Summary
Patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are at increased risk of developing atherosclerotic vascular diseases. A variety of lipoprotein abnormalities have been described as being associated with this increased risk. In this study, apo(a) isoform frequencies and lipoprotein(a) [Lp(a)] concentrations were determined in Type 1 and Type 2 diabetic patients in order to investigate a possible contribution of Lp(a) to the increased risk for atherosclerosis in diabetes. No significant differences in plasma Lp(a) concentrations were found in two ethnically different populations (Austrians from the province of Tyrol and Hungarians from Budapest) in either type of diabetes when compared to respective control groups (91 Type 1 and 112 Type 2 diabetic patients vs 202 control subjects in the Hungarian study and 44 Type 1 diabetic and 44 Type 2 diabetic vs 125 control subjects in the Austrian study). There were also no significant apo(a) isoform frequency differences between both patient groups and control subjects in the two study groups. These data, obtained from two large ethnically different populations, provide no evidence of a contribution of Lp(a) to the increased risk for atherosclerosis in diabetes.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Garcia MJ, McNamara PM, Gordon T, Kannel WB (1974) Morbidity and mortality in diabetes in the Framingham population. Diabetes 23: 105–111
Kostner GM, Karádi I (1988) Lipoprotein alterations in diabetes mellitus. Diabetologia 31: 717–722
Howard BV (1987) Lipoprotein metabolism in diabetes mellitus. J Lipid Res 28: 613–628
Ganda OP (1980) Pathogenesis of macrovascular disease in the human diabetic. Diabetes 29: 931–942
Rhoads GG, Dahlen G, Berg K, Morton NE, Dannenberg AL (1986) Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA 256: 2540–2544
Hoefler G, Harnoncourt F, Paschke E, Mirtl W, Pfeiffer KH, Kostner GM (1988) Lipoprotein(a). A risk factor for myocardial infarction. Arteriosclerosis 8: 398–401
Sandholzer C, Boerwinkle E, Saha N, Tong C, Utermann G (1992) Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease. J Clin Invest 89: 1040–1046
Bihari-Varga M, Gruber E, Rotheneder M, Zechner R, Kostner GM (1988) Interactions of lipoprotein Lp(a) and low density lipoprotein with glycosaminoglycans from human aorta. Arteriosclerosis 8: 851–857
Edelberg JM, Gonzalez-Gronow M, Pizzo SV (1990) Lipoprotein(a) inhibition of plasminogen activation by tissue-type plasminogen activator. Thromb Res 57: 155–162
Utermann G, Weber W (1983) Protein composition of Lp(a) lipoprotein from human plasma. FEBS Lett 154: 357–361
Gaubatz JW, Heideman C, Gotto AM Jr, Morrisett JD, Dahlen GH (1983) Human plasma lipoprotein (a): structural properties. J Biol Chem 258: 4582–4589
Utermann G (1989) The mysteries of lipoprotein(a). Science 246: 904–910
McLean JW, Tomlinson JE, Kuang W-J et al. (1987) cDNA sequence of human apolipoprotein (a) is homologous to plasminogen. Nature 300: 132–137
Karádi I, Kostner GM, Gries A, Nimpf J, Romics L, Malle E (1988) Lipoprotein (a) and plasminogen are immunochemically related. Biochim Biophys Acta 960: 91–97
Kratzin H, Armstrong VW, Niehaus M, Hilschman N, Seidel D (1987) Structural relationship of an apolipoprotein (a) pheno-type (570 kDa) to plasminogen: homologous kringle domains are linked by carbohydrate-rich regions. Biol Chem Hoppe-Seyler 368: 1533–1544
Utermann G, Menzel HJ, Kraft HG, Duba HC, Kemmler HG, Seitz C (1987) Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J Clin Invest 80: 458–465
Kamboh MI, Ferrell RE, Kottke BA (1991) Expressed hypervariable polymorphism of apolipoprotein (a). Am J Hum Genet 49: 1063–1074
Lindahl G, Gersdorf E, Menzel HJ, Seed M, Humphries S, Utermann G (1990) Variation in the size of human apolipoprotein(a) is due to a hypervariable region in the gene. Hum Genet 84: 563–567
Lackner C, Boerwinkle E, Leffert CC, Rahmig T, Hobbs HH (1991) Molecular basis of apolipoprotein (a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest 87: 2153–2161
Gavish D, Azrolan N, Breslow JL (1989) Plasma Lp(a) concentration is inversely correlated with the ratio of kringle IV/kringle V encoding domains in the apo(a) gene. J Clin Invest 84: 2021–2027
Kraft HG, Köchl S, Menzel HJ, Sandholzer C, Utermann G (1992) The apolipoprotein(a) gene — a transcribed hypervariable locus controlling plasma lipoprotein(a) concentration. Hum Genet (In press)
Sandholzer C, Hallman DM, Saha N et al. (1991) Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups. Hum Genet 86: 607–614
Utermann G, Hoppichler F, Dieplinger H, Seed M, Thompson G, Boerwinkle E (1989) Defects in the LDL receptor gene affect Lp(a) lipoprotein levels: multiplicative interaction of two gene loci associated with premature atherosclerosis. Proc Natl Acad Sci USA 86: 4171–4174
Maeda S, Abe A, Seishima M, Makino K, Noma A, Kawade M (1989) Transient changes of serum lipoprotein(a) as an acute phase protein. Atherosclerosis 78: 145–150
Henriksson P, Angelin B, Berglund L (1992) Hormonal regulation of serum Lp(a) levels: opposite effects after estrogen treatment and orchidectomy in males with prostatic carcinoma. J Clin Invest 89: 1166–1171
Menzel H-J, Dieplinger H, Lackner C et al. (1990) Abetalipoproteinemia with an apoB-100-lipoprotein(a) glycoprotein complex in plasma. Indication for an assembly defect. J Biol Chem 265: 981–986
Patsch W, Brown SA, Morrisett JD, Gotto AM Jr, Patsch JR (1989) A dual-precipitation method evaluated for measurement of cholesterol in high-density lipoprotein subfractions HDL2 and HDL3 in human plasma. Clin Chem 35: 265–270
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: 499–502
Schernthaner G, Kostner GM, Dieplinger H, Prager R, Muehlhauser T (1983) Apolipoproteins AI, AII, B, Lp(a) and lecithin:cholesterol acyltransferase activity in diabetes mellitus. Atherosclerosis 49: 277–293
Mertz DP, Bürvenich K (1985) Unterschiedliche Werte von Lipoprotein Lp(a) bei erwachsenen Diabetikern in Abhängigkeit von der Therapieform. Klin Wochenschr 63: 648–650
Takegoshi T, Haba T, Hirai J et al. (1990) Alterations of lipoprotein(a) in patients with diabetic nephropathy. Atherosclerosis 83: 99–100
Joven J, Vilella E (1991) Serum levels of lipoprotein(a) in patients with well-controlled non-insulin-dependent diabetes mellitus. JAMA 265: 1113–1114
Levitsky LL, Scanu A, Gould SH (1991) Lipoprotein(a) levels in black and white children and adolescents with IDDM. Diabetes Care 14: 283–287
Bruckert E, Davidoff P, Grimaldi A et al. (1990) Increased serum levels of lipoprotein(a) in diabetes mellitus and their reduction with glycemic control. JAMA 263: 35–36
Haffner SM, Tuttle KR, Rainwater DL (1991) Decrease of lipoprotein(a) with improved glycemic control in IDDM subjects. Diabetes Care 14: 302–307
Haffner SM, Tuttle KR, Rainwater DL (1992) Lack of change of lipoprotein (a) concentration with improved glycemic control in subjects with type II diabetes. Metabolism 41: 116–120
Karádi I, Romics L, Palos G et al. (1989) Lp(a) lipoprotein concentration in serum of patients with heavy proteinuria of different origin. Clin Chem 35: 2121–2123
Jenkins AJ, Steele JS, Janus ED, Best JD (1991) Increased plas-ma apolipoprotein(a) levels in IDDM patients with microalbuminuria. Diabetes 40: 787–790
Kapelrud H, Bangstad H-J, Dahl-Jorgensen K, Berg K, Hanssen KF (1991) Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria. Br Med J 303: 675–678
O'Donnell MJ, Bain SC, Barnett AH, Jones A (1991) Lp(a) concentrations. Br Med J 303: 1134
Albers JJ, Hazzard WR (1974) Immunochemical quantification of human plasma Lp(a) lipoprotein. Lipids 9: 15–26
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Császár, A., Dieplinger, H., Sandholzer, C. et al. Plasma lipoprotein(a) concentration and phenotypes in diabetes mellitus. Diabetologia 36, 47–51 (1993). https://doi.org/10.1007/BF00399092
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00399092