Objectives: To determine whether apo(a) isoforms and plasma Lp(a) concentrations in association with some lipid parameters increase the relative risk for the development of atherosclerosis in patients with diabetes mellitus (IDDM and NIDDM). Design and methods: Apo (a) isoforms, Lp(a) and plasma lipids were determined in 40 IDDM and 65 NIDDM patients and in 182 healthy individuals. Apo(a) isoforms were separated by 3 to 15% gradient SDS-PAGE followed by immunoblotting. Results: Logistic analysis showed that: Lp(a) levels >30 mg/dL (RR = 0.25, p < 0.000001; RR = 0.18, p < 0.00002), HTA (RR = 0.212, p < 0.00001; RR = 0.30, p < 0.00001), LMW-S1 apo(a) isoform (RR = 6.86, p < 0.0131; RR = 7.04, p < 0.0057) play a significant role in aterogenecity in both groups of patients with DM (IDDM and NIDDM). The 6.50-fold increase in risk was found in NIDDM patients with high Lp(a) levels (>30 mg/dL) and plasma total/HDL cholesterol ratio (4.5-5.8). Conclusion: Elevated Lp(a) levels, LMW S1 apo(a) isoform, HTA and combination of increased Lp(a) levels and total/HDL cholesterol ratio increase the risk for the development of atherosclerosis in patients with DM (IDDM and NIDDM). (C) 2003 The Canadian Society of Clinical Chemists. All rights reserved.