Study of dyslipidemia, glucose homeostasis and nitrosative stress in diabetes mellitus patients with and without coronary artery disease .

Abstract

Aims and Objectives: The risk of coronary artery disease (CAD) in diabetic subjects is increased two to four folds over age matched non-diabetic subjects. Conventional risk factors have failed to explain the increasing burden of CAD thus it is necessitating the need to search for other newer risk factors like Lipoprotein (a), homocysteine and inflammatry marker like hsCRP. Lp(a) variant of LDL is considered as one of the risk marker of coronary artery disease (CAD). Lp(a) levels shown wide ethnic variation among human population throughout the world. Endothelial dysfunction associated with diabetes has been attributed to lack of bioavailablity of nitric oxide (NO) due to reduced synthesis of NO from arginine. Material and Methods: This was hospital based case control study conducted in the department of Biochemistry. The study comprises total 195 participants, and 65 individuals in each groups has healthy controls, diabetes mellitus without CAD and diabetes mellitus with CAD patients. Detail history was taken and general physical examination was done. Fasting venous blood from the participants was used to estimate fasting blood glucose, glycated hemoglobin, total cholesterol, triglyceride, high density lipoprotein, lipoprotein (a), high sensitive C-reactive protein and nitric oxide. Observations: Serum FBG, HbA1c, TGs, VLDL, Lp(a) and hsCRP were significantly increased in DM without CAD patients and DM with CAD patients as compared to normal healthy controls. HDL-C and NO significantly decreased in DM without CAD patients and DM with CAD patients as compared to healthy controls. Raised serum Lp(a) level is associated with increased risk of CAD in DM patients. Cut-off value above 18 mg/dL in DM without CAD and above 21.6 mg/dL in DM with CAD patients and AUROC more than 0.8, this suggests that Lp(a) can be used to evaluate risk of CAD in DM patients in north Karnataka population. Lp(a) was found with positive effect and NO with negative effect on the chance of developing CAD in DM patients. With unit increase in Lp(a) level, the chance of CAD was 1.3 times higher in DM without CAD, while in the DM with CAD patients it was almost three times higher compared to healthy controls. Decreased NO levels may be a potential contributor to the pathogenesis of early vascular changes in DM and CAD patients. NO had negative effect on the chance of developing CAD in diabetic patients. Conclusion: To conclude, serum Lp(a) and hsCRP levels are elevated and NO level reduced in type-2 DM and CAD patients when compared to healthy controls. Thus estimation of Lp(a), NO and hsCRP serve as markers of CAD in type-2 DM patients where lipid profile was within normal range. Thus these tests should be included in panel of investigations for early diagnosis of CAD in DM patients and also to reduce morbidity and mortality associated with it.