Anaerobic Glycosis Is The Centre Of Different Biochemical Disarrays Associated With The Onset Of Diabetic Retinopathy

BACKGROUND: Despite almost similar hyperglycemic status and duration of the disease, some patients of type-2 diabetes mellitus develop microangiopathy within few years where as some individuals avoid this complication for a considerable period. It is assumed that some subjects of type 2 diabetes mellitus show hyperglycemia induced faster rate of anaerobic glycolytic pathway which liberate excessive intermediates of glycolysis responsible for increased intracellular Ca+ and increased extracellular glutamate and lactate, the end product of this metabolic pathway causing apoptosis of pericytes and dysfunction of endothelium of retinal capillaries. This retinal background created by excessive lactate may invite excessive secretion of vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR2) in an attempt to avoid the resultant irritating and destructive cellular condition. Associated increased activity of matrix metalloproteinases (MMP2 and MMP9) may cause degradation of extracellular matrix (ECM) and disruption of basal membrane of retinal capillaries. Aim : This longitudinal study was undertaken to assess the association of anaerobic glycolysis with lipid peroxidation, NO secretion, VEGF, VEGFR2, MMP2 and MMP9 at the time of development of earliest stage of diabetic retinopathy. METHODS: 142 patients of type-2 diabetes mellitus of 5 to 10 years duration having no retinopathy were recruited in this longitudinal study. Molecules like lactate, nitric oxide (NO), malondialdehyde (MDA), VEGF, VEGFR2, MMP2 and MMP9 were measured at the interval of one year for three years following standard methods of estimation. Detailed fundus examination and digital fundus photography were done in each patient to document appearance of microaneurysm. RESULTS : Surrogate markers of anaerobic glycolysis, oxidative stress, lipid peroxidation and consequently growth factor VEGF, it's receptor VEGFR2, MMP2 and MMP9 were significantly elevated in 32 patients of this group who developed earliest form of diabetic retinopathy compared to 108 diabetic subjects (p<0.001) CONCLUSION : Faster rate of glycolysis specially anaerobic glycolysis, lipid peroxidation and nitric oxide production occur in different extent in similar type of type 2 diabetic patients and stimulate differential expression of VEGF, KDR, MMP2 and MMP9. The whole cascade is centred on anaerobic glycolysis which is not beneficial to diabetic patients.