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Small LDL size is common in patients with type 2 diabetes and is associated with an increased risk of cardiovascular disease (1). LDL size is determined by various constituents of lipoprotein metabolism, such as lipoprotein lipase (LPL) and hepatic lipase (HL) activities, cholesteryl ester transfer protein (CETP), as well as triglyceride concentrations (2-4). Although abnormalities in LPL, HL, and CETP levels are associated with a diabetic lipoprotein profile, a relation to insulin resistance has been found only with lipase activities (5-7) but not with CETP (8,9). In this cross-sectional study, we investigated the relationship of LPL and HL activities and CETP mass with LDL size in 426 subjects with normal and impaired glucose metabolism or type 2 diabetes. RESEARCH DESIGN AND METHODS -The HoornStudy is a population-based cohort study of glucose metabolism and cardiovascular risk factors among 2,484 inhabitants of the municipality of Hoorn, which started in 1989. In 2000 -2001, a follow-up was conducted in selected subjects then aged 60 -87 years, as previously described (10). We invited all surviving subjects with type 2 diabetes (n ϭ 176) and random samples of individuals with normal glucose metabolism (n ϭ 705) or impaired glucose metabolism (n ϭ 193) based on their glucose metabolism status (World Health Organization 1999 criteria) at the previous examination in 1996 -1998 (11). Of the 1,074 individuals invited, 648 (60.3%) subjects participated. At the follow-up examination, a sample of 566 participated in the postheparin test. The Ethical Review Committee of the VU University Medical Center approved the study. Written informed consent was obtained from all participants. LDL size was measured by high-performance gel-filtration chromatography (12). CETP mass was determined using a two-antibody sandwich immunoassay (13). LPL and HL activities were measured in plasma collected 20 min after contralateral intravenous administration of heparin, using an immunochemical method (14). One hundred and seven samples were excluded from analyses because very low activities of LPL and HL in postheparin plasma indicated insufficient heparin delivery. Activities were considered as very low if LPL activity was Ͻ50 units/l and if HL activity was Ͻ72 units/l. The contribution of HDL cholesterol, triglycerides, insulin, LPL, HL, and CETP to LDL size was analyzed in univariate and multivariate linear regression models in categories of glucose metabolism, with LDL size as the dependent variable with adjustment for sex.RESULTS -Mean LDL size (in nanometers) was 21.6 Ϯ 0.4, 21.5 Ϯ 0.4, and 21.2 Ϯ 0.5 in subjects with normal, impaired glucose metabolism, and diabetes, respectively. Mean LPL activity (in units per liter) was 150 Ϯ 51, 147 Ϯ 51, and 135 Ϯ 42, respectively. There were no differences in HL activity (mean 372 Ϯ 135 units/l) and CETP mass (1.87 Ϯ 0.56 mg/l) between the three glucose metabolism categories.In this elderly population, we observed a stronger positive association between LPL activity and LDL size in subjects ...