Hp1-1 as a Genetic Marker Regulating Inflammation and the Possibility of Developing Diabetic Complications in Patients with Type 2 Diabetes—Cohort Studies

Background: This study assessed the influence of the haptoglobin phenotype on markers regulating inflammation in patients with type 2 diabetes. Methods: The haptoglobin phenotypes, soluble form of CD163 receptor (sCD163), p53 concentrations and high mobility group box protein 1 (HMGB1), interleukin 10 (IL-10) secretion in serum were assayed via ELISA tests. In the first part of the project, patients were divided into three groups which differed by the haptoglobin phenotype, and afterwards into two groups according to the criterion of the presence or absence of cardiovascular disease. Results: Diabetic patients with haptoglobin phenotype 1-1 (Hp1-1) had a significantly higher concentration of IL-10 and sCD163 compared to haptoglobin phenotype 2-1 (Hp2-1) and haptoglobin phenotype 2-2 (Hp2-2). Moreover, diabetic patients with Hp1-1 had a significantly lower concentration of p53 and HMGB1 compared to diabetic patients with Hp2-1 and Hp2-2. The results have shown that diabetics with Hp2-1 had a significantly lower postprandial glucose level compared to diabetics with Hp2-2. Apart from that, there were no differences in the occurrence of haptoglobin variants between patients with or without cardiovascular disease. Conclusions: Our study provides new data for a relationship between the type of haptoglobin in patients with type 2 diabetes and the concentration of factors that regulate the body’s inflammation. We have shown that the Hp1-1 can serve as a genetic marker of inflammatory processes.

Haptoglobin is associated with increased early perihematoma edema progression in spontaneous intracranial hemorrhage

Introduction Perihematomal edema in intracranial hemorrhage is influenced by free hemoglobin clearance and inflammation. Serum Haptoglobin (Hp) binds free hemoglobin, affecting heme clearance and free radical production. Of the three Hp phenotypes, Hp 1-1 has the greatest effect on free hemoglobin clearance. Aim To determine if individuals with Hp 1-1 phenotype have different rates of early perihematomal edema formation as compared to those with Hp 2-1 and Hp 2-2. Methods We determined Hp phenotype, intracranial hemorrhage volume, and rate of early change in perihematomal volume in participants from three prospectively collected intracranial hemorrhage cohorts. The association of Hp phenotypes 1-1, 2-1, 2-2, with early change in perihematomal volume, while controlling for key clinical characteristics was analyzed using a multivariate model. Findings One-hundred and sixty-six participants were included: 73 (44%) female, 41 ( 25%) African Americans, 34 (20%) diabetics, 133 (80%) with hypertension, and 75 (45%) active smokers. There were 15 subjects with Hp phenotype 1-1, 86 with 2-1, and 65 with 2-2. In fully adjusted analysis, Hp 1-1 had a significantly increased estimated mean rate of early change in perihematomal volume at 1.15 (95% confidence interval 0.58–1.71) as compared to all other Hp 2-1 or Hp 2-2 containing phenotypes (0.30, 95% confidence interval 0.06–0.54; 0.29 95% CI 0.02–0.56). Neither mortality nor discharge mRS differed between Hp phenotypes. Conclusion Haptoglobin phenotype is associated with early change in perihematomal volume. Hp 1-1 phenotype had significantly increased mean rate of early change in perihematomal volume within the first 96 h, suggesting that haptoglobin phenotype may be a key player in understanding the multiphasic progression of perihematomal volume in spontaneous intracerebral hemorrhage. A larger prospective observational study is warranted.

Abstract WMP97: Haptoglobin is Associated With Increased Early Perihematoma Edema Progression in Spontaneous Intracranial Hemorrhage

Introduction: Perihematomal edema in intracranial hemorrhage (ICH) is influenced by free hemoglobin clearance and inflammation. Serum Haptoglobin (Hp) binds free hemoglobin, affecting clearance as well as free radical production, resulting in inflammation. Of the three phenotypes of Haptoglobin, Hp 1-1 has the greatest effect on free hemoglobin clearance. We hypothesized that individuals with the Hp 1-1 phenotype have different rates of early perihematomal edema formation as compared to those with Hp 2-1 and Hp 2-2. Methods: We determined Hp phenotype, ICH volume, and rate of early change in perihematomal volume (ePHE) in participants from three prospectively collected ICH cohorts; Johns Hopkins University hospital (JHH), Massachusetts General Hospital (MGH), and the MISTIE III trial. The association of Hp phenotypes 1-1, 2-1, 2-2, with ePHE, while controlling for key clinical characteristics was analyzed using a multivariate model. Findings: 166 participants, 57 from JHH, 30 from MGH, and 79 from the MISTIE III trial were included: 73 (44%) female, 41(25%) African Americans, 34 (20%) diabetics, 133 (80%) with hypertension, and 75 (45%) active smokers. There were 15 subjects with Hp phenotype 1-1, 86 with 2-1 and 65 with 2-2. In the adjusted analysis, controlling for race, diabetes, hypertension, smoking status, and change in intracranial hemorrhage volume over time (cc/hr), Hp 1-1 had a significantly increased estimated mean rate of ePHE at 1·15, (95% CI 0·58-1·71) as compared to all other Hp 2-1 or Hp 2-2 containing phenotypes (0·30, 95% CI 0·06-0·54; 0.29 95% CI 0·02-0·56). Neither mortality nor discharge mRS differed between Hp phenotypes. Interpretation: Haptoglobin phenotype is associated with ePHE. Hp 1-1 significantly increased mean rate of ePHE suggests that haptoglobin phenotype may be a key player in understanding the multiphasic progression of PHE in sICH, which may help identify windows for targeted interventions to improve clinical outcomes. Conclusion: In our adjusted models, patients with the Haptoglobin 1-1 phenotype had an increased rate of ePHE formation within the first 96 hours. The Hp 1-1 phenotype may increase perihematomal progression in sICH. A larger prospective observational study is warranted.