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Aims/hypothesis: Haptoglobin(Hp) 2-2 genotype has been shown to increase coronary artery disease (CAD) risk in numerous type 2 diabetes studies but in only one type 1 diabetes cohort. We assessed the association of Hp2-2 with incident CAD over 26years of follow-up in 1303 Caucasian participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.Methods: DCCT randomized volunteers with type 1 diabetes to intensive versus conventional therapy within two cohorts: 'primary prevention' with 1-5years diabetes duration and 'secondary intervention' with 1-15years diabetes duration and early retinopathy, with or without albuminuria, but no advanced complications. CAD was defined as myocardial infarction (MI) or death judged to be from CAD, silent MI, angina, coronary revascularization, or congestive heart failure due to CAD.Results: In the entire DCCTcohort, Hp2-2 was not significantly associated with incident CAD or MI. However, in pre-specified exploratory subgroup analyses, an increased MI risk was suggested in the secondary cohort for those with Hp2-2.Conclusions/interpretation: The analysis does not statistically confirm an overall association between Hp 2-2 and incident CAD, however, some suggestions of associations were observed in secondary analyses. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (DM) is associated with early atherosclerosis and increased cardiovascular mortality. The relation between carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis, and left ventricular (LV) mass, an independent predictor of cardiovascular morbidity, has not been previously studied in type 1 DM. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter observational study designed to follow up the Diabetes Control and Complications Trial (DCCT) cohort. LV mass was measured with cardiac magnetic resonance imaging at EDIC year 15 and common cIMT was assessed using B-mode ultrasound at EDIC year 12. Multivariable linear regression models were used to assess the relation between cIMT at year 12 and LV mass at year 15. In total 889 participants had cardiac magnetic resonance imaging and cIMT measurements available for these analyses. At EDIC year 15, mean age of the participants was 49 ± 7 years, mean DM duration was 28 ± 5 years, and 52% were men. Spearman correlation coefficient (r) between LV mass and cIMT was 0.33 (p <0.0001). After adjusting for basic covariates (machine, reader, age, and gender), a significant association between LV mass and cIMT (estimate 2.0 g/m(2) per 0.1-mm cIMT increment, p <0.0001) was observed. This association was decreased by the addition of systolic blood pressure, in particular 1.15 g/m(2) per 0.1-mm cIMT increment (p <0.0001), and to a lesser extent other cardiovascular disease risk factors. Furthermore, the relation observed between LV mass and cIMT was stronger in patients with shorter duration of DM. In conclusion, cIMT was an independent predictor of larger LV mass in a well-characterized population with type 1 DM. [ABSTRACT FROM AUTHOR]

Abstract: Immune complexes containing modified LDL (LDL-IC) and NMR-determined Total LDL particle concentrations are significantly associated with intima-media thickness (IMT). We analyzed the associations between concentrations of NMR-determined lipoprotein subclasses and LDL-IC in the DCCT/EDIC cohort. LDL-IC concentrations in women and men of the DCCT/EDIC cohort did not differ significantly and were positively associated with Total LDL particle concentrations in men and women (r=0.34, r=0.32, respectively; P<.01) and with Small LDL concentration (r=0.22, r=0.13, respectively; P<.01). In women, Large LDL concentrations were also associated with LDL-IC (r=0.20, P<.01) while in men, the association was more modest (r=0.11, P<.05). Thus, both Small and Large LDL are associated with LDL-IC formation. Based on the results from statistical mediation analyses, we concluded that plasma concentrations of LDL-IC may provide a physiological link between the statistically significant association of Total LDL particle concentration with carotid artery IMT in subjects with Type 1 diabetes. Furthermore, after adjusting for conventional risk factors, there was a decrease in LDL-IC concentration even in the presence of high Total LDL particle concentrations in those women with high concentrations of Large HDL, but the association was not evident in men. This suggests that the associations between Large HDL and Total LDL particle concentrations, and their associations with LDL-IC levels, differ by gender and suggest that LDL-IC partially mediate the contribution of Total LDL particle concentration to increased carotid IMT in diabetic men. [Copyright &y& Elsevier]

Abstract: Objective: To determine the relationships between C-reactive protein (CRP) levels and features of Type 1 diabetes. Research Design and Methods: Serum CRP was measured by nephelometry in a cross-sectional study of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort (n=983) and nondiabetic subjects (n=71). Results: CRP levels [geometric mean (95% CI)] were higher in diabetic than in control subjects, 1.6 (1.5–1.7) vs. 1.2 (1.1–1.5) mg/l, P=.019. CRP was higher in diabetic women (n=438) than in men (n=545) [2.0 (1.8–2.3) vs. 1.3 (1.2–1.5), P<.001]. Diabetic subjects formerly in the DCCT intensive treatment group had higher CRP levels than those who were randomized to the conventional treatment group [1.8 (1.6–1.9), n=479 vs. 1.5 (1.3–1.6), n=456, P=.010], attributable to greater BMI in the prior intensive group. In diabetes, CRP correlated with HbA1c (r=0.13, P<.0001) and with insulin resistance traits: BMI (r=0.34, P<.0001), waist-to-hip ratio (WHR; males: r=0.35, P<.0001; females: r=0.22, P<.0001), diastolic blood pressure (r=0.07, P=.025), triglycerides (r=0.19, P<.0001), apoB (r=0.22, P<.0001), LDL particle concentration (r=0.26, P<.0001), and LDL particle size (r=−0.22, P<.0001). CRP was not associated with complications. Significant independent predictors of CRP in diabetes were gender, BMI, WHR, concurrent HbA1c, and oral contraceptive pill use. Conclusions: CRP was elevated relative to nondiabetic subjects, and in diabetes was higher in females. Elevated CRP in Type 1 diabetes was associated with poor glycemic control, larger body habitus, and other factors that comprise the insulin resistance syndrome. Nevertheless, CRP levels were not associated with complications. Longitudinal studies are warranted. [Copyright &y& Elsevier]