Does the Concentration of Oxidative and Inflammatory Biomarkers Differ by Haptoglobin Genotype in Type 1 Diabetes?

The haptoglobin (Hp) 2 allele directly predicts coronary artery disease in type 1 diabetes, potentially due to its decreased antioxidative/anti-inflammatory properties. We measured the concentrations of oxidative/inflammatory biomarkers (urinary 15-isoprostane F(2t) [IsoP], α- and γ-tocopherol, tumor necrosis factor α [TNF-α], high-sensitivity C-reactive protein [hsCRP], white blood cell [WBC] count, fibrinogen, and adiponectin) thrice during 20 years of follow-up among 454 individuals with childhood-onset type 1 diabetes (mean baseline age, 28 years and diabetes duration, 19 years). Differences in biomarkers by Hp were assessed both at baseline (i.e., the first time point of measurements) and over time (with mixed models). No differences by Hp were observed at baseline with the exception of a significant trend toward higher IsoP concentrations with the number of Hp 2 alleles (p=0.01). In multivariable mixed models, the concentrations of IsoP (β=0.05, p=0.01) and WBC count (β=0.20, p=0.06) overtime increased incrementally with the number of Hp 2 alleles. No other biomarker assessed related to Hp. Reported elevated IsoP and WBC count concentrations over time among Hp 2 allele carriers lead to the hypothesis that the antioxidative and anti-inflammatory capacity of the Hp 2 is inferior to that of the Hp 1 allele in type 1 diabetes.