Immune Response to Glycated and Oxidized LDL in IDDM Patients With and Without Renal Disease

Korpinen, Eija; Groop, Per‐Henrik; Åkerblom, Hans K.; Vaarala, Outi

doi:10.2337/diacare.20.7.1168

Cited by 27 publications

(11 citation statements)

References 9 publications

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“…When the possible correlation between oxLDL antibodies and diabetic nephropathy was first investigated no association was found between serum concentrations of oxLDL antibodies and diabetic nephropathy or nephropathy-related macroangiopathy [64]. In our study we were also unable to show a statistically significant correlation between circulating oxLDL antibody concentrations and proteinuria, although trend analysis showed a near significant correlation.…”

Section: Discussioncontrasting

confidence: 52%

Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy

et al. 2002

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Aims/hypothesis. Oxidized LDL is immunogenic and immune complexes formed by oxidized LDL and corresponding antibodies are pro-atherogenic and pro-inflammatory. Considering that macroalbuminuria is a risk factor for coronary heart disease and that common pathogenic factors for atherosclerosis and glomerulosclerosis exist, our aim was to determine whether the amount and/or characteristics of oxidized LDL-antioxidized LDL complexes correlated with the degree of albuminuria in patients with Type I (insulin-dependent) diabetes mellitus. Methods. We studied 33 macroalbuminuric patients (albumin excretion rate >300 mg/24 h) and 29 microalbuminuric patients (albumin excretion rate ≥30 mg/ 24 h and ≤300 mg/24 h) who were matched for age, sex and HbA 1C concentrations with 43 patients with normal albuminuria. In all patients we isolated and characterized oxidized LDL-anti-oxidized LDL complexes. A subgroup of 47 patients (22 with normal albuminuria, 11 with microalbuminuria, and 14 with macroalbuminuria) was randomly selected from the larger group for characterization of the antibody moiety of oxidized LDL immune complexes.Results. The concentrations of oxidized LDL immune complexes were increased in patients with macroalbuminuria (total cholesterol in immune complexes isolated from patients with macroalbuminuria was 272±20 vs 204±18 µg/ml in patients with normoalbuminuria, p<0.03). Also, the Kd of oxLDL antibodies isolated from the immune complexes was lower in patients with abnormal albuminuria than in patients with normoalbuminuria (0.86±0. Patients with Type I (insulin-dependent) diabetes mellitus are at an increased risk of developing microvascular and macrovascular disease [1,2,3], macrovascular disease being the main cause of morbidity and mortality in these patients. Nephropathy, a microvascular complication of diabetes, has been shown to be an important risk factor for macrovascular disease [4,5], suggesting that the two processes are interrelated. Several hypotheses have been put forward to explain how nephropathy

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Section: Discussioncontrasting

confidence: 52%

Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy

et al. 2002

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“…However, there is considerable disagreement between different groups about the nature of the abnormalities in modified LDL antibody levels in diabetic patients. Whereas Bellomo et al (32) reported higher levels of autoantibodies against glycated and oxidized LDL in type 2 diabetes patients than in control subjects and Festa et al (34) found a higher level of autoantibodies to oxidized LDL in type 1 diabetes patients, other investigators (33,36), including ourselves (15), have found comparable levels of these antibodies in type 1 as well as type 2 diabetic patients. In the present study, we also did not find any significant difference in the levels of free circulating anti-ox-LDL and anti-gly-LDL antibodies in the diabetic patient group as compared with the CAD patient and control groups (Fig.…”

Section: Discussionmentioning

confidence: 85%

“…The presence of antibodies against oxidized and glycated LDL in the serum of patients with diabetes has been reported by several investigators (32)(33)(34)(35)(36), including us (15). However, there is considerable disagreement between different groups about the nature of the abnormalities in modified LDL antibody levels in diabetic patients.…”

Section: Discussionmentioning

confidence: 94%

Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes.

et al. 2000

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We investigated the hypothesis that modified lipoproteins trigger an immune response leading to the production of autoantibodies and subsequently to the formation of atherogenic immune complexes (IC). We recruited 20 type 2 diabetic patients with macrovascular disease, 14 nondiabetic patients with coronary artery disease (CAD), and 34 healthy control subjects matched for age, sex, and race. Serum antibodies to oxidized and glycated LDL did not differ significantly among the 3 groups. Serum IC contained variable, but not statistically different, amounts of IgG, IgM, and IgA. In contrast, the content of cholesterol in IC isolated from diabetic patients was significantly higher than that in IC isolated from control subjects, and the content of apolipoprotein (apo)-B was significantly higher than that in IC isolated from control subjects and patients with CAD. Cholesteryl ester accumulation in human monocyte-derived macrophages incubated with IC, a measure of the atherogenic potential of IC, was significantly higher in macrophages incubated with red blood cell-adsorbed IC isolated from diabetic patients compared with IC isolated from control subjects (P < 0.03) or from patients with CAD (P < 0.04) and was strongly correlated with the content of apoB (r = 0.68, P < 0.001) and cholesterol (r = 0.61, P < 0.001) in IC. LDL from diabetic patients was more susceptible to oxidation in vitro, was significantly smaller, and contained significantly less ␣-tocopherol than LDL isolated from subjects in the other groups. In addition, the n-3 polyunsaturated fatty acid content of phospholipids and cholesteryl esters in LDL isolated from diabetic patients was significantly increased (P < 0.05) compared with that from patients with CAD or from control subjects. We postulate that LDL size, susceptibility to oxidation, and lipid fatty acid composition may play a critical role in the production of antibodies to oxidized LDL and consequently in the formation of LDL-containing IC in patients with type 2 diabetes. Diabetes

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“…In patients with diabetes, the presence in the serum of oxLDL Ab has been reported by several investigators. However, there is disagreement among different authors since some studies reported higher levels of oxLDL Ab in both type 1 and type 2 diabetic patients than in control subjects (19,35); other investigators have found comparable levels of these antibodies in type 1 as well as type 2 diabetic patients (20,36,37). In another study, not significant differences in the levels of free-circulating oxLDL Ab in the diabetic patient group compared with patients with coronary artery disease and control groups have been recorded (38).…”

Section: Results -The Main Clinical Featuresmentioning

confidence: 97%

Autoantibodies Against Oxidized LDLs and Atherosclerosis in Type 2 Diabetes

et al. 2005

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OBJECTIVE—The aim of our study was to examine, in type 2 diabetic patients, the relationship between autoantibodies against oxidatively modified LDL (oxLDL Ab) and two indexes of atherosclerosis, intimal-medial thickness of the common carotid artery (CCA-IMT), which reflects early atherosclerosis, and the ankle-brachial index (ABI), which reflects advanced atherosclerosis. RESEARCH DESIGN AND METHODS—Thirty newly diagnosed type 2 diabetic patients, 30 type 2 diabetic patients with long duration of disease, and 56 control subjects were studied. To detect oxLDL Ab, the ImmunoLisa Anti-oxLDL Antibody ELISA was used. ABI was estimated at rest by strain-gauge plethysmography. Carotid B-mode imaging was performed on a high-resolution imaging system (ATL HDI 5000). RESULTS—In patients with long duration of disease, IgG oxLDL Ab were significantly higher and ABI significantly lower compared with the other two groups. We found a correlation between IgG oxLDL Ab and CCA-IMT in all diabetic patients. A significant inverse correlation between IgG oxLDL Ab and ABI only in patients with long duration of disease was seen, demonstrating a close relationship between these autoantibodies and advanced atherosclerosis. CONCLUSIONS—IgG OxLDL Ab may be markers of the advanced phase of the atherosclerotic process and the response of the immunological system to the oxLDL, which are present within atherosclerotic lesions.

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Immune Response to Glycated and Oxidized LDL in IDDM Patients With and Without Renal Disease

Abstract: Antibodies to glycated and oxidized LDL do not seem to associate with diabetic nephropathy or nephropathy-related macroangiopathy.

Cited by 27 publications

References 9 publications

Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy

Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy

Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes.

Autoantibodies Against Oxidized LDLs and Atherosclerosis in Type 2 Diabetes

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