patients divided into A group (<5 years, n=28) and B group (≥5 years, n=34) .The independent-samples T test and Spearman rank correlation test were used for comparison and evaluated the relation. The Pearson rank correlation test was used foe evaluated the relationship between T1 mapping parameters and metabolic characteristics.

RESULTS T2DM patients had a higher value of ECV(35.21±5.03% vs. 29.33±2.7% ;p <0.001) than controls with statistical significance, the value of native T1(1296±67.09 ms vs. 1276.4±130.98 ms) and postcontrast T1 (523.6±78.3 ms vs. 504.6±26.2 ms) were slightly higher than controls, but there was no statistical significance. Besides, the myocardial mass at the end-diastole stage (54.86±19.27 g/m2 vs. 37.90±10.94 g/m2)was heavier than the controls, the cardiac function and ventricle diameter were similar(Table.1). Pearson’s correlation in Table.2 showed that ECV was positively associated with the HbA1c (R=0.373, p=0.021) and total cholesterol (TC) (R=-0.319, p=0.025). what’s more, the native T1 value was positively associated with Cre (R=0.597, P<0.001) and negatively associated with eGFR (R=0.-382; P=0.041), and the postcontrast T1 value was positively associated with eGFR (R=0.378; P=0.043). There was a significant difference in ECV between different HbA1c level group (high HbA1c vs. low HbA1c, 36.2±4.72% vs. 32.67±2.61%, p<0.001), and the myocardial mass value was difference between these two group (high HbA1c vs. low HbA1c, 59.78±2.92 g/m2 vs. 49.35±16.17 g/m2, p=0.045). While the native T1 value, postcontrast T1 value and the cardiac indicators had no differences between these two group(Table.3). Between the group A (<5 years) and group B (≥5 years), the ECV value had a statistically significant difference (A vs. B, 32.57±3.43 vs. 37.38±5.13, P<0.001) and the spearman correlation result showed that ECV was positively associated with the duration of diabetes (R=0.524,p<0.001) (Table.4).

DISCUSSION The high T1 mapping parameters value especially ECV and the heavier myocardia mass indicating the presence of myocardial fibrosis in T2DM, even early stage. The higher level HbA1c and longer duration diabetes might aggravation the diffuse myocardial fibrosis. Although HbA1c was a time-averaged glucose index, short and high glucose level might also cause myocardial damage. HbA1c and ECV and other T1 mapping parameters could detect the early fibrosis by quantity the myocardial extracellular matrix expansion.

CONCLUSION Diabetes is related to increased ECV, and ECV was correlated well with HbA1c level and duration diabetes. The trend of myocardial fibrosis in patients with hyperglycemia and long-term duration is more obvious. CMR T1 mapping might be a powerful technique for early diagnosis and intervention for cardiomyopathy.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81471721, 81471722, 81641169, 81771887 and 81771897), Program for New Century Excellent Talents in University (no: NCET-13-0386), and Program for Young Scholars and Innovative Research Team in Sichuan Province (2017TD0005) of China.

References

1. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 1974; 34:29–34. 2. J. M. Pappachan, G. I. Varughese, R. Sriraman, et al. Diabetic cardiomyopathy: pathophysiology, diagnostic evaluation and management. World Journal of Diabetes. 2013; 4(5):177-189. 3. Shivu, G. N. Relationship between coronary microvascular dysfunction and cardiac energetics impairment in type 1 diabetes mellitus. Circulation. 2010; 121(10):1209. 4. Robins, S. P. Biochemistry and functional significance of collagen cross-linking. Biochem Soc Trans. 2007; 35(5):849-52. 5. SibleyCT, Noureldin RA, Gai N, et al. T1 Mapping in cardiomyopathy at cardiac MR: comparison with endomyocardial biopsy. Radiology 2012;265: 724–32. 6. Miller CA, Naish JH, Bishop P, et al. Comprehensive validation of cardiovascular magnetic resonance techniques for the assessment of myocardial extracellular volume. Circ Cardiovasc Imaging 2013; 6:373–83. 7. P. Kellman, J. R. Wilson, H. Xue et al. Extracellular volume fraction mapping in the myocardium, part 2: initial clinical experience. Journal of Cardiovascular Magnetic Resonance,.2012; 14(1):1-8.