Increased level of plasma Cyclophilin A in early diabetic population suggesting it as a reliable pro inflammatory biomarker of coronary artery disease in diabetic patients
Authors: Chitra Sree Varadarajan V , Ajit Mullasari S , Vijayakumar Subban S , Suma M Victor V , Poornima M , Jayanthi S , Surya Ramachandran R , Kartha C C 
Published: January 2023

Abstract

Funding Acknowledgements
Type of funding sources: Other. Main funding source(s): Institute of Cardiovascular disease, Madras Medical Mission

Background
Type 2 Diabetes (DM) is a pro-inflammatory state in the pathogenesis of Atherosclerosis with the presence of many active proteins, of which CyclophilinA (CypA) has been shown to have a positive correlation with the presence and severity of vascular diseases. As Cyp A is proven to be secreted in varying levels from cells, in response to inflammatory stimuli, viz., hypoxia, infection, and oxidative stress, it is found ideal, to study it further as one of a reliable pro-inflammatory biomarker responsible for the progression of Coronary Artery Disease (CAD) in early DM.

Purpose
A prospective cross-sectional study was conducted to quantify CypA in the early phase of DM before the onset of CAD, in comparison to non-diabetic volunteers and to review it as one of the pro-inflammatory biomarkers of CAD, in association with hsCRP and other proven biomarkers (Insulin, Lipid profile, HBA1C, and Glucose).

Methods
The study subject comprised 299 patients with DM and 50 healthy volunteers. History of duration of DM and other co-morbidities was obtained. A comprehensive clinical examination and non-invasive evaluation of atherosclerotic vascular disease were done to rule out CAD. CypA was analyzed by ELISA kit in serum. P-value of &lt;0.05 was considered statistically significant.

Results
The average age group of study population is 51­ with an SD of 9.4(Male 206; Female 143). The observed range of CypA in our study is 50–1974 ng/ml, which is much higher than the values obtained in other studies (2–200 ng/ml). An increased level of CYP A is seen in DM than control group with a significant P Value of &lt;0.001 [DM - Mean 462.5 ; Median of 328 ng/ml; Control group(Non diabetic) - Mean 273 ; Median 190 ng/ml]. CypA value in early diabetics (&lt;5 years) is higher than patients with &gt;5 years of DM (one-way ANOVA).
Review of hsCRP shows statistically different levels between DM and the control group (p=0.012). Scatter plots of CypA and hsCRP concentration showed values within 500 ng/ml of CypA distributed in the mid to average risk category of hsCRP (&lt;1–3 mg/l). The probability of proposing CypA as a pro-inflammatory biomarker compared to hsCRP in DM is reviewed by the ROC curve (AUC 0.684 with a sensitivity of 80% and specificity of 50%). Increased CypA and hsCRP are observed in females than males (CypA: p=0.04 and hsCRP: p&lt;0.001). No significant difference is observed between the two groups in other variables (Insulin (P=0.69), Cholesterol (P= 0.33), TGL (P=0.77), HDL (P=0.17), LDL (P=0.06).

Conclusion
In our study CypA level is increased in the early stage of DM when compared with non-Diabetes. The range obtained is higher than the previous study values. CypA value of &lt;500 ng/ml is observed to be related to CAD when reviewed along with the hsCRP cardiac risk stratification range. The scope of CypA as a reliable pro-inflammatory biomarker of CAD in early DM is more promising and its edge over hsCRP as an early biomarker is to be reviewed further.