Risk factors and Blood borne- biochemical markers in type 2 diabetes mellitus

Kappala, Shanthi Sharon (2012) Risk factors and Blood borne- biochemical markers in type 2 diabetes mellitus. Doctoral thesis, University of Central Lancashire.

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The burden of Diabetes Mellitus (DM) is increasing worldwide and it is estimated to reach indefinite proportions of about 450 million by year 2030. Patients with type 2 diabetes mellitus (T2DM) have a significantly increased risk of developing cardiovascular diseases (CVD). Moreover, CVD is the major cause of mortality and morbidity (75%) in T2DM patients. DM itself has been long recognised as an independent risk factor for several forms of CVD including coronary heart disease (CHD), peripheral arterial disease, cardiomyopathy and congestive heart failure in both men and women. It is well-known that T2DM is associated with several factors including hyperglycaemia, hypertension, dyslipidemia, obesity all of which contribute to CVD. In order to prevent CVD, early intervention on cardiovascular risk factors is vital during clinical assessment of T2DM patients. A major role of inflammation has been well described in the development of CVD in T2DM patients. Inflammatory process and factors which contribute to CVD in T2DM patients have recently become a focus in diabetic research. Elucidation of common patho-physiological mechanisms among T2DM patients might emphasize the role of inflammation in CVD.

The main purpose of this study was to investigate any patho-physiological changes in red blood cells (RBC), white blood cells (neutrophils and lymphocytes) and plasma, measuring RBC membrane fragility and proteins, intracellular free calcium concentrations [Ca2+]i and several cations including Na+, Mg2+, Ca2+, Fe2+, Zn2+ and Cu2+, biochemical parameters and inflammatory mediators which normally serve as independent predisposing risk factors for CVD among T2DM patients compared to age-match healthy controls.

The results have shown that fura-2 loaded neutrophils and lymphocytes in blood from T2DM patients contain significantly (p<0.05) less [Ca2+]i than neutrophils and lymphocytes from healthy subjects upon stimulation with physiological doses of either fMLP or thapsigargin indicating a derangement in cellular calcium homeostasis during T2DM. Similarly, RBC membranes from T2DM patients contained significantly (p<0.05) more spectrin, ankyrin, band 3, band 4.1, glycophorin etc compared to RBC membranes from age-matched healthy control subjects. The results also show that the RBCs from T2DM patients were more fragile compared to RBC from healthy controls. Measurement of protein glycation in plasma have revealed significantly (p<0.05) more fluorescence in proteins form T2DM patients compared to control. In relation to plasma cations and intracellular markers and mediators, the results show that plasma from T2DM patients contain significantly (p<0.05) more Na+, Mg2+ , Ca2+, Fe2+, Zn2+ and Cu2+ compared to plasma levels from age-match healthy controls. Similarly, the concentrations of kidney and liver function markers such as urea, creatinine, alkaline phosphatase, ALT, AST, GGT, total protein and albumin increased significantly (p<0.05) compared to healthy controls. The same is also true for glucose, total cholesterol, triglycerides, CRP, HBA1C, WBC where the blood from T2DM patients contained elevated concentrations compared to blood from healthy age-matched control patients.

Together, the results of this study have clearly demonstrated marked and significant changes in cellular calcium homeostasis in white blood cells, RBC membrane proteins and fragility, plasma protein glycation and in plasma levels of cations, intracellular markers and mediators of T2DM patients compared to healthy controls. Therefore, it is proposed that an early integrated and multi-factorial intervention of risk factors and inflammatory markers must be done in order to reduce the risk of CVD and possible mortality of T2DM patients.

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