Elevation of Serum Cystatin C Levels as a Predictor of Cardiovascular Risk in Type 2 Diabetes Mellitus Patients: A Case-control Study

Abstract

Introduction: Patients with type 2 Diabetes Mellitus (DM) exhibit atherogenic lipid profile, increasing the risk for atherosclerosis, compared to people without diabetes. Cystatin C, a naturally occurring protease inhibitor has a key role in pathogenesis of atherosclerosis in type 2 DM patients by inhibiting the elastolytic activity of arterial extracellular matrix by cysteine protease cathepsins. Increased concentration of cystatin C in serum reflects a counterbalance of the damaging elastolytic activity which is involved in the pathogenesis of atherosclerosis in type 2 DM patients. Aim: To determine the serum levels of cystatin C and lipid profile in type 2 DM patients with good and poor glycaemic control and to find out the correlation between serum cystatin C with HbA1c levels and cardiovascular risk markers (non-High-Density Lipoprotein Cholesterol (HDLc), Total Cholesterol (TC)/HDLc, Low-Density Liporotein (LDLc)/HDLc). Materials and Methods: The present case-control study included 60 diabetic patients of 35-75 years of age including both the genders. They were divided into Group A (n=30) with HbA1c ≤6.5% and Group B (n=30) with HbA1c >6.5%. Blood samples were collected in fasting state and analysed for Fasting Blood Sugar (FBS), TC, HDLc, LDLc. FBS was analysed by Hexokinase method, HbA1c by turbidimetric inhibition immunoassay and cystatin C by Immunoturbidimetric method. Other parameters like Non-HDLc and cardiovascular risk ratios TC/HDLc and LDLc/HDLc were calculated. Statistical analysis was done by student’s t-test and statistical significance was established at p-value <0.0001. Pearson’s correlation coefficient was used to examine various parameters. Results: In the present study, it was found that diabetic patients with HbA1c >6.5% showed increased levels of serum cystatin C (1.20±0.73 mg/L), TC (182±46.48 mg/dL), LDLc (137±13.86 mg/dL) and low levels of HDLc (34.7±12.43 mg/dL) compared to diabetic patients with HbA1c ≤6.5%. Increase in serum cystatin C levels correlated well with the increased levels of HbA1c (r=0.92), non-HDLc (r=0.87) and cardiovascular risk ratios like TC/HDLc (r=0.95) and LDLc/HDLc (r=0.97). Conclusion: The elevated serum levels of cystatin C levels correlated well with increased HbA1c and lipid profile indicating the dyslipidemia and proatherogenic status in type 2 diabetic patients with poor glycaemic control. Thus, cystatin C can be considered as the predictive marker for cardiovascular disease in type 2 diabetic patients.