Haptoglobin 2–2 genotype and the risk of coronary artery disease in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC)

Abstract

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 Hp 2-2 with incident CAD over 26 years of follow-up in 1,303 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 1–5 years diabetes duration and ‘secondary intervention’ with 1–15 years 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 DCCT cohort, Hp 2-2 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 Hp 2-2. 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.

The protean role of haptoglobin and haptoglobin genotypes on vascular complications in diabetes mellitus

“…61 In the large T1DM DCCT/EDIC cohort with duration of follow-up median 26 years, a significant association of myocardial infarction was seen with Hp2-2 individuals in the secondary cohort (consisting of patients with duration of diabetes: 1–15 years with early minor complications, for example, retinopathy/microalbuminuria). 62 These data suggest that in individuals with advanced T1DM, the Hp2-2 genotypes confer a higher risk of cardiovascular complications. This is consistent with the pathophysiology that when the system is stressed as in prolonged hyperglycaemic situations the Hp2-2 genotype confers a higher risk due to deficient antioxidative or anti-inflammatory pathways.…”

“…We have summarized in Table 2 the human studies looking at association of Hp genotypes with complications in T1DM. 58–72 Studies have been conducted in three large cohorts of T1DM in the United States: 1. Coronary Artery Calcification in T1DM (CACTI); 2. the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, and 3.…”

Cardiovascular and Metabolic Protection by Vitamin E: A Matter of Treatment Strategy?

“…However, the study of De Bacquer et al reported an increased risk of cardiovascular events in non-diabetic patients with the Hp 1-1 phenotype in the Belgian Interuniversity Research on Nutrition and Health (BIRNH) survey [ 241 ]. The relevance of the Hp genotype for the cardiovascular risk in patients suffering DMT1 remains elusive [ 242 ].…”

Association between serum haptoglobin and carotid arterial functions: usefulness of a targeted metabolomics approach

“…Systemic metabolic dysfunctions, such as hyperglycaemia, insulin resistance and dyslipidaemia, give rise to an elevated risk of cardio-cerebrovascular diseases, including cerebral infarction, stroke, and heart attacks [3, 4]. The pathogenesis underlying macroangiopathy is complicated and yet not well clarified [5–8]. A group of studies was previously launched to explore the causality underlying the relationship of several novel biomarkers with macroangiopathy risk [9–11], and a causal relationship between serum haptoglobin (Hp) levels and macroangiopathy was observed in Chinese T2DM patients via Mendelian randomization analysis [12].…”