Publication Type:

Journal Article


Clinical Biochemistry, Volume 38, Number 10, p.892 - 899 (2005)





Objective: Protein glutathionylation is considered an important post-translational modification in the pathogenesis of complex diseases. The aim of this study was to examine whether hemoglobin (Hb) is modified by reduced glutathione (GSH) via oxidation of the thiol groups present in diabetes and its associated microangiopathy and to determine whether oxidative imbalance has any correlation with glutathionylated Hb (HbSSG) levels. Methods: The study group consisted of a total of 130 subjects which included non-diabetic healthy control subjects (n = 30) and type 2 diabetic patients with (n = 53) and without (n = 47) microangiopathy. All subjects were assessed for glycemic and lipidemic status, while diabetic subjects were also assessed for the diagnosis of retinopathy and nephropathy. \{RBC\} lysates from all the subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) for HbSSG β-globin chains. Levels of \{GSH\} and thiobarbituric acid substances (TBARS) levels were measured by spectrophotometric and fluorimetric methods, respectively. Results: The positivity for HbSSG in diabetic subjects with microangiopathy was significantly higher (69%) compared to diabetics without microangiopathy (22%) and control subjects (14%). In univariate regression analysis, HbSSG levels were significantly associated with the duration of diabetes, HbA1c, and \{TBARS\} levels. \{GSH\} levels were negatively correlated (r = −0.57, P < 0.001) with HbSSG in diabetic subjects. A significant inverse correlation (r = −0.42, P < 0.001) between the \{GSH\} levels and HbA1c levels was also seen in diabetic subjects. Conclusions: This is perhaps the largest LC-MS-based study to demonstrate that HbSSG levels are markedly increased in diabetic subjects with microangiopathy. Since diabetic subjects also exhibited increased lipid peroxidation and decreased \{GSH\} levels, it appears that enhanced oxidative stress may account for the increased HbSSG concentrations and altered reduction–oxidation (redox) signaling.

Cite this Research Publication

R. Sampathkumar, Balasubramanyam, M., Sudarslal, S., Rema, M., Mohan, V., and Balaram, P., “Increased Glutathionylated Hemoglobin (HbSSG) in Type 2 Diabetes Subjects with Microangiopathy”, Clinical Biochemistry, vol. 38, pp. 892 - 899, 2005.