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      Relationship of Lipoprotein(a) and Its Phenotypes with the Albumin Excretion Rate in Diabetic Patients: A Multivariate Analysis

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          Background/Aim: The possible association between lipoprotein(a) [Lp(a)] and albumin excretion rate (AER) is a topic that has generated conflicting views. The aim of this study was to determine the relationship between serum Lp(a) concentrations and AER in diabetic patients, taking into account Lp(a) phenotypes in a multivariate analysis. Methods: For this purpose 191 consecutive diabetic patients (69 type 1 and 122 type 2) were included in the study. Lp(a) was determined by ELISA and its phenotypes by SDS-PAGE followed by immunoblotting. Lp(a) phenotypes were grouped by size in small (F, B, S1, S2), big (S3, S4) and null. Results: Diabetic patients with an AER >20 µg/min presented higher Lp(a) concentrations than patients with an AER <20 µg/min: median 19 mg/dl versus 5 mg/dl (p < 0.0001). The differences remained at a significant level when the type of diabetes was considered. A linear correlation was observed between Lp(a) concentration and AER (type 1: r = 0.32, p = 0.01; type 2: r = 0.25, p < 0.05). The AER was independently correlated with Lp(a) concentrations in a multiple regression analysis (p < 0.01), and Lp(a) was independently associated with the presence of diabetic nephropathy in the logistic regression analysis. The overall frequency distribution of Lp(a) phenotypes differed significantly between patients with or without microalbuminuria (p < 0.05). In addition, the AER (µg/min) was different among the Lp(a) phenotypes: small 55 ± 122 (median 4.9), big 58 ± 123 (median 5.7) and null 3 ± 2 (median 2.3); p = 0.01. The significant difference mainly resulted from low AER (<10 µg/min) detected in all patients with the null phenotype. Conclusions: In diabetic patients the serum Lp(a) concentration is associated with AER. Thus, the elevated cardiovascular risk observed in diabetic patients with a high AER could be related to the Lp(a) concentration. Finally, patients with the null Lp(a) phenotype can be considered as a group at low risk of the development of diabetic nephropathy.

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          cDNA sequence of human apolipoprotein(a) is homologous to plasminogen.

          Lipoprotein(a) is an LDL-like lipoprotein whose concentration in plasma is correlated with atherosclerosis. The characteristic protein component of lipoprotein(a) is apolipoprotein(a) which is disulphide-linked to apolipoprotein B-100. Sequencing of cloned human apolipoprotein(a) complementary DNA shows that it is very similar to human plasminogen. It contains a serine protease domain and two types of plasminogen-like kringle domains, one of which is present in 37 copies.
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            Protein composition of Lp(a) lipoprotein from human plasma.

            The apolipoprotein composition of purified human Lp(a) lipoprotein was investigated by SDS--polyacrylamide gel electrophoresis and immunochemically. The lipoprotein contains two different polypeptides. One is identical by its app. Mr of approximately 250 000 and immunologically with apolipoprotein B of LDL (B-100). The other polypeptide has a higher app. Mr (approximately 350 000) and stains strongly with the periodate-Schiff's reagent. This high-Mr glycoprotein contains the specific Lp(a) immunoreactivity but does not react with antibodies against apo B. Apo B and Lp(a)-protein seem to be linked by disulfide bonds in the native lipoprotein. The unreduced detergent delipidized protein moiety from Lp(a) lipoprotein shows a single band of Mr approximately 700 000 in SDS--polyacrylamide gel electrophoresis and the immunoprecipitates formed against anti-Lp(a) and anti-apo B by the unreduced protein show a reaction of immunological identity.

              Author and article information

              S. Karger AG
              May 2000
              21 April 2000
              : 85
              : 1
              : 27-33
              Departments of aEndocrinology and bBiochemistry, Hospital General Vall d’Hebron, and cDepartment of Endocrinology, Hospital Mútua de Terrassa, Barcelona, Spain
              45626 Nephron 2000;85:27–33
              © 2000 S. Karger AG, Basel

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              Figures: 3, Tables: 6, References: 42, Pages: 7
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