The evolutionary conserved family of heat shock proteins (HSP) is responsible for protecting cells against different types of stress, including oxidative stress. Although the levels of HSPs can be readily measured in blood serum, the levels of HSP70 in patients with different durations of diabetes have not been studied before. We quantified serum HSP70 levels in a healthy control group (n=36) and two groups of type 2 diabetic patients, defined as newly diagnosed diabetes (n=36) and patients with diabetes duration of more than 5 years (n=37). The clinical characteristics and biochemical parameters were evaluated in the studied population. We found that serum HSP70 levels were significantly higher in patients with diabetes when compared with controls (p<0.001) and it was higher in patients with disease for more than 5 years than in newly diagnosed patients (p<0.001). Serum HSP70 was inversely correlated with fasting blood sugar in patients with diabetes for more than 5 years (r=−0.500, p=0.002), positively correlated with the history of hypertension in newly diagnosed patients (p<0.001), and positively correlated with age in patients with diabetes (r=0.531, p=0.001). Serum level of HSP70 is significantly higher in patients with diabetes and correlates with the duration of disease. Higher HSP70 in prolonged diabetes versus newly diagnosed diabetes may be an indicator of metabolic derangement in the course of diabetes.

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The pathogenesis of diabetic nephropathy, mainly characterized by macroalbuminuria, is still poorly understood, but it is reported that transforming growth factor-beta (TGF-beta) plays a key role. In vitro evidence suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of TGF-beta by human glomerular mesangial cells. This study aimed to evaluate the association between macroalbuminuria, ox-LDL, and TGF-beta in diabetic patients. A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion rate: AER > or = 300 mg/24 h) and 66 patients with normoalbuminuria (AER < or = 30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels of ox-LDL and TGF-beta were determined. Ox-LDL and TGF-beta were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria (98.93 + or - 3.99 vs. 72.45 + or - 2.48 U/l; P < 0.001 and 6.46 + or - 0.74 vs. 2.49 + or - 0.39 ng/ml; P < 0.001, respectively). In patients with macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-beta (r = 0.376; P < 0.01). AER was significantly correlated to ox-LDL (r = 0.302; P < 0.05) and TGF-beta (r = 0.306; P < 0.05) in macroalbuminuric patients. This association remained significant after adjustment for potential confounders. Adjustment for TGF-beta (ox-LDL), attenuated the association of ox-LDL (TGF-beta) with AER. In conclusion, this study demonstrated the association of TGF-beta and ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and suggested that this relationship is highly mediated through the correlation between TGF-beta and ox-LDL.