The Role of 3-Deoxyglucosone and the Activity of its Degradative Pathways in the Etiology of Diabetic Microvascular Disease

Abstract

Summary To address the role of 3-deoxyglucosone (3DG) and the activity of its major degradative pathways in diabetic nephropathy and retinopathy we have measured 3DG and its degradation products [3-deoxyfructose (3DF) and 3-deoxy-2-keto-gluconic acid (DGA)] in plasma and RBCs. In addition to these compounds, we have quantified HbA lc , renal dysfunction [glomerular filtration rate (GFR) and urinary albumin excretion(UAE)] and diabetic retinal sequelae over 2-3 years in 25 IDDM subjects with minimal complications during the earliest stages of diabetic microangiopathy. They were also measured in 58 subjects with NIDDM and 30 non-diabetic subjects. Plasma 3DG, 3DF and erythrocyte DGA were significantly elevated in diabetic subjects relative to controls. We also found a highly significant association between plasma 3DG and HbA lc concentrations, indicating that glycemic control is an important determinant of 3DG levels. An increased flux of 3DG to DGA and 3DF was associated with greater degrees of hyperglycemia, since both degradation products correlated with HbA lc values. Increasing rates of GFR also correlated with plasma 3DG levels and 3DG levels increased with increasing urinary albumin excretion (UAE). By contrast, there was an inverse correlation between plasma 3DF and UAE. Subjects showing progression of retinopathy also showed reduced plasma levels of the 3DG product 3DF relative to nonprogressors. As retinal perfusion decreased, we also observed increased 3DG levels.