Introduction
Diabetes mellitus is one of the major metabolic disorders worldwide. This metabolic disturbance is associated with high morbidity and mortality caused by micro-vascular complications [1]. Apoptosis plays an important role in normal tissue homeostasis. Dysregulated apoptotic modulators result in excessive or insufficient cell death fundamental to the initiation and progression of many human diseases including diabetes mellitus [2]. Oxidative stress as expressed by lipid peroxidation products, e.g. thiobarbituric–acid reactive substances (TBARS), is an apoptotic inducer [3]. It leads to dysregulated cell growth or apoptosis, which contributes to the development of inflammation and secondary complications of diabetes [4].
The objectives of this study are: to investigate the dysregulation of apoptotic modulators in type I and type 2 diabetes and to determine plasma levels of soluble Fas (sFas), sFas ligand (sFasL), tumor necrosis factor-alpha (TNF-α), TBARS and nitric oxide (NO); and to evaluate the relationships of these bio-indices with glycemic control, disease complications (diabetic neuropathy) and duration.
Methods
Sixty diabetic patients (30 each of type 1 and type 2 diabetes mellitus) were sub-classified into non-complicated diabetic patients and patients with diabetic neuropathy. Patients were also categorized according to glycemic control (HbA1c ≤ 7% and HbA1c > 7%) and duration of diabetes (≤ 1 year and > 1 year). Each diabetic group was compared with its related age-matched control group. The plasma levels of sFas, sFasL, and TNF-α were determined using specific ELISA assays. The plasma levels of NO and TBARS were measured by colorimetric methods. Blood HbA1c was determined by chromatography.
Results
In types 1 and 2 diabetes, plasma levels of sFas, TNF-α, TBARS and NO were significantly higher in non-complicated and complicated diabetes than controls. These indices were found significantly higher in complicated than non-complicated diabetic patients. Plasma sFasL level was insignificant in complicated in comparison with non-complicated type I and II diabetic patients. Significant increases in the investigated bio-indices were observed in type 1 diabetic patients with good and poor glycemic controls compared to controls. Poor glycemic control showed significantly higher levels of TNF-α in types 1 patients in comparison with good glycemic control. There were significant positive correlations among the investigated biochemical indices and indicators of glycemic control, oxidative stress and duration of the disease particularly in type 1 diabetes.
Discussion
Types I and II diabetes are associated with dysregulated apoptotic modulators. Could the modulation of the observed dysregulation benefits diabetic patients? This is a point that needs further clarification. However, the increased level of apoptotic modulators detected in this study seems to be implicated in diabetic neuropathy and hence should be taken in the consideration as predictive marker for such complication and in strategies for therapeutic intervention.
References
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