Increased Plasma Glycated Low-Density Lipoprotein Concentrations in Diabetes: A Marker of Atherogenic Risk

Abstract

Nonenzymatic glycation of apolipoprotein B in the low-density lipoprotein (LDL) complex has been considered a proatherogenic modification contributory to the increased susceptibility of patients with diabetes to atherosclerosis. We postulated that glycated LDL concentrations might be associated with other markers of cardiovascular disease. To explore this hypothesis, we measured glycated LDL concentrations by a monospecific immunoassay in 50 patients with type 1 and 100 patients with type 2 diabetes and examined relationships with the amount of albumin excretion and the serum cholesterol and triglyercide concentrations. Plasma glycated LDL showed a significant positive correlation (r = 0.325; P < 0.001) with urinary albumin excretion that was higher in type 1 (r = 0.463) than in type 2 (r = 0.245) patients. The mean glycated LDL concentration progressively increased with increasing albumin excretion when patients were subcategorized into groups of normoalbuminuria, low (</=100 microg/mg of creatinine), and high (101-300 microg/mg) microalbuminuria, and proteinuria. Glycated LDL also correlated positively and significantly with cholesterol (r = 0.578) and triglyceride (r = 0.350) concentrations. The significant correlations in this cross-sectional analysis between glycated LDL and urinary albumin excretion, an index of cardiovascular mortality, and cholesterol and triglyceride concentrations, traditional markers of risk for cardiovascular disease, support the hypothesis that an elevated level of glycated LDL represents an atherogenic risk factor in patients with diabetes.

Effect of irreversibly glycated LDL in human vascular smooth muscle cells: lipid loading, oxidative and inflammatory stress

“…Interestingly, Akanji et al [29] reported that serum‐glycated LDL level is increased in patients with hyperlipidaemia without diabetes (6.12 mg/dl), and further increased in patients with both hyperlipidaemia and diabetes (7.82 mg/dl) compared with 2.74 mg/dl in healthy subjects. It has been suggested that glycated LDL apoB could be utilized as an index of medium‐term glycaemic control as it correlates with glucose, fructosamine and glycated haemoglobin (HbA1c) in patients with diabetes [30].…”

Amadori-modified glycated serum proteins and accelerated atherosclerosis in diabetes: Pathogenic and therapeutic implications

“…Plasma concentrations of glycated LDL, measured by several different methods, are increased in diabetic patients (90)(91)(92)(93) and show positive associations with other markers of cardiovascular disease such as serum cholesterol and triglyceride levels (94). Interestingly, the amount of Amadori-modified LDL correlates positively with microalbuminuria (94), a marker of inflammation and an independent risk factor for cardiovascular mortality (95) that has been found to be associated with increased cardiovascular mortality in type 1 and type 2 diabetes (96-99) as well as in subjects without diabetes (100), and is considered a predictor of mortality in non-insulin dependent diabetes (101,102).…”

Homocysteinylation of low‐density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells

“…An increase of small and dense low‐density lipoproteins (LDL) and of glycated apoproteins has been described in patients with diabetes [2,3]. These compositional and physicochemical changes reflect alterations in the susceptibility to lipid peroxidation [4] and impaired interactions with cell receptors [4,5].…”