Summary
This study has explored the temporal relationship between apoprotein(a), blood pressure and albuminuria over a mean interval of 11 years in a cohort of 107 diabetic patients of whom 26 (14 Type 2 (non-insulin-dependent), 12 Type 1 (insulin-dependent) had progressively increasing albuminuria (‘progressors’). In Type 2 diabetic patients, no significant differences were noted for HbA1, blood pressure, creatinine clearance or serum lipids between progressors and non-progressors. In Type 1 diabetic patients, final systolic and diastolic blood pressures were higher in progressors compared with non-progressors and progressors showed impairment of renal function in association with a rise in blood pressure at the macroalbuminuric stage. Initial apoprotein(a) levels were similar in progressors and non-progressors of either diabetes type. Apoprotein(a) levels increased exponentially with time in 12 of 14 Type 2 progressors but only in 5 of 12 Type 1 progressors (p<0.01). In Type 2 diabetic patients, the annual increase in apoprotein(a) levels was 9.1±2.4%, which was significantly greater than in non-progressors, 2.0±1.2% (p<0.01) and also exceeded the rates of increase of apoprotein(a) in progressors with Type 1 diabetes, 4.0±1.4%, (p<0.05). Apoprotein(a) levels correlated significantly with albuminuria in 8 of 14 Type 2 progressors but only in 3 of 12 Type 1 progressors (p<0.05). The rate of increase of apoprotein(a) levels was not related to mean HbA1, creatinine or creatinine clearance levels, or to albuminuria. The rate of rise of apoprotein(a) was not influenced by initial apoprotein(a) levels, suggesting that specific apoprotein(a) isoforms do not influence albuminuria-related increases in apoprotein(a). The data are consistent with the hypothesis that apoprotein(a) levels increase in response to albuminuria and may be part of a self-perpetuating process. This study also suggests that increases in apoprotein(a) levels commence during the microalbuminuria stage in diabetic patients, which is earlier than has been documented in non-diabetic proteinuria.
Similar content being viewed by others
References
Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 311:356–360
Jarrett RJ, Viberti GC, Argyropoulos A, Hill RD, Mahmud U, Murrells TJ (1984) Microalbuminuria predicts mortality in non-insulin-dependent diabetes. Diabetic Med 1:17–19
Borch-Johnsen K, Andersen PK, Deckert T (1985) The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 28:590–596
Yudkin JS, Forrest RD, Jackson CA (1988) Microalbuminuria as a predictor of vascular disease in non-diabetic subjects. Lancet II: 530–533
Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32:219–226
Jones SL, Close CF, Marttock MB, Jarrett RJ, Keen H, Viberti GC (1989) Plasma lipid and coagulation factor concentrations in insulin-dependent diabetics with microalbuminuria. BMJ 298: 487–490
Jensen T, Stender S, Deckert T (1988) Abnormalities in plasma concentrations of lipoproteins and fibrinogen in type 1 (insulin-dependent) diabetic patients with increased urinary albumin excretion. Diabetologia 31:142–145
Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93
Wiseman MJ, Viberti GC, Mackintosh D, Jarrett RJ, Keen H (1984) Glycaemia, arterial pressure and microalbuminuria in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 26: 401–405
Christensen CK, Mogensen CE (1985) The course of incipient diabetic nephropathy. Studies of albumin excretion and blood pressure. Diabetic Med 2:97–102
Jensen T, Bjerre-Knudsen J, Feldt-Rasmussen B, Deckert T (1989) Features of endothelial dysfunction in early diabetic nephropathy. Lancet I:461–463
Stehouwer CDA, Nauta JJP, Zeldenrust GC, Hackeng WHL, Donker AJM, Den Ottolander GJH (1992) Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet 340:319–323
Jenkins AJ, Steele JS, Janus ED, Best JD (1991) Increased plasma apolipoprotein(a) levels in IDDM patients with microalbuminuria. Diabetes 40:787–790
Winocour PH, Bhatnagar D, Ishola M, Arrol S, Durrington PN (1991) Lipoprotein(a) and microvascular disease in type I (insulin-dependent) diabetes. Diabetic Med 8:922–927
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. MBJ 303:675–678
Schernthaner G, Kostner GM, Dieplinger H (1983) Apolipoproteins(A-I, A-II, B), Lp(a) lipoprotein and lecithin: cholesterol acyltransferase activity in diabetes mellitus. Atherosclerosis 49: 277–293
Jay RH, Jones SL, Hill CE et al. (1991) Blood rheology and cardiovascular risk factors in type I diabetes: relationship with microalbuminuria. Diabetic Med 8:662–667
O'Donnell MJ, Bain SC, Barnett AH, Jones A (1991) Lp(a) concentrations. BMJ 303:1134 (Letter)
Dahlen GH, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM Jr (1986) Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 74:758–765
Utermann G (1989) The mysteries of lipoprotein(a). Science 246:904–910
Kusumi Y, Wissler RW (1991) The localization of Lp(a) in the aortas of young people. Proc 9th Intl Symposium on Atherosclerosis. Abstract 230, p75
Utermann G, Menzel HJ, Kraft HG, Duba HC, Kemmler MG, Seitz C (1987) Lp(a) glycoprotein phenotypes: inheritance and relation to Lp(a) concentration in plasma. J Clin Invest 80:458–465
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
Jerums G, Cooper M, Seeman E, Murray RML, McNeil JJ (1987) Spectrum of proteinuria in type I and type II diabetes. Diabetes Care 10:419–427
Mogensen CE, Chachati A, Christensen CK et al. (1985–86) Microalbuminuria: an early marker of renal involvement in diabetes. Uremia Invest 9:85–95
Schmidt FH (1961) Enzymatic determination of glucose and fructose simultaneously. Klin Woch 39:1244–1247
Trovati M, Lorenzati R, Navone GF, Buronzo G, Paand G, Lenti G (1981) Rapid changes of glycosylated haemoglobin in diabetes submitted to artifical pancreas control. J Endocrinol Invest 4: 103–106
Craig WY, Rovlin SE, Forster NR, Nevevx LM, Wald NJ, Ledue TB (1992) Effect of sample storage on the assay of lipoprotein(a) by commercially available radial immuno diffusion and enzyme-linked immuno sorbent assay kits. Clin Chem 38:550–553
Christensen CK, Mogensen CE (1985) Effect of antihypertensive treatment on progression of incipient nephropathy. Hypertension 7 [Suppl II]:109–113
Jerums G, Tsalamandris C, Bach LA et al. (1991) The natural history of diabetic nephropathy. Proc 13th International Diabetes Federation, Washington, 1991
Karadi 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
Editorial (1991) Lipoprotein(a). Lancet II: 397–398
Short CD, Durrington PN (1990) Hyperlipidaemia and renal disease. Baillieres Clin Endo Metab 4:777–806
Parving HH, Noer I, Deckert T et al. (1976) The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics. Diabetologia 12:161–166
Williamson J, Chang K, Tilton R et al. (1987) Increased vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozotocin-induced diabetes. Prevention by aldose reductase inhibitors and castration. Diabetes 36:813–857
Jauhiainen M, Koskinen P, Ehnholm C et al. (1991) Lipoprotein(a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. Atherosclerosis 89:59–67
Haffner SM, Tuttle KR, Rainwater DL (1991) Decrease of lipoprotein(a) with improved glycemic control in IDDM subjects. Diabetes Care 14:302–307
Levitsky LL, Scanu AM, Gould SH (1991) Lipoprotein(a) levels in black and white children and adolescents with IDDM. Diabetes Care 14:283–287
Ramirez LC, Arauz-Pacheco C, Lackner C, Albright G, Adams BV, Raskin P (1992) Lipoprotein(a) levels in diabetes mellitus: relationship to metabolic control. Ann Int Med 117:42–47
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 (1992) Lack of change of lipoprotein(a) concentration with improved glycaemic control in patients with type II diabetes. Metabolism 41:116–120
Guillausseau P-J, Peynet J, Chanson P et al. (1992) Lipoprotein(a) in diabetic patients with and without chronic renal failure. Diabetes Care 15:976–979
Black IW, Wilcken DEL (1992) Decreases in apoprotein(a) after renal transplantation: implications for lipoprotein(a) metabolism. Clin Chem 38:353–357
Jerums G, Cooper ME, Seeman E, Murray RML, McNeil J (1988) Comparison of early renal dysfunction in type I and type II diabetes: differing associations with blood pressure and glycaemic control. Diab Res Clin Prac 4:133–141
Bach LA, Sharpe K (1989) Sample size for clinical and biological research. Aust NZ J Med 19:64–68
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jerums, G., Allen, T.J., Tsalamandris, C. et al. Relationship of progressively increasing albuminuria to apoprotein(a) and blood pressure in Type 2 (non-insulin-dependent) and Type 1 (insulin-dependent) diabetic patients. Diabetologia 36, 1037–1044 (1993). https://doi.org/10.1007/BF02374496
Issue Date:
DOI: https://doi.org/10.1007/BF02374496